Вы находитесь на странице: 1из 23

2/2/2014

Chronic kidney disease

Chronic kidney disease


Deborah Cohen, MD, Martin Goldberg, MD, FACP, Ankush Gulati, MD, and Fred F Ferri, MD, FACP Revised: 05 May 2010 Copyright Elsevier BV. All rights reserved.

Summary
Description
Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) work group has defined chronic kidney disease (CKD) as the presence of markers of kidney damage (abnormalities in blood, urine, or imaging tests ) for 3 months or a glomerular filtration rate (GFR) <60 mL/minute/1.73 m2for 3 months, with or without other signs of kidney damage CKD must be distinguished from acute kidney injury and from end-stage renal disease (ESRD) as defined by GFR <15 mL/minute with the uremic syndrome

Immediate action
Urgent referral to a nephrologist for dialysis is indicated when chronic renal insufficiency progresses to ESRD, as manifested by a creatinine clearance <15 mL/minute and the presence of one or more of the following uremic manifestations: Incessant vomiting Encephalopathy Overload of fluid in the lungs that cannot be removed by diuretics Metabolic acidosis Electrolyte abnormalities (especially hyperkalemia) Uremic pericarditis Uremic neuropathy Severe malnutrition Loss of energy, appetite, or weight, and anemia unresponsive to epoetin alfa and iron therapy

Background
Cardinal features
Progressive deterioration in renal function of >3 months' duration Includes chronic renal insufficiency but not ESRD Accumulation of nitrogenous waste products in the blood ( eg , urea, creatinine) Electrolyte disturbances Metabolic acidosis Volume overload Anemia Most patients will progress to ESRD
1/23

2/2/2014

Chronic kidney disease

Typically, the above features do not become clinically evident until GFR drops to <15 mL/minute CKD is divided into different stages of disease according to the GFR and presence of albuminuria: Stage 1 disease is defined by a normal GFR (>90 mL/minute/1.73 m2) and persistent albuminuria Stage 2 disease is a GFR between 60 to 89 mL/minute/1.73 m2and persistent albuminuria Stage 3 disease is a GFR between 30 and 59 mL/minute/1.73 m2 Stage 4 disease is a GFR between 15 and 29 mL/minute/1.73 m2 Stage 5 disease is a GFR of <15 mL/minute/1.73 m2or ESRD

Causes
Common causes Diabetes mellitus (most common cause in U.S. and in other developed countries) Hypertension (severe) Chronic glomerulonephritis, either idiopathic or secondary to systemic diseases such as lupus nephritis, focal segmental glomerulosclerosis, membranous nephropathy Polycystic kidney disease (most common cause in European countries, although diabetes mellitus type 2 is catching up fast) Obstructive nephropathy ( eg , due to benign prostatic hypertrophy , nephrolithiasis ) Rare causes Tubular interstitial nephritis Drug toxicity Bilateral renal artery stenosis causes CKD (ischemic nephropathy) and hypertension, but not all patients with renal artery stenosis have ESRD Viruses: hepatitis B , hepatitis C , HIV , by causing glomerular diseases Autoimmune diseases, particularly systemic lupus erythematosus associated nephritis

Epidemiology
Incidence and prevalence The prevalence of CKD is 1700 per 1,000,000 population There are 26 million adults with CKD in the U.S. and 500,000 with ESRD on dialysis The incidence continues to increase in the U.S. Demographics Age May occur at any age, although the various underlying causes are themselves more common in specific age groups. Race In the U.S., blacks are more commonly affected by chronic renal insufficiency than are whites, although it is unclear whether this difference results from genetic or socioeconomic causes
2/23

2/2/2014

Chronic kidney disease

Focal segmental glomerulosclerosis (FSGS) is more common in individuals of African descent. Hypertension and diabetes mellitus type 2 are also overrepresented in black patients Genetics Various inherited diseases result in chronic renal insufficiency (eg, polycystic kidney disease , Alport's disease ) Renal failure associated with type 1 diabetes mellitus has a strong genetic component Socioeconomic status In the U.S., patients who are impoverished with less access to health care facilities and inadequate financial support are more likely to progress to ESRD than patients with better financial support and insurance.

Codes
ICD-9 code 585 Chronic kidney disease 585.1 Stage 1 CKD 585.2 Stage 2 CKD 585.3 Stage 3 CKD 585.4 Stage 4 CKD 585.5 Stage 5 CKD 585.6 End-stage renal disease

Diagnosis
Clinical presentation
Symptoms Symptoms usually do not begin until the GFR is <15 mL/minute and, when present, suggest ESRD: Fatigue Nausea Anorexia Pruritus Insomnia Breathlessness Taste disturbances Chest pain due to pericarditis Altered mental status Signs Most signs of chronic renal insufficiency except hypertension do not appear until the GFR is <15 mL/minute and, when present, suggest ESRD: Skin pallor
3/23

2/2/2014

Chronic kidney disease

Skin excoriation Muscle wasting Asterixis (a late manifestation) Hypertension Edema Tachypnea and pulmonary rales, secondary to volume overload Pericardial rub due to pericarditis Hyperpnea or tachypnea secondary to severe metabolic acidosis Chest pain secondary to uremic pericarditis Uremic neuropathy Skin discoloring described typically as sallow Uremic fetor (smell like urine) Uremic ash (skin deposit of fine whitish powdery substance) Hypothermia Localized or generalized peripheral neuropathy Coma (uremic coma in ESRD) Uremic seizures (generalized or myoclonic)

Differential diagnosis
Acute kidney injury

Workup
Diagnostic decision Presence of small, shrunken kidneys on renal ultrasound Evidence of impaired renal function for >3 months Presence of known underlying kidney disease, eg , diabetes, glomerulonephritis, polycystic kidney disease Guidelines The National Kidney Foundation has produced the following guidelines: National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification . Kidney Disease Outcomes Quality Initiative. Am J Kidney Dis. 2002;39:S1-266 National Kidney Foundation. Testing for chronic kidney disease: a position statement from the National Kidney Foundation . Am J Kidney Dis. 2007;50:169-80 The Department of Veterans Affairs and the Department of Defense have produced the following guideline: VA/DoD Clinical Practice Guideline for the Management of Chronic Kidney Disease in Primary Care . Washington, DC: Department of Veterans Affairs and Department of Defense, 2007 The American College of Radiology has produced the following diagnostic guideline:
4/23

