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Editors Althea Mahon Karen Jenkins Project Co-ordinator Mara Cruz Casal

Chronic Kidney Disease


A Guide to Clinical Practice

This handbook is an initiative of EDTNA/ERCA Chronic Kidney Disease (CKD) Interest Group A limited edition will be available in the following languages: English, Spanish, Greek, Czech, Hebrew, Portuguese and Turkish

All rights are reserved by the author and publisher, including the rights of reprinting, reproduction in any form and translation. No part of this book may be reproduced, stored in a retrieval system or transmitted, in any form or by means, electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the publisher.

First edition: July 2007 European Dialysis and Transplant Nurses Association/ European Renal Care Association (EDTNA/ERCA) Pilatrustrasse 35, Postfach 3052, 6002 Luzern, Switzerland www.edtnaerca.org ISBN: 978-84-611-8259-6 D.L.: M-34351-2007 Layout, Binding and Printing: Imprenta Toms Hermanos
C/Ro Manzanares, 42-44 E28970 Humanes de Madrid Madrid - Spain

www.tomashermanos.com

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Acknowledgments

This book is an initiative of EDTNA/ERCACKD Interest Group. A considerable contribution has been made by all Interest Group Members: Karen Jenkins, Anastasia Liossatou, Sue Teasdale, Tai Mooi Ho Wong and Nurit Cohen in the production of this publication. I would like to take this opportunity to thank all of them. A special mention goes to Althea Mahon, Immediate Past President of EDTNA/ERCA for her support in all phases of this project: as Author, Editor and for Proof Reading. Along with Karen Jenkins they have assumed all of these roles in order to complete this book, and it has been greatly appreciated. The EDTNA/ERCA would like to thank all authors of each chapter Editors: Althea Mahon, RN, BSc Nursing, MSc Nursing
Barts and The London NHS Trust, London, UK

Karen Jenkins, RN PG Dip HE. MSc Nursing


Department of Renal Medicine, East Kent Hospitals NHS Trust, Canterbury, UK

Co-ordinator Maria Cruz Casal RN, DUE


Laboratory of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain

Acknowledgments

Reviewers: Annemarie Visser, BSc, Dietetics Diploma in Hospital Dietetics


Barts and The London NHS Trust, London, UK

Lesley Bennett BA, RN, RM, Renal Cert


Oxford Radcliffe NHS Trust, Churchill Hospital, Oxford, UK

Diane Green BSc (Hons), RD


Salford Royal Hospitals NHS Trust, Manchester, UK

Dr Cordelia Ashwanden, PhD, MSc, BSc (Hons),


Adult Ed. Cert, RGN Editor of the EDTNA/ERCA Journal of Renal Care

Ray James, BSc, MSc


Sub-editor of the EDTNA/ERCA Journal of Renal Care

Translators: Thanks to Spanish, Greek, Czech, Israeli, Portuguese and Turkish colleagues for their collaboration in the translation of this book. Sponsor: The printing of the English version of this book has been sponsored by an education grant from Roche Products Ltd (UK) Finally thanks go to the EDTNA/ERCA Executive Committee for their support of the Chronic Kidney Disease Interest Group
Maria Cruz Casal
CKD Interest Group Chair

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Preface

..............................................................................................................

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Althea Mahon, RN, BSc Nursing, MSc Nursing


Barts and The London NHS Trust, London, UK

1. Anatomy and Physiology of the Kidney ............................................................................................ 21 Melissa Chamney, RN, BN, MN, PG Dip Academic Practice, City University, London, UK 2. Assessment, Diagnosis and Management of Chronic Kidney Disease ........................................................................................ 33 Karen Jenkins, RN, PG Dip HE, MSc Nursing
Department of Renal Medicine, East Kent Hospitals NHS Trust, Canterbury, UK

3. Diagnostic Investigations in Chronic Kidney Disease ................................................................ 53 Tai Mooi Ho Wong, RN, RM, DUE, Hypertension Unit, Hospital del Mar, Barcelona, Spain Mara Cruz Casal, RN, DUE Laboratory of Nephrology. Hospital Universitario 12 de Octubre, Madrid, Spain

Table of contents

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4. Management of Anaemia in Chronic Kidney Disease ................................................................ 85 Anastasia Liossatou, RN, BN, MSc Nephrology Department, General Hospital of Kefalonia, Argostoli, Kefalonia, Greece Karen Jenkins, RN, PG Dip HE, MSc Nursing
Department of Renal Medicine. East Kent Hospitals NHS Trust, Canterbury, UK

5. Nutrition and Chronic Kidney Disease ...................................................................................... 105 Nurit Cohen, RN, BN, Master of Public Health (MPH), Nephrology Department, Soroka University Medical Center, Beer-Sheva, Israel Lina Schwarz, RN, BN Nephrology Department. Soroka University Medical Center, Beer-Sheva, Israel Diane Green, BSc (Hons), RD Salford Royal Hospitals NHS Trust, Manchester, UK 6. The Effect of Diabetes Mellitus on Chronic Kidney Disease Progression ............................................................................................... 119 Sue Teasdale, RN, MA, BSc (Hons)
Salford Royal Hospitals NHS Trust, Manchester, UK

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7. Cardiovascular Risk in Chronic Kidney Disease ...................................................................................... 135 Sue Teasdale, RN, MA, BSc (Hons)
Salford Royal Hospitals NHS Trust, Manchester, UK

8. Management of Hypertension in Chronic Kidney Disease ...................................................... 149 Mara Luisa Fernandez, RN, DUE Hypertension Unit. Hospital Universitario 12 de Octubre, Madrid, Spain Julin Segura
Consultant Nephrologist, Hypertension Unit. Hospital Universitario 12 de Octubre, Madrid, Spain

9. Patient Information

...........................................................................

165

Althea Mahon, RN, BSc, MSc Nursing Barts and The London NHS Trust, London, UK

Table of contents

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Preface The early detection of chronic kidney disease (CKD) is important as it provides the best opportunity to modify the disease and reduce the associated cardiovascular risk. CKD affects approximately 10% of the population1,2. Slowing the progression of the disease has a major impact on reducing the number of patients requiring renal replacement therapy and improving the quality of life and outcomes for patients. It is important to remember that, of those diagnosed with CKD, only a small minority will reach end stage renal failure. This pocket guide focuses on CKD stages 1-3 which has become a major health concern as a result of early detection programmes. The US NHANES study found the prevalence of stage 3 CKD and higher (i.e. a glomerular ltration rate of 60ml/min/1.73m2)1 in US adults in the unselected adult population was 4.7%. This has been supported by a large survey of 112,215 people from 12 general practice surgeries in the UK where they found the prevalence to be 4.9%3. The prevalence of CKD amongst people with other co-morbidities such as diabetes, hypertension, and coronary heart disease will be considerably higher than 4.9%. The rise in diagnosis of CKD is multifactorial and, in part, is associated with the ageing population. In addition to people living longer, there have been improvements in chronic disease management. Another important factor is the rise in the incidence of type 2 diabetes, which is expected to double in the next 25 years4. This in turn will lead to an increased incidence of diabetic nephropathy, with approximately 30% progressing to Stage 5 CKD. Other factors include an increase in CKD prevalence with age5. Men with CKD have a more rapid decline in renal function and progression of their renal disease than women6. Some ethnic populations have a higher

Preface

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prevalence of CKD such as South Asians in the UK7 and AfroCaribbeans8. People from South Asia are at higher risk of CKD linked to diabetes as there is a higher incidence of diabetes in this community9. Afro-Caribbeans and Africans are at greater risk of CKD due to their higher prevalence of hypertension10. The reality is that the majority of the CKD population have one or more co-morbid condition, with a known higher prevalence in ethnic minorities and lower socio-economic groups; combine this with the increase in childhood obesity and prevalence of diabetes and it is clear why we have an epidemic of CKD and that, without effective prevention and early detection programmes, this will continue to rise. Lastly the rise may also be due to the development of guidelines such as KDOQI11 and also nationally agreed CKD guidelines such as the UK CKD guidelines12, along with the implementation of a simple blood test-based formulae (e.g. GFR) that allows for easier and earlier diagnosis of CKD and therefore increased reporting. Whilst acknowledging that CKD is progressive, with good management, mainly focusing on lowering blood pressure, maximizing lipid control, lowering salt intake, encouraging regular exercise and weight reduction, maintaining tight diabetic control, giving smoking cessation advice and avoiding nephrotoxic drugs this progression can be slowed. Early detection and management of CKD stages 1-3 can be and should be undertaken in primary care. Healthcare professionals have a responsibility to understand the classication system of CKD, its assessment process and treatment. It is hoped that this pocket guide will be a useful tool in the assessment, diagnosis, management and treatment of the early stages of CKD.

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References
Coresh J, Astor BC, Greene T, Eknoyan G, Levey A. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third national health and nutrition survey. Am J Kidney Dis, 2003; 41, (1): 1-12. 2. John R, Webb M, Young A, Stevens PE. Unreferred chronic kidney disease: a longitudinal study. Am J Kidney Dis 2004; 43: 825-835. 3. de Lusignan S, Chan T, Stevens P, ODonoghue D, Hague N, Dzregah B et al. Identifying patients with chronic kidney disease from general practice computer records. Fam Pract 2005; 22, (3): 234-241. 4. Atkins R. The epidemiology of chronic kidney disease. Kidney Int 2005; 67, (Supp 94): S14-S18. 5. Rodriguez-Puyol D. Aging kidney. Kidney Int 1998; 54: 2247-2265. 6. Neugarten J, Acharya A, Silbiger SR. Effect of gender on the progression of nondiabetic renal disease: a meta-analysis. J Am Soc Nephrol 2000; 11(2):319-329. 7. Buck K, Feehally J. Diabetes and renal failure in Indo-Asians in the UK: a paradigm for the study of disease susceptibility. Nephrol Dial Transplant 1999; 23: 1555-1557. 8. United States Renal Data System. Annual data report: incidence and prevalence of ESRD (2003). Am J Kidney Dis 2003; 42 (Suppl 5): S37-41. 9. Lightstone L. Preventing kidney disease: the ethnic challenge. The National Kidney Research Fund: Peterborough. 2001. 10. Raleigh VS. Diabetes and hypertension in Britains ethnic minorities: implications for the future of renal services. BMJ 1997; 313:209-215. 11. National Kidney Foundation. Clinical practice guidelines for chronic kidney disease: evaluation classication and stratication. Am J Kidney Dis 2002; 39 (Supp 1): S1-266. 12. Chronic Kidney Disease in Adults: UK CKD Guidelines for Identication, Management and Referral of adults (2005). Available from: http//www.renal.org/CKDguide/ckd.html 1.

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Learning Outcomes Review knowledge and understanding of the normal anatomy and physiology of the kidney An understanding of the pathophysiology of chronic kidney disease (CKD) and the most common causes of CKD Knowledge of the signs and symptoms of CKD

Introduction: The kidneys perform a number of important regulatory, excretory and hormonal functions that will be discussed in this chapter. The most signicant role of the kidneys is to appropriately lter waste products from the blood excreting them in the urine. The kidneys process the blood to form urine, which serves several important functions. Waste products from cell activity are excreted Fluid that accumulates in the body from ingestion of food and water is removed The concentration of many substances within the body is maintained within limits The kidneys typically produce 180L of ltrate from the blood per day; however the vast majority of the ltered uid is reabsorbed into the bloodstream. Approximately 2 litres of uid is nally excreted as urine. The remaining 178 litres of

Anatomy and Physiology of the Kidney

uid are reabsorbed back into the blood stream so that normal metabolite concentration and homeostasis are maintained1. Large molecules such as red blood cells and protein are retained within the blood and smaller molecules enter the ltrate. Only excess uid and metabolic waste and toxic products are removed from the body. Kidneys play a crucial role in maintaining water and electrolyte balance. Kidneys also regulate acid base balance within a narrow range2. The purpose of this chapter is to identify the main parts of the kidney and describe their basic function. Normal Anatomy and Physiology The kidneys lie on either side of the spine, just below the ribs at the back of the body and each kidney is approximately 10 - 15 cms in length and shaped like a bean, this is proportional to the size of the individual. The right kidney is slightly lower than the left kidney due to the existence of the liver on that side3. Approximately 20% of cardiac output passes through the kidneys per minute. Under normal physiological conditions this blood ow is autoregulated, ensuring acceptable Glomerular Filtration Rate (GFR), ultraltration, selective secretion and excretion of substances which contribute to the production of urine and elimination of metabolic waste products4. A high rate of blood ow and normal blood pressure within the kidneys is essential for the formation of urine2. The kidneys receive a constant supply of blood which needs to be ltered in order to remove the excess water and waste. In this manner the kidneys also regulate the amount of various substances in the blood stream, so that homeostasis is maintained. So how does it all work? The functional unit of the kidney is called the nephron and is able to create urine by itself. Therefore it is not necessary to

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describe the entire kidney, but merely the operation of one nephron to explain the function of the kidney5. Each kidney contains approximately one million nephrons, each one of which has its own glomerulus. Inammation, damage and destruction of the glomerulus will adversely affect its capacity to lter blood and this in turn will reduce the scope of the nephron to process the ltrate and produce urine. Since the glomeruli lter waste products and water from the blood any glomerular damage will adverely affect the persons homeostasis. The kidney also contains a system of collecting ducts that carry urine through the renal pyramids into the calyces, in the renal pelvis to the ureter. The systemic blood pressure determines if blood enters the glomerulus from the afferent arteriole. Holes in the capillary lining allow small particles to pass into the renal tubule and larger proteins are retained as they cannot pass through the glomerular ltration barrier8. Glomerular ltration is the process by which ltrate is produced and it is the rst phase in urine production. The ltrate produced consists of virtually all blood components except larger molecules such as protein and red blood cells. However, many of the smaller substances that pass freely through the glomerulus are vital for normal body function. A process called tubular reabsorption is the second phase which selects certain substances from the ltrate and returns them to the blood via the peritubular capillaries, thus avoiding loss into the urine. Tubular secretion is the third phase where substances which are not ltered are secreted into the tubule and excreted. By the time the nal excretory product (urine) drains from the collecting duct into the renal pelvis it is greatly reduced in volume. The urine removes toxic waste products from the body as well as excess salt and water r4. The glomerulus is a high pressure capillary bed which causes uid to be ltered out of the blood. By contrast the peritubular capillary bed has low pressure which allows uid

Anatomy and Physiology of the Kidney

Diagram 1: The Nephron.


Proximal tubule Bowman's capsule Peritubular capillary network Distal tubule

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Collecting tubule

Glomerulus Artery Efferent arteriole Afferent arteriole

Juxtaglomerular apparatus

Collecting duct

Vein

Loop of Henle

Vasa recta

to be reabsorbed back into the blood from the tubules. As solutes are transported out of the proximal tubules in particular by the reassertion process, an osmotic gradient is established causing water to be absorbed. Consequently over 65% of the glomerular ltrate is reabsorbed before entering the Loop of Henle. Progressively lower fractions of water are reabsorbed as the ltrate passes through the tubular system. By varying the rate of reabsorption, large and small volumes of urine can be generated allowing extracellular uid volume in the body to be maintained which in turn is of importance in the control of blood pressure9. In addition to water, a number of substances of nutritional importance are reabsorbed such as glucose, proteins and amino acids. The vasa recta are involved in the very important task of concentrating the urine. Without the ability of the kidneys to concentrate urine, a great deal more water would be needed to remove solutes from the blood3.

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This would require very regular drinking and result in a high urine output. The glomerular capillaries have very high permeability, 100 to 500 times greater than the permeability of capillaries in other body tissues. When blood enters the glomerulus large quantities of uid are ltered from the blood forming the glomerular ltrate which then enters the Bowmans capsule. Although the glomerular membrane is highly permeable, it is also selective, depending on the molecular size of a given substance. The permeability to large molecules such as proteins is very low and thus these are conned to the blood. For all practical purposes the glomerular ltrate has virtually the same composition as blood plasma (containing all dissolved solutes) with the exception of proteins. The rate at which ltrate is generated is called the glomerular ltration rate (GFR). It is important that the GFR is tightly controlled. Any disparity would otherwise upset the ne balance between ltration and reabsorption, which controls the volume of urine produced. An increase in GFR would cause the ltrate to pass more rapidly through the tubules at a rate exceeding reabsorption. Similarly if the GFR decreases, all uid entering the tubules would be reabsorbed and there would be no urine output. A mechanism called auto regulation ensures that the GFR is tightly controlled. This is achieved by vasodilation of the afferent arteriole and vasoconstriction of the efferent arteriole. Although the GFR is maintained relatively constant, extremes of mean arterial pressure ultimately cause some effect in urine output. High arterial pressure leads to increase urine output whereas at pressures below 50 mmHg urine output virtually ceases. This link between arterial pressure and urine output is called pressure diuresis. A persons bladder can hold on average 400 mls of urine before they will feel the need to urinate and most people pass two litres of urine per day. The kidneys are able to vary this

Anatomy and Physiology of the Kidney

output of urine between 400 - 1500 mls to maintain a constant uid volume3. Usually when these processes fail urine production may cease altogether severely limiting the removal of waste products and excess water from the body. Some aspects of renal function are assessed by measuring the concentrations of metabolites such as urea and creatinine, both of which are excreted by the kidney. The glomerular ltration rate (GFR) is also a measure of renal function and will be discussed further in the CKD chapter. Functions of the Kidney As discussed above, the functions of the kidney include the production of urine via ltration of the blood, reabsorption of necessary electrolytes and excretion of waste products. This way the kidneys control homeostasis and uid balance as well as acid-base and electrolyte balance.
Table 1: The functions of the kidney3

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Excretory Excretion of f metabolic waste products, e.g. urea and creatinine Regulatory Regulation of: Body water volume Body uid osmolality Electrolyte balance Acid-base balance Blood pressure Metabolic Activation of vitamin D Production of Renin Production of Erythropoietin
(From Thomas, N (2002) Renal Nursing (2nd Ed), Bailliere Tindall, London, with permission of Elsevier Publications).

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They also control hormonal functions of renin production to control blood pressure, erythropoietin production to stimulate red cell production, and synthesis of vitamin D to assist with intestinal absorption of calcium. A number of hormones inuence renal function and the regulation of various substances: The Renin Angiotensin Aldosterone System maintains blood pressure Aldosterone contributes to the control of sodium and potassium by stimulating sodium re-absorption in the distal tubules and collecting ducts Anti-Diuretic Hormone increases the absorption of water Erythropoietin is produced primarily by the kidneys and is essential for haemoglobin production Vitamin D and Vitamin D3 are essential to form active Vitamin D to maintain calcium balance Parathyroid Hormone is released by the parathyroid glands to maintain calcium and phosphate levels Calcitonin affects plasma Ca+ levels What happens in Chronic Kidney Disease CKD is a progression from health to illness which results in a permanent failure of the excretory, regulatory and hormonal (metabolic) functions of the kidney. CKD can be a slowly progressive disease over many months or years which results from the gradual loss of nephrons. The function may be stable for prolonged periods of time and can be managed with conservative management strategies. CKD is often asymptomatic in the early stages and is often not diagnosed until sufcient impairment exists to retain uraemic toxins in the blood. Unfortunately the damage caused by CKD is irreversible and so unless the patient is managed appropriately, particularly at the early stages, it can then be impossible to delay or even stop their CKD progressing to later stages of established renal failure where the person will require Renal Replacement Therapy (RRT) of some form to maintain life.

Anatomy and Physiology of the Kidney

Renal Problems: There are many presentations of CKD; it is not a disease itself but the result of a number of disease processes which may affect renal function such as: Glomerular diseases (Glomerulonephritis) Cystic diseases (Adult Polycystic Disease) Systemic diseases (Multiple Myeloma) Vascular diseases (Hypertension) Obstructive disorders (Renal Stones) Drug related reactions (Paracetamol, NSAIDS) Diabetes is the fastest growing risk for renal failure in the western world and hypertension is the second leading cause of CKD. People with a family history of renal failure or a persons age are factors that cannot be controlled, but other factors such as controlling blood glucose levels and blood pressure can help renal function to be maintained for longer. The KDOQI guidelines 200310 recommend a target blood pressure should be <130 / 80 mmHg for patients with CKD, regardless of the degree of proteinuria. Signs and Symptoms of CKD: In the early stages of CKD the remaining healthy nephrons compensate for the destroyed nephrons by increasing in size and working harder. Over time their ability to adapt to the loss of nephrons fails and it is then that the signs and symptoms of CKD start to become evident. Most substances are eliminated from the body as they are produced, primarily by way of the kidneys. When these cannot be removed from the body due to renal failure this will account for some of the disordered body functions11. Since patients with CKD stages 1 to 3 rarely have symptoms they may be unaware that they have a problem with their kidneys and are often diagnosed after blood tests are

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performed for other reasons. Waste products build up at later stages of CKD, which can cause symptoms such as nausea, vomiting, itchy skin, shortness of breath, oedema and symptoms of anaemia and renal bone disease. These symptoms affect people differently, but their overall quality of life is diminished and appropriate treatment is needed to assist them. People who have diabetes and/or hypertension usually have their kidney function checked annually. This type of screening can often identify early changes in kidney function. Summary CKD is a common problem and improved detection and classication using standardized criteria is needed to improve patient outcomes12. Understanding of the anatomy and physiology of the workings of the kidneys are important to be aware of if we are to make progress and advances in this specialism. References
1. 2. 3. 4. 5. 6. 7. 8. Al-Khader A and Al-Jondeby M. Handbook for Dialysis Nurses (2nd Ed). Al Sayyari: Saudi Arabia, 2006. Thibodeau G and Patton K. The Human Body in Health & Disease (4th Ed). Elsevier Mosby: Missouri, 2005. Thomas N. Renal Nursing (2nd Ed). Bailliere Tindall: London, 2002. Montague S, Watson R and Herbert R. Physiology for Nursing Practice (3rd Ed). Elsevier: Edinburgh, 2005. Guyton A. Human Physiology and Mechanisms of disease (5th Ed). W.B. Saunders Company: Philadelphia, 1992. Ind D. Nephrology Nursing Practice Student Notes. The Queen Elizabeth Hospital: Adelaide, 2004. Stein A and Wild J. Kidney Dialysis and Transplants. Class Publishing: London. 2004. Steggall M. in Brooker C and Waugh A. Foundations of Nursing Practice, Fundamentals of Holistic Care. Mosby Elsevier: Philadelphia. 2007.

