eMedicine Specialties > Nephrology > Chronic Kidney Disease

Chronic Renal Failure

Pradeep Arora, MD, Assistant Professor of Medicine, University of Buffalo; Attending Nephrologist, Veterans Affairs Western New York Healthcare System
Mauro Verrelli, MD, FRCP(C), FACP, Assistant Professor, Department of Medicine, Section of Nephrology, University of Manitoba, Canada

Updated: Feb 4, 2010

Introduction

Background

Chronic kidney disease (CKD) is a worldwide public health problem and is now recognized as a common condition that is associated with an increased risk of cardiovascular disease and chronic renal failure (CRF).

The Kidney Disease Outcomes Quality Initiative (K/DOQI) of the National Kidney Foundation (NKF) defines chronic kidney disease as either kidney damage or a decreased kidney glomerular filtration rate (GFR) of less than 60 mL/min/1.73 m² for 3 or more months. Whatever the underlying etiology, the destruction of renal mass with irreversible sclerosis and loss of nephrons leads to a progressive decline in GFR. The different stages of chronic kidney disease form a continuum in time; prior to February 2002, no uniform classification of the stages of chronic kidney disease existed. At that time, K/DOQI published a classification of the stages of chronic kidney disease, as follows:

• Stage 1: Kidney damage with normal or increased GFR (>90 mL/min/1.73 m²)
• Stage 2: Mild reduction in GFR (60-89 mL/min/1.73 m²)
• Stage 3: Moderate reduction in GFR (30-59 mL/min/1.73 m²)
• Stage 4: Severe reduction in GFR (15-29 mL/min/1.73 m²)
• Stage 5: Kidney failure (GFR <15 mL/min/1.73 m² or dialysis)

In stage 1 and stage 2 chronic kidney disease, GFR alone does not clinch the diagnosis. Other markers of kidney damage, including abnormalities in the composition of blood or urine or abnormalities in imaging tests, should also be present in establishing a diagnosis of stage 1 and stage 2 chronic kidney disease.

The K/DOQI definition and the classification of chronic kidney disease allow better communication and intervention at the different stages.

Pathophysiology

Approximately 1 million nephrons are present in each kidney, each contributing to the total GFR. Regardless of the etiology of renal injury, with progressive destruction of nephrons, the kidney has an innate ability to maintain GFR by hyperfiltration and compensatory hypertrophy of the remaining healthy nephrons. This nephron adaptability allows for continued normal clearance of plasma solutes so that substances such as urea and creatinine start to show significant increases in plasma levels only after total GFR has decreased to 50%, when the renal reserve has been exhausted. The plasma creatinine value will approximately double with a 50% reduction in GFR. A rise in plasma creatinine from a baseline value of 0.6 mg/dL to 1.2 mg/dL in a patient, although still within the reference range, actually represents a loss of 50% of functioning nephron mass.

The residual nephron hyperfiltration and hypertrophy, although beneficial for the reasons noted, has been hypothesized to represent a major cause of progressive renal dysfunction. This is believed to occur because of increased glomerular capillary pressure, which damages the capillaries and leads initially to focal and segmental glomerulosclerosis and eventually to global glomerulosclerosis. This hypothesis has been based on studies of five-sixths nephrectomized rats, which develop lesions that are identical to those observed in humans with chronic kidney disease.

Factors other than the underlying disease process and glomerular hypertension that may cause progressive renal injury include the following:

• Systemic hypertension
• Acute insults from nephrotoxins or decreased perfusion
• Proteinuria
• Increased renal ammoniagenesis with interstitial injury
• Hyperlipidemia
• Hyperphosphatemia with calcium phosphate deposition
• Decreased levels of nitrous oxide
• Smoking

Frequency

United States

In the United States, there is a rising incidence and prevalence of kidney failure, with poor outcomes and high cost. Kidney disease is the ninth leading cause of death in the United States. Data from the United States Renal Data System (USRDS) indicated that there has been an increase of 104% in the prevalence of chronic renal failure (CRF) between the years 1990-2001. There is an even higher prevalence of the earlier stages of chronic kidney disease.

According to the Third National Health and Nutrition Examination Survey, it was estimated that 6.2 million people (ie, 3% of total US population) older than 12 years had a serum creatinine value above 1.5 mg/dL; 8 million people had a glomerular filtration rate (GFR) of less than 60 mL/min, the majority of them being in the Medicare senior population (5.9 million people). Therefore, for the first time, the US Surgeon General's mandate for America's citizenry, Healthy People 2010, contains a chapter focused on chronic kidney disease. The objectives of this chapter are to articulate goals and to provide strategies to reduce the incidence, morbidity, mortality, and health costs of chronic kidney disease in the United States. The burden of chronic kidney disease can be assessed by multiple criteria, all of which underscore the need for improved detection, treatment, and monitoring of clinical and fiscal outcomes. Reducing renal failure will require additional public health efforts, including effective preventive strategies and early detection and treatment of chronic kidney disease.

Because of the nonuniform definition of kidney disease prior to February 2002, among other factors, most patients with earlier stages of chronic kidney disease have not been recognized or adequately treated. The Third National Health and Examination Survey (NHANES III) estimated that the prevalence of chronic kidney disease in adults in the United States was 11% (19.2 million): 3.3% (5.9 million) had stage 1, 3% (5.3 million) had stage 2, 4.3% (7.6 million) had stage 3, 0.2% (400,000) had stage 4, and 0.2% (300,000) had stage 5.

Furthermore, the prevalence of chronic kidney disease stages 1-4 increased from 10% in 1988-1994 to 13.1% in 1999-2004. This increase is partially explained by the increase in the prevalence of diabetes and hypertension, the two most common causes of chronic kidney disease.

International

The incidence rates of end-stage renal disease (ESRD) have increased steadily internationally since 1989. The United States has the highest incident rate of ESRD, followed by Japan. Japan has the highest prevalence per million population, with the United States taking second place.

Mortality/Morbidity

Chronic kidney disease is a major cause of morbidity and mortality, particularly at the later stages. Although the diabetic population is at highest risk, in the United States, the general hemodialysis and peritoneal dialysis populations have 2 hospital admissions per patient per year; patients who have a renal transplant have an average of 1 hospital admission per year. The 5-year survival rate for a patient undergoing chronic dialysis in the United States is approximately 35%. This is approximately 25% in patients with diabetes. The most common cause of death in the dialysis population is cardiovascular disease.

