Chronic Kidney Disease

Author: Pradeep Arora, MD; Chief Editor: Vecihi Batuman, MD, FACP, FASN

Chronic kidney disease (CKD) is a worldwide public health problem. It is recognized as a common condition that is associated with an increased risk of cardiovascular disease and chronic renal failure (CRF). In the United States, there is a rising incidence and prevalence of kidney failure, with poor outcomes and high cost (see Epidemiology). 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 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. In 2002, K/DOQI published its classification of the stages of chronic kidney disease, as follows:
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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 on imaging studies, should also be present in establishing a diagnosis of stage 1 and stage 2 chronic kidney disease. The K/DOQI definition and classification of chronic kidney disease allow better communication among physicians and facilitate intervention at the different stages. Patients with chronic kidney disease stages 1-3 are generally asymptomatic; clinically manifestations typically appear in stages 4-5 (see Clinical). Early diagnosis and treatment of the underlying cause and/or institution of secondary preventive measures is imperative in patients with chronic kidney disease. These may delay, or possibly halt, progression. The medical care of patients with chronic kidney disease (see Treatment) should focus on the following:
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Delaying or halting the progression of chronic k idney disease Treating the pathologic manifestations of chronic kidney disease Timely planning for long-term renal replacement therapy

Approximately 1 million nephrons are present in each kidney, each contributing to the total GFR. In the face of renal injury (regardless of the etiology), the kidney has an innate ability to maintain GFR, despite progressive destruction of nephrons, by hyperfiltration and compensatory hypertrophy of the remaining healthy nephrons. This nephron adaptability allows for continued normal clearance of plasma solutes. Plasma levels of substances such as urea and creatinine start to show significant increases 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 hyperfiltration and hypertrophy of residual nephrons, 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 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:
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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


The ability to maintain potassium (K) excretion at near-normal levels is generally maintained in chronic kidney disease 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 angiotensinconverting 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

Metabolic acidosis often is a mixture of normal anion gap and increased anion gap; the latter is 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, sulfates, 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 the following:
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Negative nitrogen balance Increased protein degradation Increased essential amino acid oxidation Reduced albumin synthesis Lack of adaptation to a low protein diet

Hence, metabolic acidosis is associated with protein-energy malnutrition, loss of lean body mass, and muscle weakness. The mechanism for reducing protein may include effects on adenosine triphosphate (ATP)–dependent ubiquitin proteasomes and increased activity of branched chain keto acid dehydrogenases. Metabolic acidosis is a factor in the development of renal osteodystrophy, as bone acts as a buffer for excess acid, with resultant loss of mineral. Acidosis may interfere with vitamin D metabolism, and patients who are persistently more acidotic are more likely to have osteomalacia or low-turnover bone disease.
Salt and water handling abnormalities

Salt and water handling by the kidney is altered in chronic kidney disease. Extracellular volume expansion and total-body volume overload results from failure of sodium and free water excretion. This generally becomes clinically manifest when the GFR falls to less than 10-15 mL/min, when compensatory mechanisms have become exhausted. As kidney function declines further, sodium retention and extracellular volume expansion lead to peripheral edema and, not uncommonly, pulmonary edema and hypertension. At a higher GFR, excess sodium and water intake could result in a similar picture if the ingested amounts of sodium and water exceed the available potential for compensatory excretion.


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 include the following:
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Chronic blood loss Secondary hyperparathyroidism Inflammation Nutritional deficiency Accumulation of inhibitors of erythropoiesis

Bone disease

Renal bone disease is a common complication of chronic kidney disease. It 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:
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High-turnover bone disease due to high parathyroid hormone (PTH) levels Low-turnover bone disease (adynamic bone disease) Defective mineralization (osteomalacia) Mixed disease Beta-2-microglobulin associated bone disease

Chronic kidney disease–mineral and bone disorder (CKD-MBD) involves biochemical abnormalities, (ie, serum phosphorus, PTH, and vitamin D levels) related to bone metabolism. Secondary hyperparathyroidism develops in chronic kidney disease because of the following factors:
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Hyperphosphatemia Hypocalcemia Decreased renal synthesis of 1,25-dihydroxycholecalciferol (1,25-dihydroxyvitamin D, or calcitriol) Intrinsic alteration in the parathyroid gland, which give rises to increased PTH secretion as well as increased parathyroid growth Skeletal resistance to PTH

Calcium and calcitriol are primary feedback inhibitors; hyperphosphatemia is a stimulus to PTH synthesis and secretion.

It is markedly less common than high-turnover bone disease. Low serum calcitriol levels. If serum levels of PTH remain elevated. As the GFR falls toward chronic kidney disease stages 4-5. which as a group are commonly known as renal osteodystrophy. PTH secretion becomes maladaptive and the parathyroid glands. Low-turnover osteomalacia in the setting of chronic kidney disease is associated with aluminum accumulation. hypocalcemia. particularly in the more advanced stages. when the GFR falls. The prevalence of adynamic bone disease in the United States has increased. and hyperphosphatemia have all been demonstrated to independently trigger PTH synthesis and secretion. known as osteitis fibrosa. but several factors may contribute. but serum levels do not rise initially because of increased PTH secretion. use of vitamin D sterols. 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. and it has been described before the initiation of dialysis in some cases. which initially hypertrophy. It manifests with cysts at the ends of long bones. The pathogenesis of adynamic bone disease is not well defined. become hyperplastic. including high calcium load. This is one of several bone lesions.Phosphate retention begins in early chronic kidney disease. which increases renal excretion. a high bone turnover lesion. so serum calcitriol levels are low when the GFR is less than 30 mL/min. increasing age. peritoneal dialysis. develops. The persistently elevated PTH levels exacerbate hyperphosphatemia from bone resorption of phosphate. Etiology Causes of chronic kidney disease include the following:     Vascular disease Glomerular disease (primary or secondary) Tubulointerstitial disease Urinary tract obstruction . previous corticosteroid therapy. hyperphosphatemia develops from the inability of the kidneys to excrete the excess dietary intake. less phosphate is filtered and excreted. Increased phosphate concentration also effects PTH concentration by its direct effect on parathyroid gland (posttranscriptional effect). and increased level of N-terminally truncated PTH fragments. These lesions develop in patients with severe chronic kidney disease and are common in those with ESRD. As these stimuli persist in chronic kidney disease. 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. Hyperphosphatemia suppresses the renal hydroxylation of inactive 25-hydroxyvitamin D to calcitriol.

