PHAR 401

PHARMACOTHERAPY OF
CHRONIC KIDNEY DISEASE

Alan Lau, Pharm.D.

Professor and Director, Clinical Pharmacy Education
University of Illinois at Chicago
College of Pharmacy

Vol 2, ESRD, Ch 1

vol 2 Figure 1.10 Trends in the number of prevalent cases of ESRD, in

thousands, by modality, in the U.S. population, 1980-2012

Data Source: Reference table D.1. Abbreviation: ESRD, end-stage renal disease.

GLOBALINCREASEINDIALYSISPATIENTS
Worldwide, there has been a 165% increase in
dialysis treatments for ESRD over the past two
decades.
Notable increases occurring in parts of
Australasia, Asia, North America and Western
Europe

[Bernadette T. JASN 26:2621, 2015]

Citation

ETIOLOGYOFCKD

Primary
Diabetes
Hypertension

Others
Glomerulonephritis,
Immunediseases
FamilyhistoryofCKD
Advancingage
Systemicinfections
Lossofkidneymass

vol 2 Figure1.16Trendsin(a)prevalentESRDcasesand(b)adjusted*prevalence
ofESRD,permillion,byprimarycauseofESRD,intheU.S.population,19802012
(a)PrevalentCases

(b)Prevalencepermillion

DataSource:ReferencetablesB.1,B.1(2).*PointprevalenceonDecember31ofeachyear;Adjustedforage,sex,and
race,ThestandardpopulationwastheU.S.populationin2011ESRDpatients.Abbreviation:ESRD,endstagerenal
disease.

Vol2,ESRD,Ch1

DEFINITION
Kidney damage for 3 months with or without
reduction in GFR
GFR < 60 ml/min/1.73M2 for 3 months, with
or without kidney damage

Kidney damage: structural or functional

abnormalities of the kidney, initially without
GFR reduction

PREVALENCE OF CKD: A GROWING EPIDEMIC

CKD Stage

US CKD Population
(~20 million)

5.6 million

90 and evidence of
kidney damage

5.7 million

60-89 and evidence of kidney

damage

7.4 million

30-59

300,000

15-29

452,957*

<15 or dialysis

GFR
(mL/min/1.73 m2)

GFR=glomerular filtration rate.

*For 2003.
Coresh J, et al. J Am Soc Nephrol. 2005;16:180-188; United States Renal Data System (USRDS) 2005 Annual Data Report.
Available at: http://www.usrds.org. Accessed 3.12.07.

DEFINITIONS

Chronic renal failure - Progressive deterioration in renal

function as evidenced by in blood urea nitrogen (BUN) serum
creatinine concentration, decline in urinary creatinine
clearance and the development of uremic symptoms.

Azotemia - Biochemical abnormality that refers to elevated BUN

and serum creatinine concentration.

Uremia - Azotemia (biochemical abnormalities) that is

associated with clinical signs and symptoms.

Uremic syndrome - A clinical condition characterized by having

symptoms that result from retention of waste (nitrogenous)
products secondary to renal failure.

ETIOLOGYOFCKD

Intrinsic
Prolonged acute kidney injury (AKI)
Pyelonephritis
Glomerulonephritis
Polycystic kidney disease (PKD)

Extrinsic

Hypertension, diabetes, lupus, sickle cell disease

Toxins, drugs
Obstruction

Stone, tumor

ETIOLOGYOFCKD

Immunological disorders
Infections
Urinary obstruction
Metabolic disorders
Vascular disorders
Hereditory and congenital disorders
Nephrotoxins
Others

NORMAL FUNCTIONS OF KIDNEY

Excretion of metabolic waste products

Fluid and electrolyte homeostasis
Hormone production and metabolism
(EPO, vit D, renin-Ag)
Interconversion of metabolic
intermediates

HOWMUCHRENALFUNCTIONISNEEDED?

GFR > 90ml/min

GFR > 50ml/min
GFR < 50ml/min
GFR < 25-30 ml/min
GFR < 5-10 ml/min

APPROACHESTOCKDTREATMENT

Early detection
Reversible conditions
Slow disease progression

Risk factors
Proteinuria reduction
Smoking cessation
Diabetes mellitus
Hypertension
Hyperlipidemia
Phosphorus control
Anemia

Nutrition and metabolic support

Treatment of complications

APPROACHESTOCKDTREATMENT

Early detection
Adverse

complications and outcomes of CKD

can often be prevented or delayed through early
detection and treatment.
Earlier stages of CKD can be detected through
routine laboratory measurements, such as
albuminuria/proteinuria.