Among patients with ESRD aged 65 years and older, the mortality rates are 6 times higher than in the general population. In 2003, over 69,000 dialysis patients enrolled in the ESRD program died (annual adjusted mortality rate of 210.7 per 1000 patient-years at risk for the dialysis population, which represents a 14% decrease since peaking at 244.5 per 1000 patient-years in 1988). The highest mortality rate is within the first 6 months of initiating dialysis, which then tends to improve over the next 6 months, before increasing gradually over the next 4 years.

The mortality rates associated with hemodialysis are striking and indicate that the life expectancy of patients entering into hemodialysis is markedly shortened. At every age, patients with ESRD on dialysis have significantly increased mortality when compared with nondialysis patients and individuals without kidney disease. At age 60 years, a healthy person can expect to live for more than 20 years, whereas the life expectancy of a 60-year-old patient starting hemodialysis is closer to 4 years.

Race

Chronic kidney disease affects all races, but, in the United States, a significantly higher incidence of ESRD exists in blacks as compared to whites; the incident rate for blacks is nearly 4 times that for whites.

Sex

• In NHANES III, the distribution of estimated GFRs for the chronic kidney disease stages was similar in both sexes. Nonetheless, the USRDS 2004 Annual Data Report reveals that the incident rate of ESRD cases is higher for males with 409 per million population in 2002 compared to 276 for females.

Age

Chronic kidney disease is found in persons of all ages. The normal annual mean decline in the GFR with age from the peak GFR (approximately 120 mL/min/1.73 m²) attained during the third decade of life is approximately 1 mL/min/y/1.73 m², reaching a mean value of 70 mL/min/1.73 m² at age 70 years. Nonetheless, in the United States, the highest incidence rate of ESRD occurs in patients older than 65 years. As per NHANES III data, the prevalence of chronic kidney disease was 37.8% among patients older than 70 years. Besides diabetes mellitus and hypertension, age is an independent major predictor of chronic kidney disease. The geriatric population is the most rapidly growing kidney failure (chronic kidney disease stage 5) population in the United States.

The biologic process of aging initiates various structural and functional changes within the kidney. Renal mass progressively declines with advancing age. Glomerulosclerosis leads to a decrease in renal weight. Histologic examination is notable for a decrease in glomerular number of as much as 30-50% by age 70 years.

Ischemic obsolescence of cortical glomeruli is predominant, with relative sparing of the renal medulla. Juxtamedullary glomeruli see a shunting of blood from the afferent to efferent arterioles, resulting in redistribution of blood flow favoring the renal medulla. These anatomical and functional changes in renal vasculature appear to contribute to an age-related decrease in renal blood flow. Renal hemodynamic measurements in aged human and animals suggest that altered functional response of the renal vasculature may be an underlying factor in diminished renal blood flow and increased filtration noted with progressive renal aging. The vasodilatory response is blunted in the elderly when compared to younger patients. However, the vasoconstrictor response to intrarenal angiotensin is identical in both young and older human subjects. A blunted vasodilatory capacity with appropriate vasoconstrictor response may indicate that the aged kidney is in a state of vasodilatation to compensate for the underlyingsclerotic damage.

Given the histologic evidence for nephronal senescence with age, a decline in the GFR is expected. However, a wide variation in the rate of decline in the GFR is reported because of measurement methods, race, gender, genetic variance, and other risk factors for renal dysfunction. Because of these anatomical and physiological changes, elderly patients with chronic kidney disease may behave differently, in terms of progression and response to pharmacological treatment, than younger patients.

Therefore, a serum creatinine value of 1.2 mg/dL in a 70-kg, 25-year-old man versus a 70-kg, 80-year-old man represents an eGFR of 74 mL/min/1.73m² and 58 mL/min/1.73m², respectively. What can appear as only mild renal impairment in a 70-kg, 80-year-old man with a pathologically elevated serum creatinine of 2 mg/dL actually represents severe renal impairment when the eGFR is calculated to be 32 mL/min/1.73m². Therefore, an eGFR must be determined simply by using the Modification of Diet in Renal Disease (MDRD) equation (see Other Tests) in elderly people so that appropriate drug dosing adjustments can be made and nephrotoxins can be avoided in patients who have more extensive chronic kidney disease than would be suggested by the serum creatinine value alone.

Clinical

History

Patients with chronic kidney disease stages 1-3 (GFR >30 mL/min) are generally asymptomatic and do not experience clinically evident disturbances in water or electrolyte balance or endocrine/metabolic derangements. Generally, these disturbances clinically manifest with chronic kidney disease stages 4-5 (GFR <30 mL/min). Uremic manifestations in patients with chronic kidney disease stage 5 are believed to be primarily secondary to an accumulation of toxins, the identity of which is generally not known.

The ability to maintain potassium (K) excretion at near normal levels is generally maintained in chronic kidney disease patients as long as both aldosterone secretion and distal flow are maintained. Another defense against potassium retention in patients with chronic kidney disease is increased potassium excretion in the GI tract, which also is under control of aldosterone.

Therefore, hyperkalemia usually develops when the GFR falls to less than 20-25 mL/min because of the decreased ability of the kidneys to excrete potassium. It can be observed sooner in patients who ingest a potassium-rich diet or if serum aldosterone levels are low, such as in type IV renal tubular acidosis commonly observed in people with diabetes or with use of angiotensin-converting enzyme (ACE) inhibitors or nonsteroidal anti-inflammatory drugs (NSAIDs). Hyperkalemia in chronic kidney disease can be aggravated by an extracellular shift of potassium, such as that occurs in the setting of acidemia or from lack of insulin. Hypokalemia is uncommon but can develop among patients with very poor intake of potassium, gastrointestinal or urinary loss of potassium, diarrhea, or diuretic use.

Metabolic acidosis often is mixed, normal anion gap and increased anion gap, the latter observed generally with chronic kidney disease stage 5 but with the anion gap generally not higher than 20 mEq/L. In chronic kidney disease, the kidneys are unable to produce enough ammonia in the proximal tubules to excrete the endogenous acid into the urine in the form of ammonium. In chronic kidney disease stage 5, accumulation of phosphates, sulphates, and other organic anions are the cause of the increase in anion gap. Metabolic acidosis has been shown to have deleterious effects on protein balance, leading to a negative nitrogen balance, increased protein degradation, increased essential amino acid oxidation, reduced albumin synthesis, and a lack of adaptation to a low protein diet. Hence, this is associated with protein-energy malnutrition, loss of lean body mass, and muscle weakness. The mechanism for reducing protein may include effects on ATP-dependent ubiquitin proteasomes and increased activityofbranchedchain keto acid dehydrogenases.