Vascular diseases that can cause chronic kidney disease include the following:      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 diseases include the following:      Membranous nephropathy Immunoglobulin A (IgA) nephropathy Focal and segmental glomerulosclerosis (FSGS) Minimal change disease Membranoproliferative glomerulonephritis Rapidly progressive (crescentic) glomerulonephritis Secondary causes of glomerular disease include the following:                          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 Causes of tubulointerstitial disease include the following: .

lipid levels. prior myocardial infarction (MI). Epidemiology In the United States. and factor VIIIc. smoking.9 million) had stage 1. bacterial.2 million): 3.           Drugs (eg. sulfa. parasitic) Sjögren syndrome Chronic hypokalemia Chronic hypercalcemia Sarcoidosis Multiple myeloma cast nephropathy Heavy metals Radiation nephritis Polycystic kidneys Cystinosis Urinary tract obstruction may result from any of the following:       Urolithiasis Benign prostatic hypertrophy Tumors Retroperitoneal fibrosis Urethral stricture Neurogenic bladder Findings from the Atherosclerosis Risk in Communities (ARIC) Study. blood pressure. This increase is partially explained by the increase in the prevalence of diabetes and hypertension.000) had stage 5.3% (5. allopurinol) Infection (viral. 3% (5. von Willebrand factor. .3 million) had stage 2.[1] This study used data from 1787 cases of chronic kidney disease that developed between 1987 and 2004. Kidney disease is the ninth leading cause of death in the United States. 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. 0.2% (300. there is a rising incidence and prevalence of kidney failure.3% (7. fibrinogen. such as demographics. with poor outcomes and high cost. and 0. diabetes. The prevalence of chronic kidney disease stages 1-4 increased from 10% in 1988-1994 to 13.2% (400. Data from the United States Renal Data System (USRDS) indicated that the prevalence of chronic renal failure increased 104% between the years 1990-2001. and alcohol use.000) had stage 4.1% in 1999-2004. The investigators found a strong inverse association between serum albumin level and chronic kidney disease risk.6 million) had stage 3. After adjustments for various factors. suggest that inflammation and hemostasis are antecedent pathways for chronic kidney disease. the two most common causes of chronic kidney disease. antihypertensive use. a prospective observational cohort. the above study revealed that the risk for chronic kidney disease rose with increasing quartiles of white blood cell (WBC) count. 4.

the absolute risk and incidence was slight.5 mg/dL. Sex. A study of Israeli youth revealed that patients aged 16-25 years with persistent asymptomatic isolated microscopic hematuria had an increased risk of treated ESRD for 22 years. 1.73 m2 (hazard ratio. followed by Japan. Racial demographics Chronic kidney disease affects all races.9 million people). As per NHANES III data.8% among patients older than 70 years.2 million people (ie. the USRDS 2004 Annual Data Report reveals that the incident rate of ESRD cases is higher for males. 8 million people had a GFR of less than 60 mL/min.and age-related demographics In NHANES III. for the first time. Nonetheless. in the United States. morbidity. Because of the nonuniform definition of kidney disease prior to publication of the K/DOQI classification in 2002. Risk of ESRD among black patients was highest at an eGFR of 45-59 mL/min/1. mortality rates among black patients were equal to or higher than those among white patients at all levels of eGFR. Nonetheless. most patients with earlier stages of chronic kidney disease have not been recognized or adequately treated. among other factors. however. in the United States. Healthy People lays out 14 goals and strategies to reduce the incidence. mortality. the highest incidence rate of ESRD occurs in patients older than 65 years. For 2020. Japan has the highest prevalence per million population. it was estimated that 6.According to the Third National Health and Nutrition Examination Survey. The incidence rates of end-stage renal disease (ESRD) have increased steadily internationally since 1989. a significantly higher incidence of ESRD exists in blacks than in whites. the US Surgeon General’s latest 10-year national objectives for improving the health of all Americans. but. the prevalence of chronic kidney disease was 37. The United States has the highest incident rate of ESRD. 3% of the total US population) older than 12 years had a serum creatinine value above 1.32). including effective preventive strategies and early detection and treatment of chronic kidney disease. Therefore. the incidence rate for blacks is nearly 4 times that for whites. with the United States taking second place. 3. contains a chapter focused on chronic kidney disease. Chronic kidney disease is found in persons of all ages.08). and health costs of chronic kidney disease in the United States.[3] . Healthy People 2020. as was the risk of mortality (hazard ratio. Reducing renal failure will require additional public health efforts. Choi et al found that rates of ESRD among black patients exceeded those among white patients at all levels of baseline estimated GFR (eGFR).[2] Similarly. with 409 per million population in 2002 compared with 276 for females. the majority of them being in the Medicare senior population (5. the distribution of estimated GFRs for the chronic kidney disease stages was similar in both sexes.