2/2/2014

Chronic kidney disease

Bush WH Jr, Choyke PL, Bluth RI, et al, Expert Panel on Urologic Imaging. Renal failure . Reston, VA: American College of Radiology (ACR), 2008 The Infectious Diseases Society of America has produced the following guideline: Gupta SK, Eustace JA, Winston JA, et al. Guidelines for the management of chronic kidney disease in HIV-infected patients : recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2005;40:1559-85 The Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group has produced the following guideline: KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD) . Kidney Int Suppl. 2009;76:S1-S130 The American Academy of Family Physicians has produced the following guidance articles: Snyder S, Pendergraph B. Detection and evaluation of chronic kidney disease . Am Fam Physician. 2005;72:1723-32 Johnson CA, Levey AS, Coresh J, et al. Clinical practice guidelines for chronic kidney disease in adults: part I . Definition, disease stages, evaluation, treatment, and risk factors. Am Fam Physician. 2004;70:86976 Johnson CA, Levey AS, Coresh J, et al. Clinical practice guidelines for chronic kidney disease in adults: part II . Glomerular filtration rate, proteinuria, and other markers. Am Fam Physician. 2004;70:1091-7 Snively CS, Gutierrez C. Chronic kidney disease: prevention and treatment of common complications . Am Fam Physician. 2004;70:1921-8 Don't miss! Signs of pericarditis, including pericardial rub, pericardial tamponade Manifestations of hyperkalemia (life threatening) Questions to ask Presenting condition Have you ever been told you have blood or protein in your urine?May indicate a longer history of kidney disease than is perceived by the patient Have you ever been told your kidney tests are abnormal?May indicate a longer history of kidney disease than is perceived by the patient What medications or over-the-counter drugs do you take and for how long?This may provide clues to possible analgesic nephropathy from combinations of drugs such as NSAIDs, aspirin, and acetaminophen Do you have difficulty initiating your urinary stream, increased frequency of urination, increased urination at night after retiring?Possible obstructive symptoms of prostatism in male patients; recurrent or chronic urinary tract infection in female patients Contributory or predisposing factors Do you have any history of kidney problems?Especially inherited conditions Are you diabetic?Risk of renal disease is greater in diabetic patients Do you have high blood pressure?Risk of renal disease is greater in patients with hypertension Do you have hepatitis B , hepatitis C , or HIV ?All of these can predispose to chronic renal insufficiency
5/23

2/2/2014

Chronic kidney disease

Do you have lupus?This is another disease that can predispose to chronic renal insufficiency Family history Do any diseases run in your family?Inherited renal diseases ( eg , polycystic kidney disease , Alport's syndrome ) can lead to renal failure. Examination Check blood pressure:Hypertension is frequently associated with CKD Auscultate heart and lungs:Listen for signs of pulmonary edema, pleuritis, and pericarditis (pleural or pericardial rub), which occur in ESRD Skin:Look for excoriations caused by the patient scratching (may indicate uremic pruritus); indicates ESRD Abdomen:Kidneys may be palpable if enlarged ( eg , in polycystic kidney disease or ureteric obstruction). Presence of a palpable bladder may indicate bladder outflow obstruction Vascular:Check for bruits of carotid arteries and renal arteries, and examine for diminished peripheral pulses (femoral, dorsalis pedis, posterior tibial). The presence of generalized atheromatous disease increases the likelihood of renal artery stenosis Asterixis:Check for flapping tremors of the flexor muscles of the forearm on dorsiflexion of the wrist joint Examine retina for diabetic retinopathy Test for diminished vibration sensation,particularly in lower extremities to detect neuropathy Summary of tests Urinalysis (dipstick) should be performed in all patients and will provide rapid confirmation of a variety of abnormalities, including hematuria (if microscopic) and proteinuria Urine microscopy : Microscopic examination of urine sediment will confirm the presence or absence of red or white blood cells and casts Creatinine clearance : must be an accurate, 24-hour collection of urine, performed by a specialist; from this and concomitant serum creatinine, the GFR can be estimated Complete blood count including iron indices should be performed in all patients as anemia may be present Blood urea nitrogen and serum creatinine : Serial estimation of serum creatinine and blood urea nitrogen (BUN) is mandatory for diagnosis and monitoring of this condition Serum bicarbonate (or total CO2), to diagnose and monitor severity of metabolic acidosis Calcium , phosphorous , and intact parathyroid hormone (PTH) levels : Low calcium, high phosphorous and high PTH are commonly seen in the advanced stages of CKD as manifestations of renal osteodystrophy Serum potassium should be measured, and serial measurements may be required, as patients are at risk for hyperkalemia when they reach ESRD 24-hour urine protein or spot urine protein/creatinine ratio to quantify the magnitude of proteinuria Chest radiography should be performed if there is dyspnea or if pulmonary edema is suspected A renal ultrasound scan is the imaging investigation of choice, as it can measure the size of each kidney and determine the presence or absence of hydronephrosis

6/23

2/2/2014

Chronic kidney disease

Renal biopsy is occasionally performed, but it is generally not recommended in patients with a solitary kidney, bilateral small kidneys, or advanced renal disease as they are unlikely to respond to any form of specific medical therapy. If indicated, it would be performed by an experienced nephrologist or an invasive radiologist. If this is not feasible, an open renal biopsy might, on rare occasions, be performed by a urologist Microalbuminuria screening in diabetic patients: elevated in early diabetic nephropathy 25-hydroxy vitamin D test to assess for nutritional vitamin D deficiency Order of tests Urinalysis (dipstick) Urine microscopy Creatinine clearance Complete blood count Blood urea nitrogen and serum creatinine Serum potassium Chest radiography Renal ultrasound scan Renal biopsy Microalbuminuria screening Serum bicarbonate Calcium , phosphorous , and intact PTH levels 24-hour urine protein Spot urine specimen for protein and creatinine 25-hydroxy vitamin D Tests Body fluids Urinalysis (dipstick) Urine microscopy Complete blood count Blood urea nitrogen and serum creatinine Serum potassium Serum bicarbonate Serum calcium Serum phosphorus Intact PTH levels 24-hour urine protein Spot urine specimen for protein and creatinine 25-hydroxy vitamin D Tests of function Creatinine clearance Microalbuminuria screening Procedures Renal biopsy Imaging Chest radiography
7/23

2/2/2014

Chronic kidney disease

Renal ultrasound scan

Clinical pearls
Renal ultrasonography is most helpful in the differential diagnosis of CKD. Bilateral small kidneys definitely indicate chronic, long-standing renal disease, but normal-sized or large kidneys are also compatible with some important chronic renal diseases, including diabetic nephropathy, myeloma kidney, amyloidosis, and HIV nephropathy In the assessment of patients with CKD, prior to end-stage, it is useful to identify the category of renal disease, ie , glomerular vs tubulointerstitial. It is important, therefore, to have available a reliable urinalysis with microscopy in these patients. In chronic glomerulopathies, the urine usually contains significant numbers of red blood cells and a variety of casts, and usually moderate to heavy proteinuria (>2.0 g/24 hours). Chronic tubulointerstitial disease (which includes toxic nephropathy and obstructive nephropathy) is characterized by minimal to moderate proteinuria (<2.0 g/24 hours) and minimal hematuria The most important predictor of the rate of progression of CKD to end-stage is the magnitude of proteinuria. In fact, estimation of the protein and creatinine in an early morning spot urine specimen, and calculating the albumin:creatinine ratio, appears to be as useful a predictor as a 24-hour urine protein measurement The reciprocal of the creatinine plotted over a period of time, usually at few-monthly intervals, is the best indicator of the rate of progression to ESRD Urine dipstick does not detect microalbuminuria, the first abnormality in diabetes mellitus type 1. A sample must be sent to the laboratory with specific instructions The dipstick does not detect proteins other than albumin. If other proteins are important to detect ( eg , Bence-Jones), use of sulfosalicylic acid is required