APPROACHESTOCKDTREATMENT

Reversible conditions

Volume depletion (intake, excessive salt restriction, vomiting,

diarrhea, GI bleed, excessive diuretic use)
Serious infection (volume depletion, septic vasodilatation)
Volume overload (Congestive heart failure, ascites, nephrotic
syndrome)
Nephrotoxic agents
Uncontrolled hypertension
Hypotension
ACE inhibitors
Pericardial disease
Renal arterial disease
Urinary tract obstruction
Pregnancy
Hypercalcemia, hyperuricemia
Agents that interfere with tubular creatinine secretion (cimetidine,
trimethoprim)

MEASURESTOSLOWCKDPROGRESSION

Risk factors:
Hypertension
Diabetes

mellitus
Proteinuria
Smoking
Hyperlipidemia
Obesity

MEASURESTOSLOWCKDPROGRESSION

Treatment strategies:

Dietary protein restriction

Smoking cessation

Protective effect against proteinuria and GFR reduction not clearly

established
Smoking is associated with cardiovascular disease and may have
unfavorable effect on kidney function

Diabetes mellitus

Relatively modest benefit on renal function protection

Intensive insulin therapy can reduce albuminuria, diabetic nephropathy,

retinopathy.
HbA1c goal: about 7.0%, to prevent or delay progression of
microvascular complications. (KIDGO 2012 guidelines)

Hypertension

Systemic hypertension

Goal: <140/90 mmHg (JNC 8)

<130/80 mmHg (KDIGO 2012 guidelines for CKD with proteinuria)

Intraglomerular hypertension, proteinuria reduction

ACE inhibitors, angiotensin receptor blockers, protein restriction

MEASURESTOSLOWCKDPROGRESSION

Treatment strategies:
Hyperlipidemia
Statins

would reduce:

Risk of atherosclerotic cardiovascular disease

Rate of CKD progression (possibly through reduction of
proteinuria, inflammation and fibrosis)

Serum

phosphorus control

Phosphorus

restriction and treatment of

hyperphosphatemia

Anemia

treatment

Reduces

risk for LVH and heart failure

Reduces tissue hypoxia which may accelerate renal injury

MEASURESTOSLOWCKDPROGRESSION

Provision of adequate nutritional and metabolic

support while minimizing the patients symptoms
and toxic waste product accumulation
Optimal dietary intake
Maintain fluid and electrolyte homeostasis

Identification and treatment of CKD complications

Prevent extra-renal complications (anemia, mineral and
bone disorder)
Delay the need for dialysis or transplantation
Improve long-term outcome (reduce morbidity and
mortality)

NUTRITIONANDMETABOLICSUPPORT

Muscle wasting / malnutrition

Anthropometric

evidence
Biochemical evidence

Contributing factors
Dietary

intake
Catabolic disease
Blood loss
Dialysis
Others

NUTRITIONANDMETABOLICSUPPORT

Muscle wasting / malnutrition

Anthropometric

evidence

body

weight, height (children), skin fold thickness, body

fat, midarm muscle circumference, growth (children)

Biochemical

evidence

serum total protein, albumin, transferrin, compliments

plasma leucine, isoleucine, valine, total tryptophan,
tyrosine, essential/nonessential amino acid ratio
Normal or plasma nonessential amino acid
concentrations

NUTRITIONANDMETABOLICSUPPORT

Contributing factors:

Poor dietary intake secondary to uremia, concurrent

illnesses, depression, altered gastrointestinal function
(gastroparesis), limited food choices
Concurrent catabolic diseases

especially in septic or surgical patients who developed acute renal

failure

Blood loss
extensive blood sampling
occult gastrointestinal bleeding
blood loss related to dialysis treatment

Loss of nutrients from dialysis

Amino acids, peptides, proteins, glucose, water-soluble vitamins,
other bioactive compounds
Hemodialysis: 6-10g of free amino acid and minuscule amount of
protein is removed with each treatment
Peritoneal dialysis protein loss, especially during peritonitis

NUTRITIONANDMETABOLICSUPPORT

Contributing factors:
Endocrine

disorders

Insulin

resistance
Hyperparathyroidism
Hyperglucagonemia
Uremic

toxins
Impaired metabolism of hormones
Reduced

degradation of hormones and peptides

Impaired synthesis and degradation of amino acids

NUTRITIONANDMETABOLICSUPPORT

Metabolic abnormalities
Amino

acid and protein catabolism

Carbohydrate intolerance
Hyperlipidemia and atherosclerosis
Vitamin and trace elements