a lower serum albumin. resulting in redistribution of blood flow favoring the renal medulla. higher albuminuria. Glomerulosclerosis leads to a decrease in renal weight. The vasodilatory response is blunted in the elderly when compared to younger patients. and male sex pointed to a faster progression of kidney failure.73 m2. with relative sparing of the renal medulla. age is an independent major predictor of chronic kidney disease. 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. and other risk factors for renal dysfunction. calcium. Also.[4] . However. The biologic process of aging initiates various structural and functional changes within the kidney.73 m2. younger age. A blunted vasodilatory capacity with appropriate vasoconstrictor response may indicate that the aged kidney is in a state of vasodilatation to compensate for the underlying sclerotic damage. and a higher serum phosphate can predict an elevated risk of kidney failure. The GFR peaks during the third decade of life at approximately 120 mL/min/1. it shows an annual mean decline of approximately 1 mL/min/y/1. the vasoconstrictor response to intrarenal angiotensin is identical in both young and older human subjects.73 m2 at age 70 years. Ischemic obsolescence of cortical glomeruli is predominant. Given the histologic evidence for nephronal senescence with age. a wide variation in the rate of decline in the GFR is reported because of measurement methods. and on the individual patient. on the successful implementation of secondary preventive measures. genetic variance. Tangri et al developed and validated a model that uses routine laboratory results to predict progression from chronic kidney disease (stages 3-5) to kidney failure. The study showed that lower estimated GFR. Juxtamedullary glomeruli see a shunting of blood from the afferent to efferent arterioles. These anatomical and functional changes in renal vasculature appear to contribute to an age-related decrease in renal blood flow. and bicarbonate. reaching a mean value of 70 mL/min/1. The rate of progression depends on the underlying diagnosis. a decline in the GFR is expected. race. However.Besides diabetes mellitus and hypertension. 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. gender. Histologic examination is notable for a decrease in glomerular number of as much as 30-50% by age 70 years. The geriatric population is the most rapidly growing kidney failure (chronic kidney disease stage 5) population in the United States. Prognosis Patients with chronic kidney disease generally progress to ESRD. Renal mass progressively declines with advancing age.

a healthy person can expect to live for more than 20 years. In the NHANES III prevalence study. and approximately 25% in patients with diabetes. The 5-year survival rate for a patient undergoing chronic dialysis in the United States is approximately 35%. The morbidity and mortality of dialysis patients is much higher in the United States compared with most other countries. which often follows missed dialysis or dietary indiscretion. At age 60 years. Mortality then tends to improve over the next 6 months.[6] An elevated level of the phosphate-regulating hormone fibroblast growth factor 23 (FGF-23) has been linked with mortality in patients with ESRD. The most common cause of death overall in the dialysis population is cardiovascular disease. mortality rates are 6 times higher than in the general population. The mortality rates associated with hemodialysis are striking and indicate that the life expectancy of patients entering into hemodialysis is markedly shortened. US patients receiving dialysis are on the average older and sicker than those in other countries. A study by Raphael et al suggests that higher serum bicarbonate levels are associated with better survival and renal outcomes in African Americans.In the United States. the general hemodialysis and peritoneal dialysis populations have 2 hospital admissions per patient per year. At every age. patients with ESRD who undergo renal transplantation survive longer than those on chronic dialysis.[5] The most common cause of sudden death in patients with ESRD is hyperkalemia. over 69. Additionally. Due to liberal criteria for receiving government-funded dialysis in the US and rationing (both medical and economic) in most other countries. Isakova et al reported that elevated FGF-23 is also an independent risk factor for end-stage renal disease in patients who have fairly preserved kidney function (stages 2-4) and for mortality across the scope of chronic kidney disease. patients with ESRD on dialysis have significantly increased mortality when compared with nondialysis patients and individuals without kidney disease. In 2003. which represents a 14% decrease since peaking at 244.5 per 1000 patient-years in 1988). which is probably a consequence of selection bias.7 per 1000 patient-years at risk for the dialysis population. Among patients with ESRD aged 65 years and older. cardiovascular mortality is 10-20 times higher in dialysis patients than in the normal population. The highest mortality rate is within the first 6 months of initiating dialysis. hypoalbuminemia (a marker of protein-energy malnutrition and a powerful predictive marker of mortality in dialysis patients as well as in the general population) was independently associated with low bicarbonate as well as the inflammatory marker C-reactive protein. before increasing gradually over the next 4 years. patients who have a renal transplant have an average of 1 hospital admission per year.000 dialysis patients enrolled in the ESRD program died (annual adjusted mortality rate of 210. whereas the life expectancy of a 60year-old patient starting hemodialysis is closer to 4 years.[7] .