Consider consult
All patients with CKD should be referred to a nephrologist who will help to plan the management of any complications and, if required, prepare for initiation of dialytic therapy and/or transplantation if/when ESRD develops All patients with serum creatinine persistently above normal levels ( ie , higher than the normal range for the laboratory on two or more successive laboratory determinations) should be referred to a nephrologist as early as possible. This facilitates the development of a plan for further diagnostic procedures when indicated ( eg , renal biopsy to determine etiologic diagnosis and pathologic extent of the disease) and recommendations for indicated specific and/or supportive therapy ( eg , angiotensin-converting enzyme inhibitors in diabetic nephropathy or immunosuppressive therapy in vasculitis, lupus) Patients are shown to have improved outcomes with earlier referral to a nephrologist

Treatment
Goals
Provide support for patient and caretakers Regularly monitor patient's condition so that any deterioration can be quickly recognized and advice sought Educate patient about CKD and the options of various dialysis modalities and kidney transplant

Immediate action
Patients with ESRD with overt signs and symptoms of renal failure urgently requiring dialysis require emergency consultation with a nephrologist, who can administer therapies and monitor progress.

Therapeutic options
Summary of therapies
8/23

2/2/2014

Chronic kidney disease

The goal of management of CKD is to prevent progression of renal dysfunction and to delay need for dialysis or renal transplantation . Depending on the stage of CKD, several clinical parameters should be addressed at each visit in an effort to delay decline in renal function: Blood pressure: Should be controlled to a goal of 130/80 mm Hg or less in all patients with CKD or diabetes. If patient has proteinuria of > 1 g/24 hours, blood pressure should be even lower with a goal < 125/75 mm Hg. Most patients will require at least 3 to 4 drugs to control blood pressure, and usually one of these drugs should be an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin-II receptor blocker (ARB) Urinary protein: Reduction in proteinuria to <500 mg/day to prevent further decline in renal function is usually accomplished by using either an ACE inhibitor or an ARB alone, but frequently patients will require dual renin-angiotensin-aldosterone system (RAAS) blockade with a combination of an ACE inhibitor and/or an ARB and/or a mineralocorticoid blocker to reduce proteinuria further. It may occasionally be necessary to use triple RAAS blockade with an ACE inhibitor, ARB, and mineralocorticoid blocker ( spironolactone or eplerenone ). It is important to monitor for hyperkalemia in these patients Hyperlipidemia: Patients with CKD are considered at high risk for coronary artery disease, and patients should be treated aggressively, aiming to reduce LDL to <100 mg/dL in subjects with CKD and to a lower goal of <70 mg/dL if patients also have preexisting coronary artery disease. Most patients require treatment with a statin . Fibrates should be used cautiously in patients with CKD as they can occasionally cause acute kidney injury, which is usually reversible Volume status: Volume status should be optimized, and patients should be instructed to follow a low sodium diet. Most patients require some diuretic therapy as renal function declines. Higher doses of furosemide are often required Secondary hyperparathyroidism: PTH levels should be obtained at least once a year when patients reach stage 3 CKD. PTH levels in CKD are abnormally elevated before changes in calcium and phosphorus are seen in the blood work. Elevated PTH levels are usually treated with activated oral Vitamin D. There are 3 forms of 1-alpha-hydroxy Vitamin D (activated Vitamin D), but calcitriol is usually used as first-line therapy for CKD with careful monitoring for hypercalcemia every 3 to 4 months. Newer activated Vitamin D analogs deliver Vitamin D in a more physiologic manner and cause less hypercalcemia. These two analogs, paricalcitol and doxercalciferol , are more costly Hyperphosphatemia: Hyperphosphatemia occurs later, usually in stage 4/5 CKD. Phosphate binders are used to bind dietary phosphorus in the gastrointestinal tract. Calcium-containing binders include calcium carbonate and calcium acetate . Calcium carbonate is inexpensive and is an adequate binder of phosphorus but delivers a high calcium load and is best avoided if possible. Calcium acetate is an excellent phosphate binder but it also contains calcium. It causes less calcium loading than calcium carbonate and is usually the first-line phosphate binder in patients who are initially relatively hypocalcemic. Noncalciumbased binders are advantageous as they do not contribute to the total body calcium load. Sevelamer is a resin with no systemic absorption but is a less potent binder, requiring patients to take a large number of tablets to achieve adequate phosphate binding. It also is expensive and rarely leads to toxic megacolon but is the preferred binder of choice in most dialysis patients. Lanthanum carbonate , a heavy metal, is an excellent binder but is also costly and is absorbed into bone, the significance of which is as yet unknown. It has a chalky taste and needs to be chewed. Aluminum hydroxide is never used in patients with CKD because of the potential for systemic absorption but is on rare occasions used to bind phosphorus in patients with acute kidney injury Nutritional Vitamin D: It is now recommended that 24-hydroxy vitamin D levels be check in patients with stage 3 CKD and that repletion for six months be initiated if needed

9/23

2/2/2014

Chronic kidney disease

Anemia: Anemia is caused by erythropoietin deficiency and usually develops in late stage 3 CKD. Hemoglobin levels should be monitored every 4 to 6 months. Most patients with anemia and CKD are also iron deficient. If so, iron repletion can be accomplished orally or by intravenous infusion. Oral iron ( iron salts ) is frequently used but has poor absorption and poor patient compliance mainly because of gastrointestinal side effects. Of the intravenous iron preparations, iron dextran is less frequently used because of the risk for anaphylaxis. Sodium ferric gluconate complex and iron sucrose are both available in iron preparations and have significantly fewer risks for anaphylaxis. A new parenteral iron preparation, ferumoxytol , has recently been approved by the FDA in the U.S.. Once patients are repleted with iron, if they are still anemic, they may be started on erythropoietin-stimulating agents . Patients can be treated with recombinant erythropoietin, epoetin alfa or darbepoetin alfa . The main difference between these drugs is that darbepoetin has a longer half-life and thus can be dosed much less frequently. Patients usually receive an erythropoietin-stimulating agent every 1 to 4 weeks depending on the degree of anemia and the agent used. There is controversy about treating patients with CKD and anemia with these agents, and recent studies using recombinant erythropoietin and darbepoetin show no advantage in treating anemia with regard to cardiovascular outcomes. The recent TREAT study actually showed an increased risk of stroke in patients with a higher hemoglobin target, and current guidelines recommend treating anemia less aggressively to a target hemoglobin of 10 to 11 mg/dL. These recommendations differ for patients who are on dialysis Acidosis: In stage 4/5 CKD, patients develop a chronic metabolic acidosis. The rationale for repleting bicarbonate is to decrease progression of CKD, prevent bone buffering, and improve nutritional status. A recent study has shown repletion of bicarbonate slows progression of CKD. If the bicarbonate level is below 20 mmol/L, it can be repleted with sodium bicarbonate or sodium citrate Vascular access for dialysis: Planning for permanent vascular dialysis access should be initiated when the patient has a GFR of approximately 20 mL/minute or stage 4 CKD. The decision about access also depends on the choice of ultimate dialysis modality and transplantation options. Ideally, all patients should have an arteriovenous fistula (AVF) placed approximately 4 to 6 months prior to requiring initiation of dialysis. The non-dominant hand should be preserved for vascular access, and intravenous lines should not be placed in that arm Transplantation : Referral to a transplant center for evaluation should be made when patients reach a GFR of <20 mL/minute. If living donors are available, referral can be considered sooner. Average waiting time on a transplantation list in the U.S. in approximately 5 years Hepatitis B status: Patients should be immunized against hepatitis B if not immune when they reach stage 4 CKD before starting dialysis Dietary protein: Dietary modification is often necessary to provide adequate calories while minimizing accumulation of uremic toxins. Recommendations vary depending on individual circumstances. The optimal level of protein intake has not been determined, but it may be reasonable to restrict intake to 0.8 to 1 g/kg body weight of high biologic value protein. This should be accompanied by sodium and phosphate restriction. Dietary advice would normally be given by a specialist nephrologist or a dietitian with an interest in renal disease Medications and contrast agents: Doses of nephrotoxic or potentially nephrotoxic medications need to be reduced or the medication(s) discontinued. Patients should avoid NSAIDS, iodinated intravenous contrast, and gadolinium Patients with CKD are at increased risk for cardiovascular morbidity and mortality, and all traditional cardiovascular risk factors should be addressed to decrease cardiovascular risk. Patients with stage 3 CKD have higher risk of dying from coronary artery disease than ever reaching dialysis. Lowering homocysteine levels in dialysis patients ( eg , with high doses of folic acid or B vitamins), as in the general population, has not been shown to prevent coronary artery disease Guidelines The National Kidney Foundation has produced the following guidelines:

10/23

2/2/2014

Chronic kidney disease

National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification . Kidney Disease Outcomes Quality Initiative. Am J Kidney Dis. 2002;39:S1-S266 National Kidney Foundation. K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease . Am J Kidney Dis. 2004;43:S1-S29 National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease . Am J Kidney Dis. 2003;42:S1-S201 National Kidney Foundation.. KDOQI clinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease . Am J Kidney Dis. 2006;47:S1-S145 National Kidney Foundation. K/DOQI clinical practice guidelines for managing dyslipidemias in chronic kidney disease . Am J Kidney Dis. 2003;41:S1-S91 The Department of Veterans Affairs and the Department of Defense have produced the following guideline: VA/DoD Clinical Practice Guideline for the Management of Chronic Kidney Disease in Primary Care . Washington, DC: Department of Veterans Affairs and Department of Defense, 2007 The Infectious Diseases Society of America has produced the following guideline: Gupta SK, Eustace JA, Winston JA, et al. Guidelines for the management of chronic kidney disease in HIV-infected patients : recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2005;40:1559-85 The American Academy of Family Physicians has produced the following guidance articles: Snyder S, Pendergraph B. Detection and evaluation of chronic kidney disease . Am Fam Physician. 2005;72:1723-32 Johnson CA, Levey AS, Coresh J, et al. Clinical practice guidelines for chronic kidney disease in adults: part I . Definition, disease stages, evaluation, treatment, and risk factors. Am Fam Physician. 2004;70:86976 Johnson CA, Levey AS, Coresh J, et al. Clinical practice guidelines for chronic kidney disease in adults: part II . Glomerular filtration rate, proteinuria, and other markers. Am Fam Physician. 2004;70:1091-7 Snively CS, Gutierrez C. Chronic kidney disease: prevention and treatment of common complications . Am Fam Physician. 2004;70:1921-8 Order of therapies Angiotensin-converting enzyme (ACE) inhibitors Angiotensin-II receptor blockers Diuretics ( furosemide ) Phosphate binders ( calcium carbonate , calcium acetate , lanthanum carbonate , sevelamer ) Vitamin D analogs ( calcitriol , paricalcitol , doxercalciferol ) Sodium bicarbonate Iron ( iron salts , parenteral iron ) Erythropoietin-stimulating agents Statins Dialysis Renal transplantation
11/23

2/2/2014

Chronic kidney disease

Efficacy of therapies Efficacy of treatment of chronic renal insufficiency varies by underlying etiology, patient compliance, and comorbidities. Medications and other therapies Medications Angiotensin-converting enzyme (ACE) inhibitors Angiotensin-II receptor blockers (ARBs) Furosemide Calcium carbonate Calcium acetate Lanthanum carbonate Sevelamer Calcitriol Paricalcitol Doxercalciferol Sodium bicarbonate Iron salts Parenteral iron Erythropoietin-stimulating agents Statins Surgical therapy Renal transplantation Other therapies Dialysis

Clinical pearls
Control of the level of serum phosphate is very important in the treatment and prevention of renal osteodystrophy. This is accomplished by strict dietary phosphate restriction and the use of phosphatebinding medications in the intestinal tract. Because of the risk of aluminum intoxication, aluminumcontaining binders are no longer used in patients with CKD; however, calcium and non-calcium phosphate binders are used ACE inhibitors and ARBs are now established as playing an important role in retarding the rate of progression to end-stage disease in patients with diabetes mellitus type 1 (ACE inhibitors) and type 2 (ARBs). These drugs may be used together to reduce proteinuria further. Spironolactone has also shown to have an additive effect on reducing proteinuria when used together with an ACE inhibitor or ARB. Patients must be monitored for hyperkalemia. There is also increasing evidence that these drugs may be effective in proteinuric renal disease of diverse etiologies, independent of their antihypertensive action. There are some risks in their use, however. If the patient has renal vascular disease with bilateral renal artery stenosis, he/she is vulnerable to developing acute kidney injury following the initiation of ACE inhibitor therapy. Also, while on ACE inhibitors and/or ARBs, patients are intolerant to even moderate increases in dietary potassium intake Remarkable progress has been made in the management of diabetic nephropathy, the major cause of CKD in the U.S.. The following measures are most important in retarding progression to end-stage: early referral to a nephrologist once the urinary dipstick is positive for protein or microalbuminuria is detected; initiation of therapy with ACE inhibitors and/or ARBs once the diagnosis is made; rigorous control of blood pressure; if feasible, tight control of glycemia

Never
Never commence treatment for hyperkalemia without knowing a recent serum potassium result and preferably not without discussing it with a renal physician Never change the drug regimens of patients who have had renal transplants without discussing with a renal physician first
12/23

2/2/2014

Chronic kidney disease

Management in special circumstances


Coexisting disease Coexisting disease that has caused or contributed to the poor renal function ( eg , diabetes, hypertension , bladder outflow obstruction, hyperlipidemia) should be treated vigorously with the aim of slowing the decline in renal function Some coexisting diseases add to the complexity of managing patients who reach ESRD and require dialysis (notably congestive heart failure , chronic obstructive pulmonary disease ) Anemia has emerged as one of the most important factors in the CKD state. It predicts development of left ventricular hypertrophy and adverse outcomes if not aggressively treated There is an increased prevalence of coronary artery disease in CKD, and CKD is an independent risk factor for coronary artery disease. Patients with CKD should be considered at high risk for coronary artery disease and should have lower lipid level goals (LDL <100 mg/dL) Coexisting medication Drugs that are renally excreted may need to have their doses reduced in patients with renal insufficiency or ESRD: Patients with a GFR >50 mL/minute can, in general, have the same dosing as patients with normal renal function Patients with a GFR of 10 to 50 mL/minute need reduced doses Patients with a GFR <10 mL/minute need substantially reduced doses Nephrotoxic drugs may need to be stopped altogether The situation may change if a patient with ESRD starts dialysis, since some drugs will be removed by the dialysis Special patient groups Patients with renal allograft: Any change in a patient's renal function should be discussed with the patient's nephrologist before treatment is changed. Patient satisfaction/lifestyle priorities Children and adults of working age are likely to request treatment that will allow them to have as normal life as possible and interfere as little as possible with schooling, ability to work, etc Elderly patients may frequently prefer simpler, less invasive treatments