Normochromic normocytic anemia principally develops from decreased renal synthesis of erythropoietin, the hormone responsible for bone marrow stimulation for red blood cell (RBC) production. It starts early in the course of disease and becomes more severe as the GFR progressively decreases with the availability of less viable renal mass. No reticulocyte response occurs. RBC survival is decreased, and tendency of bleeding is increased from the uremia-induced platelet dysfunction. Other causes of anemia in chronic kidney disease patients include chronic blood loss, secondary hyperparathyroidism, inflammation, nutritional deficiency, and accumulation of inhibitors of erythropoiesis.

Anemia is associated with fatigue, reduced exercise capacity, impaired cognitive and immune function, and reduced quality of life. Anemia is also associated with the development of cardiovascular disease, the new onset of heart failure, or the development of more severe heart failure. Anemia is associated with increased cardiovascular mortality.

Renal bone disease is a common complication of chronic kidney disease and results in both skeletal complications (eg, abnormality of bone turnover, mineralization, linear growth) and extraskeletal complications (eg, vascular or soft tissue calcification). Different types of bone disease occur with chronic kidney disease, as follows: (1) high turnover bone disease due to high parathyroid hormone (PTH) levels; (2a) low turnover bone disease (adynamic bone disease); (2b) defective mineralization (osteomalacia); (3) mixed disease; and (4) beta-2-microglobulin associated bone disease.

Secondary hyperparathyroidism develops because of hyperphosphatemia, hypocalcemia, decreased renal synthesis of 1,25-dihydroxycholecalciferol (1,25-dihydroxyvitamin D, or calcitriol), intrinsic alteration in the parathyroid gland that give rises to increased PTH secretion as well as increased parathyroid growth, and skeletal resistance to PTH.

• Calcium and calcitriol are primary feedback inhibitors; hyperphosphatemia is a stimulus to PTH synthesis and secretion.
• Phosphate retention begins in early chronic kidney disease; when the GFR falls, less phosphate is filtered and excreted, but serum levels do not rise initially because of increased PTH secretion, which increases renal excretion. As the GFR falls toward chronic kidney disease stages 4-5, hyperphosphatemia develops from the inability of the kidneys to excrete the excess dietary intake. Hyperphosphatemia suppresses the renal hydroxylation of inactive 25-hydroxyvitamin D to calcitriol, so serum calcitriol levels are low when the GFR is less than 30 mL/min. Increased phosphate concentration also effects PTH concentration by its direct effect on parathyroid gland (posttranscriptional effect).
• Hypocalcemia develops primarily from decreased intestinal calcium absorption because of low plasma calcitriol levels and possibly from calcium binding to elevated serum levels of phosphate.
• Low serum calcitriol levels, hypocalcemia, and hyperphosphatemia have all been demonstrated to independently trigger PTH synthesis and secretion. As these stimuli persist in chronic kidney disease, particularly in the more advanced stages, PTH secretion becomes maladaptive and the parathyroid glands, which initially hypertrophy, become hyperplastic. The persistently elevated PTH levels exacerbate hyperphosphatemia from bone resorption of phosphate.
• If serum levels of PTH remain elevated, a high bone turnover lesion, known as osteitis fibrosa, develops. This is one of several bone lesions, which as a group are commonly known as renal osteodystrophy. These lesions develop in patients with severe chronic kidney disease and are common in those with ESRD.
• The prevalence of adynamic bone disease in the United States has increased, and it has been described before the initiation of dialysis in some cases. The pathogenesis of adynamic bone disease is not well defined, but several factors may contribute, including high calcium load, use of vitamin D sterols, increasing age, previous corticosteroid therapy, peritoneal dialysis, and increased level of N-terminally truncated PTH fragments. Low turnover osteomalacia in the setting of chronic kidney disease is associated with aluminum accumulation and is markedly less common. Dialysis-related amyloidosis from beta-2-microglobulin accumulation in patients who have required chronic dialysis for at least 8-10 years is another form of bone disease that manifests with cysts at the ends of long bones.

Other manifestations of uremia in ESRD, many of which are more likely in patients who are inadequately dialyzed, include the following:

• Pericarditis - Can be complicated by cardiac tamponade, possibly resulting in death.
• Encephalopathy - Can progress to coma and death
• Peripheral neuropathy
• Restless leg syndrome
• GI symptoms - Anorexia, nausea, vomiting, diarrhea
• Skin manifestations - Dry skin, pruritus, ecchymosis
• Fatigue, increased somnolence, failure to thrive
• Malnutrition
• Erectile dysfunction, decreased libido, amenorrhea
• Platelet dysfunction with tendency to bleeding

Physical

The physical examination often is not very helpful but may reveal findings characteristic of the condition underlying chronic kidney disease (eg, lupus, severe arteriosclerosis, hypertension) or complications of chronic kidney disease (eg, anemia, bleeding diathesis, pericarditis).

Causes

• Vascular disease - Renal artery stenosis, cytoplasmic pattern antineutrophil cytoplasmic antibody (C-ANCA)–positive and perinuclear pattern antineutrophil cytoplasmic antibody (P-ANCA)–positive vasculitides, antineutrophil cytoplasmic antibody (ANCA)–negative vasculitides, atheroemboli, hypertensive nephrosclerosis, renal vein thrombosis
• Primary glomerular disease - Membranous nephropathy, immunoglobulin A (IgA) nephropathy, focal and segmental glomerulosclerosis (FSGS), minimal change disease, membranoproliferative glomerulonephritis, rapidly progressive (crescentic) glomerulonephritis
• Secondary glomerular disease - Diabetes mellitus, systemic lupus erythematosus, rheumatoid arthritis, mixed connective tissue disease, scleroderma, Goodpasture syndrome, Wegener granulomatosis, mixed cryoglobulinemia, postinfectious glomerulonephritis, endocarditis, hepatitis B and C, syphilis, human immunodeficiency virus (HIV), parasitic infection, heroin use, gold, penicillamine, amyloidosis, light chain deposition disease, neoplasia, thrombotic thrombocytopenic purpura (TTP), hemolytic-uremic syndrome (HUS), Henoch-Schönlein purpura, Alport syndrome, reflux nephropathy
• Tubulointerstitial disease - Drugs (eg, sulfa, allopurinol), infection (viral, bacterial, parasitic), Sjögren syndrome, chronic hypokalemia, chronic hypercalcemia, sarcoidosis, multiple myeloma cast nephropathy, heavy metals, radiation nephritis, polycystic kidneys, cystinosis
• Urinary tract obstruction - Urolithiasis, benign prostatic hypertrophy, tumors, retroperitoneal fibrosis, urethral stricture, neurogenic bladder
• See related CME at Guidelines for Hepatitis C in Chronic Kidney Disease Issued.