these disturbances become clinically manifest with chronic kidney disease stages 4-5 (GFR < 30 mL/min). they do not experience clinically evident disturbances in water or electrolyte balance or endocrine/metabolic derangements. Altered salt and water handling by the kidney in chronic kidney disease can cause peripheral edema and. Patient Education Patients with chronic kidney disease should be educated about the following:        Importance of compliance with secondary preventive measures Natural disease progression Prescribed medications (highlighting their potential benefits and adverse effects) Avoidance of nephrotoxins Diet Renal replacement modalities.Reproductive issues Female patients with advanced chronic kidney disease commonly develop menstrual irregularities. many of which are more likely in patients who are inadequately dialyzed. include the following:   Pericarditis . Pregnancy in chronic kidney disease can be associated with accelerated renal decline. Anemia is also associated with the development of cardiovascular disease. Other manifestations of uremia in ESRD. Uremic manifestations in patients with chronic kidney disease stage 5 are believed to be primarily secondary to an accumulation of toxins. hemodialysis. In advanced chronic kidney disease and ESRD. Metabolic acidosis in stage 5 may manifest as protein-energy malnutrition. Generally. the identity of which is generally not known. and transplantation Permanent vascular access options for hemodialysis History Patients with chronic kidney disease stages 1-3 (glomerular filtration rate [GFR] >30 mL/min) are generally asymptomatic. the new onset of heart failure. pulmonary edema and hypertension. and reduced quality of life. including peritoneal dialysis. and muscle weakness.Can be complicated by cardiac tamponade.Can progress to coma and death . not uncommonly. Anemia is associated with fatigue. reduced exercise capacity. possibly resulting in death Encephalopathy . loss of lean body mass. impaired cognitive and immune function. pregnancy is associated with markedly decreased fetal survival. women with ESRD are typically amenorrheic and infertile. Anemia is associated with increased cardiovascular mortality. or the development of more severe heart failure.

80-year-old man. Therefore. nausea. that same value represents an eGFR of 58 mL/min/1. which includes age as a variable. in a 70-kg.73m2. vomiting. However. what might appear to be only mild renal impairment with a serum creatinine of 2 mg/dL actually represents severe renal impairment when the eGFR is calculated to be 32 mL/min/1. respectively. Diagnostic Considerations Because of anatomic and physiologic changes. increased somnolence. pruritus. elderly patients with chronic kidney disease may behave differently.73m2.2 mg/dL in a 70-kg. lupus. using a formula such as the Modification of Diet in Renal Disease (MDRD) equation. in elderly patients an eGFR must be determined. Thus. severe arteriosclerosis. diarrhea Skin manifestations . and anorexia—that can coexist with chronic disease symptoms. as assessed using self-report scales. anemia. A serum creatinine value of 1.[8] The study compared the BDI and 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. failure to thrive Malnutrition Erectile dysfunction.Anorexia. than younger patients. sleep disturbance. in terms of progression and response to pharmacologic treatment. amenorrhea Platelet dysfunction with tendency to bleeding Physical Examination The physical examination often is not very helpful. However. bleeding diathesis. it may reveal findings characteristic of the condition that is underlying chronic kidney disease (eg.73m2. Screening for depression Forty-five percent of patients with chronic kidney disease have depressive symptoms at dialysis therapy initiation. This . but in a 70-kg.        Peripheral neuropathy Restless leg syndrome GI symptoms . hypertension) or complications of chronic kidney disease (eg. these scales may emphasize somatic symptoms—specifically. pericarditis). fatigue. 25-year-old man represents an estimated glomerular filtration rate (eGFR) of 74 mL/min/1.Dry skin. were the best cutoff scores for identification of a major depressive episode in their study's patient population. decreased libido. Hedayati et al reported that the 16-item Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR[16]) and the Beck Depression Inventory (BDI) are effective screening tools and that scores of 10 and 11. ecchymosis Fatigue. 80-year-old man.

double-stranded DNA antibody levels .Conditions associated with some glomerulonephritides Urinalysis Dipstick proteinuria may suggest a glomerular or tubulointerstitial problem. suggests proliferative glomerulonephritis. A lipid profile should be performed in all patients with chronic kidney disease because of their increased risk of cardiovascular disease. the following tests may be ordered as part of the evaluation of patients with chronic kidney disease:        Serum and urine protein electrophoresis . Serum phosphate.will allow appropriate drug dosing adjustments to be made and nephrotoxins to be avoided in patients who have more extensive chronic kidney disease than would be suggested by the serum creatinine value alone. and intact parathyroid hormone (PTH) levels are obtained to look for evidence of renal bone disease. with calculation of renal function. as patients may have hypoalbuminemia due to urinary protein loss or malnutrition.Helpful if positive in diagnosis of microscopic polyangiitis Anti–glomerular basement membrane (anti-GBM) antibodies . Venereal Disease Research Laboratory (VDRL) serology . Normochromic normocytic anemia is commonly seen in chronic kidney disease.Helpful if positive in diagnosis of Wegener granulomatosis and polyarteritis nodosa Perinuclear pattern antineutrophil cytoplasmic antibody (P-ANCA) .Screen for a monoclonal protein possibly representing multiple myeloma Antinuclear antibodies (ANA). In certain cases.Highly suggestive of underlying Goodpasture syndrome Hepatitis B and C. basic metabolic panel. Serum albumin levels may also be measured. vitamin D. The blood urea nitrogen (BUN) and creatinine levels will be elevated in patients with chronic kidney disease.Screen for systemic lupus erythematosus Serum complement levels . Hyperkalemia or low bicarbonate levels may be present in patients with chronic kidney disease. Other underlying causes of anemia should be ruled out. Renal ultrasound and other imaging studies may be indicated. HIV. Pyuria and/or WBC casts . The urine sediment finding of RBCs. and urinalysis. RBC casts.May be depressed with some glomerulonephritides Cytoplasmic and perinuclear pattern antineutrophil cytoplasmic antibody (C-ANCA and P-ANCA) levels . Approach Considerations Testing typically includes a complete blood count (CBC).