Patient and caregiver issues


Forensic and legal issues Emergency treatment can be life-saving; occasionally this may need to be carried out without the patient's consent. Impact on career, dependants, family, friends CKD is a long-term illness. As it progresses to ESRD, it may have a severe impact on a patient's ability to attend school, to work, or to undertake sporting or social activities. Treatment regimens may also be very disruptive. Health-seeking behavior Has there been a delay in seeking medical attention?

13/23

2/2/2014

Chronic kidney disease

The symptoms of CKD are often nonspecific ( eg , fatigue, general malaise, anorexia), and renal insufficiency is often long-standing by the time it comes to medical attention Many patients are told that they have hypertension, diabetes, or a rise in serum creatinine levels. Failure to obtain adequate medical care at an early stage often means that they present with severe renal insufficiency or with ESRD. Adequate medical care early in the illness could often slow or prevent the decline in renal function

Follow-up
Plan for review All patients require regular (often life-long) review with serum potassium, blood urea nitrogen, and creatinine estimation. Factors affecting frequency of review include the severity of the condition and the age of the patient. Information for patient or caregiver The chronic nature of the condition and the need for life-long therapy will need to be discussed with the patient.

Ask for advice


Question 1 How does one advise a patient approaching ESRD on the best mode of renal replacement therapy, dialysis vs transplantation? Answer 1 First, make it absolutely clear that, regardless of the ultimate mode of therapy, most patients start out on a form of dialysis. This is due to the limitation on the availability of cadaver donor kidneys. Even if the patient and physician agree that transplantation is desirable, the average wait for a cadaver kidney in most parts of the U.S. is 4 to 5 years. If a living related donor is available and is found to be a suitable donor immunologically and medically, then the wait is much shorter and often transplantation can be performed before the patient requires initiation of dialysis. Regarding dialysis, the patient's wishes and the home environment are the major factors in deciding between peritoneal dialysis at home and hemodialysis in a center. Home hemodialysis is being actively encouraged and is becoming more popular. Question 2 How does a physician manage congestive heart failure effectively in patients with advanced renal disease? Answer 2 The best two-word answer to this question is 'with difficulty.' If the creatinine clearance is <15 mL/minute, the best decision is to initiate dialysis and rectify the fluid overload, since the native kidneys no longer have the capacity to handle the sodium and fluid excesses even with potent diuretic therapy. On the other hand, at earlier phases of CKD (GFR >30 mL/minute), many compliant patients can be treated effectively with a combination of measures including rigorous dietary sodium restriction, careful control of hypertension, and the use of loop-acting diuretics such as furosemide. Thiazide diuretics as first-line drugs are essentially ineffective in advanced renal failure, but occasionally they are effective in combination with loop-acting drugs. Question 3 Patients with CKD often feel weak and tired with poor energy levels but they may not be ready for dialysis based on their creatinine clearance. Why is this so? Answer 3

14/23

2/2/2014

Chronic kidney disease

One of the most common and often ignored complications of CKD is the development of anemia due to epoetin alfa deficiency (mainly), which causes these symptoms. It is also associated with left ventricular hypertrophy and increased mortality. The treatment of this anemia requires weekly to biweekly doses of epoetin alfa injections along with iron supplementation. An alternative is darbepoetin, which is usually dosed every 4 weeks. A referral to a nephrologist is best sought for this complex management. Patients feel remarkably better after treatment with these injections and correction of the anemia.

Consider consult
Diabetic patients may be referred even before a rise in serum creatinine level is evident on the basis of microalbuminuria results Degree of urgency of referral depends on the severity of the renal damage and rapidity of the deterioration of renal function, and whether the patient is approaching ESRD soon as manifested by serum creatinine level >6.0 mg/dL; 24-hour creatinine clearance <15 mL/minute; uremic symptoms of nausea, vomiting, severe anorexia, bleeding, encephalopathy; intractable congestive heart failure; metabolic acidosis; and hyperkalemia

Summary of evidence
Evidence
ACE inhibitors and ARBs ACE inhibitors reduce the decline in renal function even if blood pressure is not raised: In patients with chronic nephropathies and proteinuria of 3g or more per day, the ACE inhibitor ramipril reduces the rate of decline of GFR and halves the combined risk of doubling of serum creatinine concentration or ESRD, compared with placebo plus conventional antihypertensive drugs at the same level of blood pressure control [1] Level A In patients with chronic nephropathy and at high risk of rapid progression to ESRD, ramipril reverses the tendency of GFR to decline with time. Moreover, a treatment period of 36 months or longer eliminates the need for dialysis. Even patients previously treated with antihypertensive drugs, other than ACE inhibitors, benefit from shifting to ramipril [2] Level A Treatment of CKD patients with ACE inhibitors delays disease progression compared with placebo, across a spectrum of disease causes and renal dysfunction [3] Level A ARBs, including losartan and irbesartan, can slow the rate of progression of type 2 diabetic nephropathy: Losartan, compared with placebo, reduces the incidence of a doubling of the serum creatinine concentration and ESRD, but has no effect on the rate of death. The benefit exceeds that attributable to changes in blood pressure [7] Level A The risk of a doubling of the serum creatinine concentration is a third lower in irbesartan-treated patients, compared with placebo. Treatment with irbesartan is also associated with a 23% reduction in relative risk of ESRD compared both to placebo and to amlodipine. These differences are independent of any changes in blood pressure [8] Level A Combination of ACE inhibitor and ARB further reduces proteinuria: The National Kidney Foundation suggests that ACE inhibitors and ARBs may be used in combination to reduce proteinuria in patients with CKD; however, larger outcomes trials are needed [4] Level C Adding aldosterone block ers to ACE inhibitors or ARBs further reduces proteinuria:

15/23

2/2/2014

Chronic kidney disease

Data suggest that adding mineralocorticoid receptor blockers (MRBs) to ACE inhibitor and/or ARB therapy yields significant decreases in proteinuria without adverse effects of hyperkalemia and impaired renal function; however, routine use of MRBs as additive therapy in patients with CKD cannot be recommended as routine yet [5] Level A A systematic review and meta-analysis of 10 studies involving 845 patients with CKD evaluated the effect of adding an aldosterone antagonist to ongoing treatment with an ACE inhibitor or an ARB versus adding placebo. Although addition of an aldosterone antagonist reduced proteinuria and systolic and diastolic blood pressure, it did not lead to improvement in GFR [6] Level A Calcium and noncalcium-containing phosphate binders Calcium and noncalcium-containg phosphate binders are useful when dietary restriction does not not accomplish target serum phosphate levels in patients with CKD: In hemodialysis patients, calcium acetate controls serum phosphorus and calcium phosphate levels more effectively than the 'non-calcium' phosphate binder, sevelamer hydrochloride [10] Level B A systematic review and meta-analysis of randomized controlled trials assessing the benefits and harms of phosphate binders in CKD showed there were insufficient data to establish the comparative superiority of non-calcium-binding agents over calcium-containing phosphate binders for all-cause mortality and cardiovascular end points [9] Level A Vitamin D analogs Vitamin D analogs reduce serum PTH: In patients with pre-dialysis CKD, calcitriol reduces both serum PTH and bone resorption indices, compared with placebo - suggesting a mechanism of action that suppresses parathyroid hyperfunction, which in turn leads to preservation and/or restoration of bone metabolism. Calcitriol can, therefore, be a useful adjunct in the treatment of renal bone disease [11] Level B A small trial involving patients in the pre-dialysis phase of CKD showed an increase in bone mineral density during calcitriol treatment over one year, compared with placebo. This effect may also be (partly) due to suppression of secondary hyperparathyroidism [12] Level B A systematic review of 60 trials of vitamin D compounds in patients with CKD requiring dialysis showed that these compounds lowered serum PTH levels better than placebo but also increased phosphorous levels and tended to increase calcium levels. Newer agents such as paricalcitol, maxacalcitol and doxercalciferol increased risk for hypercalcemia. All of the studies, however, were not powered adequately to assess the effect of these vitamin D compounds on clinical outcomes such as bone pain, risk for parathyroidectomy, or risk for death as has been suggested by observational data [13] Level A Sodium bicarbonate Supplementation with sodium bicarbonate to treat chronic metabolic acidosis may slow progression to ESRD: A small RCT in 134 adults with CKD with creatinine clearance between 15 and 30 mL/minute and serum bicarbonate levels between 16 and 20 mmol/L showed that supplementary bicarbonate was associated with slower progression to ESRD and better nutritional parameters. [14] Level B Erythropoietin-stimulating agents Erythropoietin-stimulating agents for treatment of chronic anemia, but there is controversy regarding the appropriate target hemoglobin level: A three-year RCT including 603 patients with stage 3 or 4 CKD with a serum hemoglobin level between 11 and 12.5 g/dL, evaluated the effect of beginning treatment with subcutaneous erythropoietin at the start of the trial versus initiating it when the hemoglobin fell to 10.5 g/dL. Early correction of the anemia to normal did not affect the risk of a first cardiovascular event [15] Level A
16/23

2/2/2014

Chronic kidney disease

An open label trial including 1432 patients with CKD randomized patients to epoetin alfa to achieve a hemoglobin level of 13.5 g/dL versus a target hemoglobin level of 11.3 g/dL. After 16 months, use of the 13.5-g/dL target was associated with a higher incidence of the composite outcome of death, myocardial infarction, hospitalization for heart failure, and stroke [16] Level A An RCT including 4038 patients with diabetes mellitus, CKD, and anemia compared the use of darbepoetin alfa to correct the anemia to a target level of 13 g/dL or 9 g/dL. At the end of the study, the use of the drug did not reduce the risk for either of two composite outcomes, death or a cardiovascular event, or death or a renal event, and was associated with an increased risk for stroke [17] Level A Statins Studies have shown no benefit to treating lipids aggressively with statins in dialysis patients, and lower LDL levels often reflect malnutrition in these patients: A systematic review of 14 RCTs comparing statins with placebo in 2086 patients receiving hemodialysis and/or continuous ambulatory peritoneal dialysis found that after 12 weeks of treatment, statins decreased cholesterol levels in dialysis patients similar to the general population. In patients on hemodialysis and taking statins, nonfatal cardiovascular events were reduced, but cardiovascular and overall mortality were not decreased [18] Level A A similar systematic review of 16 studies on the use of statins in kidney transplant recipients demonstrated lipid lowering but no effect on mortality [19] Level A A systematic review of 26 studies including more than 25,000 patients showed that HMG CoA reductase inhibitors given to patients with CKD not requiring dialysis decreased 24-hour urinary protein excretion and did not improve kidney function as measured by creatinine clearance. Total and LDL cholesterol were reduced as was all-cause mortality [20] Level A A multicenter RCT involving 2776 adults on maintenance hemodialysis and randomized to rosuvastatin or placebo showed that LDL cholesterol levels were reduced but there was no effect on cardiovascular deaths, nonfatal myocardial infarction, or nonfatal stroke after a median follow-up period of 3.8 years [21] Level A An RCT (the 4D study) showed that atorvastatin had no statistically significant effect on the composite of cardiovascular death, nonfatal myocardial infarction, and stroke in patients with type 2 diabetes undergoing hemodialysis [22] Level A Dialysis A systematic review identified only one, small, trial comparing the relative effectiveness of continuous ambulatory peritoneal dialysis (CAPD) with hemodialysis for people with kidney failure. It found no statistical difference between them in death or quality-adjusted life years score (QALYs) at 2 years. The size of the trial, however, meant there were insufficient data to allow definitive conclusions to be drawn [23] Level B Six large-scale, registry studies and three prospective cohort studies conducted in the U.S., Canada, Denmark, and the Netherlands were reviewed to compare mortality among ESRD patients receiving hemodialysis verus peritoneal dialysis. Peritoneal dialysis was generally found to be associated with equal or better survival among non-diabetic patients and younger diabetic patients. However, in the U.S., hemodialysis was associated with better survival for diabetic patients aged 45 and older. Peritoneal dialysis was generally associated with equivalent or better survival during the first year or two of dialysis. Overall patient survival was similar for peritoneal dialysis and hemodialysis, but important differences exist within select subgroups of patients, particularly those subgroups defined by age and the presence or absence of diabetes [24] Level B A systematic review of 12 randomized controlled trials (RCTs), or quasi-RCTs, sought to determine if modifications of the transfer set (Y-set or double bag systems) used in CAPD exchanges are associated with a reduction in peritonitis in patients with ESRD undergoing peritoneal dialysis. It found that significantly fewer patients suffered peritonitis with Y-set and double bag systems compared with standard exchange systems [25] Level A
17/23

2/2/2014

Chronic kidney disease

References [ [10] , [25] , [1] , [2] , [3] , [7] , [8] , [11] , [12] , [4] [5] [6] [9] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24]

Outcomes
Prognosis
Depends on individual variables, comorbidities, and patient compliance with therapy. Progression of disease Therapeutic failure Patients with chronic renal insufficiency who do not respond to simple measures (diet, diuretics, antihypertensive agents) are likely to progress to ESRD Selected patients on long-term dialysis may be considered for renal transplantation All patients should be referred to a nephrologist Terminal illness Some patients with CKD fail to respond to treatment; some repeatedly reject donor kidneys; and for some, a suitable donor never becomes available. In such cases further treatment choices are usually very limited If a patient's quality of life is poor with no likelihood of improvement, it may not be appropriate to continue with treatment or to initiate any new therapies This should be discussed, as appropriate, with the patient, other physicians caring for the patient, and the patient's family or caregivers

Clinical complications
Fertility is substantially reduced in female patients with ESRD, and erectile dysfunction is common in male patients.