Anatomy and Physiology of the Kidney

Seeley R, Stephens T and Tate P. Anatomy and Physiology (7th Ed). McGraw Hill: New York, 2006. 10. US National Kidney Foundation. Kidney Disease Outcomes Quality Initiative (KDOQI), www.kdoqi.org, accessed 15th March 2007. 11. Vander A. Renal Physiology (3rd Ed). McGraw Hill: New York. 1985. 12. Coresh J, Astor B, Greene T, Eknoyan G, Levy A. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: third national health and nutrition examination survey, Am J of Kidney Dis 2003; 41 (1): 1-12. 9.

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Learning Outcomes
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To gain knowledge and understanding of the risk factors and prevalence of Chronic Kidney Disease (CKD) To understand how kidney function is measured To gain knowledge and understanding of the classication of CKD To gain insight into the referral process and management of CKD

Introduction Chronic kidney disease (CKD) is now recognised as a major health problem. Studies carried out both in the United States1 and the United Kingdom2 to investigate the prevalence, progression and referral rates of CKD in the general adult population, have shown that older age, diabetes and hypertension are strongly associated with moderate or severely decreased renal function. The growing prevalence of CKD means that measures need to be taken to accurately measure kidney function, stage of kidney disease, devise referral criteria and develop clear management plans. Epidemiology of CKD The number of patients with chronic kidney disease (CKD), and the subsequent need for renal replacement therapy (RRT), has reached epidemic proportion and is anticipated to rise further. CKD affects approximately 10% of the population

Assessment, Diagnosis and Management of CKD

worldwide1 and it is estimated that over 1.1 million patients with end stage renal disease (ESRD) currently require maintenance dialysis. A gure which is increasing at a rate of 7% per year3. If the trend continues, by 2010 the number will exceed 2 million4. This gure excludes third world countries, where there is less availability of, and access to, dialysis services, and is, therefore, an underestimate of the true demand. In the UK the incidence of ESRD has doubled over the last ten years and has now reached 101 patients per million of population (pmp)5. This is below the European and USA averages of approximately 135 and 336 pmp respectively6. Studies such as the NHANES (National Health and Nutrition Examination Survey) which provided data on the adult unselected population estimated that 4.7% of US adults had CKD stage 3 or higher (dened as estimated glomerular ltration rate (eGFR) <60ml/min/1.73m2). They also estimated that up to 11% of the general population (19.2 million) has some degree of CKD1. Risk Factors of CKD Risk factors for CKD include: Diabetes Cardiovascular disease Smoking Obesity Sedentary lifestyle Low socio-economic status UK studies have shown a higher incidence of CKD in deprived areas7,8 consistent with both USA and Swedish studies9. Obesity has become a global issue in developed countries adding to the population of people with chronic disease. Those with diabetes and hypertension are at greatest risk and have a higher rate of renal problems than those in the normal population10. The reality is that the majority of the CKD population have one or

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more co-morbid conditions with a known higher prevalence in ethnic minorities and lower socio-economic groups. This along with the increase in childhood obesity and prevalence of diabetes make it clear why there is becoming an epidemic of CKD and that, without effective prevention and early detection of CKD this will continue to rise. Measurement of kidney function Traditionally kidney function has been determined by measuring serum creatinine alone. However, serum creatinine alone is not an accurate index of the level of kidney function as there is not a direct relationship between glomerular ltration rate (GFR) and serum creatinine. By the time the creatinine becomes elevated, there may already be a 50% reduction in kidney function. The use of the serum level of creatinine as an index of Glomerular Filtration Rate (GFR) to measure kidney function rests on three important assumptions: Creatinine is an ideal ltration marker whose clearance approximates GFR Creatinine excretion rate is constant among individuals and over time Measurement of serum creatinine is accurate and reproducible across clinical laboratories Although the serum creatinine concentration can provide a rough index of the level of GFR, none of these assumptions is strictly true, and numerous factors can lead to errors in estimation of the level of GFR from the serum creatinine concentration alone. Factors other than the level of GFR can also inuence creatinine secretion include11: Kidney disease Reduced muscle mass

Assessment, Diagnosis and Management of CKD

Malnutrition Ingestion of cooked meat Trimethoprim; Cimetidine Ketoacidosis


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Creatinine is mainly derived from the metabolism of creatine in muscle, and its generation is proportional to the total muscle mass. As a result, mean creatinine generation is higher in men than in women, in younger than in older individuals, and in blacks than in whites. This leads to differences in serum creatinine concentration according to age, gender, and race, even after adjusting for GFR12. In addition, measurement of creatinine clearance is not easy. Urinary clearance measurements require timed urine collections, which are difcult to obtain and often involve errors in collection. Furthermore, day-to-day variation in creatinine excretion exists, making estimation of GFR, even from a valid 24-hour urine collection, imprecise. Therefore it is recommended that kidney function should be assessed by an estimation of glomerular ltration rate (eGFR) not creatinine alone. To do this there are specic formulae available. The most widely used are: Modication of Diet in Renal Disease (MDRD) Cockcroft Gault Equations estimating GFR based on serum creatinine are more accurate and precise than estimates of GFR from measurement of serum creatinine alone. Studies have documented that creatinine production varies substantially across sex, age, and ethnicity12. Equations have the advantage of providing an estimate of GFR which empirically combine all of these average effects while allowing for the marked differences in creatinine production between individuals13.

Chronic Kidney Disease:

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Modication of Diet in Renal Disease (MDRD) The four-variable Modication of Diet in Renal Disease (MDRD) formula is used to estimate GFR in mls per minute11. The formula requires the gender, age, serum creatinine and ethnicity (black/non-black) of the patient. Assumption of Caucasian ethnicity can be made when using MDRD if ethnicity is unknown. MDRD calculation: The 4-variable Modication of Diet in Renal Disease (MDRD) equation: GFR (ml/min/1.73 m2) = 186 x {[Serum Creatinine mol/l/88.4] -1.154} x {age (years) -0.203} x 0.742 if female and x 1.21 if African American. Cockcroft Gault (1976) calculation14 The formula takes into consideration: weight, gender serum creatinine and age. However this technique tends to underestimate creatinine clearance in obese patients and overestimates it in patients who may be on a low protein diet. Cockcroft Gault equation In men: (140-age) x weight in kg Creatinine clearance = ------------------------------------------------- 1 72 x serum creatinine

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In women: (140-age) x weight in kg Creatinine clearance = ------------------------------------------------- 0.85 72 x serum creatinine

Assessment, Diagnosis and Management of CKD

The eGFR can be related to percentage of kidney function. For example, an eGFR 20mls/min/1.73m2 = 20% kidney function. A normal eGFR is considered to be more than 90mls/min/1.73m2. How often should eGFR be measured? eGFR should be measured at initial assessment and then at least annually in all adult patients with: 1. Previously diagnosed CKD including: Identied renal pathology (e.g. polycystic kidney, biopsy proven glomerular nephritis, reux nephropathy) Persistent proteinuria Urologically unexplained haematuria 2. Conditions associated with a high risk of silent development of obstructive kidney disease: Bladder voiding dysfunction (outow obstruction, neurogenic bladder) Urinary diversion surgery Urinary stone disease (more than one episode/year) 3. Conditions associated with a high risk of silent development of parenchymal kidney disease: Hypertension, diabetes mellitus, heart failure Atherosclerotic coronary, cerebral, or peripheral vascular disease 4. Conditions requiring long-term treatment with potentially nephrotoxic drugs For example: ACE inhibitors (ACEI) Angiotensin Receptor Blockers (ARBs), Non steroidal anti39

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inammatory Drugs (NSAIDs), Lithium, Mesalazine, Cyclosporin, Tacrolimus 5. Multi-system diseases that may involve the kidney For example systemic lupus erythematosus (SLE), vasculitis, myeloma, rheumatoid arthritis In summary, a normal range for serum creatinine should no longer be given and management of the patient needs to be based on eGFR. Until laboratories are able to report eGFR MDRD and Cockcroft Gault calculators can be downloaded from www.renal.org or www.nephron.com. Should you rely on eGFR for acute renal failure patients? No, the eGFR is not appropriate for a patient with acute renal failure, as it relies on a stable serum creatinine for its predictive accuracy. eGFR cannot be used in children. Staging of kidney disease The presence of chronic kidney disease should be established, based on presence of kidney damage and level of kidney function (glomerular ltration rate - GFR), irrespective of diagnosis. Among patients with chronic kidney disease, the stage of disease should be assigned based on the level of kidney function, irrespective of diagnosis, according to the K/DOQI CKD classication13 (Table 1).

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Assessment, Diagnosis and Management of CKD

Table 1: Classication of CKD

Stage 1 2 3 4 5

Description Kidney Damage with Normal or n eGFR Kidney Damage with mild p eGFR Moderate p eGFR Severe p eGFR Kidney Failure

eGFR (ml/min/1.73m) t90 60-89 30-59 15-29 < 15 (or dialysis)


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Denition of Chronic Kidney Disease CKD is dened as either evidence of kidney damage or an eGFR <60ml/min/1.73m2 for 3 months. Kidney damage is dened as pathological abnormalities or markers of damage including abnormal blood or urine tests or imaging studies13,15. K/DOQI suggests that: All individuals with eGFR <60 ml/min/1.73 m2 for 3 months are classied as having chronic kidney disease, irrespective of the presence or absence of kidney damage. The rationale for including these individuals is that reduction in kidney function to this level or lower represents loss of half or more of the adult level of normal kidney function All individuals with kidney damage are classied as having chronic kidney disease, irrespective of the level of eGFR. The rationale for including individuals with eGFR 60 ml/min/1.73 m2 is that eGFR may be sustained at normal or increased levels despite substantial kidney damage and that patients with kidney

Chronic Kidney Disease:

A Guide to Clinical Practice (Stages 1-3)

damage are at increased risk of the two major outcomes of chronic kidney disease: loss of kidney function and development of cardiovascular disease
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Other markers of kidney damage: Persistent microalbuminuria (measured by an albumin creatinine ratio) Persistent proteinuria (after exclusion of other causes e.g. urological) Persistent haematuria Structural abnormalities of the kidney Biopsy proven chronic glomerulonephritis Patients found to have eGFR 60-89ml/min/1.73m2 without one of these markers should not be considered to have CKD or be subject to further investigation. Rate of change of eGFR is important when considering disease progression and need for referral. eGFR is considered stable if there is <2ml/min/1.73m2 fall over 6 months or more. Referral criteria The changes in reporting of kidney function are already having an effect on the number of referrals to nephrologists. To provide guidance for referral the UK renal association have drafted a set of referral guidelines which are available from www.renal.org. Of course referral criteria may differ amongst European countries and guidelines relevant to the local area of practice should be considered. Table 2 shows UK recommendations15 for referral as an example.

Assessment, Diagnosis and Management of CKD

Table 2: UK Recommendations

Estimated GFR

Referral criteria
Immediate referral Exceptions may include: patients in whom CKD supervenes as part of another terminal illness; patients in whom further investigation and treatment is inappropriate; those who have stable function and appropriate investigations and management interventions have been performed and have an agreed care pathway Urgent referral - routine if known to be stable Routine referral if: Progressive fall in eGFR/increase in creatinine, microscopic haematuria Urinary PCR >45mg/mmol Unexplained anaemia (Hb,11g/dl) abnormal calcium, phosphate, or potassium Uncontrolled BP >150/90 on 3 agents Referral not required Immediate referral for Malignant hypertension Hyperkalaemia (potassium >7.0mmol/L) Urgent referral for: Proteinuria with oedema and low serum albumin (Nephrotic syndrome) Routine referral for: Dipstick proteinuria and urine PCR >100mg/mmol Dipstick proteinuria and microscopic haematuria Macroscopic haematuria but urological tests negative

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<15ml/min/1.73m2

15-29 ml/min/1.73m2

30-59 ml/min/1.73m2

60-89 ml/min/1.73m2

Renal problems irrespective of eGFR

Chronic Kidney Disease:

A Guide to Clinical Practice (Stages 1-3)

Management of CKD The KDOQI guidelines13,16 suggest that patients with chronic kidney disease should be evaluated to determine: Diagnosis (Type of kidney disease) Co-morbid conditions Severity assessed by level of kidney function Complications related to level of kidney function e.g. anaemia Risk for loss of kidney function Risk for cardiovascular disease Treatment of CKD should include: Specic therapy, based on diagnosis Evaluation and management of co-morbid conditions Slowing the loss of kidney function Prevention and treatment of cardiovascular disease Prevention and treatment of complications of decreased kidney function Preparation for kidney failure and renal replacement therapy Replacement of kidney function by dialysis and transplantation, if signs and symptoms of uraemia are present A clinical action plan should be developed for each patient, based on the stage of disease as dened by the K/DOQI CKD classication13 (Table 3). Provision should be made for the implementation of care plans for all adult patients with CKD irrespective of age and should be shared between primary, secondary and tertiary care. The progression of CKD can be slowed down by focusing on: Blood pressure control Lipid control

44

Assessment, Diagnosis and Management of CKD

Glycaemic control Healthy living - exercise Smoking cessation Avoiding nephrotoxic drugs
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Both the UKPDS17 and DCCT18 study groups have shown that good glycaemic control can decrease macrovascular disease in type I and type II diabetes as well as slowing the progression from albuminuria to microalbuminuria.
Table 3: K/DOQI CKD classication13

Description

eGFR (ml/min/1.73m2)

Action

Kidney damage with normal or GFR

90

Diagnosis and treatment Treatment of co-morbid conditions Slowing progression Cardiovascular risk reduction

Kidney damage with mild GFR

60-89

Estimating process

Moderate GFR

30-59

Evaluate and treat complications

Severe GFR

15-29

Preparation for kidney replacement therapy

Kidney failure

< 15 Replacement therapy or (or dialysis) conservative management

Chronic Kidney Disease:

A Guide to Clinical Practice (Stages 1-3)

46

The use of angiotensin-converting enzyme (ACE inhibitors) or angiotensin receptor blockers (ARBs) are effective at reducing progression when there is concurrent proteinuria. Target blood pressure may vary across Europe but in the UK, one study19 showed that maintaining a blood pressure below 130/75 mmHg, correlated to a reduction in the progression of renal disease in people with type 2 diabetics with albuminuria. It is essential that robust mechanisms are put in place in both primary and secondary care for the early detection and management of CKD. Education is of great importance for both health care professionals and patients. There are many challenges ahead for educating patients about CKD. Perhaps the most important issue is how to avoid labeling of patients and how to reduce anxiety when patients are rst told that they have kidney disease. Prevention of kidney disease is crucial - but essentially the management is the same for renal disease, diabetes and cardiovascular disease - the priority is reducing cardiovascular risk. The latest initiative in Europe is the forming of the European Kidney Health Alliance (EKHA) which is aims to raise the awareness of CKD on a European Union level. There are four major stakeholders, ISN, ERA-EDTA, EDTNA/ERCA and CEAPIR representing the multidisciplinary team and patients. Summary Strategies for the management of people with chronic kidney disease need to be in place to aid the prevention and help slow down the progression of the disease. The International Society of Nephrology (ISN) has for some time had a focus on prevention and the COMGAN group believe in improving global outcomes of kidney disease20. The new initiative by the Kidney Disease: Improving Global Outcomes (KDIGO) group aims to

Assessment, Diagnosis and Management of CKD

develop a global approach to managing the CKD epidemic. Their mission statement is Improve the care and outcomes of kidney disease patients worldwide through promoting coordination, collaboration and integration of initiatives to develop and implement clinical practice guidelines. KDIGO and the ISN are now working together on developing a CKD strategy21. Nephrology services need to adapt to cope with the increase in the number of referrals which have been evident since the introduction of eGFR reporting. Renal disease is a chronic disease and as such needs a multi-disciplinary approach in order to manage not only the renal disease but also its cardiac and diabetic complications. This will involve the education and training of general practitioners who are the main contact point for many patients in the community so that they feel condent in managing CKD stages1, 2 & 3 (without risk factors) in the community and thereby reduce the burden of referrals to the nephrology units. Developing guidelines is pivotal in addressing the current problem; however the key to success lies in the implementation process. Nurses are in a good position to take on this role as there are clear guidelines available for managing CKD. For example in the UK, the Renal Association in collaboration with the Royal College of Physicians and General Practitioners have provided a comprehensive document to support both nephrology units and community services. Many UK units have adapted these guidelines to meet the local community needs and demands. The introduction of such guidelines is also supported by renal teams providing education to community physicians and nurses, advising them when and how refer patients with CKD. Joint working with renal units, community health care providers, specialist service providers and patient groups is raising the awareness of CKD and removing barriers which have previously stood in the way of providing holistic patient care.

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Chronic Kidney Disease:

A Guide to Clinical Practice (Stages 1-3)

48

Within Europe there are differences in roles and responsibilities of nurses as was seen in the data from the European Network of Renal Care Associations (ENRCA) project. This group in 2004 is made up of 10 National Associations (UK, Spain, Israel, Croatia, Slovenia, Turkey, Greece, Belgium (Flanders), Italy, Portugal and Cyprus) and the EDTNA/ERCA. They surveyed 10% of renal units in each country to identify the task portfolio and responsibilities of nurses and allied healthcare professionals. They found that, for instance, the UK and Israel had many nurse-led services in place whilst pre-dialysis care was not usually performed by nurses in Spain. What will become evident is how CKD is managed in the future within these countries. Although many roles and responsibilities have been physician-led in the past, this is an ideal opportunity for nurses to review their way of thinking throughout Europe and diversify the skills of healthcare professionals. Management of CKD requires a collaborative approach and there is a need to be creative to enable patients to receive a seamless journey of care. Frequently asked Questions 1. Why is serum creatinine alone not a good measurement of kidney function? A: Serum creatinine is affected by the level of GFR and by factors independent of GFR, including age, gender, race, body size, diet, certain drugs, and laboratory analytical methods 2. What is GFR? A: GFR is glomerular ltration rate 3. What is a normal GFR? A: More than 90 mls/min

Assessment, Diagnosis and Management of CKD

4. How can I calculate eGFR? A: Laboratory measurement or download a calculator from www.renal.org g/ or www.nephron.co p m 5. How does eGFR relate to kidney function? A: It corresponds with percentage of kidney function i.e. eGFR 20mls/min = 20% kidney function 6. What is staging of CKD? A: It is dened by the eGFR e.g. Stage 3 kidney disease refers to an eGFR between 30-59 mls/min 7. At what stage should a patient be referred to a Nephrologist? A: This will depend on local guidelines but generally at stages 3-5 8. Where should patients referred to a Nephrologist be managed? A: This will depend on the individual health care system, but often it shared by the family doctor and Nephrologist References
1. Coresh J, Astor BC, Greene T, Eknoyan G, Levey A. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third national health and nutrition examination survey. Am J Kidney Dis 2003; 41, (1): 1-12. John R, M Webb, Young A, Stevens PE. Unreferred chronic kidney disease: A longitudinal study. Am J Kidney Dis 2004; 43; (5): 825-835. Lysaght MJ. Maintenance dialysis population dynamics: current trends and long-term implications. J Am Soc Nephrol 2002; 13: 37-40. Xue J, Ma J et al. A forecast of the number of patients with end-stage renal disease in the United States to the year 2010. J Am Soc Nephrol 2001; 12:2753-2758. The Renal Association. UK Renal Registry. The sixth annual report 2004. Available at www.renalreg.com/home.htm

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2.

3. 4.

5.

Chronic Kidney Disease:


6.

A Guide to Clinical Practice (Stages 1-3)

7. 50 8.

9.

10.

11.

12.

13.

14. 15.

16.

17.

18.

Anandarajah S, Tai T, de Lusignan S, Stevens P, ODonoghue D, Walker M, Hilton S. The validity of searching routinely collected general practice computer data to identify patients with chronic kidney disease (CKD) : a manual review of 500 medical records. Nephrol Dial Transplant 2005; 20, (10) :2089-2096. Roderick P et al. What determines geographical variation rates of acceptance onto renal replacement therapy in England? J Health Serv Res Policy 1999; 4, (3): 139-146. Drey N. The epidemiology of diagnosed chronic renal failure in Southampton in South West Hampshire Health Authority. PhD Thesis Southampton: University of Southampton, 2000. Young EW, Mauger EA, Jiang KH, Port FK and Wolfe RA. Socioeconomic status and end-stage renal disease in the United States. Kidney Int 1994; 45, (3): 907-911. Kissmeyer L, Kong C, Cohen J, Unwin RJ, Woolfson RG and Neld GH. Community Nephrology : audit of screening for renal insufciency in a high risk population. Nephrol Dial Transplant 1999; 14: 2150-2155. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N and Roth D. more accurate method to estimate glomerular ltration rate from serum creatinine: a new prediction equation. Modication of Diet in Renal Disease Study Group Ann Intern Med 1999;130 (6):461-79. Perrone RD, Madias NE and Levey AS. Serum creatinine as an index of renal function: New insights into old concepts. Clin Chem 1992; 38:1993-1953. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classication, and stratication. Am J Kidney Dis 2002; 39 (Suppl 2):S1246. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31-41. Chronic Kidney Disease in Adults: UK CKD Guidelines for Identication, Management and Referral of Adults. 2005. Available from: http//.www.renal.org/CKDguide/ckd.html Levey AS, Coresh J, Balk E et al. National Kidney Foundation Practice Guidelines for chronic kidney disease: evaluation, classication and stratication. Ann Intern Med 2003;139: 137147. UK Prospective Diabetes Study Group. Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352 :837-853. The DCCT Research Group. The effect of intensive treatment of diabetes on the development and progression of longterm complications in insulin-dependent diabetes mellitus. New Engl J Med 1993; 329: 977-986.