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. or diffuse adenopathy. Renal Function Formulas 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.[10] Imaging Studies Renal ultrasonography Renal ultrasonography is useful to screen for hydronephrosis. Although 24-hour urine collection for total protein and creatinine clearance (CrCl) can be performed.85 Alternatively.5 g is within the nephrotic range. Plain abdominal x-ray is particularly useful to look for radio-opaque stones or nephrocalcinosis.[9] However. this procedure is often used to diagnose renal stones. however. less than 2 is characteristic of tubulointerstitial problems.73 m2. Kidneys usually are normal in size in advanced diabetic nephropathy. . and it can report eGFR ≥60 mL/min/1. The formulas are as follows:   CrCl (male) = ([140-age] × weight in kg)/(serum creatinine × 72) CrCl (female) = CrCl (male) × 0. where affected kidneys initially are enlarged from hyperfiltration. tumor. Radiography A retrograde pyelogram may be indicated if a high index of clinical suspicion for obstruction exists despite a negative finding on renal ultrasonography. Stevens et al found that the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is more accurate than the MDRD Study equation overall and across most subgroups. also may be observed. Intravenous pyelography is not commonly performed because of the potential for renal toxicity from the intravenous contrast.73 m2. and a value of greater than 3-3. This equation does not require a patient's weight. Small echogenic kidneys are observed in advanced renal failure. such as polycystic kidneys. MDRD underestimates measured GFR at levels >60 mL/min/1. which may not be observed in early obstruction. the Modification of Diet in Renal Disease (MDRD) Study equation could be used to calculate the GFR. A value of greater than 2 g is considered to be within the glomerular range. or involvement of the retroperitoneum with fibrosis. Structural abnormalities.

Approach Considerations Early diagnosis and treatment of the underlying cause and/or institution of secondary preventive measures is imperative in patients with chronic kidney disease. which can be life threatening in a minority of occurrences. findings of segmental and globally sclerosed glomeruli and tubulointerstitial atrophy. often with tubulointerstitial mononuclear infiltrates. IV contrast–enhanced CT scans should be avoided in patients with renal impairment to avoid acute renal failure. and radionuclide scan A computed tomography (CT) scan is useful to better define renal masses and cysts usually noted on ultrasound. Dehydration also markedly increases this risk. this risk significantly increases in patients with moderate-to-severe chronic kidney disease. Early nephrologic referral is of extreme importance. A renal radionuclide scan is useful to screen for renal artery stenosis when performed with captopril administration. However. Renal Biopsy Percutaneous renal biopsy is performed most often with ultrasound guidance and the use of a mechanical gun. Magnetic resonance imaging (MRI) is very useful in patients who require a CT scan but who cannot receive intravenous contrast. occasionally with solitary kidneys. Surgical open renal biopsy can be considered when the risk of renal bleeding is felt to be great. it also quantitates differential renal contribution to total GFR. These may delay. generally. The most common complication of this procedure is bleeding.A voiding cystourethrogram (VCUG) is the criterion standard for diagnosis of vesicoureteral reflux CT. or possibly halt. MRI. radionuclide scans are unreliable in patients with a GFR of less than 30 mL/min. it is the most sensitive test for identifying renal stones. although renal arteriography remains the criterion standard. It is not indicated when renal ultrasound reveals small echogenic kidneys on ultrasound because this finding represents severe scarring and chronic irreversible injury. It is reliable in the diagnosis of renal vein thrombosis. or when percutaneous biopsy is technically difficult to perform. as are CT scan and renal venography. Magnetic resonance angiography also is becoming more useful for diagnosis of renal artery stenosis. . progression. Also. Renal histology in chronic kidney disease reveals findings compatible with the underlying primary renal diagnosis and. 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.

the physician needs to closely monitor the patient's nutritional status. Data support the use of ACE inhibitors or ARBs in diabetic kidney disease with or without proteinuria. these agents 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%) is indicated. bilateral renal artery stenosis [RAS].The medical care of patients with chronic kidney disease should focus on the following:    Delaying or halting the progression of chronic kidney disease Treating the pathologic manifestations of chronic kidney disease Timely planning for long-term renal replacement therapy 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. The National Kidney Foundation guidelines suggest that if a patient is started on protein restriction. Aggressive blood pressure control to target values per current guidelines is indicated. However. Hyperkalemia may be completely asymptomatic until a lethal arrhythmia occurs. this must be treated as hyperkalemia until the potassium level is not elevated. The tracing shows a wide QRS and very large T waves. Calcium salts are the most rapid acting of the agents used to treat hyperkalemia. Avoid these agents in advanced renal failure. with close monitoring for renal deterioration and for hyperkalemia (see the image below). or RAS in a solitary kidney. The National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (KDOQI) has issued 13 clinical practice guidelines for managing all stages of chronic kidney disease and related complications. Predialysis low serum albumin is associated with a poor outcome among dialysis patients. In the setting of a minimally symptomatic patient with renal failure. a meta-analysis suggests a beneficial role for 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. Systolic blood pressure control is considered more important and is also considered difficult to control in elderly patients with chronic kidney disease. in nondiabetic kidney disease. Delaying or Halting Progression of Chronic Kidney Disease Treatment of the underlying condition if possible is indicated. Use angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) as tolerated.

