Chronic Renal Disease

Definition
Chronic kidney disease (CKD) o Encompasses a spectrum of different pathophysiologic processes associated with abnormal kidney function and a progressive decline in glomerular filtration rate (GFR) Chronic renal failure o A pathophysiologic process with multiple causes that lasts > 3 months and results in progressive, irreversible attrition of the number and function of nephrons o Frequently leads to end-stage renal disease (ESRD) o Typically corresponds to CKD stages 35 (See Classification.) ESRD

Clinical state in which irreversible loss of endogenous renal function has occurred o Stage of CKD in which the accumulation of toxins, fluid, and electrolytes normally excreted by the kidneys results in the uremic syndrome o Patients are permanently dependent on renal replacement therapy (dialysis or transplantation) to avoid life-threatening uremia. o Stage 5 CKD (See Classification.) Uremia o A clinical syndrome reflecting dysfunction of all organ systems due to untreated or undertreated acute or chronic renal failure
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Epidemiology

Prevalence
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In the U.S. 6% of adults have mild CKD (GFR, 6090 mL/min per 1.73 m2) 4.5% have moderate to severe CKD (GFR < 60 mL/min per 1.73 m2). Incidence o ESRD (stage 5 CKD) in the U.S. ~95,000 new cases each year Primary cause o Diabetes (44%) o Hypertension (27%) o Glomerulonephritis (8%)

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Cystic kidney (2%) Other (18%)

Age Seen at all ages, but incidence increases with age. Sex Similar incidence in men and women

Risk Factors
Diabetes Hypertension Family history of heritable renal disease Older age Autoimmune disease African ancestry Previous episode of acute renal failure Presence of proteinuria, abnormal urinary sediment, or structural abnormalities of the urinary tract

Etiology
Most common causes of CKD o Diabetic nephropathy Leading cause in many parts of the world o Hypertensive nephropathy o Glomerulonephritis o Renovascular disease (ischemic nephropathy) o Polycystic kidney disease o Reflux nephropathy and other congenital renal diseases o Interstitial nephritis, including analgesic nephropathy o HIV-associated nephropathy o Transplant allograft failure ("chronic rejection") o Exposure to drugs and toxins Pathophysiology o Reduction of renal mass causes structural and functional hypertrophy of surviving nephrons. o Compensatory nephron hypertrophy is mediated by vasoactive molecules, cytokines, and growth factors. o Nephron hypertrophy is due initially to adaptive hyperfiltration and in turn mediated by increases in glomerular capillary pressure and flow. o Eventually, these short-term adaptations prove maladaptive, in that they predispose to sclerosis of the remaining viable nephrons.

Associated Conditions

Cardiovascular disease o CKD is a major risk factor for cardiovascular morbidity and mortality.

Symptoms & Signs

Patients are often asymptomatic in the early stages. Some symptoms and signs of CKD are associated with specific causes. General (systemic) symptoms of uremia o Fatigue o Malaise o Nausea o Vomiting o Hiccupping o Shortness of breath o Edema o Weight change o Muscle cramps o Decreased mental acuity o Decreased urine output o Easy bleeding and bruising o Decreased sensation in hands and feet, neuropathy Possible findings on physical examination o Abdominal masses (i.e., polycystic kidneys) o Diminished pulses (i.e., atherosclerotic peripheral vascular disease) o Abdominal bruit (i.e., renovascular disease) o Foreshortened fingers due to resorption of the distal phalangeal tufts (advanced CKD and secondary hyperparathyroidism) o Subcutaneous nodules (advanced CKD and secondary hyperparathyroidism) o Excoriations (uremic pruritus) o Pallor (anemia) o Muscle wasting o Nitrogenous fetor o Pericarditis o Pleuritis o Asterixis

Differential Diagnosis
Acute renal failure

Differentiate from CKD by establishing its chronicity. Past creatinine and urea concentrations Findings consistent with CKD o Urinary sediment that is inactive or reveals proteinuria and broad casts o Evidence of chronic metabolic bone disease with hyperphosphatemia, hypocalcemia,
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elevated parathyroid hormone (PTH) level, and radiologic bone disease o Normocytic, normochromic anemia o Bilaterally reduced kidney size (< 8.5 cm) on imaging studies

Diagnostic Approach
Establish GFR to stage disease. Exclude acute renal failure. Determine the cause of early-stage CKD. o Use clinical presentation and noninvasive tests, if possible. o Use renal biopsy if the cause cannot be established. In advanced CKD, definitive diagnosis is less feasible and of less therapeutic significance.