Differential Diagnoses

Acute Renal Failure

Workup

Laboratory Studies

• Serum electrolytes, BUN, and creatinine - The BUN and creatinine levels will be elevated in patients with chronic kidney disease. Hyperkalemia or low bicarbonate levels may be present in patients with chronic kidney disease.
• Serum calcium, phosphate, vitamin D, and intact parathyroid hormone (PTH) levels are obtained to look for evidence of renal bone disease.
• CBC count - Normochromic normocytic anemia is commonly seen in chronic kidney disease. Other underlying causes of anemia should be ruled out.
• Serum albumin - Patients may have hypoalbuminemia due to urinary protein loss or malnutrition.
• Lipid profile - A lipid profile should be performed in all patients with chronic kidney disease because of their increased risk of cardiovascular disease.
• Urinalysis - Dipstick proteinuria may suggest a glomerular or tubulointerstitial problem. The urine sediment finding of RBCs, RBC casts, suggests proliferative glomerulonephritis. Pyuria and/or WBC casts are suggestive of interstitial nephritis (particularly if eosinophiluria is present) or urinary tract infection.
• Spot urine collection for total protein-to-creatinine ratio allows reliable approximation (extrapolation) of total 24-hour urinary protein excretion. A value of greater than 2 g is considered to be within the glomerular range, and a value of greater than 3-3.5 g is within the nephrotic range; less than 2 is characteristic of tubulointerstitial problems.
• Twenty-four–hour urine collection for total protein and CrCl
• In certain cases, the following tests may be ordered as part of the evaluation of patients with chronic kidney disease:
  • Serum and urine protein electrophoresis to screen for a monoclonal protein possibly representing multiple myeloma
  • Antinuclear antibodies (ANA), double-stranded DNA antibody levels to screen for systemic lupus erythematosus
  • Serum complement levels - May be depressed with some glomerulonephritides
  • C-ANCA and P-ANCA levels - Helpful if positive in diagnosis of Wegener granulomatosis and polyarteritis nodosa or microscopic polyangiitis, respectively
  • Anti–glomerular basement membrane (anti-GBM) antibodies - Highly suggestive of underlying Goodpasture syndrome
  • Hepatitis B and C, HIV, Venereal Disease Research Laboratory (VDRL) serology - Conditions associated with some glomerulonephritides

Imaging Studies

• Plain abdominal x-ray - Particularly useful to look for radio-opaque stones or nephrocalcinosis
• Intravenous pyelogram - Not commonly used because of potential for intravenous contrast renal toxicity; often used to diagnose renal stones
• Renal ultrasound - Small echogenic kidneys are observed in advanced renal failure. Kidneys usually are normal in size in advanced diabetic nephropathy, where affected kidneys initially are enlarged from hyperfiltration. Structural abnormalities, such as polycystic kidneys, also may be observed. This is a useful test to screen for hydronephrosis, which may not be observed in early obstruction, or involvement of the retroperitoneum with fibrosis, tumor, or diffuse adenopathy. Retrograde pyelogram may be indicated if a high index of clinical suspicion for obstruction exists despite a negative study finding.
• Renal radionuclide scan - Useful to screen for renal artery stenosis when performed with captopril administration but is unreliable for GFR of less than 30 cc/min; also quantitates differential renal contribution to total GFR
• CT scan - CT scan is useful to better define renal masses and cysts usually noted on ultrasound. Also, it is the most sensitive test for identifying renal stones. IV contrast-enhanced CT scans should be avoided in patients with renal impairment to avoid acute renal failure; this risk significantly increases in patients with moderate-to-severe chronic kidney disease. Dehydration also markedly increases this risk.
• MRI is very useful in patients who require a CT scan but who cannot receive intravenous contrast. It is reliable in the diagnosis of renal vein thrombosis, as are CT scan and renal venography. Magnetic resonance angiography also is becoming more useful for diagnosis of renal artery stenosis, although renal arteriography remains the criterion standard.
• Voiding cystourethrogram (VCUG) - Criterion standard for diagnosis of vesicoureteral reflux

Other Tests

• The Cockcroft-Gault formula for estimating CrCl should be used routinely as a simple means to provide a reliable approximation of residual renal function in all patients with chronic kidney disease. The formulas are as follows:
  • CrCl (male) = ([140-age] X weight in kg)/(serum creatinine X 72)
  • CrCl (female) = CrCl (male) X 0.85
• Alternatively, the Modification of Diet in Renal Disease (MDRD) Study equation could be used to calculate the GFR. This equation does not require a patient's weight.^{[3 ]}

Procedures

• Percutaneous renal biopsy is performed most often with ultrasound guidance and the use of a mechanical gun. It generally is indicated when renal impairment and/or proteinuria approaching the nephrotic range are present and the diagnosis is unclear after appropriate other workup. It is not indicated in the setting of small echogenic kidneys on ultrasound because these are severely scarred and represent chronic irreversible injury. The most common complication of this procedure is bleeding, which can be life threatening in a minority of occurrences.
• Surgical open renal biopsy can be considered when the risk of renal bleeding is felt to be great, occasionally with solitary kidneys, or when percutaneous biopsy is technically difficult to perform.

Histologic Findings

Renal histology in chronic kidney disease reveals findings compatible with the underlying primary renal diagnosis and, generally, findings of segmental and globally sclerosed glomeruli and tubulointerstitial atrophy, often with tubulointerstitial mononuclear infiltrates.