Assessment, Diagnosis and Management of CKD

19. McIntosh A, Hutchinson A, Marshall S, Barnes S, Brown V, Hooper S et al. Clinical Guidelines and Evidence Review for Type 2 Diabetes. Renal Disease: Prevention and Early Management. Shefeld: ScHARR, University of Shefeld, 2002. http://www.nice.org.uk 20. Kam-Tao Li P, Weening J, Dirks J et al. A report with consensus statements of the International Society of Nephrology 2004 Consensus Workshop on Prevention of Progression of Renal Disease, Hong Kong, June 29, 2004. Kidney Int 2005; 67 (Supp 94): S2-S7. 2005. 21. Eknoyan G, Lameire N, Barsoum R, Eckardt K, Levin A et al. The burden of kidney disease: Improving global outcomes. Kidney Int 2004; 66: 1310-1314.

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A Guide to Clinical Practice (Stages 1-3)

Learning Outcomes
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To demonstrate an understanding of the different types of diagnostic investigations including urine, blood, imaging and renal biopsy tests To interpret results within the clinical setting

Introduction Routine clinical assessment involves undertaking in-depth physical examination, social, medical and medication histories. Diagnostic investigations play an important role in the assessment of the cause and severity of kidney disease. Chronic Kidney Disease (CKD) is characterised by the gradual and progressive loss of functioning nephrons and, as discussed in chapter 1, has various causes. Damage to the kidneys is usually irreversible and is often insidious in nature, taking place over many years depending on the aetiology. In most cases there are no signs or symptoms in the early stages of CKD. However, with the introduction of routine estimated glomerular function rate (eGFR) measurement, CKD is often uncovered as an incidental nding during routine blood tests. Blood Tests The normal function of the kidneys is to excrete waste products which are a by-product of metabolism and there are various blood tests that can yield a wealth of information. The following table provides a guide to the normal range, an explanation about the test and how to interpret the results1,2,3,4. The normal range for tests will vary in different countries and hospitals.

Blood Test 70-110 mg/dl (3.9-5.5 mmol/L)

Explanation and Interpretation of Result

Normal Range

Fasting Used to detect undiagnosed diabetes or assess diabetes control glucose

Increased blood urea may indicate kidney damage. Normally, urea rises in Urea conjunction with creatinine levels in CKD, but at times levels may remain nitrogen within normal limits when the creatinine levels are high. A signicant (BUN) elevated urea in a previously healthy person can occur in acute renal failure due to severe infection or major crush injuries

Adult: 8-18 mg/dl (2.5-6.4 mmol/L)

Some causes of non-kidney related high urea levels: High protein diet and/or strenuous exercise Certain drugs (e.g. corticosteroids, tetracycline) Gastrointestinal tract haemorrhage Prolonged malnutrition and/or dehydration Adult: 0,6 - 1.2 mg/dl (50 - 110 mol/L) Slight variation is expected between male and female

Creatinine Creatinine is not a good marker of CKD as a 50% loss of kidney function occurs before any evidence of an elevated creatinine is seen

Diagnostic Investigations in CKD

Other causes of elevated creatinine: Ageing process as the kidney function declines by 10% per decade from the age of 40 High meat content diets People with a large muscle mass

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56

Blood Test 3.5 - 5.0 mEq/L (3.5 - 5.0 mmol/L)

Chronic Kidney Disease:

Explanation and Interpretation of Result

Normal Range

Potassium Hyperkalaemia yp , may occur in: Kidney disease Burns Insulin deciency Post-traumatic conditions (surgical and accidental) Disseminated intravascular coagulation (DIC) Diabetes mellitus Side effect of some medications e.g. ACE inhibitors

A Guide to Clinical Practice (Stages 1-3)

Hypokalaemia yp may occur in: Persistent vomiting and diarrhoea Renal tubular acidosis Diuretic treatment Excess insulin (causes an increase uptake of potassium) Sodium Hypernatremia yp can occur in: Reduced uid intake and dehydration Diabetes insipidus Metabolic acidosis Excessive infusion of isotonic uids in renal impairment

135 - 145 mEq/L (135 - 145 mmol/L)

Hyponatremia yp can occur in: Cases of excess body uid Burns Vomiting, and diarrhoea Nephritis Diabetic acidosis

Arterial pH The pH is measured via arterial blood and is a measure of the number of 7.35 - 7.45 pH units hydrogen ions and indicates the acidity or alkalinity of the blood 22 - 30 mEq/L (22 - 30 mmol/L) 2.0 - 7.0 mg/dl (120 - 420 mol/L) Slight variation is expected between male and female

Bicarbonate Buffers are chemical substances that keep the pH of blood within a normal range. Bicarbonate is the most important buffer in the blood

Uric acid Elevated uric acid may be seen in: Gout Arthritis Kidney disease Certain diuretics Acute shock and pre-eclampsia

Total Hyperproteinaemia yp p with a normal albumin/globulin ratio may occur in proteins hypovolaemia

6.0 - 8.0 g/dl (60 - 80 g/L)

Hyperproteinaemia yp p with a low albumin/globulin ratio may suggest an autoimmune disease (e.g. SLE, shock, long-term infection or multiple myeloma)

Diagnostic Investigations in CKD

Hypoproteinaemia yp p related with low albumin levels of <35 g/l may be seen in patients who are malnourished and in nephrotic syndrome where large amount of protein leaks into the urine. It is also present in liver disease, burns and haemorrhage

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58

Blood Test 4.0 - 6.0 g/dl 40 - 60 g/L

Explanation and Interpretation of Result

Normal Range

Albumin Hyperalbuminaemia yp may be associated with hypovolaemia

Chronic Kidney Disease:

Hypoalbuminaemia yp is frequent in renal patients with poor dietary intake, on peritoneal dialysis due to protein loss in dialysate. It is a common feature in nephrotic syndrome

Hypercalcaemia yp may indicate hyperparathyroidism, or may be due to Total calcium diuretics (thiazides). Its high level can result in renal calculi and renal tubular disease

8.8 - 10.3 mg/dl 2.20 - 2.58 mmol/L

Hypocalcaemia yp may occur in certain metabolic disorders (e.g. decient parathyroid hormone) and may be due to phosphate retention in chronic renal failure 2.4 - 4.1 mg/dl (0.8 - 1.4 mmol/L)

Phosphorous Hyperphosphataemia yp p p can be seen in conjunction with hypocalcaemia in various types of renal failure

Hypophosphataemia yp p p occurs in renal tubular disease resulting in osteomalacia 30 - 120 (37C) Units/L

A Guide to Clinical Practice (Stages 1-3)

Alkaline Levels are raised when bone disease develops in CKD. It varies with age phosphatase and gender

Other conditions associated with elevated levels are seen in young children experiencing rapid growth, in pregnancy, liver and intestinal ulcerative disease

Parathyroid PTH is produced in the parathyroid gland and regulates extracellular Varies according to hormone calcium assay method (PTH) It rises progressively with declining kidney function

Lipids and Dyslipidaemia is common in CKD, especially in patients with nephrotic Total cholesterol: triglycerides syndrome or a kidney transplant. The 3 major types of cholesterol are Low < 200 mg/dl Density Lipoprotein (LDL), High Density Lipoprotein (HDL) and Very Low (desirable) Density Lipoprotein (VLDL) Elevated levels (except HDL) are associated with cardiovascular events, LDL: <130 mg/dl (desirable) a major cause of morbidity and mortality HDL: >60 mg/dl (desirable) Triglycerides: <150 mg/dl (desirable)

CRP

The presence of CRP usually indicates acute inammation. Positive results Normal value is < 5mg/L may also occur in late pregnancy or with the use of oral contraceptives

Diagnostic Investigations in CKD

Serum The ve protein groups move at different speeds in an electrical eld and Normal pattern electro- this test measures the rate of movement. It is most commonly used to phoresis detect multiple myeloma

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Chronic Kidney Disease:

A Guide to Clinical Practice (Stages 1-3)

Full Blood Count (FBC) / Complete Blood Count (CBC)


Leukocytosis, (high WBC count) 4,500 - 10,000 / mm3 count / is associated with: White blood Leukaemia cell count Infectious diseases (WBC) Inammatory disease (allergy or rheumatoid arthritis)
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Leukopenia (low WBC count) can be due to: Systemic lupus erythematosus Bone marrow failure Liver and spleen diseases Haemoglobin The RBCs should be normocytic (Hb) (normal shape) and normochromic (normal colour). However in iron deciency anaemia they are microcytic (small) and hypochromic (pale) See chapter management 4 on Male: 14.5 - 16.0 g/dl

Female: 13.0 - 15.5 g/dl Hb level in CKD7 should be > 11 g/dl in anaemia all patients

Haematocrit The haematocrit will be low in (HCT) renal anaemia, in conjunction with a low haemoglobin level

Male: 39 - 49 % Female: 33 - 43 % 18 - 300 ng/mL (18 - 300 g/L)

Ferritin

In renal failure, levels should be maintained above 100 ng/mL see Chapter 4

Vitamin B12 Its deciency causes macrocytic anaemia

150 - 1000 ng/L

Diagnostic Investigations in CKD

Coagulation screenings
Bleeding time Prolongation occurs in patients with vascular abnormalities, thrombocytopenia and thromboasthenia 3 - 6 minutes (Ivy method)

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Activated Partial Thrombo Plastin Time (APTT)

A prolonged APTT occurs in a variety of disorders (e.g. liver cirrhosis, disseminated intravascular coagulation (DIC). Patient on anticoagulant therapy may have an APTT time of 1.5 to 2.5 times control values

22 - 37 seconds (Values vary between labs.)

Platelet Use to check for any clotting count / abnormality thrombocyte count

130,000 400,000/mm3

Chronic Kidney Disease:

A Guide to Clinical Practice (Stages 1-3)

Serology
Auto antibodies eg antinuclear antibodies: ANA/ANCA Anti-GBM The measurement of abnormal antinuclear antibodies amount and pattern provides a diagnosis for certain diseases Positive anti-nuclear antibodies are seen in systemic lupus erythromatosus or scleroderma Positive anti-neutrophil cytoplasmic antibodies (ANCA): seen in systemic and renal vasculitis Positive anti-glomerular basement membrane (Anti-GBM): very suggestive of Goodpastures syndrome HBsAg, HIV HCV Routine performed as part of renal screening Negative is normal Negative is normal

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Immunoglobulins

IgG 5.5 These are commonly referred to as 16.5 g/L antibodies and IgG, IgM and IgA are measured to identify certain IgA 0.8 - 4 g/L autoimmune diseases and allergies IgM 0.4 - 2 g/L e.g. IgA nephropathy, Multiple myeloma etc

Urine Tests Urinalysis plays an essential part in the assessment of any patient with CKD. The assessment should include observation of the physical appearance of the urine together with dipstick testing and further laboratory analysis. Dipstick tests have mostly replaced cumbersome laboratory testing for routine rapid clinical work, however, machines are also available to

Diagnostic Investigations in CKD

perform urinalysis with good reliability. A laboratory microscopy, culture and sensitivity (MC&S) test can identify and detect the presence of any cells, casts, crystals or bacteria in the urine. Why is urinalysis important? To aid in the diagnosis of kidney disease To screen a population for asymptomatic kidney disease To monitor the progression of disease To monitor the effectiveness or complications of therapy To detect diabetes, urine infection and other urinary tract problems such as calculi or cancers5 When undertaking a urine assessment it is important to observe the appearance, smell and to undertake a dipstick urinalysis. In some situations it may be necessary to measure the volume of urine produced over a 24 hour period. The following provides a brief overview of normal and abnormal ndings when undertaking a urinalysis. Observational Assessment Odour: Abnormal odour occurs most often due to incorrect handling and storage or if there is an infection. However, eating certain foods can also cause an abnormal and distinctive odour e.g. asparagus. In the presence of excess ketones in the blood (ketotic state), the urine will have a distinctive sweet or fruity smell (although a sizeable percentage of the population is unable to detect this smell). This is especially important in the diagnosis of patients with diabetic ketoacidosis, a life threatening condition. Colour: Urine normally appears pale to dark yellow depending on its concentration, however it can appear darker if left to stand for too long.

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Chronic Kidney Disease:


Table 1: Urine colour6,7

A Guide to Clinical Practice (Stages 1-3)

Colour Pale

Causes High uid intake Polyuria (renal tubules cannot reabsorb uid) Diabetes insipidus Diabetes mellitus

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Turbid/cloudy

Bacterial infection/pus Crystallization of salts e.g. calcium, urate and oxalate

Red or dark urine. Blood in the urine (haematuria) - vary from smoky to tea colour and vary in strength e.g. bright or dark

Urinary tract infections Trauma to the kidney Internal damage to the glomeruli in the kidney Smoky: Can indicate bleeding from the kidney Eating beetroot or other vegetable dyes. Porphyria Menstruation Medications e.g. rifampicin

Foam or froth Normal urine will foam slightly when stored in a container and shaken

Heavy proteinuria (lots of white foam when container shaken)

Diagnostic Investigations in CKD

Volume::The normal amount of urine collected within a 24 hour period of time can range from 500mls/day to 1500mls/ day. Abnormal amounts are as follows: Anuria: Oliguria: Polyuria: failure or inability of the kidneys to produce urine: <50-100 ml per day where <400 ml of urine is produced per day is a condition of excessive production of urine >2.5L/day

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Dipstick/Urinalysis Dipstick tests provide a cheap and simple way to assess various substances in the urine. They are only reliable when the manufacturers instructions are followed e.g. length of time dipping in urine, leaving to stand before reading the result, keeping the lid on when not in use. Inaccuracies may also be caused by patient factors such as: Menstruation e.g. positive result for blood Medications, such as diuretics or high doses of vitamin C (ascorbic acid) taken with certain antibiotics (such as tetracycline) Some antibiotics, such as erythromycin and trimethoprim. Radiological contrast material6,7 Normal urine is made up of 95% water and 5% solids, mainly urea and sodium chloride. It is slightly acidic, with a pH of 6.0 and the normal specic gravity is 1.010-1.030 g/ml.

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Table 2: Dipstick test6,7

Substance

Interpretation
Inuenced by diet, recent eating, bacterial infection and storage time. Acidic pH pH< 5 = risk of uric acid stones Alkaline pH pH > 7 = commonly found in vegetarians pH> 8 = renal tubular acidosis or urine infection >1.030 (no proteinuria or glycosuria) - radiographic contrast >1.020 Usually in volume depletion 1.000 - 1005 (xed SG) - occurs in diabetic insipidus May be unrealiable if: Water and electrolyte imbalance is present Low protein diets Chronic liver disease Pregnancy A positive result is indicative of hyperglycaemia or a low renal glucose threshold

pH (acidity or alkalinity of the urine)

Chronic Kidney Disease:

The normal range is 4.5 - 8.0 dependent on diet

Specic Gravity (SG) (g/ml)

A Guide to Clinical Practice (Stages 1-3)

Measures solute load in the urine. Is a useful indicator of renal concentrating ability

Glucose

Protein

Normal urine should not contain more than a trace of protein. It is possible for levels of proteinuria up to 150 mg/24 hour before any protein shows up on a dipstick Persistent small increases in protein or albumin in the urine are an early sign of kidney injury and often precede any detectable change in the serum creatinine concentration or eGFR Persistently high levels of protein damage the kidney and contribute to progressive loss of kidney function; this is particularly evident in patients with proteinuria levels greater than 1gm/day High levels of proteinuria are always important; however intermittent low levels of proteinuria may not be as signicant. Some examples of causes of intermittent proteinuria are: Dehydration Emotional stress Fever Heat injury Inammatory process Intense activity Most acute illnesses Orthostatic (postural) disorder

Diagnostic Investigations in CKD

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Substance
The presence of nitrites usually indicates an infection. The presence of ketones may be seen in hyperemesis of pregnancy, starvation or ketoacidosis Urine does not normally contain any bilirubin, only small amount as urobilinogen. It appears in the presence of liver disease or bile duct obstruction A positive test indicates haematuria, haemoglobinuria or myoglobinuria False positive readings may be due to contamination with menstrual blood Haematuria is dened as >3 RBC/hpf of centrifuged sediment under microscope False positives can be increased by dehydration which concentrates the number of RBCs produced and exercise False negatives may occur if the urine is left to stand for several hours prior to microscopy as during this time the red blood cells may lyse

Interpretation

Nitrites

Ketones

Chronic Kidney Disease:

Bilirubin

A Guide to Clinical Practice (Stages 1-3)

Blood

Microalbumin

The presence of small amounts of albumin is of importance as a predictor of kidney damage and is the rst indicator of kidney disease in diabetics Microalbuminuria is dened as persistent albumin/creatinine ratios >2.5mg/mmol (male) or >3.5mg/mmol (female) on 2-3 occasions or urinary albumin excretion of 20-200 g/min Testing should be avoided during acute illness or menstruation to reduce the incidence of false readings8,9 Microalbuminuria may indicate the following: sub-clinical cardiovascular disease vascular endothelial dysfunction prognostic marker for kidney disease: - in diabetes mellitus - in hypertension8,9

Diagnostic Investigations in CKD

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Chronic Kidney Disease:

A Guide to Clinical Practice (Stages 1-3)

Other specic urine tests Osmolality: normal range 500-800 mosmolkg1. This provides an indication of the kidneys ability to concentrate and dilute the urine and provides a more accurate assessment of renal tubular concentrating ability than the specic gravity. A urine osmolality test should preferably be done on an early morning urine sample as water depletion during the night should concentrate the urine.
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Protein/Creatinine Ratio (PCR) Assessment of urinary protein can be carried out on a single, preferably early morning, urine sample. Several studies have shown that, as patients nd the accurate provision of a 24-hour urine collection very difcult, the PCR to be more accurate than the gold standard of the 24-hour urine protein measurement. The PCR will not detect microalbuminuria. A PCR >100 mg/ mmol (1g/day) requires specialist renal management and these patients should be referred to a nephrologist. Likewise if the PCR is >45 mg/mmol but the patient also has microscopic haematuria they should also be referred10. It is important to note that in nephrotic syndrome, heavy proteinuria is a main clinical feature with proteinuria >3.5 g/day (150 mg/24 hr). Other features are: Peripheral oedema, especially around the eyes, feet, and hands Hypoalbuminaemia: low levels of protein in the blood <30 g/l Hypercholesterolemia, specically elevated low density lipoproteins Coagulation abnormalities Bence-Jones Protein analysis This is ideally tested on an early morning urine sample. A positive result may indicate the presence of multiple myeloma

Diagnostic Investigations in CKD

in 70-80% of cases and is a useful diagnostic tool. It can also be seen in amyloidosis, Waldenstroms macroglobulinaemia, cryoglobulinaemia and chronic lymphocytic leukaemia6. Myoglobin levels This is ideally tested on an early morning urine sample. Myoglobin in the urine is found in conditions such as rhabdomyolysis, the breakdown of muscle tissue usually due to a crush injury or trauma to the area, seizures or severe exercise. The myoglobin is released from the muscle tissue into the bloodstream and is nephrotoxic as when it is ltered by the kidneys it causes blockages in the renal tubules and leads to acute tubular necrosis6. Urinary Catecholamines Urinary catecholamines such as adrenaline or noradrenaline or their metabolites such as vanylmandelic acid (VMA) can be tested for in a 24-urine sample. A level twice the upper limit of normal is virtually diagnostic of phaeochromocytoma, however several 24-hour samples may be needed if there is clinical suspicion of this tumour as levels uctuate greatly. Hypertension may cause mildly elevated results. When collecting the samples it is necessary to keep the container refrigerated. Certain foods including coffee, tea, bananas, chocolate, cocoa, citrus fruits, and vanilla can increase urinary catecholamine and these should be avoided for several days prior to the test. Centrally acting sympathomimetic drugs such as methyl dopa will also affect the results as may acute stress and vigorous exercise8. Microscopy, Culture and Sensitivity Microscopy of the centrifuged urinary sediment will show up bacteria, blood cells, casts and crystals. Urinary culture will

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identify bacterial and fungal urinary infection which can then be tested for sensitivity to various antibiotic and antifungal agents. Bacteria: Bacterial urinary tract infections are common. Predisposing factors include: Gender - women have a shorter urethra and are more susceptible to urinary tract infections (UTI) Sexually active women Pregnancy Incomplete emptying of the bladder Immunosuppression e.g. HIV patients, transplant patients Diabetes mellitus Vesico-ureteral reux Urethral catheterisation A signicant nding is bacteria >100 000 / ml. If multiple organisms are seen, then a contaminated sample is likely.
Table 3: Most common causes of UTIs11

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Bacteria Escherichia coli (E. Coli) Staphylococcus epidermis (S. epidermis) Proteus species Klebsiella species Pseudomonas aeruginosa

Normally present in GI tract, faeces Skin, external genital tract GI tract, faeces, hospital environment GI tract, faeces, external genital tract GI tract, faeces (rare), hospital environment

Diagnostic Investigations in CKD

Blood cells (erythrocytes) When intact, they are biconcave disks with smooth appearance. Abnormal is to nd >3 per high power eld. When the erythrocytes are distorted, irregular or misshaped, they are know as dysmorphic blood cells and usually suggest glomerular disease, especially when accompanied by proteinuria and blood casts. Red blood cells may be seen in the following: Acute tubular necrosis Upper and lower urinary tract infections Nephrotoxicity Tumours Kidney trauma Renal calculi Renal infarcts Physical stress Other causes not kidney related are: Trauma from urinary catherization Menstruation Excessive exercise can cause microscopic haemeturia and is common, it is advisable to re-test in 48-72 hrs White cells (leukocytes) These are disks with granular cytoplasm and nucleus. Pathological ndings are indicated if white cells are >5 per high power eld. The presence of increased white cells in the urine is termed pyuria and indicates inammation or infection of the urinary tract. The presence of eosinophils may indicate an allergic interstitial nephritis. White cells can be presents as a result of a contaminant from the vagina or urethral meatus.