Laboratory Tests
Serial creatinine and blood urea nitrogen measurements Estimation of GFR by using 1 of 2 equations based on measured plasma creatinine concentration (PCr), age, sex, and ethnic origin o Equation from the Modification of Diet in Renal Disease (MDRD) study Estimated GFR (mL/min/1.73 m2 body surface area) = 1.86 (PCr)1.154 (age)0.203 Multiply by 0.742 for women. Multiply by 1.21 for African Americans. o CockcroftGault equation Estimated creatinine clearance (mL/min) = [(140 age) body weight (kg)]/[72 PCr (mg/dL)] Multiply by 0.85 for women. o The normal annual mean decrease in GFR with age beginning at age 2030 years is 1 mL/min/m2/1.73 m2. Reaches a mean value in men of 70 mL/min/m2 at age 70 years GFR is slightly lower in women than in men. Chemistry in ESRD (stage 5 CKD) o Hyperkalemia o Metabolic acidosis o Hyperphosphatemia o Hypocalcemia Complete blood count o Anemia, usually normocytic and normochromic Evaluate iron, B12, folate levels. Urinalysis o Broad, waxy casts

o Proteinuria 24-hour urine collection o To quantify proteinuria o Heavy proteinuria (>3.5 g/d) in addition to hypoalbuminemia, hypercholesterolemia, and edema suggests nephrotic syndrome. Immunologic tests for systemic lupus erythematosus and vasculitis o If history and physical examination warrant Serum and urinary protein electrophoresis in all patients > 35 years of age with unexplained CKD and anemia o Excludes paraproteinemia In the presence of glomerulonephritis, underlying infectious etiologies should be assessed. o Hepatitis B o Hepatitis C o HIV

Imaging
Avoid exposure to intravenous radiocontrast dye where possible because of nephrotoxicity. Renal ultrasonography o Provides estimate of kidney size and symmetry and rules out renal masses and obstructive uropathy o Symmetric small kidneys support diagnosis of CKD. o Normal kidney size suggests possibility of an acute process. Polycystic kidney disease, amyloidosis, diabetes, and HIV-associated renal disease may lead to CKD with normal kidney size. o Asymmetric kidney size suggests unilateral developmental abnormality or chronic renovascular disease. Vascular imaging o Duplex Doppler sonography of the renal arteries, radionuclide scintigraphy, or magnetic resonance angiography Should be strongly considered if revascularization is possible Spiral CT without contrast o May be useful in assessing kidney stones o Reveals pathognomonic features, such as papillary calcification and necrosis in analgesic-associated chronic tubulointerstitial nephropathy Voiding cystourethrography o To exclude reflux

May be indicated in some patients with a history of enuresis or with a family history of reflux In most cases, by the time CKD is established, reflux has resolved, and even if present, its repair does not stabilize renal function.
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Diagnostic Procedures

Renal biopsy o May be the only way to establish etiology in early CKD Reserved for patients with near-normal kidney size, in whom diagnosis cannot be made by less invasive means and a reversible underlying disease process remains possible o Extent of tubulointerstitial scarring on kidney biopsy provides the most reliable pathologic correlate indicating prognosis for continued deterioration toward ESRD (stage 5 CKD). o Contraindications Bilateral small kidneys Polycystic kidney disease Uncontrolled hypertension Urinary tract or perinephric infection Bleeding diathesis Respiratory distress Morbid obesity o Approach Ultrasonography-guided percutaneous biopsy is favored. Surgical approaches, including laparoscopic biopsy, may be considered in special circumstances, such as biopsy of a solitary kidney. o In patient with CKD in whom a kidney biopsy is indicated, bleeding time should be measured, and if increased: Desmopressin should be administered immediately before the procedure A brief run of hemodialysis (without heparin) may also be considered before renal biopsy to normalize the bleeding time Staging o At increased risk GFR > 90 mL/min/1.73m2, with CKD risk factors o Stage 1: kidney damage with normal or increased GFR

Classification

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GFR 90 mL/min/1.73m2 Stage 2: kidney damage with mildly decreased GFR GFR of 6089 mL/min/1.73m2 Stage 3: moderately decreased GFR GFR of 3059 mL/min/1.73m2 Stage 4: severely decreased GFR GFR of 1529 mL/min/1.73m2 Stage 5: renal failure GFR < 15 mL/min/1.73m2, or receiving dialysis