Treatment

Medical Care

The medical care of patients with chronic kidney disease should focus on the following:

• Delaying or halting the progression of chronic kidney disease
  • Treatment of the underlying condition if possible
  • Aggressive blood pressure control to target values per current guidelines. Systolic blood pressure control is considered more important and is also considered difficult to control in elderly patients with chronic kidney disease.
  • Use of ACE inhibitors or angiotensin receptor blockers as tolerated, with close monitoring for renal deterioration and for hyperkalemia (avoid in advanced renal failure, bilateral renal artery stenosis [RAS], RAS in a solitary kidney). Data support the use of ACE inhibitors/angiotensin receptor blockers in diabetic kidney disease with or without proteinuria. However, in nondiabetic kidney disease, ACE inhibitors/angiotensin receptor blockers are effective in retarding the progression of disease among patients with proteinuria of less of than 500 mg/d.
  • Aggressive glycemic control per the American Diabetes Association (ADA) recommendations (target HbA1C <7%)
  • Protein restriction - Although the Modification of Diet in Renal Disease (MDRD) Study failed to show the effect of protein restriction in retardation of the progression of kidney disease, a meta-analysis suggests a beneficial role for protein restriction. The National Kidney Foundation (NKF) guidelines suggest that if a patient is started on protein restriction, the physician needs to closely monitor the patient's nutritional status. Predialysis low serum albumin is associated with a poor outcome among dialysis patients.
  • Treatment of hyperlipidemia to target levels per current guidelines
  • Avoidance of nephrotoxins - IV radiocontrast, nonsteroidal anti-inflammatory agents, aminoglycosides
  • Encourage smoking cessation, as smokers tend to reach ESRD earlier than nonsmokers.
  • De Brito-Ashurst et al studied whether bicarbonate supplementation preserves renal function in chronic kidney disease (CKD).^{[4 ]}Adult patients (n=134) with chronic kidney disease (ie, creatinine clearance [CrCl] 15-30 mL/min/1.73 m² and serum bicarbonate 16-20 mmol/L) were randomly assigned to receive oral sodium bicarbonate supplementation or standard care for 2 years. A slower decline in CrCl was observed in the bicarbonate group than in the control group (1.88 vs 5.93 mL/min/1.73 m²; P <0.0001). Patients in the bicarbonate group were also less likely to experience rapid disease progression than were members of the control group (9% vs 45%; P <0.0001), and fewer patients who received bicarbonate supplementation developed ESRD (6.5% vs 33%; P <0.001). In addition to the benefits listed above, nutritional parameters improved with bicarbonate supplementation.
• Treating the pathologic manifestations of chronic kidney disease, including the following:
  • Anemia with erythropoietin, with the goal being 11-12 g/dL, as normalization of hemoglobin in patients with chronic kidney disease stages 4-5 has been associated with an increased risk of combined outcome. Before starting Epogen, iron stores should be checked, and the aim is to keep iron saturation at 30-50% and ferritin at 200-500.
  • Hyperphosphatemia with dietary phosphate binders and dietary phosphate restriction
  • Hypocalcemia with calcium supplements with or without calcitriol
  • Hyperparathyroidism with calcitriol or vitamin D analogs
  • Volume overload with loop diuretics or ultrafiltration
  • Metabolic acidosis with oral alkali supplementation
  • Uremic manifestations with chronic renal replacement therapy (hemodialysis, peritoneal dialysis, or renal transplantation): Indications include severe metabolic acidosis, hyperkalemia, pericarditis, encephalopathy, intractable volume overload, failure to thrive and malnutrition, peripheral neuropathy, intractable gastrointestinal symptoms, and the GFR less than 10 mL/min.
  • Cardiovascular complications
• Timely planning for chronic renal replacement therapy
  • Early education regarding natural disease progression, different dialytic modalities, renal transplantation, patient option to refuse or discontinue chronic dialysis
  • Timely placement of permanent vascular access (arrange for surgical creation of primary arteriovenous fistula, if possible, and preferably at least 6 months in advance of anticipated date of dialysis)
  • Timely elective peritoneal dialysis catheter insertion
  • Timely referral for renal transplantation

Consultations

• Early nephrology referral (decreases morbidity and mortality)
• Renal dietitian
• Vascular surgery for permanent vascular access
• General surgery for peritoneal catheter placement
• Referral to renal transplant center

Diet

• Protein restriction early in chronic kidney disease as a means to delay a decline in the GFR is controversial; however, as the patient approaches chronic kidney disease stage 5, this is recommended to delay the onset of uremic symptoms. Patients with chronic kidney disease who already are predisposed to becoming malnourished are at higher risk for malnutrition with overly aggressive protein restriction. Malnutrition is a well-established predictor of increased morbidity and mortality in the ESRD population and must be avoided if possible.
• Phosphate restriction starting early in chronic kidney disease
• Potassium restriction
• Sodium and water restriction as needed to avoid volume overload
• See related CME at New Guidelines Address Nutritional Needs of Children With Chronic Kidney Disease.

Medication

Phosphate-lowering agents

Hyperphosphatemia is treated with dietary phosphate binders and dietary phosphate restriction. Hypocalcemia is treated with calcium supplements and possibly calcitriol. Hyperparathyroidism is treated with calcitriol or vitamin D analogs.

A small trial (n=61) by Fishbane et al examined the effect of paricalcitol on protein excretion in patients with chronic kidney disease.^{[5 ]}In this double-blind, randomized study, more patients in the paricalcitol group achieved a 10% reduction in proteinuria than did members of the control group (57.1% vs 25.9%, respectively; P=0.03).

Calcium acetate (Calphron, PhosLo)

For treatment of hyperphosphatemia in chronic kidney disease. Combines with dietary phosphorus to form insoluble calcium phosphate, which is excreted in feces.

Dosing

Adult

1334 mg PO with each meal; increase to bring serum phosphate value to 6 mg/dL as long as hypercalcemia does not develop; may require as much as 2668 mg

Pediatric

Not established

Interactions

May increase effect of quinidine; may decrease effects of tetracyclines, atenolol, salicylates, iron salts, and fluoroquinolones; IV administration antagonizes effects of verapamil; large intakes of dietary fiber may decrease calcium absorption and levels

Contraindications

Hypercalcemia; hypophosphatemia; renal calculi

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hypercalcemia or hypercalcuria may occur when therapeutic amounts are administered

Calcium carbonate (Caltrate, Oystercal)

For treatment of hyperphosphatemia or as a calcium supplement in chronic kidney disease. Successfully normalizes phosphate concentrations in patients with chronic kidney disease. Combines with dietary phosphate to form insoluble calcium phosphate, which is excreted in feces. Marketed in a variety of dosage forms and is relatively inexpensive.