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Epithelial cells These cells line all of the urinary and genital tracts. The presence of squamous epithelial cells implies contamination, transitional epithelial cells are normal. Renal Epithelial cells They are the most clinically important of the epithelial cells that may be found in urine and result from a variety of disorders, especially acute tubular necrosis, viral infections involving the kidney and in renal transplant rejection. Casts The discovery of casts in the urine sediment is the result of solidication of protein within the lumen of the kidneys tubules. At the time of cast formation, any material present within the tubule e.g. cells, fat, or bacteria is trapped within the cast matrix7,11.
Type Hyaline casts also known as Tamm-Horsfall proteins Cause These come from the renal tubules and are the least important of casts. They may be seen without signicant proteinuria. They are often found in people who undertake strenuous exercise, fever and the use of diuretics. Large numbers are related with moderate or severe renal disease and may be seen in pyelonephritis May be seen in renal parenchymal disease. Their quantication and progression are of great importance in diagnosis Indicates bleeding of renal origin often glomerulonephritis. However are also seen in patients who participate in contact sports Their nding indicates inammation/ infection. May be indicative of interstitial nephritis, pyelonephritis or glomerulonephritis

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Granular or cellular

Red Blood Cells Leukocyte

Diagnostic Investigations in CKD

Crystals It is important to interpret the presence of crystals in conjunction with urinary pH and concentration. Abnormal forms may indicate metabolic disorders, such as the presence of cystine crystals in the urine of people with cystinuria, an inherited metabolic condition. In acidic uric the presence of uric acid crystals and elevated serum uric acid may be associated with gout. Triple phosphate crystals are associated with an alkaline pH and infection. Culture Microoganisms are identied after culturing the urine for 24/48 hours. A gram stain will determine the exact organisim and also which antibiotics the organism is sensitive and resistent to. Cytology A cytology exam of urine is used to detect cancer and inammatory diseases of the urinary tract. Collection of a clean-catch (midstream) urine sample is required. Kidney Function Tests
In healthy individuals, from 40 years of age onwards, GFR diminishes at about 10 ml/ min per decade eGFR should not be used as a marker of kidney function in acute renal failure patients 70 125 ml/min

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Estimated Glomerular Non-renal causes of increased eGFR: High protein diet ltration Diurnal variation rate Pregnancy (eGFR) (GFR) / Non-renal causes of decreased eGFR: Low protein diet Liver disease Ageing

See Chapter 2 for eGFR calculation and classications of CKD

Chronic Kidney Disease:

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Imaging Tests They are diagnostic methods in medicine that use certain techniques to produce internal images of the body. The techniques employed are: X-rays Sound waves Magnetic elds Radioactive particles

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These techniques work on the principle that rays, sound waves and particles interact differently with various types of tissues. They are detected and converted into images after passing through body tissues. Contrast agents are sometimes used in conjunction with X-ray tests to enhance better images. In nephrology practice, imaging tests are employed according to their specic capability to detect structural or functional problems. However, when there is renal damage, caution is taken in choosing the type of imaging test to conrm diagnosis. This is because the contrast agent used in some of these tests may further worsen the already impaired renal function. Caution should be taken in all investigations involving x-rays and contrast media if a woman is possibly pregnant and all patients should be asked if they suffer from any allergies (e.g. iodine) or asthma.

Description and Objective of Use: ImagingTests6,8,12,13

Test

Indications

Precautions

X-ray / radiograph

Plain abdominal x-rays can show the contour All women should be asked if they are of kidneys, ureters and bladder (KUB). It is pregnant or could be pregnant useful in the initial assessment of the size, shape, position and the presence of one or two kidneys. Likewise, of any abnormalities, especially kidney calculi

Intravenous A contrast medium (usually iodine based) is Check for allergies to contrast agent, pyelography injected into the vein and enters the blood as there is a potential for an allergic (IVP) / stream. It collects in the kidneys and the anaphylactic reaction urinary tract outlining the whole urinary Caution is taken in women who may Intravenous collecting system. X-ray lms are then taken urography at intervals and the progress of the contrast be pregnant; they must notify the radiologist (IVU) dye is observed. Used to study the kidneys Contrast media is nephrotoxic. In those (calyces and pelvis), the ureters and urinary with known CKD, kidney function should bladder be checked post procedure. Acute renal failure may result after the procedure. If possible patients should increase oral uid intake and urinary output should be monitored

Diagnostic Investigations in CKD

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Test

Indications Precautions Follow local policies for fasting and Useful to detect: bowel preparation. Usually includes renal calculi a mild laxative to be taken the night enlarged prostate tumours in the kidney, ureters or urinary before the test to clear the bowel which will allow for adequate visibility of the bladder urinary system

Retrograde A cystoscope is inserted into the urethra The patient needs to be nil by mouth pyelography and a small ureteric catheter is passed in a for 6 hours (check local policy) as it is retrograde manner into the kidney. Contrast usually done under general anaesthetic media is then injected through the catheter in an operating theatre. Written consent into the pelvis of the kidneys and ureter. is required X-rays are then taken. Used to outline calculi, calyceal defects and tumours in the ureter or After the procedure, patients should be advised to check their urine for renal pelvis signs of any blood (haematuria), and It can also be done after an IVP or notify if they have a fever or pain. If not ultrasound to dene deformities such as contraindicated, the patient should be encouraged to drink plenty of water to hydronephrosis avoid urinary infection. Prophylactic antibiotic may be ordered Contrast media is nephrotoxic. In those with known CKD, kidney function should be checked post procedure. Acute renal failure may result after the procedure. If possible patients should increase oral uid intake and urinary output should be monitored

A Guide to Clinical Practice (Stages 1-3)

Renal arterio- Angiogram involves the injection of contrast Prior to the test, anticoagulant therapy graphy/ renal medium into a blood vessel to carry out X- should be withheld according to medical angiogram ray examination. Useful in diagnosing renal instruction artery stenosis, tumours and injuries of Written consent is necessary. Patient vessels should be informed of any restricted activity after the procedure and to report of any haematoma at the site of puncture or any haematuria Contrast media is nephrotoxic. In those with known CKD, kidney function should be checked post procedure. Acute renal failure may result after the procedure. If possible patients should increase oral uid intake and urinary output should be monitored

Diagnostic Investigations in CKD

Abdominal Ultrasound scan / sonography

Aids in the diagnosis of kidney disease by dening the kidneys size, echogenicity, presence or absence of hydronephrosis, lesions and cysts. It is also used to guide the operator in renal biopsy

None

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Test Computed Tomography (CT) scan / computed axial tomography (CAT) scan

Indications Precautions Shows in detail the renal anatomy and its If contrast media used, those with known adjacent structures. The use of contrast CKD, kidney function should be checked enhances the visibility of the renal cortex post procedure. Acute renal failure may from the medulla. It is the test of choice in result after the procedure. If possible patients should increase oral uid intake the study of renal mass and renal trauma and urinary output should be monitored

Magnetic Resonance Image (MRI) scan

Produces cross-sectional images of the body. None if non-toxic contrast media used Gadolinium, a non-nephrotoxic contrast agent, may be used intravenously. MRI gives very clear and detailed images of soft-tissue structures. Hence, it is useful in revealing mass lesions, renal vein thrombosis, etc None

A Guide to Clinical Practice (Stages 1-3)

Renogram

Renogram: a renal scintigraphy in which dynamic and rapid serial imaging is done following the intravenous injection of an isotope (e.g. 99MTc-MAG3, an ideal radioisotope due to its ltration by glomeruli and elimination exclusively by tubular secretion). It is used to evaluate renal function, e.g. in the of transplanted kidneys

Renal Scan Renal Scan: a renal scintigraphy in which two to four hours prior to the test, a small amount of radioisotope (e.g. 99MTc-DMSA) is injected intravenously. Various static images are then taken. It is often used to evaluate renal cortical lesions

Renal Biopsy

Percutaneous An invasive procedure by which a special Prior to the procedure, patient should renal biopsy needle is introduced into the lower pole of have his/her blood coagulation checked the kidney (preferably the left as it is more Written consent needed easily accessible and not near the liver) to obtain a piece of tissue specimen for study. Patient should be informed of 24h It is used to establish diagnosis, to orientate complete bed-rest after native biopsy or according to unit policy and observe treatment regime and to classify prognosis puncture site for signs of bleeding and check urine for signs of haematuria Indicated in CKD: Conserved kidney size (> 9 cm) Proteinuria Microscopic haematuria
Diagnostic Investigations in CKD

Contraindicated: Single kidney (except transplanted) Gross obesity Uncontrolled hypertension Severe anaemia Uncontrolled coagulopathy Kidney with hydronephrosis or cysts Reduced size kidney (< 9 cm)

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References
1. 2. 3. 4. Mahon, A. Investigations in Renal Failure. EDTNA ERCA J. 2004 Jan-Mar; 30(1): 4-8. Laposata M. SI Unit Conversion Guide. The New England Journal of Medicine. NEJM Books: Boston. 1992. http://www.nlm.nih.gov/medlineplus/encyclopedia.html Locatelli F et al. Revised European Best Practice Guidelines for the Management of Anemia in Patients with Chronic Renal Failure. Nephrol Dial Transplant 2004; 19 (suppl 2): 1-47. Munson K and Jorgenson Linne J. Urinalysis and Body Fluids. A color Text and Atlas. Chapters 2, 3, 4. Elsevier: Toronto. 1995. Thomas, N Renal Nursing (2nd Edition). BaillireTindall: Edinburgh. 2002. French TW and Blue JT. Urine Sediment Atlas. Cornell University: New York. 1997. Fairley KF, Johnson R and Feehally J. Comprehensive Clinical Nephrology. Mosby: London. 2001. Brenner B. Benner and Rectors The Kidney 2 Vol Set (7th Edition). W.B. Saunders Company: Ontario. 2004. CKD guideline Guidelines for Chronic Kidney Disease: Identication, management and referral. http://www.renal.org/ JSCRenalDisease/JSCRenalDisease.html Higgins C. Understanding laboratory investigation. Blackwell Science: Oxford. 2000. Brenner, B. Rector, F. The Kidney, Fourth Edition Volume1. W.B. Saunders Company: Ontario. 1991. http://www.radiologyinfo.org/index

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5. 6. 7. 8. 9. 10.

11. 12. 13.

Further Reading
Sociedad Espaola de Nefrologa. Diagnstico Sindrmico y Exploraciones Diagnsticas 1998. Harcourt Brace de Espaa: S.A. Pattison J.et al. A Colour handbook of Renal Medicine 2004. Manson Publishing Ltd: London. Steddon S, Ashman N, Chesser A & Cunningham J. Oxford Handbook of Nephrology and Hypertension 2006. Oxford University Press: Oxford.

Diagnostic Investigations in CKD

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Learning Outcomes
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To gain insight into the prevalence of anaemia in Chronic Kidney Disease (CKD) To develop an understanding of the causes, signs and symptoms of anaemia in CKD patients To understand which CKD patients to screen for anaemia To review the current anaemia guidelines To understand the current recommended management strategies for anaemia management in CKD patients To reect on the benets of correcting anaemia in CKD patients

Denition of Anaemia in CKD The World Health Organisation denes anaemia as haemoglobin (Hb) level of less than 11g/dl in pregnant women and children aged 6 months to 5yrs, less than 12g/dl for non pregnant women and less than 13g/dl for men1. Management of anaemia should be considered in chronic kidney disease (CKD) when the Hb level is less than or equal to 11 g/dl. An estimated glomerular ltration rate (eGFR) of less than 60ml/min/1.73m should trigger investigation into whether anaemia is due to CKD. When the eGFR is greater than or equal to 60ml/min/1.73m2 the anaemia is more likely to be related to other causes2.

Management of Anaemia in CKD

Anaemia of Chronic Kidney Disease (ACKD) Many conditions are associated with ACKD, mainly because many chronic, systemic conditions lead to abnormalities in haemopoiesis (production of red blood cells)3. Anaemia in patients with CKD may develop in response to a wide variety of causes as systemic diseases have different effects on the kidney and the bone marrow. Causes of ACKD 1.Reduced Erythropoietin Production Anaemia in CKD is normally normochromic and normocytic. Erythropoietin deciency is the primary cause of anaemia associated with CKD. Erythropoietin is predominantly produced by peri-tubular cells in the kidney and is the hormone responsible for maintaining the proliferation and differentiation of erythroid progenitor cells in the bone marrow. Loss of peri-tubular cells leads to an inappropriately low level of circulating erythropoietin. The production of inammatory cytokines (common in CKD) such as interleukin 1 and Tubular Necrosis Factor (TNF alpha) can inhibit the maturation of the progenitor cells4 and lead to the reduction in production of erythropoietin. 2.Haemolysis The reason for impaired red blood cell survival (haemolysis) in CKD is not well understood although it is thought that uraemia plays a central role. In this situation a Coombs test is useful to look at the survival of the red cells. Normal red blood cell survival is 120 days in patients with CKD it may be reduced to 90 days. 3.Iron Deciency2 Iron has an essential role in supporting erythropoiesis with 65% of the iron stored in the body used to form haemoglobin. Iron deciency should be considered in people with stage 3 and 4 CKD if the ferritin level is less than 100g/l.

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Measurements of Iron Status Serum Ferritin: This refers to the amount of iron stored in the body. The body requires 150mg of iron to raise the haemoglobin by 1g/dl. As red cell production increases iron stores are depleted. Iron stores need to be adequate otherwise red blood cell survival is reduced. Serum ferritin is commonly used as a standard marker for measuring iron deciency. However it can be falsely raised in cases of infection and inammatory conditions. It is useful to measure the C reactive protein (CRP) at the same time as the ferritin. If the CRP is also raised then this will indicate that there is an infection or inammatory condition and that the raised ferritin is not a true indication of the iron status at that time. % Transferrin Saturation (%Tsats): This is the bodys transport system for iron. This needs to be >20% to be effective; however this is not a very reliable tool as %Tsats constantly alter. More than one measurement is required to ascertain an average reading. % Hypochromic Red Cells: This is dened as an individual cell with a haemoglobin concentration <10%. Normally 2.5% of red blood cells are hypochromic. If iron stores are insufcient and/or mobilisation of iron is inadequate the amount of hypochromic red blood cells increase in number and when they are greater than 10%, iron supplementation is required5. Denition of Iron Deciency Absolute Iron Deciency: Iron stores are inadequate to support the erythropoietic needs of the bone marrow, dened by a low serum ferritin level less than 100g/L. Functional Iron Deciency: Iron stores are adequate but cannot supply bone marrow quickly enough with the

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Management of Anaemia in CKD

iron required to support demands of erythropoiesis when stimulated acutely. This is dened by normal or high serum ferritin, % transferrin saturation less than 20% or % hypochromic red cells greater than 10%. 4.Vitamin B12 and Folate Deciency Vitamin B12, also called cobalamin, is required to maintain healthy nerve cells, red blood cells and DNA. Vitamin B12 is bound to protein in food. Hydrochloric acid in the stomach releases B12 from the protein during digestion. Once released, B12 combines with a substance called intrinsic factor (IF) before it is absorbed into the bloodstream. Vitamin B12 deciency is dened when B12 levels are less than 160ng/l. Pernicious anemia is a form of anaemia that occurs when there is an absence of intrinsic factor. Absence of intrinsic factor prevents normal absorption of B12 and results in pernicious anemia. Treatment for pernicious anaemia is by an initial treatment course of intramuscular hydroxycobalamin injections, 1mg three times a week, for two weeks followed by three monthly maintenance injection of 1mg which will continue indenitely6. Folate and folic acid are forms of a water-soluble B vitamin. Folate is essential for the production and maintenance of new red blood cells. Folate is also needed to make DNA and RNA. Those with renal disease should have a serum folate level > 20g/l. Supplementation with folic acid 5mg once a day should be given if the serum folate level is <20g/l.
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Causes of Anaemia Other than CKD Not all types of anaemia in patients with CKD will be renal anaemia and causes of anaemia other than CKD should be actively investigated and excluded before a diagnosis of anaemia associated with CKD is made2.
Table 1: Other causes of anaemia

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Chronic blood loss Hypothyroidism Chronic infection or inammation Hyperparathyroidism Aluminium toxicity Bone marrow inltration Pure red cell aplasia Malignancy

Table 2: Screening for anaemia of CKD

Investigations should be performed when Hb<12g/dl (men) or 11g/dl for women and should include the following tests: Haemoglobin Red cell folate concentration Serum B12 Serum ferritin Serum % transferrin saturation % Hypochromic red cells Tests for haemolysis (Haptoglobin, lactate dehydrogenase, Coombs test) Reticulocyte count C-Reactive protein (CRP) Assessment of occult gastrointestinal blood loss Nutritional status of the patient

The above tests will exclude causes for anaemia other than CKD, especially bone marrow suppression and haemolysis. It is important to screen for other causes of anaemia in order to reach the correct diagnosis. Haematological abnormalities need to be clearly recognised and appropriate treatment given.

Management of Anaemia in CKD

Table 3: Signs and Symptoms of ACKD

Dizziness or light headedness Fatigue and weakness Headache Irritability Less endurance in exercise Shortness of breath, especially with exercise Pale skin and eyes Rapid heartbeat Reduced cognitive function
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Signs & Symptoms of Anaemia of CKD The anaemia of chronic disease (ACD) may occur insidiously and is easy to overlook amid the general malaise related to the disease itself. Many of the signs and symptoms can be considered to be due to the effects of chronic disease but are in fact also signs and symptoms of anaemia7. The prevalence of anaemia in patients with CKD The importance of anaemia in CKD has been increasingly recognised since the introduction of erythropoietin (EPO) therapy in the late 1980s. However, until recently it has not been fully appreciated that anaemia begins to develop early in the course of CKD. NHANES III study found lower levels of kidney function to be associated with lower haemoglobin levels and a higher prevalence and severity of anaemia8. In the UK one study showed the population prevalence of stage 3-5 CKD in this study was estimated to be 4.9%.

Chronic Kidney Disease:

A Guide to Clinical Practice (Stages 1-3)

Table 4: Stages of CKD and prevalence of anaemia

Stage eGFR of CKD (ml/min/1.73m2) 2 3 4 60 30 15

Median Hb in men (g/dl) % 14.9 13.8 12.0

Median Hb in women (g/dl) % 13.5 12.2 10.3

Prevalence of anaemia* % 1 9 33

*Hb<12g/dl in men, Hb <11g/dl in women.