Treatment Approach
Treatment is aimed at slowing progression of CKD and managing underlying causes and complications of the disease. Treatment should begin well before a measurable decline in baseline GFR has occurred. Patient education is a vital component of treatment, especially in ESRD (stage 5 CKD). Clinical action plan by stage
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Stage 1 (GFR 90 mL/min per 1.73 m2) Diagnosis and treatment Treatment of comorbid conditions Slowing progression Cardiovascular disease risk reduction Stage 2 (GFR = 6089 mL/min per 1.73 m2) Estimating progression Stage 3 (GFR = 3059 mL/min per 1.73 m2) Evaluating and treating complications Stage 4 (GFR = 1529 mL/min per 1.73 m2) Preparation for kidney replacement therapy Stage 5 (GFR < 15 mL/min per 1.73 m2) Kidney replacement (if uremia present)

Specific Treatments
Managing fluid, electrolyte, and acidbase disorders Extracellular fluid volume expansion o Loop diuretics, with dietary salt restriction Mainstay of therapy Occasionally in combination with metolazone Side effects: hypovolemia, with precipitation of further decrease in GFR Hyperkalemia o Acute Intravenous calcium chloride or gluconate

Intravenous insulin with glucose Intravenous bicarbonate Oral or per rectum ion exchange resin (sodium polystyrene sulfonate) o Chronic Dietary potassium restriction Avoidance of potassium-containing or -retaining medications or salt substitutes Sodium polystyrene sulfonate, 1530 g PO qd in juice or sorbitol Metabolic acidosis o Sodium bicarbonate, calcium bicarbonate, or sodium citrate, 2030 mmol/d, divided in 2 doses o Titrate to maintain bicarbonate at > 20 mEq/L. Hyponatremia o Uncommon in predialysis patients o Water restriction

Managing bone disease and disorders of calcium and phosphate metabolism Hyperphosphatemia leads to reduced serum calcium concentration, which in turn causes secondary hyperparathyroidism and osteitis fibrosa cystica. o Reduce plasma phosphate concentration. Phosphate-restricted diet Oral phosphate-binding agents Calcium carbonate Calcium acetate Nonabsorbable, noncalcium-containing polymer (sevelamer) Daily oral calcitriol, or intermittent oral or intravenous pulses o Recommended target levels Plasma phosphate: 1.4 mmol/L (4.5 mg/dL) Plasma calcium: 2.5 mmol/L (10 mg/dL) Maintain the calciumphosphate product in the normal range to avoid metastatic calcification. o Analogues of calcitriol are available (e.g., paricalcitol). Suppress PTH secretion with less attendant hypercalcemia. Calcimimetic agents (e.g., cinacalcet) o Enhance the sensitivity to calcium-suppressive effects on PTH secretion o Target: PTH level between 150 and 300 pg/mL Aluminum-induced osteomalacia

Therapy is based on complete cessation of aluminum combined with use of a chelating agent, such as deferoxamine.
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Management of cardiovascular abnormalities Hypertension o Maintain blood pressure < 130/85 mmHg. o In patients with CKD plus diabetes or proteinuria > 1 g/24 h, reduce blood pressure further to 125/75 mmHg. o Volume control with salt restriction and diuretics is the mainstay of therapy. o When volume management is not sufficient Choice of antihypertensive agent is similar to that in the general population, with the added consideration of cardioprotective benefit provided by angiotensin-converting enzyme inhibition or angiotensin receptor blockade. Cardiovascular disease o Hyperhomocystinemia may respond to vitamin therapy. Folate supplementation, 15 mg/d o Hyperlipidemia Manage aggressively according to guidelines of the National Cholesterol Education Program. Reduce low-density lipoprotein cholesterol level to < 100 mg/dL. If dietary measures are inadequate, the preferred lipid-lowering medications are 3-hydroxy3-methylglutaryl coenzyme A reductase inhibitors. Uremic pericarditis o Absolute indication for initiation of dialysis or intensification of the prescription in patients already receiving dialysis o Because of the propensity to hemorrhagic pericardial fluid, heparin-free dialysis is indicated. o Pericardiectomy should be considered for recurrent cases if more conservative measures fail.