Dosing

Adult

1-2 g PO divided bid/qid; with meals as a phosphorous binder; between meals as a calcium supplement

Pediatric

45-65 mg/kg/d PO divided qid

Interactions

May decrease effects of tetracyclines, atenolol, salicylates, iron salts, and fluoroquinolones; IV administration antagonizes effects of verapamil; large intakes of dietary fiber may decrease calcium absorption and levels

Contraindications

Renal calculi; hypercalcemia; hypophosphatemia; digitalis toxicity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hypercalcemia or hypercalcuria may occur when therapeutic amounts are administered

Calcitriol (Rocaltrol, Calcijex)

Used to suppress parathyroid production and secretion in secondary hyperparathyroidism and for treatment of hypocalcemia in chronic kidney disease by increasing intestinal calcium absorption.

Dosing

Adult

0.25 mcg PO qd/qod
0.5 mcg IV qd 3 times/wk
Increase at 4- to 8-wk intervals by 0.25-mcg/d to achieve target PTH level and to maintain serum calcium levels at 9-10 mg/dL

Pediatric

Initial: 15 ng/kg/d PO
Maintenance: 5-40 ng/kg/d PO

Interactions

Cholestyramine and colestipol decrease absorption; magnesium-containing antacids and thiazide diuretics can increase calcitriol effects

Contraindications

Documented hypersensitivity; hypercalcemia; malabsorption syndrome

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Adequate response to calcitriol in improving hypocalcemia depends on adequate dietary calcium intake; serum calcium phosphate product must not exceed 70 mg/dL to minimize metastatic tissue and blood vessel calcification; avoid hypercalcemia

Doxercalciferol (Hectorol)

A vitamin D analog (1-alpha-hydroxyergocalciferol) that does not require activation by the kidneys. Indicated for the treatment of secondary hyperparathyroidism in end-stage renal disease.

Dosing

Adult

10 mcg PO 3 times/wk at dialysis; adjust dose as needed to lower blood iPTH to 150-300 pg/mL; increase dose by 2.5 mcg/8 wk if iPTH is not lowered by 50% and fails to reach the target range; not to exceed 20 mcg/3 times/wk
Alternatively, 4 mcg IV 3 times/wk; may adjust dose by 1-2 mcg/8 wk to maintain iPTH levels

Pediatric

Not established

Interactions

Coadministration with drugs that impair absorption of fat soluble vitamins (eg, cholestyramine) may decrease doxercalciferol absorption; increases the risk of hypermagnesemia with magnesium-containing products (eg, antacids)

Contraindications

Documented hypersensitivity; recent hypercalcemia or hyperphosphatemia

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

May cause headache, malaise, dyspnea, or hypercalcemia; caution in renal osteodystrophy with hyperphosphatemia (potential for metastatic calcification)

Lanthanum carbonate (Fosrenal)

Noncalcium, nonaluminum phosphate binder indicated for reduction of high phosphorus levels in patients with end-stage renal disease. Directly binds dietary phosphorus in upper GI tract, thereby inhibiting phosphorus absorption.

Dosing

Adult

Initial: 250-500 mg PO tid pc (chewable tabs); adjust dose q2-3wk to target serum phosphorus level
Maintenance: 500-1000 mg PO tid pc

Pediatric

Not established

Interactions

Drugs known to interact with antacids (eg, alendronate, amprenavir, ciprofloxacin, itraconazole, tetracycline, thyroid hormones) should not be administered within 2 h

Contraindications

Documented hypersensitivity; bowel obstruction; hypophosphatemia

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Deposited into developing bone, including growth plate (long-term effects unknown); common adverse effects typically diminish over time but include headache, abdominal pain, nausea, diarrhea, constipation, and vomiting; in clinical trials, dialysis graft occlusion occurred more frequently than with placebo; caution with GI motility diseases (eg, Crohn disease, ulcerative colitis) or recent GI surgery

Sevelamer (Renagel)

Indicated for the reduction of serum phosphorous in patients with ESRD. Binds dietary phosphate in the intestine, thus inhibiting its absorption. In patients on hemodialysis, it decreases the frequency of hypercalcemic episodes relative to patients on calcium acetate treatment.

Dosing

Adult

Initial: 800-1600 mg PO tid with meals
Maintenance: Increase or decrease by 400-800 mg per meal q2wk to maintain serum phosphorous at 6 mg/dL or less

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity; bowel obstruction; hypophosphatemia

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in patients with dysphagia, severe GI tract motility disorders, or swallowing disorders; does not contain calcium or alkali supplementation (monitor serum calcium, bicarbonate, and chloride levels)

Paricalcitol (Zemplar)

For treatment of secondary hyperparathyroidism in ESRD. Reduces PTH levels, stimulates calcium and phosphorous absorption, and stimulates bone mineralization.

Dosing

Adult

0.04-0.1 mcg IV bolus 3 times/wk; adjust dose based on PTH levels

Pediatric

Not established

Interactions

Do not use phosphate or vitamin D-related compounds concomitantly with paricalcitol; caution if administered with digoxin (digitalis toxicity is potentiated by hypercalcemia)

Contraindications

Documented hypersensitivity; hypercalcemia; vitamin D toxicity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in breastfeeding; adverse effects include GI tract distress, dry mouth, lightheadedness, edema, chills, or fever

Growth factors

Used to treat anemia of chronic kidney disease by stimulating RBC production.

Epoetin alfa (Epogen, Procrit)

Stimulates division and differentiation of committed erythroid progenitor cells. Induces release of reticulocytes from bone marrow into blood stream.

Dosing

Adult

50-150 U/kg IV/SC 3 times/wk

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity; uncontrolled hypertension

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in porphyria, hypertension, and history of seizures; decrease dose if hematocrit increase exceeds 4 U in any 2-wk period

Iron salts

Nutritionally essential inorganic substances used to treat anemia.

Ferrous sulfate (Feosol, Feratab, Slow FE)

Used as a building block for hemoglobin synthesis in treating anemia of chronic kidney disease with erythropoietin.

Dosing

Adult

325 mg PO qd/tid

Pediatric

<15 kg: 5 mg/kg/d PO
15-30 kg: 160 mg PO qd

Interactions

Absorption is enhanced by ascorbic acid; interferes with tetracycline absorption; food and antacids impair absorption

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

GI tract upset; iron toxicity is observed with ingestion of large amount and can be fatal, especially in children; parenteral (IV) administration may cause several reactions, including headaches, malaise, fever, generalized lymphadenopathy, arthralgia, and urticaria; can cause severe anaphylaxis; other reactions include phlebitis at infusion site

Iron dextran (DexFerrum, InFed)

Used to treat microcytic, hypochromic anemia resulting from iron deficiency when oral administration is unfeasible or ineffective.
Utilized to replenish iron stores in individuals on erythropoietin therapy who cannot take or tolerate oral iron supplementation.
A 0.5-mL (0.25 mL in children) test dose should be administered prior to starting therapy.
Available as 50 mg iron/mL (as dextran).