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In those patients with stage 3-5 CKD the prevalence anaemia, dened as a haemoglobin level of <12g/dl in men and post-menopausal women and 11g/dl in premenopausal women, was 12.0%, with a haemoglobin level <11g/dl in 3.8%9. Anaemia in Diabetes and CKD Those with CKD stage 3 and diabetes have a greater incidence of anaemia, 22% compared to 7.9% in non-diabetics10. Anaemia occurs early in the course of diabetic kidney disease and is associated with inappropriately low erythropoietin concentrations11. A comparison of those with Type 2 diabetes and CKD and those with non-diabetic CKD, showed that those with Type 2 diabetes were signicantly more anaemic12. Similar ndings have also been demonstrated in people with Type 1 diabetes and CKD compared with those without diabetes. Cross-sectional surveys of patients with diabetes, have also demonstrated that at all levels of eGFR, anaemia was more prevalent in those with diabetes compared with the general population13,14. With increasing albuminuria, the prevalence of anaemia was higher at each level of renal function, and that

Management of Anaemia in CKD

levels of erythropoietin were inappropriately low in those with anaemia15. Cardiovascular Effects of Anaemia. Possible adverse effects of anaemia in patients with CKD include reduced oxygen utilization, increased cardiac output and left ventricular hypertrophy (cardiac dilatation) increased wall thickness. In a study of 318 non-dialysis patients a mean decrease in Hb of 0.5 g/dl from baseline of 12.8 1.9 g/dl was found to be one of three factors that was associated with left ventricular hypertrophy (LVH)16. Whether early anaemia treatment prevents development of LVH, reduces cardiovascular mortality and morbidity, delays progression of CKD and reduces stroke and heart failure related hospitalisations, is clearly still open to question. However, there are currently three large studies seeking to answer these questions. The Correction of Haemoglobin and Outcomes in Renal Insufciency (CHOIR)17 study, the CREATE18 trial (Cardiovascular Risk reduction by Early Anaemia Treatment with epoetin beta) and the TREAT19 (Trial to Reduce Cardiovascular Events with Aranesp Therapy) study should help to determine the optimal management of pre-dialysis renal anaemia. Guidelines for Management of Anaemia When should Anaemia of CKD be treated? There are many anaemia guidelines and standards and each country may use country specic. The Kidney Disease Outcomes Quality Initiative guidelines of the National Kidney Foundation (NKF K/DOQI)20 dene anaemia in CKD as a haemoglobin concentration of less than 11 g/dL in premenopausal females and pre-pubertal patients, and less than 12 g/dL in adult males and postmenopausal females.
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The Revised European Best Practice Guidelines (EBPG)5 dene anaemia as an Hb fall below the mean Hb level of the population mean -2 Standard Deviation (SD) (i.e. <95%), as follows: <11.5 g/dl in adult female patients <13.5 g/dl in adult male patients <12.0 g/dl in adult male patients aged over 70 The UK NICE guidelines suggest a trigger for treatment when Hb 11g/dl. Target or aspirational ranges of haemoglobin levels also vary with each guideline. Having so many sets of guidelines and haemoglobin ranges can be confusing. However, it is important to have an agreed set of evidence based guidelines to use in your unit when managing anaemia of CKD.
Table 5 - Target haemoglobin levels for treatment of ACKD using available guidelines

94

Target H

aemia Ma ageme t

ideli es
e ised

D
g dL g dL er limit ot de i ed

D
g dL

e ised
g dL er limit i di id alised ca tio

D
g dL ith mai te a ce g dL

D
g dL D g dL o D g dL D g dL o D

M a ada
g dL g dL

D
g dL

Management of Anaemia in CKD

Treatment of Renal Anaemia Associated with CKD Managing Iron deciency The correction of iron deciency anaemia is essential before considering the use of any erythropoiesis stimulating agents (ESA). In people with functional iron deciency, iron supplements should be given concurrently when initiating ESA therapy as adequate iron stores are necessary to allow an optimal response to ESA therapy2. ESA therapy should not be initiated in the presence of absolute iron deciency without also managing the iron deciency. Treatment with intravenous iron may, by itself, correct anaemia amongst some patients with CKD. Oral iron Oral Iron can be poorly absorbed and the absorption can be inhibited by other drugs such as calcium based phosphate binders and aluminum and by taking it with food and tea. Vitamin C however assists absorption and taking iron supplements with a glass of orange juice may help. However with many renal patients having to cope with dietary changes and restrictions, this may not always be possible. The side effects of oral iron such as constipation, diarrhoea and atulence can often prevent it being taken regularly. However, oral iron is used in practice mainly for non-dialysis and peritoneal dialysis patients where the practicalities of administering intravenous iron are limiting. Intravenous Iron Intravenous iron is currently available as two preparations in the UK: Iron Dextran (Cosmofer r) Iron Sucrose (Venofer r). Iron Dextran (Cosmofer r)6 A complex of ferric hydroxide with dextrans containing 5% (50mg/ml) of iron. Dose: by intravenous slow infusion (up to 4hours) calculated according to bodyweight and iron decit (not recommended in a child under 14 years).
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Cautions: facilities for cardiopulmonary resuscitation must be at hand; increased risk of allergic reaction in immune or inammatory conditions; hepatic impairment; renal impairment; oral iron not to be given until 5 days after last injection; pregnancy. Contra-indications: history of allergic disorders including asthma and eczema; infection; active rheumatoid arthritis. Side-effects: nausea, dyspepsia, diarrhoea, chest pains, hypotension, dyspnoea, arthralgia, myalgia, pruritis, urticaria, rash, fever, shivering, ushing, headache; rarely anaphylactic reactions; injection site reactions including phlebitis reported.
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There are concerns regarding risk of anaphylaxis with Iron Dextran. Dextran antibodies can exist but this is unknown until Iron Dextran is given to the patient and within seconds an anaphylactic reaction may occur. This means that this drug must be given in an environment where there are full resuscitation facilities available. The advantage of Iron Dextran is that it can be given as a single dose infusion which is advantageous if the patient has to travel long distances for treatment. It cannot be given undiluted as a bolus dose. Iron Sucrose (Venofer r)6 A complex of ferric hydroxide with sucrose containing 2% (20mg/ml) of iron. Dose: by slow intravenous injection (over 5-10 minutes) or by intravenous infusion, calculated according to body-weight and iron decit, consult product literature (not recommended in children). Cautions: oral iron therapy should not be given until 5 days after last injection; facilities for cardiopulmonary resuscitation must be at hand; pregnancy.

Management of Anaemia in CKD

Contraindications: history of allergic disorders including asthma, eczema and anaphylaxis; liver disease; infection. Side-effects: nausea, vomiting, taste disturbances, headache, hypotension; less frequently paraesthesia, abdominal disorders, myalgia, fever, ushing, urticaria, peripheral oedema; rarely anaphylactoid reactions; injection site reactions including phlebitis have been reported. Venofer r can be safely given to patients across all modalities either as an infusion, or undiluted as a bolus dose via a buttery needle. It is the most commonly used intravenous iron supplementation in renal medicine. Haemodialysis patients are able to receive intravenous iron during dialysis without it being removed by dialysis. Therefore all haemodialysis patients who require iron supplementation can have intravenous iron rather than oral iron. The amount given will vary from unit to unit but a standard dose would be 100mg every fortnight as a maintenance dose. Or if the patient required a course of iron 1g it would be given over a 5-10 week period depending on the unit protocol. Peritoneal and non-dialysis patients may receive intravenous iron when their serum ferritin is <100g/dl, % Tsats<20% or %hypochromic Red Cells >10%. Patients who are intolerant of oral iron may be given maintenance intravenous iron every 6-8 weeks to maintain their serum ferritin >100g/l. In countries where the above preparations are not available Ferrous Gluconate may be used. Further information regarding this product should be sought from the pharmaceutical provider. Monitoring Iron Stores All patients who are receiving erythropoiesis stimulating agents (ESAs) require iron supplementation to support the demands made on the iron stores. Regular monitoring of iron
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stores is essential during treatment. In CKD patients with a stable haemoglobin level not being treated with ESAs, iron stores should be measured every three to six months5. Patients who are being treated with ESAs should have their iron status checked every 4 weeks during the correction phase (three months) and thereafter every three months5. Patients who are receiving regular intravenous iron therapy should have their iron status checked every three months and the intravenous therapy discontinued for at least a week prior to performing the tests5. Iron toxicity needs to be avoided and if the serum ferritin is persistently above 500g/l, and/or >40% Tsats greater than 40% iron supplementation should be withheld for up to three months as long as there are no signs of functional iron deciency. Iron status should be measured monthly in these situations. Erythropoiesis Stimulating Agents (ESAs) Treatment with ESAs should be offered to people with anaemia of CKD who are likely to benet in terms of quality of life and physical function2. The choice of ESA should be discussed with the person with anaemia of CKD when initiating treatment and at subsequent review, taking into consideration the patients dialysis status, the route of administration and the local availability of ESAs. There is no evidence to distinguish between ESAs in terms of efcacy2. There are several commercial Erythropoiesis Stimulating Agents (ESAs) available. Those currently licensed for use in CKD are: Epoetin alfa Epoetin beta Darbepoetin alfa Epoetin delta They all work in a similar way by continually stimulating the bone marrow to produce red blood cells.

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Management of Anaemia in CKD

Route of Administration The stage of CKD, treatment setting and patient choice should determine the route of ESA administration and type of ESA used. Convenience favours subcutaneous (SC) administration in non dialysis and peritoneal dialysis patients and intravenous (IV) administration in haemodialysis patients. However some preparations require higher doses when given intravenously and this needs to be considered. Frequency of administration The CKD stage, treatment setting, efcacy considerations, and type of ESA should determine the frequency of administration. Convenience favours less frequent administration, particularly in non haemodialysis patients. Dosing The initial ESA dose and ESA dose adjustments should be determined by the patients Hb level, the target Hb level, the observed rate of increase in Hb level, and clinical circumstances. ESA doses should be decreased, but not necessarily withheld, when a downward adjustment of Hb level is needed. Scheduled ESA doses that have been missed should be replaced at the earliest possible opportunity. ESA administration in ESAdependent patients should continue during hospitalisation. Hypertension, vascular access occlusion, inadequate dialysis, history of seizures, or compromised nutritional status are not usually contraindications to ESA therapy. Managing Non-Response to ESAs The patient with anaemia and CKD should undergo evaluation for specic causes of non response whenever the Hb level is inappropriately low for the ESA dose administered.

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Table 6 Screening for non-response

A Guide to Clinical Practice (Stages 1-3)

100

The following also need to be considered: Chronic blood loss (e.g. from gastrointestinal or genitourinary tracts) Iron deciency Folate / Vitamin B12 deciency Reticulocyte count Infection/inammation Tuberculosis, systemic lupus erythematosus (SLE) Chronically rejecting transplants Hyperparathyroidism / osteitis brosa Aluminium/chloramine toxicity Haemoglobinopathies (alpha, beta thalassaemia, sickle cell anaemia) Multiple myeloma, myelobrosis, myelodysplasia Malignancy Malnutrition Drugs interaction such as high dose ACE inhibitors Inadequate dialysis Antibodies to Epoetin - red cell aplasia

A process of elimination will determine the cause of nonresponse to treatment. However if none of the above are lacking and have all been fully investigated then a bone marrow aspiration may be necessary to rule out any other haematological cause of anaemia or non-response to treatment. The Benets of Treating ACKD Untreated anaemia has a number of adverse consequences both for the patient as well as for the healthcare system ranging from effects on quality of life, cognitive function and libido through to increased mortality and morbidity with its associated costs.

Management of Anaemia in CKD

The major risk is cardiovascular disease (CVD), with one of the earliest manifestations of left ventricular hypertrophy (LVH). Anaemia has both direct and indirect effects on left ventricular function and growth. Age, hypertension, and the level of Hb are independent predictors for the presence of LVH. A number of other studies have shown that anaemia predicts increased left ventricular mass, left ventricular dilatation, heart failure and death, and that anaemia is associated with increased hospitalisation rates and increased mortality21,22. Anaemia is also a potent risk marker for poor outcome amongst patients with acute myocardial infarction. The patients who are most likely to gain the greatest long-term benet from correction of anaemia in CKD are those who are approaching dialysis. Early intervention to correct anaemia has the potential to impact on the progression of chronic kidney disease and effect patient morbidity, hospitalisation rates, quality of life and mortality. Managing ACKD People offered ESA therapy and their primary care physicians should be given information about why ESA therapy is required, how it works and what benets and side effects may be experienced. When managing the treatment of people with anaemia of CKD, there should be agreed protocols dening roles and responsibilities of healthcare professionals. People with anaemia of CKD should have access to a designated contact person or persons who have principal responsibility for their anaemia management and who have skills in the following activities2: Monitoring and managing a caseload of patients in line with locally agreed protocols Providing information, education and support to empower patients and their families and carers to participate in their care

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Co-ordinating an anaemia service for people with CKD, working between secondary and primary care and providing a single point of contact, to ensure patients receive a seamless service of the highest standard Prescribing medicines related to anaemia management and monitoring their effectiveness In the UK ACKD is predominantly managed by nurses23, often with the help of electronic algorithms. Nurses across Europe are now increasingly taking on this role. References
102 1. World Health Organization. Iron Deciency Anaemia, Assessment, Prevention and Control: a guide for programme managers. 2001. National Collaborating Centre for Chronic Conditions. Anaemia management in chronic kidney disease: national clinical guideline for management in adults and children. Royal College of Physicians: London. 2006. Spivak JL. The blood in systemic disorders. Lancet 2000; 355: 1707-12. Peirera BJG, Sundaram S, Barrett TW, Butt NK, Porat R and King AJ. Cytokine production by human peripheral blood mononuclear cells stimulated by a Pseudomonas aeruginosa culture ltrate: Role of plasma and polymyxin B. International Journal of Articial Organs 1996; 19;(5):276-283. Revised European Best Practice Guidelines for Management of anaemia in patients with chronic renal failure. Nephrol Dial Transplant 2004; 19 ;(suppl 2) S1-S47. British National Formulary. March 2007. Jenkins K. Anaemia in CKD Chapter 3 in Thomas N, editor. Advanced Renal Nursing. Blackwell Publishing: London. 2005. Coresh J, Astor BC, Greene T et al. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Am J of Kidney Dis 2003; 41(1):112. De Lusignan S, Stevens PE, ODonoghue D et al. Identifying patients with chronic kidney disease from general practice computer records. Family Practice 2005;22(3):234241.

2.

3. 4.

5.

6. 7. 8.

9.

Management of Anaemia in CKD

10. El Achkar TM, Ohmit SE, McCullough PA et al. Higher prevalence of anemia with diabetes mellitus in moderate kidney insufciency: The Kidney Early Evaluation Program. Kidney Int 2005; 67(4): 14831488. 11. Bosman DR, Winkler AS, Marsden JT et al. Anemia with erythropoietin eciency occurs early in diabetic nephropathy. Diabetes Care 2001;24(3):495 499. 12. Ishimura E, Nishizawa Y, Okuno S et al. Diabetes mellitus increases the severity of anemia in non-dialysed patients with renal failure. Journal of Nephrology1998; 11(2):8386. 13. Thomas MC, MacIsaac RJ, Tsalamandris C et al. Unrecognized anemia in patients with diabetes: a cross-sectional survey. Diabetes Care 2003;26(4):11641169. 14. Thomas MC, MacIsaac RJ, Tsalamandris C et al. The burden of anaemia in Type 2 diabetes and the role of nephropathy: a crosssectional audit. Neph Dialysis Transplant 2004;19(7):17921797. 15. Thomas MC, Cooper ME, Tsalamandris C et al. Anemia with impaired erythropoietin response in diabetic patients. Archives of Internal Medicine 2005;165(4):466469. 16. Levin A, Thompson CR, Ethier J et al. Left ventricular mass index increase in early renal disease: impact of decline in hemoglobin. Am J of Kidney Dis 1999; 34(1):125134. 17. Singh AK, Szczech L, Tang KL et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 2006; 355:208598. 18. Macdougall IC. CREATE: New strategies for early anaemia management in renal insufciency. Nephrol Dial Transplant 2003;18: Suppl 2. 19. Mix TCH, Brenner RM, Cooper ME, de Zeeuw D, Ivanovich P, Levey AS et al. Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT): Evolving the management of cardiovascular risk in patients with chronic kidney disease. American Heart Journal 2005;149 (3): 408-413. 20. NKF-KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease. Am J Kidney Dis 2006; 47:S1-S146. 21. Jones M, Schenkel B, Just J. Epoetin alfas effect on left ventricular hypertrophy and subsequent mortality. International Journal of Cardiology 2005;100 (2):253265. 22. Weiner DE, Tighiouart H, Vlagopoulos PT et al. Effects of anemia and left ventricular hypertrophy on cardiovascular disease in patients with chronic kidney disease. Journal of The American Society of Nephrology 2005;16 (6):18031810. 23. Bennett L. The anaemia research nurse in effective multidisciplinary management of patients on erythropoietin. EDTNA/ERCA Journal 1998; 24(3):3839.

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Learning Outcomes To gain knowledge and understand the role of diet in the treatment of patients with Chronic Kidney Disease (CKD) stages 1-3 To explain the role of diet in hypertension management To gain knowledge in the dietary management of hyperlipidaemia To understand the measures that should be taken to slow down the progression of CKD

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Introduction Nutritional therapy is one of the cornerstones of treatment for patients with CKD stages 1-3. Early CKD is very common, but the majority of patients with early CKD do not progress to end stage renal disease (ESRD), but do have an increased risks of cardiovascular disease. Optimal management of the risk factors for cardiovascular disease also reduces the risk of progression from early CKD to ESRD. The Aims of Nutritional Therapy To prevent progression from early CKD to ESRD To reduce the risk factors for cardiovascular disease

Nutrition and Chronic Kidney Disease (Stages 1-3)

Diet Therapy for CKD Stages 1 - 2 Recent research shows that 0.9% of the general population have CKD1. Those aged 75 years 50%, have CKD caused by the normal ageing of their kidneys. This can increase the chances of high blood pressure, heart disease or stroke. Although age is a non-modiable risk factor, the time it takes to reach stage 4 and 5 CKD provides an opportunities to slow the progression of CKD, treat underlying co-morbidities, and to prevent the systemic complications that develop in the course of gradual loss of kidney function1, 2. A common factor associated with this is hypertension, which contributes to the progression of CKD and is a major risk factor for cardiovascular disease3. Hypertension Hypertension management should focus on weight reduction and reducing sodium intake. Other variables include alcohol, potassium, calcium and a low fat diet that needs to includes fruit and vegetables (5-9 portions daily) and low fat dairy produce (2-4 servings daily) which will be rich in potassium, magnesium, calcium and will modestly reduce blood pressure4. It is helpful to consider sodium and uid together as they are closely linked in the management of blood pressure. The bodys sodium and uid status is the main determinant of blood pressure. Dietary restrictions should be implemented if patients are hypertensive to an intake of <100mmols sodium (6g salt) per day. A study by Law et al (1991)5 demonstrated that in people aged 50-59 years, a reduction in daily sodium intake of 50mmol (about 3g of salt), attainable by moderate dietary salt reduction, after a few weeks, lowered systolic blood pressure by an average of 5mmHg, and by 7mmHg in those with high blood pressure (>170 mmHg); diastolic blood pressure would be lowered by about half as much5. The DASH study also demonstrated that a moderate sodium restriction
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showed a reduction in blood pressure of 5mmHg for systolic and 2mmHg for diastolic blood pressure in hypertensive individuals and the lower the sodium intake the greater the lowering of blood pressure6. Most of the sodium people consume is from the salt added to processed foods such as breakfast cereals, bread and tinned foods. The majority of manufactured foods now provide nutritional labelling information with include data of the sodium content. Educational information needs to be provided to patients as 1.25g salt (0.5g sodium) or more per 100g is a lot of salt whereas, 0.25g salt (0.1g sodium) or less per 100g is a little salt. In order to reduce a persons sodium intake you need to provide advice on a reduction of salt added during cooking and at the table before food is eaten, avoiding food which is high in salt such as manufactured food, ready made meals, smoked or cured foods.
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Lipids CKD patients are at a high risk for atherosclerotic cardiovascular disease. Hyperlipidaemia is common in patients with CKD, particularly those with nephrotic syndrome. In addition to accelerating the development of systemic atherosclerosis, experimental studies suggest that high lipid levels also may promote progression of renal disease7. Furthermore, the benecial effect of lipid lowering is similar to that of lowering the blood pressure in at least some models of chronic renal disease8. The amount and type of fat are prescribed on an individual basis and depend on factors such as serum lipid levels, protein intake and body weight9. In addition to dietary changes, statins are prescribed for treating high LDL cholesterol (low-density lipoprotein) and reducing the levels to <100mg/dL (<2.59mmol/L)10. Dietary restrictions include a diet containing <10% of energy intake derived from saturated fatty acids (SFA). Some individuals (i.e. people with LDL cholesterol > 100mg/dl) may benet from lowering SFA intake

Nutrition and Chronic Kidney Disease (Stages 1-3)

to <7% of energy intake. Dietary cholesterol intake should be less than <300mg/day. Practically this means a reduction in saturated dietary fat such as butter, ghee, cakes, biscuits and instead using monounsaturated fats such as olive oil9. The intake of trans-unsaturated fatty acids should be minimized. Recommendations also include two to three servings of sh per week to provide dietary n-3 polyunsaturated fatty acids (n-3 PUFA)11. Diabetes In people with diabetes, excessive consumption of protein may be harmful. Experts recommend that people with diabetic nephropathy consume the recommended dietary allowance for protein, but avoid high-protein diets. For those with greatly reduced kidney function, a diet containing reduced amounts of protein may help delay the onset of kidney failure12. Anyone following a reduced-protein diet should work with a dietitian to ensure adequate nutrition. Antihypertensive drugs and low-protein diets can slow kidney disease when signicant nephropathy is present. Intensive management of blood glucose is important for people with type 1 and type 2 diabetes, especially for those in early stages of diabetic nephropathy13. Intensive management is a treatment regimen that aims to keep blood glucose levels close to normal. The regimen includes testing blood glucose frequently, administering insulin frequently throughout the day on the basis of food intake and physical activity, following a diet and activity plan, and consulting a health care team frequently. Diet Therapy for CKD Stage 3 As patients progress to CKD stage 3, dietary advice depends on many factors including existing co-morbidities, medications, blood biochemistry, nutritional status, weight and usual dietary intake. Lifestyle advice as in stages 1-2 will form the main basis of diet therapy; however additional advice on protein,

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phosphate, potassium, vitamins and minerals might also be provided dependent on the individual requirements of the patient. Protein Intake Control of protein intake may delay the progression of CKD and improve the effects of excessive accumulation of nitrogenous waste14. A re-analysis of The Modication of Diet in Renal Disease (MDRD) demonstrated that a 0.2g/kg a day reduction in protein intake correlated with a 1.15ml/min/year reduction in the rate of decline in glomerular ltration rate (GFR). This decline has been shown to correlate with a 41% prolongation of renal survival15. A Cochrane systematic review further demonstrates the benets of decreasing protein intake in the diet on delaying the progression of CKD12. Unfortunately, the evidence is not conclusive and opinions are divided and further research is required in the future. Currently, there are variant recommendations of dietary protein intake for CKD patients (Table 1)
Table 1: Current recommendations of dietary protein intake for CKD patients

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Glomerular Filtration Rate (GFR) > 30 ml / min < 30 ml / min 20 - 30 ml / min

Recommended protein intake (g/kg ideal body weight) 0.75 g / kg 0.6 g / kg 0.6 - 1.0 g / kg

Professional organisation K/DOQI K/DOQI EDTNA / ERCA

Although the benet of protein restriction may be sufcient to delay renal replacement therapy for several years, there is a large cost in terms both of effort on the part of the healthcare team and patient, and of the relatively poor palatability of more severe protein restriction. Only highly compliant patients are

Nutrition and Chronic Kidney Disease (Stages 1-3)

likely to comply with this regimen over a prolonged period16. At present, optimal dietary treatment of non-diabetic patients with CKD is uncertain. A reasonable regimen consists of rigorous blood pressure control and the intake of approximately 0.8 to 1.0g/kg of high biologic value protein per day, with the lower value used in patients with progressive disease. It is possible, although not proven, that vegetable proteins and egg whites are a safer sources of protein, since they are less likely to increase glomerular ltration16. Low-protein diets reduce the generation of nitrogenous wastes and inorganic ions, which cause many of the clinical and metabolic disturbances characteristic of uraemia such as hyperphosphataemia, metabolic acidosis, hyperkalaemia, and other electrolyte disorders16. Nephrotic syndrome comprises of a group of symptoms including proteinuria (exceeding 3.5 grams per day), low blood protein levels, hypercholesterolemia, and oedema caused by various disorders that damage the kidneys, particularly the basement membrane of the glomerulus. It can both decrease protein excretion and diminish hepatic albumin synthesis; the net result is usually no change in the plasma albumin concentration16.
9, 17 Recommended nutritional management g : Treatment of hypertension - low salt diet, (NKF K/DOQI: 1 - 2 g sodium/day)

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Protein intake of 0.8 - 1.0 g protein / kg ideal body weight Adequate energy intake Treat hyperlipidaemia: - manipulate fat intake - lipid-lowering drugs Maintain uid balance

Chronic Kidney Disease:

A Guide to Clinical Practice (Stages 1-3)

Renal Bone Disease and Nutritional Interventions Hyperphosphataemia A tendency toward phosphate retention begins early in CKD, due to the reduction in the ltered phosphate load. Although this problem is initially mild with hyperphosphataemia being a relatively late event, phosphate retention is intimately related secondary to the common development of hyperparathyroidism. High circulating levels of parathyroid hormone play an important role in the development of renal osteodystrophy and possibly in other uraemic complications18. Phosphate The K/DOQI practice guidelines made the following recommendations for the goal serum phosphate at different levels of CKD19. At an estimated GFR between 15 and 59 ml/min/ 1.73m2 (stage 3 and 4 CKD), the serum phosphate should be between 2.7 and 4.6 mg/dl (0.87 and 1.49 mmol/L) The calcium phosphate product (corrected calcium x phosphate) should be maintained below <55 mg/dl, (<4.4 mmol/L) in patients with stage 3 to 5 CKD Potassium Hyperkalaemia in CKD stages 1-3 is rare, however patients with CKD should be monitored on a regular basis to avoid hyper or hypokalaemia. In CKD stages 1-3 non-dietary reasons could be the cause of a hyperkalaemic episode and should be considered, this include blood transfusions, anaesthetics, insulin insufciency, acidosis and medication20. Drugs that can cause hyperkalaemia include angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptive blockers (ARB), beta-blockers, potassium-sparing diuretics (spironolactone), non-steroidal anti-inammatory drugs and ciclosporine.