Management of hematologic abnormalities

Anemia o See also Anemia of Renal Disease. o Target hemoglobin concentration: 110120 g/L

Normalization of the hemoglobin concentration has not been demonstrated to be of incremental benefit to dialysis patients. Erythropoiesis stimulating agents (ESAs) Use the lowest dose that will maintain a hemoglobin level to avoid the need for recurrent blood transfusions. Discontinue ESAs if the patient remains transfusion dependent. ESAs are associated with cardiovascular events in patients with renal failure who receive supratherapeutic doses. Epoetin alfa Starting dosage: 50150 U/kg weekly IV or SC (once, twice, or 3 times weekly) Target hemoglobin level 1112 g/dL Optimal rate of correction: increase hemoglobin level by 12 g/dL over 4 weeks Erythropoietin-refractory anemia in the face of adequate availability of iron and vitamin factors often suggests: o Inadequate dialysis o Uncontrolled hyperparathyroidism o Aluminum toxicity o Chronic blood loss or hemolysis o Associated hemoglobinopathy o Malnutrition o Chronic infection o Multiple myeloma o Another cancer Pure red blood cell aplasia may lead to a preference for the intravenous route for some ESA formulations. Darbepoetin alfa Starting dosage o 0.45 g/kg, administered as a single IV or SC injection once weekly or o 0.75 g/kg, administered as a single IV or SC injection once every 2 weeks Iron Treat patients receiving ESAs with oral ferrous sulfate, 325 mg PO tid. Monitor iron stores by measuring transferrin saturation and serum ferritin. If patient is iron deficient (serum iron level < 50 mg/dL, transferrin saturation < 20%, and serum

ferritin level < 100 g/L) despite oral iron therapy, administer iron, 50100 mg IV twice weekly for 5 weeks. o If iron indices are still low, repeat the same course. Withhold iron therapy when transferrin saturation is > 50% and/or serum ferritin level is > 800 ng/mL (>800 g/L). Complications of excessive iron therapy o Hemosiderosis, accelerated atherosclerosis, increased susceptibility to infection, and possibly an increased propensity for cancer o Adequate supply of the other major substrates and cofactors for erythrocyte production, especially vitamin B12 and folate, must be assured. o Blood transfusion Avoid unless anemia fails to respond to ESA and the patient is symptomatic. May contribute to suppression of erythropoiesis in CKD Increases the risk of hepatitis, hemosiderosis, and transplant sensitization Abnormal hemostasis o Coagulopathy may be reversed with: Desmopressin Cryoprecipitate Conjugated estrogens Blood transfusion ESAs o Patients with CKD are at greater risk for thromboembolic complications and should receive appropriate dose-adjusted anticoagulant prophylaxis when indicated. Slowing progression of CKD Therapeutic interventions aim to stabilize GFR or reduce annual rate of decline. Protein restriction o Benefit is controversial.[1][2] Some studies have shown that protein restriction may be effective in slowing the progression of CKD, especially proteinuric and diabetic renal diseases. Modification of Diet in Renal Disease study was unable to demonstrate a benefit in delaying

progression to advanced stages of CKD with dietary restriction of protein intake. o Nonetheless, restriction of dietary protein intake has been recommended for patients with CKD. Concern is that protein restriction may worsen already poor nutritional status. National Kidney Foundation Disease Outcomes Quality Initiative (NKF KDOQI) guidelines state that there is insufficient evidence for or against. o NKF KDOQI clinical practice guidelines recommend: Daily protein intake of between 0.60 and 0.75 g/kg per day, depending upon: o Patient adherence o Comorbid disease o Presence of proteinuria o Nutritional status At least 50% of the protein intake should be of high biologic value. Stage 5 CKD: Patients may enter a state of protein-energy malnutrition. o Protein intake of up to 0.90 g/kg per day might be recommended. o Sufficient energy intake is important to prevent protein-calorie malnutrition, and 35 kcal/kg is recommended. Reducing intraglomerular hypertension and proteinuria o 125/75 mmHg is the target blood pressure in patients with proteinuria and CKD. o Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are effective antiproteinuric agents. Contraindications or adverse effects o Intractable cough o Anaphylaxis o Hyperkalemia not controlled by dietary restriction o Renovascular ischemic disease Reduction in proteinuria from angiotensin receptor blockers and angiotensin-converting enzyme inhibitors is similar, but their combination is more effective than either drug alone. o Uncertainty concerning long-term adverse effects and outcomes that are important