Dosing

Adult

>50 kg: 100 mg IV (2 mL); not to exceed 2 mL/d

Pediatric

5-10 kg: 50 mg IV (1 mL)

Interactions

Chloramphenicol-induced bone marrow toxicity may cause increased iron levels

Contraindications

Documented hypersensitivity; anemias that are not involved with iron deficiency; hemochromatosis; hemolytic anemia; acute phase of infectious kidney disease

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Monitor for allergic reactions (eg, flushing, hypotension, nausea)

Iron sucrose (Venofer)

Used to treat iron deficiency (in conjunction with erythropoietin) due to chronic hemodialysis. Iron deficiency is caused by blood loss during the dialysis procedure, increased erythropoiesis, and insufficient absorption of iron from the GI tract. Iron sucrose has shown a lower incidence of anaphylaxis than other parenteral iron products.

Dosing

Adult

5 mL (100 mg elemental iron) IV by slow injection or infusion during dialysis session; typically requires a minimum cumulative dose of 1000 mg of elemental iron over 10 consecutive dialysis sessions to achieve a favorable hemoglobin or hematocrit response; not to exceed 3 doses per wk

Pediatric

Not established

Interactions

Decreases bioavailability of orally administered iron

Contraindications

Documented hypersensitivity; iron overload; anemia unrelated to iron deficiency

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

May cause hypotension (related to IV administration rate or cumulative dose), cramps, headache, nausea, vomiting, diarrhea, or anaphylaxis

Ferric gluconate (Ferrlecit)

Replaces iron found in hemoglobin, myoglobin, and specific enzyme systems. Allows transportation of oxygen via hemoglobin.

Dosing

Adult

125 mg elemental iron/10 mL IV; may require cumulative dose of 1 g elemental iron to achieve favorable response in patients receiving hemodialysis

Pediatric

Not established

Interactions

Vitamin C may increase absorption of oral iron when administered concurrently; absorption of oral preparation of iron and tetracyclines decreased when administered concurrently; concurrent administration of H2 blockers or proton pump inhibitors may inhibit iron absorption

Contraindications

Documented hypersensitivity; hemochromatosis; hemolytic anemia

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Flushing and transient hypotension may occur; may augment hemodialysis-induced hypotension

Recombinant Human Erythropoietin

Stimulates development of erythroid progenitor cells.

Darbepoetin (Aranesp)

Erythropoiesis stimulating protein closely related to erythropoietin, a primary growth factor produced in kidney that stimulates development of erythroid progenitor cells. Mechanism of action is similar to that of endogenous erythropoietin, which interacts with stem cells to increase red cell production. Differs from epoetin alfa (recombinant human erythropoietin) in containing 5 N-linked oligosaccharide chains, whereas epoetin alfa contains 3. Has longer half-life than epoetin alfa (may be administered weekly or biweekly).

Dosing

Adult

0.45 mcg/kg IV/SC qwk initially; adjust dose (not to exceed 3 mcg/kg/wk) or frequency (eg, q2wk); to maintain target Hgb (not to exceed 12 g/dL); do not increase dose more frequently than qmo

Switching from epoetin alfa: Base dose on total weekly erythropoietin dose and frequency of administration

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity; uncontrolled hypertension

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Elevation in Hgb > 1 g/dL/2wk increases risk of MI, neurologic events (eg, seizures, stroke) and exacerbations of hypertension, CHF, thrombosis, ischemia, and edema; adverse effects include infection, hypertension, hypotension, myalgia, headache, and diarrhea (some of adverse events may be due to chronic renal failure or dialysis); severe skin rash may occur (rare)

Calcimimetic agents

These agents reduce parathyroid hormone levels.

Cinacalcet (Sensipar)

Directly lowers intact parathyroid hormone (iPTH) levels by increasing sensitivity of calcium sensing receptor on chief cell of parathyroid gland to extracellular calcium. Also results in concomitant serum calcium decrease. Indicated for secondary hyperparathyroidism in patients with chronic kidney disease on dialysis.

Dosing

Adult

30 mg PO qd initially; titrate upward slowly (no more frequent than q2-4wk intervals) by 30 mg increments to target iPTH of 150-300 pg/mL

Take with meals or immediately following; do not crush, chew or cut tablets

Pediatric

Not established

Interactions

Strong CYP450 2D6 inhibitor; may increase serum levels of CYP 2D6 substrates (eg, flecainide, vinblastine, thioridazine, tricyclic antidepressants); coadministration with CYP450 3A4 inhibitors (eg, ketoconazole, erythromycin, itraconazole) may decrease cinacalcet clearance

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Serum calcium reduction may cause lowered seizure threshold, paresthesia, myalgia, cramping, and tetany; monitor calcium and phosphorus levels closely within 1 wk following initial dose or dose changes, and then monthly (secondary hyperparathyroidism) and q2 mo (parathyroid carcinoma); do not initiate treatment if serum calcium below 8.4 mg/dL; adynamic bone disease may occur if iPTH levels suppressed below 100 pg/mL; caution with hepatic impairment; common adverse effects include nausea and vomiting

Follow-up

Further Inpatient Care

• Patients who develop potentially life-threatening complications of chronic kidney disease should be hospitalized and closely monitored.

Further Outpatient Care

• Patients with chronic kidney disease should be referred to a nephrologist early in the course of their disease and have continued nephrologic follow-up until initiation of chronic renal replacement therapy.
• A multidisciplinary approach to care, including involvement of the nephrologist, primary care physician, renal dietitian, nurse, and social worker, should be initiated early in the course of chronic kidney disease, with close patient follow-up.

Transfer

• Patients with chronic kidney disease acutely presenting with indications for dialytic therapy should be transferred to a hospital center where acute dialysis can be performed.

Prognosis

• Patients with chronic kidney disease generally progress to ESRD. The rate of progression depends on the underlying diagnosis, on the successful implementation of secondary preventative measures, and on the individual patient.
• Patients on chronic dialysis have a high incidence of morbidity and mortality.
• Patients with ESRD who undergo renal transplantation survive longer than those on chronic dialysis.