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Vitamins and minerals Vitamin and mineral requirements are not well dened in CKD, but non-dialysed patients treated with a controlled-protein diet may need some vitamin supplements. Vitamin preparations should contain the daily recommended intake of water-soluble vitamins, including folate2. The normal dietary intake of Vitamin C is 60mg/day and should not exceed 100mg/day because it plays a role in the formation of oxalosis2,18. Fat-soluble vitamins and especially vitamin A, should be avoided as renal function decreases as this is raised in renal failure2, 20. Routine supplementation of water-soluble vitamins will most likely outweigh the risk of deciency, especially in those patients who are unable to manage an adequate dietary intake18. Mineral supplementation, including trace elements, is not recommended in this patient population. Iron supplementation should be individualized and iron levels monitored closely2. It is important to avoid prescribing iron supplementation with phosphate binders to prevent drug interaction20. Zinc supplementation is only indicated once zinc deciency has been established20. Summary r of f Diet and Lifestyle Advice Improving diet and lifestyle is a critical component for reducing cardiovascular disease risk factors. The current recommendations are: to balance calorie intake and physical activity to achieve and maintain a healthy body weight (BMI 20-25) to eat a diet rich in vegetables and fruit choose wholegrain, high bre foods such as whole grain cereals and wholemeal bread to include oily sh in the diet two or three times a week such as mackerel, sardines, salmon or fresh tuna limit saturated fat to <7% of the total calorie intake and cholesterol to <300mg/day by choosing lean meats

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and low fat dairy products and minimizing the intake of hydrogenated fats (found in biscuits, crisps) to minimize the intake of food and drinks with added sugars to prepare food with little or no salt to consume alcohol in moderation to ensure good blood glucose control if the person suffers from diabetes

Appendix I
Nutrition recommendation for CKD patient without dialysis

Recommendations20 0.6-1.0 g/kg IBW/day (high biologic value >50%)* 30-35 kcal/kg IBW/day 50%-60% of total calories 30%-40% of total calories 7%-10% of total calories

American Dietetic Association14 0.75 g / kg / day Based on energy expenditure 50-60 % of total calories 25-35 % of total calories <7 % of total calories

Protein

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Energy Carbohydrates Total Lipids Saturated Lipids Polyunsaturated Lipids Monounsaturated Lipids

7%-10% of total calories

Up to 10 % of total calories

10%-20% of total calories

Up to 20 % of total calories

Nutrition and Chronic Kidney Disease (Stages 1-3)

Sodium

1800 - 2500 mg/day (80 - 100 mmol sodium or 5 - 6 g salt per day)*

Varies 1 - 4 g / day to no added salt, depending on co-morbidities

Potassium

1.0 mmol/kg IBW with K+ >5.5 mmol/l*

Usually no restriction unless serum levels are raised

Phosphorus

600 - 1000 mg/day (19 - 31 mmol/l)*

Monitor and restrict if > 4.6 mg/dl (>1.49 mmol/L)

Calcium

1000 - 1500 mg/day

1200 - 1500 mg / day, maintain serum level at lower end

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Fluids

Urine volume 24-hours + 750 ml DRI, no supplement DRI, individualized supplementation if indicated

No restriction

Magnesium

No supplement

Iron

Individualize from stages 3 - 5

Zinc
* EDTNA/ERCA 2001

DRI, supplement if deciency conrmed

Individualize from stages 3 - 5

Chronic Kidney Disease:

A Guide to Clinical Practice (Stages 1-3)

Appendix 2
Vitamins

Vitamins - diet may be supplemented with these quantities Quantity 1.5 mg / day21 1.8 mg / day21 5 mg / day21 20 mg / day21 5 mg / day21 3 g / day20,21, Daily Recommended Intake (DRI) 60 - 100mg/day3 (DRI) 1 mg / day21 No supplement2,20, 21 Individualize from stages 3 - 52 ,20, 21 15 IU / day21 No supplement2 ,20, 21

Thiamine Riboavin Pantothenic Acid Niacin Pyridoxine Vitamin B12 Vitamin C Folic Acid Vitamin A
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Vitamin D Vitamin E Vitamin K

References
1. Sarnak MJ, Levey AS. Cardiovascular disease and chronic renal disease: a new paradigm. Am J Kidney Dis 2000; 35 (4 Suppl 1): S117-31. Levey AS, Beto JA, Coronado BE, et al. Controlling the epidemic of cardiovascular disease in chronic renal disease: What do we know? What do we need to learn? Where do we go from here? National Kidney Foundation Task Force on Cardiovascular Disease. Am J Kidney Dis 1998; 32 (5): 853-906. Bakris GL, Williams M, Dworkin L, et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Am J Kidney Dis 2000; 36 (3): 646-61. Karppanen H, Karppanen P, Mervaala E. Why and how to implement sodium, potassium, calcium and magnesium changes in food items and diet? J Hum Hypertens 2005; 19 Suppl 3: S10-9.

2.

3.

4.

Nutrition and Chronic Kidney Disease (Stages 1-3)

5.

6. 7. 8.

9.

10.

11. 12.

13.

14. 15.

16. 17. 18. 19. 20. 21.

Law MR, Frost CD, Wald NJ. By how much does dietary salt reduction lower blood pressure? III--Analysis of data from trials of salt reduction. BMJ 1991; 6;302(6780):819-24. Sacks et al. DASH trial. N Engl J Med 2001; 344: 3-10. Fried L, Orchard T, Kasiske B. Effect of lipid reduction on the progression of renal disease: A meta-analysis. Kidney Int 2001; 59: 260-269. Klahr S, Levey AS, Beck GJ, Caggiula AW, Hunsicker L, Kusek JW, Striker G. The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modication of Diet in Renal Disease Study Group. N Engl J Med. 1994; Mar 31;330 (13): 877-84. McCann L, editor. Pocket Guide to Nutrition Assessment of the Patient with Chronic Kidney Disease 3rd ed. National Kidney Foundation: New York. 2002. NKF-K/DOQI Clinical Practice Guidelines for Management of Dyslipidemias in Patients with Kidney Disease. Am J Kidney Dis 2003; 41 (4 Suppl 3): I-IV, S1-91. Calder PC. N-3 fatty acids and cardiovascular disease: evidence explained and mechanisms explored. Clinical Science 2004; 107: 1-11. Fouque D, Laville M, Boissel JP. Low protein diets for chronic kidney disease in non diabetic adults. The Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD001892. DOI: 10.1002/14651858.CD1892.pub2. 2006. Diabetes Control and Complication Trail Research Group (DCTT). The effect of intensive therapy on the development and progression of diabetic nephropathy in the Diabetes and Complication Trial. Kidney Int 1995; 47 (6); 1703-20. Byham-Gray L, Wiesen K, editors. A Clinical Guide to Nutrition Care in Kidney Disease.1st ed. Faulhaber Publisher: Chicago. 2004. Levey AS, Adler S, Caggiuka AW et al. Effects of dietary protein restriction on the progression of advanced renal disease in the Modication of diet in Renal Disease study. Am J Kidney Dis 1996; 27:652 - 663. Rose BD. Protein restriction and progression of chronic kidney disease. Up-To-Date; 8/2006: 14.3. NKF-K/DOQI Clinical practice guidelines for nutrition in CRF. Am J Kidney Dis 2000; 35 (6), suppl 2: S9, S56-63. Cronin RE, Treatment of hyperphosphatemia in chronic renal failure. Up-To-Date; 08/2006: 14.3. NKF-K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease. Am J Kidney Dis 2003; (4) Suppl 3: S1-201. Jacobs C. Costs and benets of improving renal failure treatment where do we go? Nephr Dial Transpl 2006; 21: 2049 2052. Kopple JD, Massry SG. Nutritional Management of Renal Disease. 1st ed. Williams and Wilkins: Baltimore. 1997.

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Learning Outcomes To gain knowledge and understanding about diabetes mellitus and the effect on kidney function To explain the effects of Chronic Kidney Disease (CKD) on diabetes control To gain an understanding of the treatment of diabetes

Introduction Diabetes mellitus is the leading cause of end stage renal failure within the western world and the number of people developing diabetes is increasing rapidly. The world wide number of diabetes cases reached 171 million in the year 2000 and this is predicted to rise to over 300 million by 2030, with a prevalence globally of 4.4% in all age groups1. Reasons for this rapid rise include an ageing population, unhealthy diets, sedentary lifestyles and the increase in obesity. The World Health Organisation states that the number of deaths attributed annually to diabetes is around 3.2 million, with diabetes being the major causes of premature illness and death in most countries, mainly through the increased risk of cardiovascular disease (CVD)2. Diabetes is among the leading causes of CKD, but its frequency varies between populations. According to the European Dialysis and Transplant Registry 2004 the percentage of people with diabetes as the leading cause of CKD ranges from 4.6% in Finland to 45.2% in Austria3.

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The Effect of Diabetes Mellitus on Progression CKD

What is Diabetes mellitus? Diabetes Mellitus is a condition that results in chronic high blood sugar levels (hyperglycaemia) due to insulin deciency, insulin resistance or a combination of these two factors. Type yp 1 Diabetes - usually occurs in children or young adults, but can occur at any age and accounts for approximately 510% of all cases of diabetes2. It results from destruction of the cells that produce insulin, mainly by the autoimmune destruction of the pancreatic beta cells. People with type 1 diabetes are dependent on insulin injections to survive as they do not produce any of their own insulin. Type yp 2 Diabetes - accounts for the majority of cases of diabetes (90-95%) and results from a combination of insulin deciency and insulin resistance. The level of hyperglycaemia is usually less severe and can be managed initially with a combination of lifestyle change and oral medication. As the disease progresses however the need for insulin injections to manage blood sugar levels becomes more likely. Lifestyle factors such as obesity and a sedentary lifestyle contribute to the increased risk of developing type 2 diabetes as do genetic factors and ethnicity. In the presence of typical symptoms of diabetes - weight loss, polyuria, polydipsia, blurred vision and glycosuria - a single fasting plasma glucose level of >7.0mmol1 or a random plasma glucose of >11.1mmol1 is diagnostic. In the absence of symptoms two such values are needed. A formal glucose
Table 1: Diagnosis of Diabetes

12 1

Diabetes Fasting plasma glucose > 7.0mmmol/l (126mg/dl) or or 2hr plasma glucose after a 75g oral > 11.1mmol/l (200mg/dl) glucose load

Chronic Kidney Disease:

A Guide to Clinical Practice (Stages 1-3)

tolerance test can be ordered where a fasting glucose level is taken then the patient is given 75g of glucose and, 2 hours later, a further glucose level taken. Blood sugar monitoring (BM) tests can not be used for diagnosis2. How does Diabetes Affect Renal Function? Although people with diabetes can develop any type of kidney disease, the reason for the high risk of CKD in diabetes is related to the risk of developing diabetic nephropathy. This is a condition characterised by glomerular hyperfunction and hypertrophy, followed by microalbuminuria and then nally progressive decline in renal function to end stage disease. The exact cause of this is not completely understood but hyperglycaemia plays a role in damaging the microcirculation within the kidney. Hypertension which is highly prevalent particularly in type 2 diabetes also plays a key part. Can Diabetic Nephropathy p p y be Prevented? - Not all patients with diabetes will develop diabetic nephropathy. The prevalence is estimated to be 25-30% in type 2 diabetes, and among white patients with type 1 diabetes of 15-30 years duration, in the United Kingdom, fewer than 20% will have established nephropathy4. The prevalence of nephropathy is higher among patients of Asian or African-Caribbean origin. Genetic factors, ethnicity, age and gender are all factors that can not be altered. However the risk of developing nephropathy can be reduced by controlling modiable risk factors such as glycaemic control and blood pressure. The Diabetes Control and Complications Study demonstrated the benets of achieving good diabetes control in reducing the risk of developing diabetic nephropathy. Patients with type 1 diabetes assigned to intensive insulin treatment who achieved a mean HbA1c of 7.2% (compared with 9.1% in the control group) delayed the onset of microvascular complications

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The Effect of Diabetes Mellitus on Progression CKD

such as diabetic nephropathy and also had a slower rate of progression of microvascular damage once established5. The United Kingdom Prospective Diabetes (UKPDS) study reported similar ndings in a large randomised control study of people with type 2 diabetes. A 1% reduction in HbA1c result was associated with a 37% reduction in the risk of developing microvascular complications and a 21% reduction in risk of any morbidity end point or death related to diabetes6. There was no specic threshold found in either of these studies to indicate a level above which patients were at greater risk; any improvement in HbA1c is benecial in reducing the risk of complications and the nearer normal the HbA1c concentration the better. The European Association for Study of Diabetes (EASD) recommend a target HbA1c of 6.5% or below7. How does CKD affect diabetes control? Once CKD is established diabetes becomes difcult to control. Advancing CKD is associated with an increase in insulin resistance, this can result in more insulin being required or a conversion from tablets to insulin. However as the disease progresses to end stage renal failure there is a reduction in insulin degradation resulting in a marked reduction in insulin requirements or even cessation of insulin / tablets in type 2 diabetes. Potential problems in achieving good diabetic control in CKD: Risk of severe hypoglycaemia with aggressive control, particularly if dietary intake is unpredictable Lack of symptoms of hypo- or hyper-glycaemia Potential for inaccuracy of blood test results Presence of other diabetes related complications e.g. neuropathy or retinopathy Effect of impaired renal function on treatments used to control hyperglycemia

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Measuring Level of Diabetes Control HbA1c - diabetes control can be assessed by serial measurement of HbA1c levels. This gives an assessment of glycaemic control for the previous 3months (assuming a normal red blood cell life). High urea levels may interfere with some of the methods used to measure HbA1c, it is important check with the laboratory which assay they use and whether or not results will be affected by urea levels. Home Blood Glucose Monitoring g - patient self monitoring via home blood glucose meters is useful to determine the optimum insulin regime and monitor the effect on a daily basis of changes in treatment. Hydration levels, uric acid and the maltose used in some peritoneal dialysis uids, will affect some test strips. It is essential to check with the manufacturers any potential interference that may lead to inaccurate results before using home blood glucose results to change treatment. Managing the Patient With Diabetes
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All patients with diabetes should be seen at least annually by a family doctor or hospital consultant so that their condition can be monitored and any complications detected early. They may be seen more often by diabetes nurses and diabetes educators to ensure that they have the right skills and knowledge to be able to self manage their diabetes where this is appropriate. Care of the person with diabetes should include8,9: Providing education to ensure self caring e.g. how to blood glucose monitor and how to adjust insulin if blood sugars are not controlled Assessing cardiovascular risk factors with the aim to reduce cardiovascular risk e.g. smoking cessation; consider aspirin and statins if appropriate; target BP (<130/80mmHg), total cholesterol (<4mmol/l) and HbA1c (<6.5%)

The Effect of Diabetes Mellitus on Progression CKD

Annual screening for complications including eyes, feet and urine test for microalbuminuria/ proteinuria Support with lifestyle changes such as increasing physical activity and reducing weight and choosing a healthy diet Consider use of an angiotensin converting enzyme (ACE) inhibitor or angiotensin 2 antagonist if microproteinuria or overt proteinuria present Refer to a nephrologists when CKD stage 3-4, or sooner if there is a rapid deterioration in renal function which may suggest a non-diabetes related kidney disease Treatments Used to Achieve Good Diabetes Control Lifestyle y Changes g A healthy balanced diet low in rened sugars is recommended in diabetes. When CKD is present particularly in advanced stages dietary restrictions are complex and advice from a dietician should be sort to enable the person to combine the various aspects of the dietary recommendations Exercise is an important aspect to maintain ideal weight and help control blood glucose levels
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Pharmacology
Table 2: Oral Hypoglycaemic agents used in type 2 diabetes

Agents Sulphonylurea- act on the pancreas to increase insulin secretion. Only effective if patient still produces some of their own insulin e.g. Glicalzide, Glipizide, Glyburide, Glimepiride Alpha- Glucosidase

Side Effects Usually mild and infrequent may cause gastrointestinal side effects nausea, vomiting diarrhoea or constipation

Cautions in CKD Risk of hypoglycaemia Accumulation of drug if renal function impaired, reduce dose or avoid using once patient reaches end stage renal failure

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Hypoglycaemia, weight gain Frequently cause Not recommended in CKD due to increased gastro-intestinal Inhibitors - delays side effects levels of the drug digestion and if kidney function absorption of starch e.g atulence impaired and sucrose and abdominal e.g. Acarbose bloating, diarrhoea Meglitinides- stimulate Gastrointestinal Caution advised insulin secretion due to the risk of side effects, hypoglycaemia rarely e.g Repaglinide, hypoglycaemia Nateglinide Biguanides- suppress Gastrointestinal Excreted mainly unchanged in the urine side effects hepatic glucose such as nausea, thus if renal function is production and increase insulin impaired accumulation vomiting, sensitivity in diarrhoea, of the drug occurs. peripheral tissue Should not be used if atulence, creatinine clearance is metallic taste e.g. Metformin reduced due to risk of lactic acidosis. Caution needed once GFR is <50ml

The Effect of Diabetes Mellitus on Progression CKD

Thiazolidinediones - increase insulin sensitivity e.g. Rosiglitazone, Pioglitazone

Gastrointestinal side effects, weight gain, headache anaemia, oedema, rare reports of liver toxicity

Metabolised by the liver thus not affected by dialysis and accumulation does not occur in CKD. However associated with heart failure and oedema and should be avoided in advanced CKD, especially if there is pre-existing heart failure

Insulin
Table 3: Insulin used in type 1 diabetes and in some patients with type 2 diabetes

Insulin Type

Examples

Onset of action 5-10 mins must be injected with food 30 mins Inject 20-30mins before food

Peak action

Duration of action

Rapid Acting

Aspart Lispro Gluilisine Actrapid Humulin S Hypurin Neutral

30-90 mins

Up to 4 hours

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Short Acting

1-2 hours

Up to 6-7 hours

Insulatard Humulin I Intermediate Insuman Acting basal Hypurin Isophane Long acting Analogues Detemir Glargine

60 mins

3-6 hours

18-24 hours

1.5-2 hours

Minimal peak

18- 24 hours

Chronic Kidney Disease:

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Insulin Regimes
Subcutaneous insulin injections

Examples

One or two injections per day of a basal insulin (eg Glargine, Detemir, Isophane Basal Bolus Regime insulin ) with meal time injections of a short acting insulin (eg Aspart, Lispro,Glulisine, Soluble insulin) Twice daily Mixed insulin One injection of a mixture of basal and short acting insulin given with breakfast and evening meal One or two injections per day of basal insulin (eg Glargine, Detemir, Isophane insulin) given at breakfast, evening meal or pre bed. Usually given in combination with oral diabetes medication

Basal Insulin only

Injections of short acting insulin given with each meal (eg Aspart, Lispro,Glulisine, Meal time only insulin Soluble insulin). Usually given in combination with oral diabetes medication and not suitable for use in type 1 diabetes
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Continuous Subcutaneous Insulin via a pump Short acting insulin (eg Aspart, Lispro,Glulisine, Soluble insulin) administered subcutaneously via a small portable electronic pump device Pumps are an advantage in allowing ne adjustment to be made to insulin doses but they are expensive and there is potentially an increased risk of diabetic ketoacidosis developing Inhaled Insulin Relatively new to the market, inhaled insulin is short acting and is given at meal times via an inhalation device directly into the lungs. Must be used in conjunction with a subcutaneous basal insulin injection in type 1 diabetes. Contraindicated in smokers and those with respiratory diseases e.g. asthma