to patients limits applicability of these findings to clinical practice. o Calcium-channel blockers (diltiazem and verapamil) may be used as second-line therapy. Slowing diabetic renal disease Glucose control o Target plasma values Preprandial glucose: 90130 mg/dL Average bedtime glucose: 110150 mg/dL Hemoglobin A1c: < 7% o Reduction in GFR mandates dose adjustment of many antihyperglycemic agents. Metformin should not be used when plasma creatinine concentration is > 1.5 mg/dL. Control blood pressure and proteinuria. o Onset of microalbuminuria precedes the decline in GFR in patients with diabetes and heralds renal as well as cardiovascular complications. o Antihypertensive treatment reduces albuminuria and diminishes risk of progression of albuminuria, even in normotensive patients with diabetes. o Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have specific renoprotective properties in diabetic patients with microalbuminuria or overt proteinuria.

Medication dose adjustment Although CKD does not affect the loading dose of most drugs, maintenance doses of many drugs need to be adjusted. o Drugs that should be avoided include meperidine, metformin, and other oral hypoglycemics with a renal route of elimination. o Commonly used medications that require a reduction in dosage or changes in interval include allopurinol, many antibiotics, several antihypertensives, and antiarrhythmics. o Refer to the American College of Physicians handbook Drug Prescribing in Renal Failure for a comprehensive listing of recommended dose adjustments.

Many drugs have nephrotoxicity as a prominent side effect, to which patients with CKD are more susceptible. NSAIDs aggravate the tendency to sodium retention, hypertension, hyperkalemia, and hyponatremia and further reduce GFR in patients with CKD. There is no advantage to more selective inhibitors of cyclooxygenase-2. o For drugs of which > 70% excretion is by a nonrenal (e.g., hepatic or intestinal) route, dose adjustment may not be needed.
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Renal replacement therapy See also Dialysis. Indications o Pericarditis o Progressive neuropathy attributable to uremia o Encephalopathy o Muscle irritability/intractable muscle cramping o Anorexia and nausea not ameliorated by reasonable protein restriction o Protein-energy malnutrition o Fluid and electrolyte abnormalities refractory to conservative measures Volume overload unresponsive to diuretic therapy Hyperkalemia unresponsive to dietary potassium restriction Progressive metabolic acidosis that cannot be managed with alkali therapy Imminent development of uremic complications o Patients with poor compliance with conservative management should be considered for earlier initiation of renal replacement therapy. o There is no "usual" level of blood urea nitrogen, serum creatinine, or GFR indicating the need to start dialysis. Serum creatinine concentration must be 700 mol/L (8.0 mg/dL) and the creatinine clearance must be 10 mL/min to qualify for reimbursement from Medicare. Options o Hemodialysis o Peritoneal dialysis

Renal transplantation Less rejection if transplantation is done before dialysis is started

Monitoring
Albuminuria is a key adjunctive tool for monitoring nephron injury and response to therapy in many forms of CKD. o 24-hour urine collection is the gold standard for measurement of albuminuria. o Albumin-specific dipstick measurement or quantitation by measurement of albumin-to-creatinine ratio in a spot first morning urine sample Often more practical to obtain Correlates well, but not perfectly, with 24hour urine collections o Persistence of > 17 mg albumin/g creatinine in adult men and 25 mg albumin/g creatinine in adult women usually signifies chronic renal damage, irrespective of GFR. Monitor natural history and response to therapy, especially in CKD consequent to diabetes, hypertension, or glomerulonephritis. Microalbuminuria testing is recommended in all patients with diabetes at least annually, and more frequently to follow therapeutic interventions. Nutritional status must be monitored carefully during protein restriction. o Protein-energy malnutrition is a clear-cut indication for initiation of renal replacement therapy. Follow and plot the rate of decline in GFR. o Any acceleration in the rate of decline should prompt a search for superimposed acute processes that may lead to an acute and reversible decline in GFR in patients with CKD. Superimposed volume depletion Accelerated and uncontrolled hypertension Urinary tract infection Superimposed obstructive uropathy (e.g., due to stone disease or papillary necrosis) Nephrotoxic effect of medications (e.g., NSAIDs) and radiocontrast agents Reactivation or flare of the original underlying etiologic disease process