a synthetic analog of calcitriol. iron stores should be checked. more patients in the paricalcitol group achieved a 10% reduction in proteinuria than did members of the control group (57. especially in men.[12] Encourage smoking cessation. A study by Plantinga et al found that a great number of individuals with chronic kidney disease may be unaware of their disease and thus may be at risk for further kidney injury through use of NSAIDs. London et al summarize the best evidence and the Kidney Disease Improving Global Outcomes (KDIGO) recommendations on how to manage chronic kidney disease–mineral and bone disorder.1% vs 25. and aminoglycosides is indicated. 1 mg/d.[13] Treating Pathologic Manifestations of Chronic Kidney Disease The following should be addressed:         Anemia with erythropoietin (Epogen) 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 long-term renal replacement therapy (hemodialysis. . respectively).[14] The KDIGO guidelines are issued after weighing the quality and the depth of evidence.[11] In this doubleblind. the goal is a hemoglobin level of 11-12 g/dL. Before starting erythropoietin. with placebo for 6 months. who tended to be heavier smokers than women in this cross-section. which compared paricalcitol.9%. or renal transplantation) Cardiovascular complications With erythropoietin treatment. The aim is to keep iron saturation at 30-50% and ferritin at 200-500. nonsteroidal anti-inflammatory agents (NSAIDs). suggesting that primary care physicians should be involved in communication regarding the risks of NSAID. and propose a common-sense approach to the evaluation and treatment of mineral and bone disorder in different stages of chronic kidney disease. peritoneal dialysis. Treatment of hyperlipidemia to target levels per current guidelines is indicated. as normalization of hemoglobin in patients with chronic kidney disease stages 4-5 has been associated with an increased risk of combined outcome. including IV radiocontrast. can reduce protein excretion in patients with chronic kidney disease. when available. as smokers tend to reach end-stage renal disease (ESRD) earlier than nonsmokers. cessation decreased the risk. randomized study. Avoidance of nephrotoxins. Those who knew of their chronic kidney disease were less likely to use NSAIDs.A small trial (n=61) by Fishbane et al found that paricalcitol (Zemplar). A large-population Norwegian study found that although smoking posed a great risk factor for the future onset of kidney failure.

73 m2). Experts recommend alkali therapy to maintain the serum bicarbonate concentration above 22 mEq/L.93 mL/min/1. In addition to the benefits listed above. Patients in the bicarbonate group were also less likely to experience rapid disease progression than were members of the control group (9% vs 45%). De Brito-Ashurst et al found that patients with chronic kidney disease who receive bicarbonate supplementation show a slower decline in renal function.The evidence for the benefits and risks of correcting metabolic acidosis is very limited. and only 3 small trials in dialysis patients. Indications for renal replacement therapy include the following:          Severe metabolic acidosis Hyperkalemia Pericarditis Encephalopathy Intractable volume overload Failure to thrive and malnutrition Peripheral neuropathy Intractable gastrointestinal symptoms Glomerular filtration rate (GFR) less than 10 mL/min Timely Planning for Long-Term Renal Replacement Therapy Consider the following:     Early education regarding natural disease progression. with no randomized controlled trials in patients not yet in end-stage renal disease (ESRD). if possible. and fewer patients who received bicarbonate supplementation developed ESRD (6.[15] In this study. These trials suggest that there may be some beneficial effects on both protein metabolism and bone metabolism. but the trials were underpowered to provide robust evidence.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. and preferably at least 6 months in advance of anticipated date of dialysis) Timely elective peritoneal dialysis catheter insertion Timely referral for renal transplantation .88 vs 5. patient option to refuse or discontinue chronic dialysis Timely placement of permanent vascular access (arrange for surgical creation of primary arteriovenous fistula. renal transplantation. creatinine clearance [CrCl] 15-30 mL/min/1.5% vs 33%). none in children. 134 adult patients with chronic kidney disease (ie. different dialytic modalities. nutritional parameters improved with bicarbonate supplementation.

The following dietary restrictions may also be indicated:    Phosphate restriction starting early in chronic kidney disease Potassium restriction Sodium and water restriction as needed to avoid volume overload The National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (KDOQI) has issued a Clinical Practice Guideline for Nutrition in Chronic Renal Failure. as well as a 2008 revision of recommendations for Nutrition in Children with Chronic Kidney Disease. A meta-analysis found that dietary salt reduction significantly reduced blood pressure in individuals with type 1 or type 2 diabetes. make a strong case for a reduction in salt intake as a means of slowing the progression of diabetic nephropathy. this strategy is recommended to delay the onset of uremic symptoms. The recommendation for the general population in public health guidelines is less than 5-6 g/d. Dietary salt reduction may help slow progression of kidney disease in both type 1 and type 2 diabetes. A randomized controlled trial by Slagman et al found that moderate dietary sodium reduction (approximately 2500 mg/day of Na+ or 6 g/d of NaCl) added to ACE inhibition compared with dual blockade (ACE inhibitor and angiotensin receptor blocker) was more effective in reducing both proteinuria and blood pressure in nondiabetic patients with modest chronic kidney disease. [17] Consultations and Long-Term Monitoring Consultations may include the following:      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 . along with other evidence relating salt intake to blood pressure and albuminuria in hypertensive and normotensive patients. emphasizing the beneficial effect of dietary salt reduction in the management of nondiabetic patients . Patients with chronic kidney disease who already are predisposed to becoming malnourished are at higher risk for malnutrition with overly aggressive protein restriction. Furthermore. low-sodium diet added to dual therapy yielded additional reductions in both blood pressure and proteinuria. as the patient approaches chronic kidney disease stage 5.Diet Protein restriction early in chronic kidney disease as a means to delay a decline in the GFR is controversial. however.[16] These findings. Malnutrition is a well-established predictor of increased morbidity and mortality in the ESRD population and must be avoided if possible.