The Effect of Diabetes Mellitus on Progression CKD

KDOQI guidelines 2005 suggest that newer insulin regimes and insulin preparations should be used to maintain good glycaemic control in CKD. Insulin analogues are associated with reduced risk of hypoglycaemia and increased predictability in their actions, thus helping to maintain better control8. How to decide which insulin regime is best The choice of insulin regime often depends on a number of factors: the type of diabetes, the patients personal preference, the risk of hypoglycaemia, eating habits and persons lifestyle. If someone is active and has an erratic lifestyle a basal bolus regime is usually preferable to give more exibility. If someone is less active and needs help with their injections then a once daily or twice daily regime would be more suitable. Cautions for Insulin Use in CKD The kidneys play an important role in metabolising insulin, however there is little change in the metabolic clearance rate in CKD until there has been a substantial reduction in GFR. At this point there is a dramatic reduction in insulin clearance increasing the risk of severe hypoglycaemia occurring if insulin doses are not adjusted. The effect on individual patients will vary depending on factors such as dietary intake, presence of other diabetes complications and the types of treatments they are prescribed. An integrated multidisciplinary approach is required to minimise problems and maintain adequate diabetes control.
Table 4: Recommendations for adjusting insulin with decline in renal function10

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No dose adjustment required GFR 10-50ml/min GFR <10ml/min Reduce to 75% of baseline dose Reduce by as much as 50%

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Side Effects of Insulin Insulin has few side effects, occasionally people may develop sensitivity to insulin resulting in redness and inammation at the injection site but this is rare. The main concern when someone takes insulin is the risk of hypoglycaemia (blood sugars <4mmol/s) resulting in symptoms of sweating, pallor, dizziness, shaking, confusion and possible collapse. Action to take if hypoglycaemia occurs: If conscious give patient a sugary drink, 3 glucose tablets or Glucogel Follow this with a carbohydrate based snack e.g. bread, biscuits If unconscious do not give anything by mouth use intramuscular Glucagon or intravenous dextrose Another side effect of insulin is possible problems with injection sites with skin/ fat atrophy or hypertrophy occurring. This can be prevented by advising people to regularly change their injection sites.
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What to do if patient is unwell If the patient is unwell it is important to do the following: Not to stop the insulin or tablets, they may even need to be increased as hyperglycaemia is common in the presence of illness Increase blood glucose monitoring Ensure hydration, maintaining uid balance Refer to a medic if vomiting to prevent ketoacidosis Other Complications of Diabetes The person with diabetes who develops CKD is likely to have also developed a number of other complications related to

The Effect of Diabetes Mellitus on Progression CKD

their diabetes. This is due to the fact that the vascular damage that is occurring within the kidney also occurs in other areas. These complications include: Peripheral neuropathy and peripheral vascular disease resulting in high risk of foot ulceration and amputation Autonomic neuropathy resulting in postural hypotension or gastric disturbances e.g. gastroparesis Cardiovascular Disease e.g. angina, stroke, myocardial infarction or heart failure Retinopathy resulting in visual impairment and possible blindness Sexual dysfunction e.g. erectile dysfunction in men The risk of these complications occurring can be reduced through tight control of blood pressure, cholesterol and blood sugar levels. Key Points Summary Diabetes is the leading cause of end stage renal disease in the western world The number of people developing diabetes is increasing rapidly world wide The risk of developing diabetic kidney disease can be reduced through good diabetes control (HbA1c <6.5%) Once CKD is established diabetes becomes difcult to control and careful adjustment of treatment is needed to avoid problems

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Frequently asked Questions 1 What is Diabetes Mellitus? Diabetes is a condition that results in chronic high blood sugar levels and is the result of insulin deciency, insulin resistance or a combination of these two factors. 2 What is the difference between type 1 and type 2 diabetes? Type 1 diabetes is caused by an auto immune response in which the body destroys the cells that make insulin. The person with type 1 diabetes is dependent on insulin injections to survive as they do not make any of their own. In type 2 diabetes the person still produces some insulin but not enough or may be insulin resistant and can be treated with diet, tablets but some patients will need insulin. 3 Why do a lot of patients with diabetes have CKD? Diabetic nephropathy which results in microalbuminuria then progressive decline in renal function is caused by high blood sugar levels. People with diabetes are also more likely to have high blood pressure which contributes to CKD.
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4 Can diabetic nephropathy be prevented? Yes, good diabetes control and tight control of blood pressure reduces the risk of diabetic nephropathy 5 How does CKD affect diabetes control? A person with CKD is likely to have difculty in managing blood sugar levels and may be at risk of severe hypoglycaemia due to poor clearance of medication 6 Are diabetes treatments safe to use in CKD? Many of the oral medications used to treat diabetes become contra-indicated in advanced CKD or should be used with caution. Insulin can be used safely in all stages of CKD and is not affected by dialysis. However signicant reductions in dose may be needed once GFR falls below 20.

The Effect of Diabetes Mellitus on Progression CKD

References
Wild S, Roglic G, Green A et al. Global Prevalence of Diabetes. Diabetes Care 2004; 27, (5): 1047-1053. 2. World Health Organisation, Facts and Figures, 2007. http://www.who.int/diabetes/facts/world_gures/en 3. ERA-EDTA. European Dialysis and Transplantation Registry, 2004. http://www.era-edta-reg.org/index.jsp 4. Harvey JN, Rizvi K, Craney L, Messenger J, Shah R, Meadows PA. Population-based survey and analysis of trends in the prevalence of diabetic nephropathy in Type 1 diabetes. Diabetes Medicine 2001; 18: 998-1002. 5. DCCT. Diabetes Control and Complications Trial Research Group The effect of intensive treatment of diabetes on the development and progression of long term complications in insulin-dependant diabetes mellitus. N Engl Med 1993; 329:304. 6. Stratton I, Adler A, Neil A et al. Association of glycemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000; 321: 405-412. 7. EASD. Guidelines on Diabetes, pre diabetes and cardiovascular disease. EASD 2007. http://www.easd.org/ 8. National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Cardiovascular Disease in Dialysis Patients. NKF 2005. http://www.kidney.org/professionals/KDOQI/guidelines_cvd/guide11.htm 9. British Cardiac Society, British Hypertension Society, Diabetes UK, HEART UK, Primary Care Cardiovascular Society, The Stroke Association JBS2: Joint British Society Guidelines on Prevention of Cardiovascular Disease in Clinical Practice. BMJ 2005; 91, (suppl v). 10. Snyder RW and Berns JS. Use of insulin and oral hypoglycaemic medications in patients with diabetes mellitus and advanced kidney disease. Semin Dial 2004;17: 365. 1.

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Learning Outcomes To gain knowledge and understanding of the Cardiovascular (CV) risk associated with Chronic Kidney Disease (CKD) To evaluate and understand how CV risk can be reduced in patients with CKD

Introduction Cardiovascular disease (CVD) occurs as a result of disease processes affecting the heart and blood vessels with the underlying cause being atherosclerosis. This results in cardiovascular (CV) events such as myocardial infarction, stroke, and heart failure. CVD is the leading cause of death in end stage kidney disease1. The risk of developing cardiovascular disease is multifactorial and the increased risk starts early in the course of chronic kidney disease (CKD). When cardiovascular events occur morbidity and mortality is higher amongst patients with CKD and the implications of CV disease are for many far greater than the risk of the progression to end stage renal failure. If the burden of CV risk in CKD is to be reduced, all patients with CKD need to be offered preventative advice and treatments to reduce this risk. What is the risk of CV disease in CKD? It is well recognised that patients with end stage renal failure have much higher CV mortality and morbidity rates than patients without renal failure. The death rate is 5-90 times

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greater in dialysis patients than the general population, the difference being greatest in the younger age group1. However what may not be well recognised is the fact that this increased CV risk starts early in the course of CKD. A study of more than 1.1 million adults from the Kaiser Permanente Renal Registry in San Francisco, found that when kidney function measured as estimated glomerular function (eGFR) dropped, the risk of death and cardiovascular events such as heart disease and stroke, increased. Compared with patients whose eGFR was at least 60ml/min/1.73m2: The increased risk of death ranged from 17% in those with eGFR 45-59ml/min/1.73m2 to 600% in those with eGFR <15ml/min/1.73m2 The increased risk of cardiovascular disease (CVD) events ranged from 43% in those whith eGFR 45-59ml/min/1.73m2 to 343% in those whith eGFR <15ml/min/1.73m2 The KDOQI3 Guidelines state that: patients with chronic kidney disease, irrespective of diagnosis, are at increased risk of CVD, including coronary heart disease, cerebrovascular disease, peripheral vascular disease, and heart failure. Both traditional and chronic kidney disease related (non-traditional) CVD risk factors may contribute to this increased risk. All patients with chronic kidney disease should be considered in the highest risk group for cardiovascular disease, irrespective of levels of traditional CVD risk factors3 Traditional Risk Factors for CV Disease Non Modiable CVD Risk Factors Age > 55yrs for men, age >65yrs women Family history of early CV death Ethnicity
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Modiable CVD risk factors The Interheart study identied that there were nine potentially modiable risk factors for developing cardiovascular disease, which are as follows4: Smoking Dyslipidaemia Hypertension Diabetes Abdominal obesity Psychosocial factors Lack of daily consumption of fruit and vegetables Regular excessive alcohol intake Lack of regular physical activity Smoking.- Smoking is a major contributory factor to CV risk, cardiac events fall 50% in people who stop smoking and the risk of CVD, including acute myocardial infarction, stroke and peripheral vascular disease, also decreases signicantly over the rst two years after stopping smoking5. The CV risks relating to smoking are no different in patients with CKD to that of the general population however the consequences may be far greater including a more rapid progression of CKD. Dyslipidaemia.- In worldwide studies, 46% of coronary heart disease deaths are attributable to raised cholesterol levels and cardiovascular risk increases directly in relation to the concentration of total cholesterol6. In the presence of CKD, triglyceride clearance may be impaired leading to raised serum triglycerides and HDL cholesterol, which is cardio protective, is decreased. Hypertension.- Hypertension leads to left ventricular hypertrophy and is a major risk factor for CV disease. The risk for both coronary heart disease and stroke increases progressively with every increment in blood pressure above 110/75mmHg7. High blood pressure can be both a cause of CKD and a consequence of it. The prevalence of hypertension

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among patients with CKD reported in previous studies has ranged from 60 to 100%, depending on the study population, the cause and the level of renal dysfunction8. Diabetes.- Diabetes is now well recognised as a major CV risk factor with up to 75% of people with diabetes dying from CV disease. The relationship between blood sugar levels and CV risk is continuous with every 1% rise in HbA1c level associated with 14% more deaths9. If diabetes and CKD are present together the patient is considered to be very high risk of a CV event. In 5 years 32% of patients with type 2 diabetes who develop microalbuminuria are dead with cardiovascular disease accounting for 53% of these deaths10. Weight control.- Excess body weight is associated with high blood pressure, raised cholesterol and type 2 diabetes, contributing to morbidity and mortality from heart disease and stroke11. Obesity also plays an important role in progression of kidney disease. CKD Related CV Risk Factors Intensive treatment of conventional CV risk factors has not resulted in improved outcomes in CKD patients12. This implies that other CV risks factors exist that are specic to CKD patients, these are discussed below: Vascular Calcication.- CKD patients have excessive vascular calcication. Signicant coronary calcication has been observed in end stage renal failure patients as early as in their 30s and this has been noted to progressively increase overtime13. Vascular calcication leads to increased stiffness in arterial walls, reduced vascular compliance and increased systolic blood pressure, this puts stress on the heart and eventually leads to CV morbidity and mortality.
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Calcium and Phosphorus Metabolism.- CKD is associated with changes in mineral metabolism. Abnormal calcium and phosphorous metabolism are independent predictors of death in ESRD due to vascular calcication13. Inammation.- Inammation which is common in the uraemic state is linked to high CV mortality. Also atherosclerosis which is common in CKD patients represents an inammatory state which leads to worsening anaemia14. Anaemia.- The available evidence, consisting of large database analysis and population studies, clearly show that low haemoglobin (Hb) levels are associated with higher rates of hospitalisations, cardiovascular disease, cognitive impairment, and other adverse patient outcomes, including mortality15. When anaemia is present the workload on the heart increases which can lead to left ventricular hypertrophy, increasing the risk of death from heart failure or ischaemic heart disease. How can CV risk be reduced? CV risk reduction can be achieved through lifestyle and risk factor intervention, appropriate drug therapies to lower blood pressure, modify lipids and reduce glycaemia, as well as the use of anti-thrombotic medication. As most patients with CKD have multiple risk factors for CVD a multi-disciplinary, coordinated approach will be necessary. The data available to support CV risk reduction is not specic to reducing risk in CKD however evidence from general population studies supports the following key interventions: The key lifestyle interventions to reduce CV risk are: To stop smoking.- cardiac events fall 50% in people who stop smoking and the risk of CVD also decreases signicantly over the rst two years after stopping smoking5 Make healthier food choices.- nutritional intake is an important part of reducing CV risk through reductions in

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for example salt, fat and alcohol intake. However due to the complexity of dietary restrictions in CKD a full nutritional assessment with a dietitian will be necessary to help people to make healthier choices that not only reduce traditional CV risk but also take into account CKD specic risk factors such as anaemia and bone disease rather than bone metabolism Increase aerobic activity.- regular moderate physical activity can reduce overall CV risk. For example, brisk walking for half an hour per day reduces relative CHD risk by 20%16. The goal for all people with CKD should be 30 mins of exercise most days of the week, however for those not currently active low levels are recommended initially with a gradual increase Optimise weight and weight distribution (e.g. reducing central obesity) Reducing weight to a body mass index (BMI) of 25 is preferable, however, a reduction of 5-10% of initial body weight is still associated with signicant health benets including improved blood pressure, lipid and glucose metabolism17
Table 1: Key Treatment Targets3, 18

Waist Circumference Body Mass Index Blood Pressure

Men < 102cm (Asian men < 90cm) Women < 88cm (Asian women < 80cm) < 25 < 130mmHg and < 80mmHg (though this target may vary depending on other clinical factors) LDL-C < 100mg/dl (< 2.6mmol/l) Triglycerides < 200mg/dl (2.26mmol/l) Fasting 6.0mmol/l HbA1c < 6.5%
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Lipids

Glucose

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Blood Pressure.- meta-analysis and systematic reviews of blood pressure lowering have consistently demonstrated the benet of blood pressure reduction in reducing CV risk, the benet of treatment driven by the quality of blood pressure control19. KDOQI guidelines place all those with CKD in the highest risk group for CV development and as such will require pharmacological as well as lifestyle intervention to lower blood pressure to <130/80mmHg3. A multi-disciplinary approach used to deliver multiple interventions for blood pressure and other CV risk factors has been shown to be benecial to help reduce CV risk20. Lipid Lowering.- The benet of lipid lowering in reducing cardiovascular risk has been demonstrated in numerous randomised control trails and is considered to be even more benecial in people at high CV risk. The ASCOTT-LLA and the Heart Protection Study demonstrated that lowering LDL-C levels by 1mmol/l in high risk patients with only moderately raised levels reduced risk of coronary heart disease by 25% and 36% respectively21. NKF KDOQI guidelines recommend aggressive treatment of raised cholesterol levels in CKD22. Lifestyle advice to reduce total and LDL cholesterol, lower triglycerides and increase HDL and drug therapy with statins is indicated in most high risk people and can be used safely and effectively in CKD.
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Antithrombotic Treatments.- anti-thrombotic treatments have been shown to have signicant positive benets in patients at high risk of CVD23. Low dose Aspirin is indicated if 10 yr CV risk is >20% and blood pressure is controlled to <150/90 mmHg24. Targets for CKD specic CV risk factors3 Correction of anaemia.- target Hb levels 11-12 g/dl. (Hb<12.0 g/dl in men, Hb<11.0 g/dl in women). (See anaemia chapter for further information). More evidence

Cardiovascular Risk in CKD

is needed as to the most appropriate Hb values to reduce CVD risk Correction of serum phosphate/calcium.- target phosphorus levels (3.5-5.5 mg/dl / 1.13-1.78 mmol/l) Parathyroid Hormone level should also be controlled to reduce CV risk with a target PTH-150/300 pg/ml (16.5-33.0 pmol/l) Non-calcium based binders should be used if there is severe vascular calcication Key Points The risk of CV disease is very high in CKD The majority of people from CKD will die from CVD and for many it is more important than the implications of reaching end stage renal failure People with CKD will have traditional risk factors for CKD the same as the general population but also have CKD specic risk factors increasing the risk further CV risk can be reduced in CKD by addressing individual CV risk factors As CV risk factors will be numerous; a coordinated multidisciplinary approach to treatment will be essential

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Frequently Asked Questions What is Cardiovascular Disease? Cardiovascular disease (CVD) occurs as a result of disease processes affecting the heart and blood vessels with the underlying cause being atherosclerosis. This results in CV events such as myocardial infarction, stroke, and heart failure. What is the risk of CVD in CKD? The risk of CVD starts early in the course of CKD. When microalbuminuria is present even before eGFR starts to fall CV risk is already increasing and the risk progresses substantially as the person approaches end stage renal failure. What traditional CVD risk factors affect people with CKD? Smoking, dyslipidaemia, hypertension, diabetes, abdominal obesity, psychosocial factors, lack of daily consumption of fruit and vegetables, regular excessive alcohol intake, lack of regular physical activity. What specic CKD related CVD risk factors are there? Anaemia, vascular calcication, abnormal calcium and phosphorous metabolism, inammation. How can CV risk be reduced? A multi-disciplinary, multi-intervention approach is necessary to help people deal with the numerous CV risk factors they are likely to need. This will include lifestyle modication e.g. stop smoking, reduce weight, exercise more and make healthier food choices. Pharmacological treatment will also usually be needed to achieve strict targets for blood pressure, lipid and glycaemic control as well as to control anaemia and bone metabolism problems.

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References
1. US Renal Data System USRDS Annual Data Report. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases: Bethesda MD. 2002. Go A, Chetow G, Fan D, McCulloch C, and Hsu C. Chronic Kidney Disease and the risks of death, cardiovascular events and hospitalisation. N Engl J of Med 2004; 35: 1296-1305. NKF KDOQI Guideline 15. Association of Chronic Kidney Disease with Cardiovascular disease. NKF 2002. http://www.kidney.org/ professionals/kdoqi/guidelines_ckd/p7_risk_g15.htm Yusuf S, Hawken S and Ounpuu S et al. Effect of potentially modiable risk factors associated with myocardial infarction in 52 countries. The interheart study. Lancet 2004; 364, (9438): 937-52. World Health Organisation. CVD prevention and control: missed opportunities. 2007. http://www.who.int/cardiovascular_diseases/ prevention_control/en/ Magnus P & Beaglehole R. The real contribution of the major risk factors to the coronary epidemic. Arch Intern Med 2001; 161, (22): 2657. Lloyd-Jones D, Evans & J Levy D. Hypertension in adults across the age spectrum: current outcomes and control in the community JAMA 2005; 294:466. Whelton PK, Perneger TV, Brancati FL & Klag MJ. Epidemiology and prevention of blood pressure-related renal disease. J Hypertens Suppl 1992; 10: S77S84. Stratton I, Adler A, Neil H, Mathews D et al -on behalf of the UKPDS study group Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000; 321 (7258): 405-12. Royal College of General Practitioners UK. Type 2 diabetes :Diabetic renal disease :prevention and early management. RCGP: University of Shefeld UK. 2002. Field A, Coakley E, Must A et al. Impact of overweight on the risk of developing common chronic diseases during a 10-year period. Arch Intern Med 2001; 61(13):1581-6. Rakhit D, Marwick T, Armstrong K et al. Effect of aggressive risk factor modication on cardiac events and myocardial ischemia in patients with CKD. Heart 2006; 92:1402-1408. Goodman W, Goldein J, Kuizon B et al. Coronary artery calcication in young adults with end stage renal failure undergoing dialysis. N Engl J of Med 2000; 342:1478-1483 Ross R. Atherosclerosis - an inammatory disease. N Engl J Med 1999; 340:115-126.

2.

3.

4.

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6.

7.

8.

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10.

11.

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15. Levin A and Foley RN. Cardiovascular disease in chronic renal insufciency. Am J Kidney Dis 2000; 36:S24-S30. 16. Tanasescu M, Leitzmann M, Rimm EB et al. Exercise type and intensity in relation to CHD in men. JAMA 2002; 288(16): 19942000. 17. Department of Health. National Service Framework for Coronary Heart Disease. Department of Health 2000. 18. British Cardiac Society, British Hypertension Society, Diabetes UK, HEART UK, Primary Care Cardiovascular Society, The Stroke Association. JBS2: Joint British Society Guidelines on Prevention of Cardiovascular Disease in Clinical Practice. BMJ 2005; 91, S5. 19. Williams B, Poulter N, Brown M, Davis M, Mcinnes G, Potter J et al. British Hypertension Society Guidelines: Guidelines for the management of hypertension: report of the 4th working party of the British Hypertension Society. BHS IV. Journal of Human Hypertension 2004; 18, 139-185. 20. Gaede P, Vedel P, Larsen N et al. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 2003; 348:383-393. 21. Sever P, Dahlof B, Poulter N et al. Prevention of coronary and stroke events with Atorvastatin in hypertensive patients who have average or lower than average cholesterol concentrations, ASCOTT-LLA: a multicentre randomised control trial. Lancet 2003; 361(9364): 1149-58. 22. NKF KDOQI. Managing Dyslipidemias in Chronic Kidney Disease Am J of Kidney Dis 2003; April. 23. Anti-thrombotic Trialist Collaborative. Collaboration and meta analysis of randomised trials of ant-platelet therapy for the prevention of death, myocardial infarction and stroke in high risk people. BMJ 2002; 324:71-86. 24. Chronic Kidney Disease in Adults: UK CKD Guidelines for Identication, Management and Referral of Adults 2005. Available from: http//.www.renal.org/CKDguide/ckd.html. 25. Heart Protection Study Collaborative. Heart protection study of cholesterol lowering with Simvastatin in 20,536 high risk individuals: a randomised placebo controlled trial. Lancet 2002; 360:7-22.