NUTRITIONANDMETABOLICSUPPORT

Amino acid and protein catabolism

Impaired

protein synthesis

High

concentrations of several non-essential amino acids

and low concentrations of essential amino acids
(including the branch-chained amino acids valine,
isoleucine and leucine) were found in CKD. Abnormal
intracellular amino acid concentrations may also impair
nitrogen utilization.
Impaired insulin-mediated muscle amino acid uptake
and protein synthesis (?)
Increased
Amino

muscle protein catabolism

acid and protein metabolism may also be

impaired by catabolic hormone concentrations, such as
glucagon and PTH.

NUTRITIONANDMETABOLICSUPPORT

Carbohydrate intolerance
Tissue insensitivity, primarily in muscles, to the action
of insulin is the predominant factor for glucose
intolerance.
Impaired -cell response to glucose is also observed.
The abnormal carbohydrate metabolism may be
responsible, in part, for the incidence of
atherosclerosis.

Hyperglycemia

per se results in the production of abnormal

circulating protein and may contribute to structural changes in
capillary basement membranes.
Insulin resistance may decrease the activity of lipoprotein
lipase to result in hypertriglyceridemia which will enhance the
risk of atherosclerosis.

NUTRITIONANDMETABOLICSUPPORT

Hyperlipidemia and atherosclerosis

Hypertriglyceridemia,

with increase in very low

density (VLDL) triglycerides and low density (LDL)
triglycerides is common in uremia.
VLDL triglycerides removal from plasma is
decreased secondary to reduced activity of adipose
tissue triglyceride lipase and plasma lipoprotein
lipase.
Cardiovascular disease is a common cause of
death in uremic patients on dialysis or after renal
transplantation

NUTRITIONANDMETABOLICSUPPORT

Vitamins and trace elements

Certain water-soluble vitamins (pyridoxine, ascorbic

acid, folic acid) are deficient in renal failure because of:
low

intake (appetite loss, nausea, vomiting and dietary

restriction)
loss during hemodialysis

Increased amounts of vitamin A are common in uremia.

No evidence that vitamin E and K requirements are
changed
Iron and zinc deficiency are common and aluminum
overload may be seen in certain uremic patients

NUTRITIONALMANAGEMENT

Protein intake

Protein intake is usually restricted to minimize production of

nitrogenous, potentially toxic, waste products.
0.4-0.5 g/kg of protein is required to maintain nitrogen
balance in the CKD patients. The need for essential amino
acids is important.
At risk of CKD progression: <1.3 g/kg/day (KDIGO 2012
guidelines)
GFR <30ml/min: 0.8 g/kg/day (KDIGO 2012 guidelines)
Hemodialysis: 1.2 g/kg/day
Peritoneal dialysis (CAPD): 1.2-1.3 g/kg/day
Additional protein for patients with nephrotic syndrome
BUN concentration is frequently monitored. Reduce protein
intake when BUN concentration is > 80-100 mg%
(non-dialysis patients)

NUTRITIONALMANAGEMENT

Energy requirements
Adequate amount of energy is needed for optimal
utilization of the protein ingested. Inadequate energy
intake will result in catabolism of body fat and muscle,
producing a decrease of lean body mass.
<60 years old: 35 Kcal/kg/day
60 years old: 30-35 Kcal/kg/day
The actual recommend intake may vary according to
the activity level and body weight of the patient
Children will need more calories (50-100 Kcal/kg/day)
to satisfy energy requirement for growth

NUTRITIONALMANAGEMENT

Treatment of hyperlipidemia
Therapeutic

lifestyle changes (TLC):

Diet:

reduced lipid intake and limit carbohydrate to 35%

of calories to minimize postprandial insulin response and
VLDL secretion, and to lower plasma triglyceride
concentration.
Healthy weight (BMI 20-25)
Physical activity compatible with cardiovascular health
and tolerance
Drugs
HMG-CoA

reductase inhibitors (statins) for lowering LDL

and cholesterol

NUTRITIONALMANAGEMENT

Vitamin supplements
Renaltab,

Nephrovite: 1 tablet PO qd

(containing thiamine, riboflavin, niacinamide, pyridoxine,

cyanocobalamin, pantothenic acid, folic acid, biotin,
vitamin C, vitamin E, chromium, manganese,
molybdenum, zinc)