with close patient follow-up. Routine consultation of the appropriate references should be undertaken when prescribing any new drug to a patient with chronic kidney disease. In addition. A multidisciplinary approach to care. View full drug information . which is excreted in feces. which occurs with increased frequency in patients receiving dialysis. Sakaguchi et al found a high incidence (65%) of OSA in patients with nondialysis chronic kidney disease. View full drug information Calcium acetate (PhosLo. It combines with dietary phosphorus to form insoluble calcium phosphate. including involvement of the nephrologist. The study also found that decreased GFR was associated with an increased risk of OSA. doses and intervals of drugs that are excreted or metabolized renally should be adjusted accordingly for the residual glomerular filtration rate (GFR). should be initiated early in the course of chronic kidney disease. and social worker. with about one third of those having moderate or severe OSA. Hyperphosphatemia is treated with dietary phosphate binders and dietary phosphate restriction. Some drugs are contraindicated in moderate-to-severe renal impairment because of potentially serious effects from drug or metabolite accumulation. Hyperparathyroidism is treated with calcitriol or vitamin D analogs. to reduce hyperphosphatemia. nurse. primary care physician.[18] Medication Summary In chronic kidney disease. a Japanese study has shown a connection between OSA and nondialysis chronic kidney disease. typically with calcium.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. Phosphate-Lowering Agents Class Summary Dietary phosphate binders promote the binding of phosphate. Patients should be monitored for obstructive sleep apnea (OSA). renal dietitian. Eliphos) This agent is used for treatment of hyperphosphatemia in chronic kidney disease. Hypocalcemia is treated with calcium supplements and possibly calcitriol.

It is marketed in a variety of dosage forms and is relatively inexpensive.25-dihydroxycholecalciferol or 1.Calcium carbonate (Caltrate. nonaluminum phosphate binder indicated for reduction of high phosphorus levels in patients with end-stage renal disease.25-dihydroxyvitamin D3). It directly binds dietary phosphorus in the upper GI tract. which is excreted in feces. View full drug information Doxercalciferol (Hectorol) Doxercalciferol is a vitamin D analog (1-alpha-hydroxyergocalciferol) that does not require activation by the kidneys. the hormonally active form of vitamin D. Calcium carbonate combines with dietary phosphate to form insoluble calcium phosphate. Vectical) Calcitriol (1. View full drug information Sevelamer (Renagel. Oystercal. Calcijex. It successfully normalizes phosphate concentrations in patients with chronic kidney disease. View full drug information Lanthanum carbonate (Fosrenol) Lanthanum carbonate is a noncalcium. thus inhibiting its . View full drug information Calcitriol (Rocaltrol. is used to suppress parathyroid production and secretion in secondary hyperparathyroidism and for treatment of hypocalcemia in chronic kidney disease by increasing intestinal calcium absorption. This agent binds dietary phosphate in the intestine. Alcalak) This agent is used for treatment of hyperphosphatemia or as a calcium supplement in chronic kidney disease. Renvela) Sevelamer is indicated for the reduction of serum phosphorus levels in patients with end-stage renal disease (ESRD). thereby inhibiting phosphorus absorption. It is indicated for the treatment of secondary hyperparathyroidism in end-stage renal disease (ESRD). Oysco.

stimulates calcium and phosphorus absorption. It induces release of reticulocytes from the bone marrow into the blood stream.absorption. It reduces parathyroid hormone levels. View full drug information Paricalcitol (Zemplar) Paricalcitol is a synthetic analog of calcitriol that is used for treatment of secondary hyperparathyroidism in ESRD. . Darbepoetin has longer a half-life than epoetin alfa. Procrit) This agent stimulates division and differentiation of committed erythroid progenitor cells. View full drug information Darbepoetin (Aranesp) Darbepoetin is an erythropoiesis-stimulating protein closely related to erythropoietin. whereas epoetin alfa contains 3 such chains. Its mechanism of action is similar to that of endogenous erythropoietin. and may be administered weekly or biweekly. sevelamer treatment results in fewer hypercalcemic episodes than calcium acetate treatment. Iron Salts Class Summary Iron salts are nutritionally essential inorganic substances used to treat anemia. Darbepoetin contains 5 N-linked oligosaccharide chains. View full drug information Epoetin alfa (Epogen. In patients on hemodialysis. a primary growth factor produced in kidney that stimulates development of erythroid progenitor cells. and stimulates bone mineralization. which interacts with stem cells to increase red cell production. Growth Factors Class Summary Growth factors are used to treat anemia of chronic kidney disease by stimulating red blood cell (RBC) production.

25 mL in children) test dose should be administered prior to starting therapy.5-mL (0. and specific enzyme systems. Fer-In-Sol. Slow FE. View full drug information Iron sucrose (Venofer) Iron sucrose is used to treat iron deficiency (in conjunction with erythropoietin) in patients receiving long-term hemodialysis. allowing transportation of oxygen via hemoglobin. . hypochromic anemia resulting from iron deficiency. Nulecit) Ferric gluconate replaces the iron found in hemoglobin. myoglobin. InFed) Iron dextran is used to treat microcytic. There is a lower incidence of anaphylaxis with iron sucrose than with other parenteral iron products. and to replenish iron stores in individuals on erythropoietin therapy. This agent is available as 50 mg iron/mL (as dextran). when oral administration is infeasible or ineffective. MyKidz Iron 10) Ferrous sulfate is used as a building block for hemoglobin synthesis in patients with anemia of chronic kidney disease who are being treated with erythropoietin. increased erythropoiesis. View full drug information Ferumoxytol (Feraheme) This agent is indicated for iron replacement in adults with chronic kidney disease who have iron deficiency anemia. A 0. Fer-iron. and insufficient absorption of iron from the GI tract. View full drug information Ferric gluconate (Ferrlecit.View full drug information Ferrous sulfate (Feosol. Iron deficiency in these patients is caused by blood loss during the dialysis procedure. View full drug information Iron dextran (DexFerrum.