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Learning Outcomes

To gain knowledge of the management of hypertension in patients with Chronic Kidney Disease (CKD) To understand the specic indications and contraindications of antihypertensive medications To highlight specic precautions when using antihypertensive drugs in patients with CKD

Introduction The aim of this chapter is to provide an overview of the pharmacological management of hypertension. The term CKD encompasses chronic renal failure of many different origins1. Trials investigating the effect of different therapies on the evolution of renal function have usually included patients with primary renal diseases and/or early or established diabetic nephropathy2. Current international hypertension guidelines3,4 recognise microalbuminuria, elevation serum creatinine and a reduction in estimated GFR (eGFR) as major cardiovascular (CV) risk factors and further increase the risk if pre-existing CV risk factors already exist. In fact, patients progressing to end-stage renal disease (ESRD) are a minority in individuals developing the different forms of CKD, and could be considered as survivors because CV disease accounts for the death of the great majority of patients with CKD before the development of ESRD5,6.

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The fact that CKD and CV disease are so closely associated has raised interest in investigating the evolution of renal function in trials involving hypertensive, as well as heart failure and post-myocardial infarction patients. This interest is fully justied by the demonstration, in all these situations, of the predictive capacity of renal function alterations for the development of CV events or death. From its earliest stages, the presence of CKD must be considered as presenting an increased CV risk in any hypertensive patient and in any patient presenting with established forms of cardiovascular disease7. Reduction of CV events in CKD population requires the implementation of effective integral therapeutic interventions that simultaneously protect both the kidney and the cardiovascular system. These interventions have to be implemented at the earliest stage possible in CKD, the attainment of strict blood pressure (BP) control is essential and hypertension should be treated rst in any patient with an elevated global CV risk. Hypertensive nephropathy was very common in untreated primary hypertension. In one study proteinuria was present in 42% and CKD present in 18% of a series of 500 patients followed until death8. With the advent of antihypertensive therapy the cardiovascular and renal prognosis of hypertensive patients improved dramatically, and the general belief is that only a very small percentage of patients (<2%) develop CKD. However, some studies have indicated that the prognosis of renal function is not so good in hypertensive patients, and that renal insufciency is still prevalent in essential hypertension7.

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Mechanisms of Action Antihypertensive Therapy

and

Renal

Effects

of

Diuretics There are three main types of diuretics as follows: Loop diuretics Thiazides Distal potassium-sparing agents Loop Diuretics The prime action of loop diuretics occurs in the thick ascending limb of the loop of Henle. The addition of loop diuretic decreases the absorption of sodium. Loop diuretics can cause hyponatraemia, hyperkalaemia, hypomagnesaemia and metabolic alkalosis. They raise the plasma concentrations of urate and cholesterol, and can impair carbohydrate tolerance. Acute renal failure can develop if the diuresis or fall in blood pressure is excessive. Thiazides The major site of action of thiazide diuretics is the proximal distal convoluted tubule, where they block the coupled reabsorption of sodium and chloride. Unlike loop diuretics, they do not block reabsorption in the loop of Henle; therefore thiazides do not impair the urine concentrating mechanism. Thiazide therapy raises the serum urate concentration, and they are contraindicated in patients with gout. Thiazides can impair carbohydrate tolerance and increase plasma cholesterol concentration. Distal Potassium-Sparing Agents These agents act on the principal cells in the distal convoluted tubule and initial connecting tubule and the cortical collecting duct, where they inhibit entry of sodium. Their main action is to reduce the excretion of potassium; however, hyperkalaemia is a potentially lethal complication of using these drugs. The risk is dose-dependent and increases considerably in patients with CKD or in those receiving potassium

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supplements. Hyperkalaemia is potentiated by other drugs that impair potassium excretion or raise the plasma potassium, such as angiotensin-converting enzyme (ACE) inhibitors, non-steroidal anti-inammatory drugs (NSAID), beta-blockers or heparin which limits aldosterone synthesis. -Adrenergic Antagonists E-Adrenergic antagonists (beta blockers) attenuate sympathetic stimulation through competitive antagonism of catecholamines at E-adrenergic receptors. The initial systemic haemodynamic effects are decreases in heart rate (HR) and cardiac output (CO) and an increase in total peripheral vascular resistance (TPVR) proportional to the degree of cardiac depression. In general, E-adrenergic antagonists have little or no clinically important effect on glomerular ltration rate (GFR), effective renal plasma ow (ERPF), or renal vascular resistance (RVR). The long-term oral administration of E-adrenergic antagonists usually has no effect on sodium, potassium or free water excretion. This means body uid composition and weight are unchanged. Central D - Adrenergic Agonists Central D2-adrenergic agonists have a direct effect on specic pre-synaptic and post-synaptic D2-adrenergic receptors located at midbrain and medullary sites. The net pharmacologic effect is a reduction in catecholamine release and turnover. In general, central D2-adrenergic agonists have little or no clinically important effect on GFR or ERPF. Fractional excretion of sodium and potassium is unchanged, and body uid composition and weight are not modied. Peripheral D -Adrenergic Antagonists D1-adrenergic antagonists induce dilation of both resistance and capacitance vessels by selectively inhibiting post-junctional D1-adrenergic receptors. The net physiologic effect is a decrease in TPVR. D1-adrenergic antagonists have
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little or no clinically important effect on GFR or ERPF. However, fractional sodium excretion is reduced and the extracellular uid compartment is expanded. Direct-Acting Vasodilators Direct-acting vasodilators may have an effect on both arterial resistance and venous capacitance. The net physiologic effect is a decrease in TPVR associated with increases in HR and CO. Monotherapy with Hydrallazine and minoxidil is associated with salt and water retention and expansion of plasma and extracellular uid volumes. Retention of salt and water is not related to a reduction in GFR; it may be due to a direct drug effect on the proximal convoluted tubule. Calcium Antagonists The calcium antagonists are a chemically heterogeneous group of drugs sharing a common antihypertensive mechanism of action: interference with entry of calcium into smooth muscle cells of resistance arterioles through L-type voltage-operated channels. The net physiologic effect of calcium antagonists is a decrease in TPVR. All of the calcium antagonists induce an acute natriuresis and diuresis. This effect appears to be independent to a direct drug effect on either the proximal tubule or segments located more distally than the loop of Henle. Angiotensin-Converting Enzyme Inhibitors (ACEI) Angiotensin-converting enzyme (ACE) inhibitors lower blood pressure by decreasing TPVR. In general, ACE inhibitors maintain GFR, increase ERPF, and decrease RVR in patients who have essential hypertension with normal renal function. Urinary protein excretion is decreased. In patients with impaired GFR, a marked improvement in renal function may occur. The decrease in proteinuria is unrelated to changes in systemic blood pressure, GFR, ERPF, or ltration fraction. ACE inhibitors may produce functional renal insufciency in patients who have essential hypertension with severe bilateral

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hypertensive nephrosclerosis, in patients with severe bilateral renal artery stenosis, or in patients with stenosis of the renal artery of a solitary kidney. Finally, ACE inhibitors have been demonstrated to reset sodium and water homeostasis, by an initial natriuresis and water diuresis, and to spare potassium loss. Clinically signicant potassium retention may occur, especially in the presence of renal disease, therefore concurrent administration of potassium supplements, potassium sparing diuretics, or drugs impairing potassium excretion should be avoided. Angiotensin II Receptor Blockers (ARBs) Angiotensin II receptor blockers reduce TVPR and systemic arterial pressure in hypertensive patients. In patients with essential hypertension,ARBs generally have no discernible effect on GFR as assessed by creatinine clearance. In patients with renalimpairment and renovascular occlusivedisease, reversible increases in serum creatinine have been reported following commencement on ARB. Angiotensin II receptor antagonists produce a modest natriuretic action through blockade.
Table 1. Showing most indications and contraindications of the major classes of antihypertensive medications4.

Contraindications Class Conditions for use Congestive heart failure Elderly hypertensives Diuretics (Thaizdies) Isolated systolic hypertension Hypertensives of African origin Compelling Possible

Gout

Pregnancy

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Class

Conditions for use Renal insufciency Congestive heart failure Congestive heart failure

Compelling

Possible

Diuretics (Loop)

Diuretics

Renal failure Hyperkalaemia

(Anti Post myocardial aldosterone) infarction

Angina pectoris

Betablockers

Peripheral Chronic vascular disease obstructive Glucose pulmonary intolerance Congestive heart disease failure (up-titration) Athletes and (COPD) Pregnancy physically active A-V block patients Tachyarrhythmias (Grade 2 or 3) Post myocardial infarction

Asthma

Elderly patients Isolated systolic hypertension Calcium Angina pectoris antagonists Peripheral vascular (Dihydrodisease pyridines) Carotid atherosclerosis Pregnancy Tachyarrhythmias Congestive heart failure

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Angina pectoris Calcium antagonists Carotid atherosclerosis (Verapamil, diltiazem) Supraventricular tachycardia

AV block (grade 2 or 3) Congestive heart failure

Congestive heart failure LV dysfunction Angiotensinconverting enzyme (ACE) inhibitors Post myocardial infarction Non-diabetic nephropathy Type I diabetic nephropathy Proteinuria Type 2 diabetic nephropathy Angiotensin Diabetic II receptor microalbuminuria antagonists Proteinuria (AT1 blockers) Left ventricular hypertrophy ACE-inhibitor cough
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Pregnancy Hyperkalaemia Bilateral renal artery stenosis

Pregnancy Hyperkalaemia Bilateral renal artery stenosis

Prostatic Orthostatic Alfa-blockers hyperplasia (BHP) hypotension Hyperlipidaemia

Congestive heart failure

Chronic Kidney Disease:

A Guide to Clinical Practice (Stages 1-3)

Table 2. Describes the most common and specic side effects of antihypertensive medications and relevant precautions that should be considered for their administration9.

Side effects

Precautions

Hypokalaemia Hyperuricaemia Metabolic alkalosis Hyponatremia Hypernatremia Diuretics* Dyslipidaemia Dehydration Glucose intolerance Erectile dysfunction Hyperkalaemia (potassium sparing diuretics) Avoid high doses use* Avoid potassium sparing diuretics with renal insufciency

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In patients with cardiac failure start with a minimal dose and they require Cold extremities close clinical monitoring Beta-blockers Bronchoconstriction before increasing the dose Dyslipidaemia Fatigue Glucose intolerance Never stop abruptly

Bradycardia

Management of Hypertension in CKD

Low extremities oedema Headache Palpitations Calcium antagonists Tachycardia Sweating Face redness Nocturia Constipation and bradycardia with Verapamil Cough in 5-20% of patients Hyperkalaemia Acute decrease in renal function ACEI First dose hypotension in patients with volume depletion Rash Angioedema ARB Similar to ACEI except without the cough First dose hypotension Orthostatic hypotension Care in patients with intermittent claudication as there may be possible renal artery stenosis present Monitor kidney function prior to and post commencement For volume depletion patients the depletion must be corrected before treatment Similar to ACEI Give rst dose at bedtime Alfa-blockers Check for orthostatic hypotension prior to commencement in elderly patients and diabetics patients
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Due to the bradycardic effect, Verapamil and Diltiazem shouldnt be use together with betablockers

Chronic Kidney Disease:

A Guide to Clinical Practice (Stages 1-3)

Renal Protection The renoprotection provided by antihypertensive agents depends on their capacity to lower systemic blood pressure and also on their specic effects on renal haemodynamics; these effects can positively or negatively inuence intraglomerular pressure. In hypertensive patients with CKD, antihypertensive therapy should aim for a target of 130/80mmHg initially using an ACE inhibitors or ARB to inhibit the renin-angiotensin system and then adding diuretics and other agents as needed4. ACE inhibitors, ARBs and possibly aldosterone antagonists are indicated because they reduce proteinuria in both diabetic and non-diabetic nephropathy. In the presence of proteinuria higher than 1 g/day, the recommended target for blood pressure control is 125/75 mmHg3, 4 A reduction in proteinuria to 0.5 g/day is associated with a slower progression of both renal and cardiovascular disease. Similarly, both ACE inhibitors and ARBs are associated with a slower GFR decline although without a return to normal values. There may also be an argument for using a non-dihydropyridine (DHP) calcium channel blocker (CCB) although DHP CCBs may increase proteinuria and even accelerate the decline in GFR. The possible specic adverse effects of DHP CCBs may result in countering the benets of better blood pressure control. Precautions should be taken into consideration for the use of concomitant treatments that can cause drug induced hyperkalaemia in CKD patients10, especially combinations of the following: ACEI and ARB Potassium sparing diuretics Potassium supplements Non-steroids antiinammatory (NSAIDs) drugs COX-2 inhibitors

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Heparin and low molecular weight heparins Digoxin toxicity (but not at therapeutic levels) Ciclosporin and Tacrolimus Beta-blockers, Trimethoprim, Ketoconazole and Pentamidine

Treatment of Hyperkalaemia If eGFR 60 ml/min, commence on a loop diuretics and continue to treat with ACEI or ARB with serum potassium 5.5mmol/L If the potassium >5.5mmol/L correct the hyperkalaemia with a loop diuretics and correct the metabolic acidosis, if present, with bicarbonate Do not use spironolactone dosage >25mg per day if using ACEI Advice on dietary restriction of potassium Stop NSAIDs Discontinue ACEI/ARB or spironolactone if potassium continually >5.5.mmol/l Lifestyle Changes Along with the use of antihypertensive medication, education on health promotion should be addressed in this group of patients. It is important to ensure that all advice is provided in a culturally sensitive way and various types of educational tools are provided e.g. DVD, written information leaets etc. The following health advice should be given along with the advice given for the reduction in cardiovascular risk factors10: Weight loss - obesity (BMI>30kg/m2) Healthy eating and reduction in salt intake Exercise Education in alcohol intake Reduction in caffeine intake Reduce stress Smoking cessation

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Conclusions Individuals with CKD usually present with hypertension and multiple other risk factors for CV disease. The risk attributable to CKD or to the presence of the other factors may be totally independent. An integral CV protection programme is required in patients presenting with CKD. Antihypertensive and other cardiovascular drugs, like statins or aspirin, can also prevent further decline in renal function. It is important to ensure a good understanding of the indications for of use, contraindications and side effects antihypertensive medications, along with the benets that can be achieved by effective and early treatment of hypertension. References
1. K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis 2004; 43: S1-S290. Casas JP, Chua W, Loukogeorgakis S, et al. Effect of inhibitors of the renin-angiotensin system and other antihypertensive drugs on renal outcomes: systematic review and meta-analysis. Lancet 2005; 366: 2026-2033. Chobanian A, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The JNC 7 Report. JAMA 2003; 289: 2560-2572. Guidelines Committee: 2003 European Society of HypertensionEuropean Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens 2003; 21: 1011-1053. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalisation. N Engl J Med 2004; 351: 1296-1305. Weiner DE, Tabatabai S, Tighiouart H, et al. Cardiovascular outcomes and all-cause mortality: exploring the interaction between CKD and cardiovascular disease. Am J Kidney Dis 2006; 48: 392-401. Segura J, Garca-Donaire JA, Praga M, Ruilope LM. Chronic kidney disease as a situation of high added risk in hypertensive patients. J Am Soc Nephrol 2006; 17 Suppl 2: S136-140.

2.

3.

4.

5. 162

6.

7.

Management of Hypertension in CKD

8.

Perera GA. Hypertensive vascular disease: description and natural history. J Chronic Dis 1995; 1: 33-42. 9. Manual de intervencin de enfermera en Hipertensin y Riesgo Cardiovascular. Group EHRICA. 10. Steddon S, Ashman N, Chesser A and Cunningham J. Oxford Handbook of Nephrology and Hypertension. Oxford University Press: Oxford 2006.

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Patient Information People who are diagnosed with chronic kidney disease (CKD) should be provided with adequate and appropriate information. Informing and educating people to enable them to live with and manage their chronic disease empowers them to take control of their own health. The following are some suggestions of the information that people with CKD stage 1-3 should receive and also a list of useful websites. Where are the kidneys? Most people are born with two kidneys, however you can live a normal life with one kidney. The kidneys are located at the back of your body just below your rib cage and they are about the size of your st.

Interior vena cava Right kidney Right ureter

Abdominal aorta Left kidney

Left ureter

Urinary bladder Urethra

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NORMAL ANATOMY OF THE KIDNEYS AND URINARY TRACT


(www.kidney.org)

Patient Information

What do the kidneys do? They lter the blood and remove excess uid, toxins and waste products. They regulate susbtances in your body such as calcium and phosphate (from cheese and milk products) for healthly bones, potassium which regulates your heart rhythm (from tomatoes, bananas etc) and many other substances that you get from your food which your body needs to stay healthy. They remove excess uid and also help control your blood pressure, produces a hormone called erythropoietin, (EPO) which stimulates the bone marrow to produce healthy red blood cells so you do not become anaemic. The waste products from the body are removed by the kidney and leave your body as urine. What does the term chronic kidney disease (CKD) mean? This term means that the kidneys have been damaged and are not working as well as they should normally. How common is CKD? Around 1 in 10 people have CKD; however it is less common in young adults. In the older person it is more common due to the natural ageing of the kidneys. A number of diseases can damage the kidneys such as diabetes, hypertension (high blood pressure) and some inherited conditions. Almost all of these will damage both your kidneys at the same time. How do you know if you have CKD? In most cases CKD does not cause any symptoms, and is detected because they have a test that shows an abnormality. These may be urine tests for blood or protein; an X-ray or scan of the kidneys; or a blood test to measure kidney function. Most cases are discovered by your GP/family doctor as part of normal care.

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What are the causes CKD? The most common causes of CKD is, diabetes, high blood pressure and the natural agening process of the kidney. There are other causes such as inammation of the kidneys (e.g. glomerulonephritis), inherited diseases (e.g. polycystic kidney disease) and autoimmune diseases (e.g. systemic lupus erythematosus). Only a small number of causes of CKD can be completely cured. Measurement of kidney function A blood test called eGFR (estimated glomerular ltration rate) is used to measure kidney function and is calculated from a substance in the blood called creatinine. Creatinine is a waste product excreted by the kidneys. What is normal kidney function? Normal kidney function is when the eGFR is 90 ml/min/ 1.73m2 in young adults. Some people have an eGFR between 60-90 ml/min and this is considered normal kidney function if there is no blood or protein in the urine or any disease or identied problem with the kidney. Over the age of 40 years the eGFR falls by 1ml/min per year and so in the older person (over 75 years) the eGFR may be lower (i.e. 50-60 ml/min). What does it mean to have CKD Stage 1, 2 or 3? Stage g 1: It means there is mild damage to the kidney and is not something that you should be overly concerned about. The eGFR is >90 ml/min/1.73m2, with blood or protein in your urine and/or some sign of kidney damage has shown up on a test.
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Stage g 2: It means there is mild damage to the kidney and is not something that you should be overly concerned about. The

Patient Information

eGFR is between 60-90 ml/min/1.73m2, with blood or protein in your urine and/or some sign of kidney damage has shown up on a test. Stage g 3:It means that there is some moderate damage to the kidney. The eGFR is between 30-59 ml/min. What is the treatment for CKD? It is important to treat high blood pressure. If it is above 140/85 mmHg on three consecutive occasions, you will need some blood pressure medication. The aim is to get your blood pressure to 130/80 mmHg or lower. It is also important to have your cholesterol level checked and you may be advised to take an aspirin a day. Those people with diabetes need to have good control of their blood sugar to prevent further damage to the kidneys. How often will I need to have my kidney function checked? You may be asked to either have your kidney function checked every six months or annually. This will involve a blood and urine test. Your GP/family doctor will refer you to a kidney specialist if your kidney function declines. What can I do to help? Try to live a healthy lifestyle as you are more at risk of getting heart disease and developing further damage to your kidneys. Try to do the following: If you are overweight, you should lose weight Try to exercise regularly Stop smoking

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If you have diabetes, make sure you speak with your diabetes team and you have good control of your diabetes It is important to take your blood pressure medications if you have been given them to keep your blood pressure down and prevent further damage to your kidneys Reduce the amount of salt in the diet in order to help control your blood pressure Eat a healthy balanced diet, lower the amount of cholesterol in your diet Drink about 2 litres of uid a day (2 litres is about 10 cups or 6 mugs). There is no benet in drinking large amounts of uid, except in people who get lots of urine infections, or in a few other special cases Avoid anti-inammatory drugs (includes some that you can buy over the counter without a prescription unless your GP/family doctor has approves them e.g. Ibuprofen Consider buying an automatic blood pressure monitor to check your blood pressure at home Have an annual u vaccination, and have the pneumonia (pneumococcal) vaccine once (talk to your GP/family doctor about this) Attend for your kidney function checks when asked to by your GP/family doctor or nurse If you do have a kidney disease, tell your family as they may need to check with their GP/family doctor that it not a disease that runs in the family You need to let other doctors and nurses know that you have a problem with your kidneys e.g. if you go to accident and emergency or have an operation or procedure
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Patient Information

Add your national kidney patient association details to the leaet so your patients can make contact with them. Useful Patient Information Websites Renal patient information: www.renalpatient.org Kidney patient guide: www.kidneypatientguide.org.uk National Kidney Federation: www.kidney.org.uk Kidney Research UK: www.nkrf.org.uk The National Kidney Foundation: www.kidney.org

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