Patient Education

• Patients with chronic kidney disease should be educated about the importance of compliance with secondary preventative measures, natural disease progression, prescribed medications (highlighting their potential benefits and adverse effects), avoidance of nephrotoxins, diet, chronic renal replacement modalities, including peritoneal dialysis, hemodialysis, and transplantation, and permanent vascular access options for hemodialysis.
• For excellent patient education resources, visit eMedicine's Diabetes Center. Also, see eMedicine's patient education article Chronic Kidney Failure.

Miscellaneous

Medicolegal Pitfalls

• Early diagnosis and treatment of the underlying cause or/and institution of secondary preventative measures in chronic kidney disease is imperative to try to delay, or possibly halt, progression. Early nephrologic referral is of extreme importance.
• Timely initiation of chronic renal replacement therapy is imperative to prevent the uremic complications of chronic kidney disease that can lead to significant morbidity and death.
• In chronic kidney disease, doses and intervals of drugs that are excreted or metabolized renally should be adjusted accordingly for the residual GFR. Some drugs are contraindicated in moderate-to-severe renal impairment because of potentially serious effects from drug or metabolite accumulation. Routine consultation of the appropriate references should be undertaken when prescribing any new drug to a patient with chronic kidney disease.

Special Concerns

• Female patients with advanced chronic kidney disease commonly develop menstrual irregularities; women with ESRD are typically amenorrheic and infertile.
• Pregnancy in chronic kidney disease can be associated with accelerated renal decline. In advanced chronic kidney disease and ESRD, pregnancy is associated with markedly decreased fetal survival.
• Forty-five percent of patients with chronic kidney disease (CKD) have depressive symptoms at dialysis therapy initiation, as assessed using self-report scales. However, these scales may emphasize somatic symptoms, specifically, sleep disturbance, fatigue, and anorexia, that can coexist with chronic disease symptoms. Hedayati et al conducted a validation study to determine whether these scales could lead to overestimation of depression diagnosis.^{[6 ]}The study compared the Beck Depression Inventory (BDI) and the 16-item Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR(16)) with a gold-standard structured psychiatric interview in 272 patients with stage 2-5 chronic kidney disease who had not been treated with dialysis.
• The above study's authors found the QIDS-SR(16) and the BDI to be effective screening tools, concluding that a score of 10 or 11, respectively, was the best cutoff score for identification of a major depressive episode in the study's patient population.

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Keywords

chronic renal failure, chronic kidney failure, end-stage renal disease, kidney failure, kidney disease, CRF, ESRD, chronic renal impairment, chronic renal insufficiency, CRI, glomerular filtration rate, GFR, systemic hypertension, proteinuria, hyperlipidemia, glomerulosclerosis, nephrotoxins, hyperphosphatemia, calcium phosphate deposition, type IV renal tubular acidosis, diabetes mellitus, hyperkalemia

metabolic acidosis, normochromic normocytic anemia, decreased synthesis of erythropoietin, uremia-induced platelet dysfunction, secondary hyperparathyroidism, osteitis fibrosa, renal osteodystrophy, osteomalacia, adynamic bone disease, dialysis-related amyloidosis, pericarditis, cardiac tamponade, encephalopathy, peripheral neuropathy, restless leg syndrome, systemic lupus erythematosus, severe arteriosclerosis, renal artery stenosis, cytoplasmic pattern antineutrophil cytoplasmic antibody, C-ANCA, perinuclear pattern antineutrophil cytoplasmic antibody–positive vasculitides, P-ANCA–positive vasculitides, antineutrophil cytoplasmic antibody–negative vasculitides, ANCA–negative vasculitides, atheroemboli

hypertensive nephrosclerosis, renal vein thrombosis, primary glomerular disease, membranous nephropathy, immunoglobulin Anephropathy, IgA nephropathy, focal segmental glomerulosclerosis, FSGS, membranoproliferative glomerulonephritis, rapidly progressive glomerulonephritis, crescentic glomerulonephritis, secondary glomerular disease, rheumatoid arthritis, mixed connective tissue disease, scleroderma

Goodpasture syndrome, Wegener granulomatosis, mixed cryoglobulinemia, postinfectious glomerulonephritis, endocarditis, hepatitis B, hepatitis C, syphilis, human immunodeficiency virus, HIV, parasitic infection, heroin use, penicillamine, gold, amyloidosis, light chain deposition disease, Alport syndrome

thrombotic thrombocytopenic purpura, TTP, Henoch-Schönlein purpura, hemolytic-uremic syndrome, HUS, reflux nephropathy, tubulointerstitial disease, Sjögren syndrome, chronic hypokalemia, chronic hypercalcemia, sarcoidosis, multiple myeloma cast nephropathy, heavy metals, radiation nephritis, polycystic kidneys, cystinosis

urinary tract obstruction, urolithiasis, benign prostatic hypertrophy, retroperitoneal fibrosis, urethral stricture, neurogenic bladder

Contributor Information and Disclosures

Author

Pradeep Arora, MD, Assistant Professor of Medicine, University of Buffalo; Attending Nephrologist, Veterans Affairs Western New York Healthcare System
Disclosure: Nothing to disclose.

Coauthor(s)

Mauro Verrelli, MD, FRCP(C), FACP, Assistant Professor, Department of Medicine, Section of Nephrology, University of Manitoba, Canada
Mauro Verrelli, MD, FRCP(C), FACP is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Society of Nephrology, Canadian Medical Association, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Medical Editor

Laura L Mulloy, DO, FACP, Professor of Medicine, Chief, Section of Nephrology, Hypertension and Transplantation Medicine, Glover/Mealing Eminent Scholar Chair in Immunology, Medical College of Georgia
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

George R Aronoff, MD, Director, Professor, Departments of Internal Medicine and Pharmacology, Section of Nephrology, Kidney Disease Program, University of Louisville School of Medicine
George R Aronoff, MD is a member of the following medical societies: American Federation for Medical Research, American Society of Nephrology, Kentucky Medical Association, and National Kidney Foundation
Disclosure: Nothing to disclose.

CME Editor

Rebecca J Schmidt, DO, FACP, FASN, Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine
Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association
Disclosure: Abbott Grant/research funds Speaking and teaching; Genzyme Honoraria Consulting; Amgen Honoraria Speaking and teaching; Ortho Biotech Honoraria Speaking and teaching

Chief Editor

Vecihi Batuman, MD, FACP, FASN, Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, Southeast Louisiana Veterans Health Care System
Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, and International Society of Nephrology
Disclosure: Nothing to disclose.

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