Consider consult
Patients with CKD should have a plan for long-term follow-up that includes the following specialists: A nephrologist to develop plans for future renal replacement therapy ( eg , dialysis, transplantation) and to present patient with the latest knowledge on ameliorating the progression to end-stage disease Transplant surgeon and transplant coordinators for placement on the list Social workers/case managers/dialysis professionals, as this is a lifestyle-changing treatment modality

Prevention
Primary prevention
Pre-existing renal disease should be carefully monitored. It may not be possible to prevent renal failure from occurring but if recognized early, its long-term effects may be lessened. Early referral to a nephrologist is strongly advised Diabetes mellitusand all aspects of this disease should be treated promptly and patients should be monitored to reduce the risk of complications such as renal failure Hypertensionshould be treated aggressively to prevent permanent renal damage Modifiable risk factors
18/23

2/2/2014

Chronic kidney disease

Tobacco Patients with progressive renal disease should be advised to stop smoking. Medication history Care should be taken when prescribing potentially nephrotoxic drugs to at-risk patients. Reduce the dose or use alternative medication if possible. Other Those with a family history of hereditary renal disease should be monitored regularly, so that any deterioration in renal function can be recognized early and the potential for permanent renal damage may be reduced. (It may not be possible to prevent renal failure from occurring.)

Secondary prevention
Once permanent renal damage has occurred, a return to completely normal renal function is unlikely to occur Thus, recurrence as such does not occur; however, all patients should be followed so that any deterioration in their condition can be recognized early Early referral to a nephrologist is strongly recommended

Screening
Screening for microalbuminuria is appropriate for patients with diabetes mellitus.

Resources
References
Evidence references [1] Gruppo Italiano di Studi Epidemiologici in Nefrologia (GISEN). A long-term, randomised clinical trial to evaluate the effects of ramipril on the evolution of renal function in chronic nephropathies. J Nephrol 1991;3:193-202 [2] Ruggenenti P, Perna A, Gherardi G, et al. Renal function and requirement for dialysis in chronic nephropathy patients on long-term ramipril: REIN follow-up trial. Lancet 1998;352:1252-6 CrossRef [3] Kshirsagar AV, Joy MS, Hogan SL, et al. Effect of ACE inhibitors in diabetic and nondiabetic chronic renal disease: a systematic overview of randomized placebo-controlled trials. Am J Kidney Dis 2000;35:695-707 [4] Kidney Disease Outcomes Quality Initiative (K/QODI): K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004;43:S1-S290 [5] Bomback AS, Kshirsagar AV, Amamoo MA, Klemmer PJ. Change in proteinuria after adding aldosterone blockers to ACE inhibitors or angiotensin receptor blockers in CKD: a systematic review. Am J Kidney Dis. 2008;51:199-211 [6] Navaneethan SD, Nigwekar SU, Sehgal AR, Strippoli GF: Aldosterone antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev 2009:CD007004 CrossRef [7] Brenner BM, Cooper ME, deZeeuw D, et al. The RENAAL Study investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001;345:861-9 CrossRef [8] Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. The Collaborative Study Group. N Engl J Med 2001;345:85160 CrossRef [9] Navaneethan SD, Palmer SC, Craig JC, et al. Benefits and harms of phosphate binders in CKD: a systematic review of randomized controlled trials. Am J Kidney Dis. 2009;54:619-637 CrossRef [10] Qunibi WY, Hootkins RE, McDowell LL, et al. Treatment of hyperphosphatemia in hemodialysis patients: The
19/23

2/2/2014

Chronic kidney disease

Calcium Acetate Renagel Evaluation (CARE Study). Kidney Int 2004;65:1914-26 CrossRef [11] Nordal KP, Dahl E. Low dose calcitriol versus placebo in patients with predialysis chronic renal failure. J Clin Endocrinol Metab 1988;67:929-36 [12] Przedlacki J, Manelius J, Huttunen K. Bone mineral density evaluated by dual-energy X-ray absorptiometry after one-year treatment with calcitriol started in the predialysis phase of chronic renal failure. Nephron 1995;69:433-7 [13] Palmer SC, McGregor DO, Craig JC, et al. Vitamin D compounds for people with chronic kidney disease requiring dialysis. Cochrane Database Syst Rev. 2009;CD005633 CrossRef [14] de Brito-Ashurst I, Varagunam M, Raftery MJ, Yaqoob MM: Bicarbonate supplementation slows progression of CKD and improves nutritional status. J Am Soc Nephrol. 2009;20:2075-2084 CrossRef [15] Drueke TB, Locatelli F, Clyne N, et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med. 2006;355:2071-2084 CrossRef [16] Singh AK, Szczech L, Tang KL, et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 2006; 355:2085-98. CrossRef [17] Pfeffer MA, Burdmann EA, Chen CY, et al. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med. 2009;361:2019-2032 CrossRef [18] Navaneethan SD, Nigwekar SU, Perkovic V, et al. HMG CoA reductase inhibitors (statins) for dialysis patients. Cochrane Database Syst Rev. 2009;(3):CD004289 CrossRef [19] Navaneethan SD, Perkovic V, Johnson DW, et al. HMG CoA reductase inhibitors (statins) for kidney transplant recipients. Cochrane Database Syst Rev. 2009;(2):CD005019 CrossRef [20] Navaneethan SD, Pansini F, Perkovic V, et al. HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis. Cochrane Database Syst Rev. 2009;(2):CD007784 [21] Fellstrom BC, Jardine AG, Schmieder RE, et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009;360:1395-1407 CrossRef [22] Krane V, Winkler K, Drechsler C, Lilienthal J, Marz W, Wanner C, German Diabetes and Dialysis Study Investigators. Effect of atorvastatin on inflammation and outcome in patients with type 2 diabetes mellitus on hemodialysis. Kidney Int. 2008;74:1461-1467 CrossRef [23] Vale L, Cody J, Wallace S, et al. Continuous ambulatory peritoneal dialysis (CAPD) versus hospital or home haemodialysis for end-stage renal disease in adults. Cochrane Database of Systematic Reviews 2004, Issue 4 | Cochrane Review [24] Vonesh EF, Snyder JJ, Foley RN, Collins AJ. Mortality studies comparing peritoneal dialysis and hemodialysis: what do they tell us? Kidney Int Suppl. 2006;(103):S3-S11 CrossRef [25] Daly C, Campbell M, Cody J, et al. Double bag or Y-set versus standard transfer systems for continuous ambulatory peritoneal dialysis in end-stage renal disease. Cochrane Database of Systematic Reviews 2000, Issue 3 | Cochrane Review Guidelines The National Kidney Foundation has produced the following guidelines: National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification . Kidney Disease Outcomes Quality Initiative. Am J Kidney Dis. 2002;39:S1-S266 National Kidney Foundation. K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease . Am J Kidney Dis. 2004;43:S1-S29
20/23