Complications

Endocrine and metabolic o Secondary hyperparathyroidism

Osteitis fibrosa cystica Osteomalacia o Hyperuricemia o Hypertriglyceridemia o Protein-energy malnutrition o Infertility and sexual dysfunction o Amenorrhea o Amyloidosis Neuromuscular o Peripheral neuropathy o Restless legs syndrome o Paralysis o Seizures o Sleep disorders Cardiovascular and pulmonary o Arterial hypertension o Cardiomyopathy o Congestive heart failure o Accelerated atherosclerosis Dermatologic o Hyperpigmentation o Pruritus o Calciphylaxis Heralded by livedo reticularis and advances to patches of ischemic necrosis, especially on the legs, thighs, abdomen, and breasts o Nephrogenic fibrosing dermopathy Progressive subcutaneous induration, especially on the arms and legs Similar to scleromyxedema Seen in patients with CKD, most commonly on dialysis Exposure to the magnetic resonance contrast agent gadolinium may precipitate this syndrome. GI o Peptic ulcer o GI bleeding o Constipation Hematologic and immunologic o Anemia o Splenomegaly and hypersplenism o Increased susceptibility to infection o Bleeding diathesis
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Prognosis
Cardiovascular disease is the leading cause of morbidity and mortality in patients with CKD at all stages.

Estimates of the increase in cardiovascular disease risk attributable to CKD range from 10- to 200-fold, depending on the stage of CKD, other risk factors, and comorbid conditions. Prognosis of diabetic patients receiving long-term renal replacement therapy is very poor, owing to accelerated cardiovascular disease.
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Prevention
Prevention is best accomplished by aggressively treating disorders that lead to CKD.

ICD-9-CM
585.9 Chronic kidney disease, unspecified (includes chronic renal disease)

See Also

Acute Renal Failure Anemia of Renal Disease Approach to Peripheral Neuropathy Chronic Pancreatitis Diabetic Nephropathy Dialysis Hyperphosphatemia Polycystic Diseases of the Kidney

Internet Sites
Professionals o Clinical Practice Guidelines for Chronic Kidney Disease in Adults American Academy of Family Physicians o Homepage National Institute of Diabetes & Digestive & Kidney Diseases o KDOQI home National Kidney Foundation Kidney Disease Outcomes Quality Initiative Guidelines Patients o Chronic renal failure MedlinePlus o What Is CKD? American Association of Kidney Patients

References
1. Johnson DW: Dietary protein restriction as a treatment for slowing chronic kidney disease progression: the case against. Nephrology (Carlton)11:58, 2006 [PMID:16509934] 2. Mandayam S, Mitch WE: Dietary protein restriction benefits patients with chronic kidney disease. Nephrology (Carlton) 11:53, 2006 [PMID:16509933]

General Bibliography
Brenner BM et al: Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med345:861, 2001 [PMID:11565518] Cozzolino M, Dusso AS, Slatopolsky E: Role of calciumphosphate product and bone-associated proteins on vascular calcification in renal failure. J Am Soc Nephrol 12:2511, 2001 [PMID:11675430] Gabardi S, Abramson S: Drug dosing in chronic kidney disease. Med Clin North Am 89:649, 2005 [PMID:15755472] Ketteler M, Schlieper G, Floege J: Calcification and cardiovascular health: new insights into an old phenomenon. Hypertension 47:1027, 2006 [PMID:16618842] Levey AS et al: CKD: Common, harmful and treatable World Kidney Day 2007. Am J Kidney Dis 49(2), 2007 Lim VS, Kopple JD: Protein metabolism in patients with chronic renal failure: role of uremia and dialysis. Kidney Int 58:1, 2000 [PMID:10886544] Maxwell AP: Novel erythropoiesis-stimulating protein in the management of the anemia of chronic renal failure. Kidney Int 62:720, 2002 [PMID:12110039] Meguid El Nahas A, Bello AK: Chronic kidney disease: the global challenge.Lancet 365:331, 2005 Jan 22-28 [PMID:15664230] National Kidney Foundation: K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis39:S1, 2002 [PMID:11904577] Schiffrin EL, Lipman ML, Mann JF: Chronic kidney disease: effects on the cardiovascular system. Circulation 116:85, 2007 [PMID:17606856] Snyder S, Pendergraph B: Detection and evaluation of chronic kidney disease. Am Fam Physician 72:1723, 2005 [PMID:16300034] Zandi-Nejad K, Brenner BM: Strategies to retard the progression of chronic kidney disease. Med Clin North Am 89:489, 2005 [PMID:15755464] This topic is based on Harrisons Principles of Internal Medicine, 17th edition, chapter 274, Chronic Kidney Disese by JM Bargman and K Skorecki.