2/2/2014

Chronic kidney disease

National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease . Am J Kidney Dis. 2003;42:S1-S201 National Kidney Foundation.. KDOQI clinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease . Am J Kidney Dis. 2006;47:S1-S145 National Kidney Foundation. K/DOQI clinical practice guidelines for managing dyslipidemias in chronic kidney disease . Am J Kidney Dis. 2003;41:S1-S91 National Kidney Foundation. K/DOQI clinical practice guidelines and clinical practice recommendation for anemia in chronic kidney disease: 2007 update of hemoglobin target . Am J Kidney Dis. 2007;50:471-530 The Department of Veterans Affairs and the Department of Defense have produced the following guideline: VA/DoD Clinical Practice Guideline for the Management of Chronic Kidney Disease in Primary Care . Washington, DC: Department of Veterans Affairs and Department of Defense, 2007 The American College of Radiology has produced the following diagnostic guideline: Bush WH Jr, Choyke PL, Bluth RI, et al, Expert Panel on Urologic Imaging. Renal failure . Reston, VA: American College of Radiology (ACR), 2008 The Infectious Diseases Society of America has produced the following guideline: Gupta SK, Eustace JA, Winston JA, et al. Guidelines for the management of chronic kidney disease in HIV-infected patients : recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2005;40:1559-85 The Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group has produced the following guideline: KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD) . Kidney Int Suppl. 2009;76:S1-S130 The American Academy of Family Physicians has produced the following guidance articles: Snyder S, Pendergraph B. Detection and evaluation of chronic kidney disease . Am Fam Physician. 2005;72:1723-32 Johnson CA, Levey AS, Coresh J, et al. Clinical practice guidelines for chronic kidney disease in adults: part I . Definition, disease stages, evaluation, treatment, and risk factors. Am Fam Physician. 2004;70:86976 Johnson CA, Levey AS, Coresh J, et al. Clinical practice guidelines for chronic kidney disease in adults: part II . Glomerular filtration rate, proteinuria, and other markers. Am Fam Physician. 2004;70:1091-7 Snively CS, Gutierrez C. Chronic kidney disease: prevention and treatment of common complications . Am Fam Physician. 2004;70:1921-8 Further reading McClellan WM. Epidemiology and risk factors for chronic kidney disease. Med Clin North Am. 2005;89:419-45 Levin A, Stevens LA. Executing change in the management of chronic kidney disease: perspectives on guidelines and practice. Med Clin North Am. 2005;89:701-9 Stevens LA, Levey AS. Measurement of kidney function. Med Clin North Am. 2005;89:457-73 Zandi-Nejad K, Brenner BM. Strategies to retard the progression of chronic kidney disease. Med Clin North Am. 2005;89:489-509

21/23

2/2/2014

Chronic kidney disease

Andersen MJ, Agarwal R. Etiology and management of hypertension in chronic kidney disease. Med Clin North Am. 2005;89:525-47 Pendse S, Singh AK. Complications of chronic kidney disease: anemia, mineral metabolism, and cardiovascular disease. Med Clin North Am. 2005;89:549-61 Goodman WG. Calcium and phosphorus metabolism in patients who have chronic kidney disease. Med Clin North Am. 2005;89:631-47 Gabardi S, Abramson S. Drug dosing in chronic kidney disease. Med Clin North Am. 2005;89:649-87 Codreanu I, Perico N, Remuzzi G. Dual blockade of the renin-angiotensin system: the ultimate treatment for renal protection? J Am Soc Nephrol. 2005;16:S34-S38 Tonelli M, Bohm C, Pandeya S, et al. Cardiac risk factors and the use of cardioprotective medications in patients with chronic renal insufficiency. Am J Kidney Dis. 2001;37:484-9 Wilcox CS. New Insights into Ddiuretic Uuse in Ppatients with Cchronic Rrenal Ddisease. J Am Soc Nephrol. 2002;13:798-805 Qamar M, Bender F, Rault R, Piraino B. The United States' perspectives on home dialysis. Adv Chronic Kidney Dis. 2009;16:189-97 Juergensen E, Wuerth D, Finkelstein SH, et al. Hemodialysis and peritoneal dialysis: patients' assessment of their satisfaction with therapy and the impact of the therapy on their lives. Clin J Am Soc Nephrol. 2006;1:1191-6. Epub 2006 Aug 30 Abdel-Kader K, Myaskovsky L, Karpov I, et al. Individual quality of life in chronic kidney disease: influence of age and dialysis modality. Clin J Am Soc Nephrol. 2009;4:711-8. Epub 2009 Apr 1 Saxena R, West C. Peritoneal dialysis: a primary care perspective. J Am Board Fam Med. 2006;19:380-9 Salusky IB. A new era in phosphate binder therapy: what are the options? Kidney Int Suppl. 2006; (105):S10-5 Sprangers B, Evenepoel P, Vanrenterghem Y. Late referral of patients with chronic kidney disease: no time to waste. Mayo Clin Proc. 2006;81:1487-94 Molitch ME. Management of dyslipidemias in patients with diabetes and chronic kidney disease. Clin J Am Soc Nephrol. 2006;1:1090-9. Epub 2006 Jul 26 Campbell KH, Dale W, Stankus N, Sachs GA. Older adults and chronic kidney disease decision making by primary care physicians: a scholarly review and research agenda. J Gen Intern Med. 2008;23:329-36 House AA, Silva Oliveira S, Ronco C. Anti-inflammatory drugs and the kidney. Int J Artif Organs. 2007;30:1042-6 Perazella MA. Advanced kidney disease, gadolinium and nephrogenic systemic fibrosis: the perfect storm. Curr Opin Nephrol Hypertens. 2009;18:519-25 Rozen-Zvi B, Gafter-Gvili A, Paul M, et al. Intravenous versus oral iron supplementation for the treatment of anemia in CKD: systematic review and meta-analysis. Am J Kidney Dis. 2008;52:897-906. Epub 2008 Oct 8 Rothberg MB, Kehoe ED, Courtemanche AL, et al. Recognition and management of chronic kidney disease in an elderly ambulatory population. J Gen Intern Med. 2008;23:1125-30. Epub 2008 Apr 29 Muntner P, Jones TM, Hyre AD, et al. Association of serum intact parathyroid hormone with lower estimated glomerular filtration rate. Clin J Am Soc Nephrol. 2009;4:186-94 Mange KC, Joffe MM, Feldman HI. Effect of the use or nonuse of long-term dialysis on the subsequent survival of renal transplants from living donors. N Engl J Med. 2001;344:726-31

22/23

2/2/2014

Chronic kidney disease

Jamison RL, Hartigan P, Kaufman JS, et al. Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: a randomized controlled trial. JAMA. 2007;298:1163-70

Associations
National Kidney and Urologic Disease Information Clearing House 3 Information Way Bethesda, MD 20892-3580 Tel: (800) 891-5390 Fax: (703) 738-4929 http://kidney.niddk.nih.gov/

National Kidney Foundation 30 East 33rd Street New York, NY 10016 Tel: (800) 622-9010 or (212) 889-2210 Fax: (212) 689-9261 http://www.kidney.org/

Patient and caregiver information Contributors


Deborah Cohen, MD Martin Goldberg, MD, FACP Ankush Gulati, MD Fred F Ferri, MD, FACP

23/23