It is indicated for secondary hyperparathyroidism in patients with chronic kidney disease on dialysis. called nephrons. 0. in early renal disease. MD. Chief Editor: Vecihi Batuman. Azotemia  Author: Moro O Salifu. It also results in a concomitant decrease in serum calcium. View full drug information Cinacalcet (Sensipar) Cinalcet directly lowers intact parathyroid hormone (iPTH) levels by increasing the sensitivity to extracellular calcium of calcium-sensing receptors on chief cells of the parathyroid gland. MPH. Urine formation ensures that the body eliminates the . FASN Background Azotemia is an elevation of blood urea nitrogen (BUN) (reference range. As shown in this figure. MD.Calcimimetic Agents Class Summary These agents reduce parathyroid hormone levels. FACP. substantial decline in GFR may lead to only a slight elevation in serum creatinine.7-1. Elevation in serum creatinine is apparent only when the GFR falls to about 70 mL/min. The graph shows the relationship of the glomerular filtration rate (GFR) to steady-state serum creatinine and blood urea nitrogen (BUN) levels. FACP. as depicted in the following graph. Each human kidney contains approximately 1 million functional units.4 mg/dL) levels. which are primarily involved in urine formation. 8-20 mg/dL) and serum creatinine (normal value.

as shown below. An inverse relationship between serum creatinine and GFR exists. a bedside formula (Cockroft and Gault) using the patient's serum creatinine. as follows: CrCl (mL/min) = (140 age) X weight (kg) / (72 X serum creatinine) in mg/dL (X 0. resulting in azotemia. . This is due to compensatory hypertrophy and hyperfiltration of the remaining healthy nephrons. CrCl (mL/min) = creatinine [g/d]/serum creatinine [mg/dL]) X 70. and the rest (2 L/d) is excreted. Urine formation by each nephron involves 3 main processes. Because creatinine normally is filtered as well as secreted into the renal tubules. products of metabolic activities and excess water in an attempt to maintain a constant internal environment (homeostasis). and V is the 24-hour volume/1440 (number of min in 24 h). age. and lean weight (in kg) can be used to estimate the GFR. Using the 24-hour creatinine in grams and the serum creatinine in milligrams. P is the serum creatinine in mg/dL. An elevation in serum creatinine is apparent only when the GFR falls to about 60-70 mL/min. especially as kidney failure progresses because of maximal tubular excretion. Second. the adequacy of the collection must be established prior to calculation of the creatinine clearance. as follows: filtration at the glomerular level. and secretion by the cells of the tubules into this filtrate. When 24-hour creatinine is measured. About 99% (178 L/d) is reabsorbed. substantial renal damage can take place before any decrease in GFR occurs. The quantity of glomerular filtrate produced each minute by all nephrons in both kidneys is referred to as the glomerular filtration rate (GFR). However. The CrCl is best calculated by obtaining a 24-hour collection for creatinine and volume and then using the following formula: CrCl (mL/min) = U/P X V where U is the 24-hour creatinine in mg/dL. selective reabsorption from the filtrate passing along the renal tubules. substantial decline in GFR may lead to only slight elevation in serum creatinine. Average GFR is about 125 mL/min (10% less for women) or 180 L/d. because it is expensive and not widely available.85 for women). such as iothalamate. and disease process usually can be monitored by the estimated GFR (eGFR) using different methods. precise knowledge of the GFR is not required. More accurate determinations of GFR require the use of inulin clearance or a radiolabeled compound. Measuring renal function Radionuclide assessment of GFR is the criterion standard for measuring kidney function. First. An adequate 24-hour collection usually reflects a creatinine generation of 15-20 mg/kg in women and 20-25 mg/kg in men. as seen in the image above. Perturbation of any of these processes impairs the kidney's excretory function. serum creatinine concentration and creatinine clearance (CrCl) more commonly are used to estimate GFR. the CrCl may cause the GFR to be substantially overestimated. In practice. the serum creatinine and CrCl are not sensitive measures of kidney damage for 2 reasons. Alternatively.

it is called nonoliguric ARF. renal-renal azotemia. creatinine. However. it is called oliguric ARF. resulting in renal afferent arteriolar vasoconstriction and renin secretion through β 1 -receptors. and acute kidney injury (AKI). and bicarbonate. Constriction of the afferent arterioles causes a decrease in the intraglomerular pressure. stimulates aldosterone release. Prerenal azotemia Prerenal azotemia refers to elevation in BUN and creatinine levels because of problems in the systemic circulation that decrease flow to the kidneys. refers to elevation in BUN and creatinine levels because of problems in the kidney itself. Pathophysiology There are 3 pathophysiologic states in azotemia. This leads to sympathetic nerve activation. including a rise in serum creatinine levels of about 30% from baseline or a sudden decline in output below 500 mL/d. or the Levey formula. When volume or pressure is decreased. software for estimating GFR by the MDRD formula is available for most pocket digital assistants (PDA) and can be found on the Internet. Because serum creatinine levels alone cannot detect earlier stages of chronic kidney disease (CKD). calcium. The net result of these 4 mechanisms of salt and water retention is decreased output and decreased urinary excretion of sodium (< 20 mEq/L). This formula is known as the MDRD formula. which exerts its effect in the medullary collecting duct for water reabsorption. as well as BUN. a condition called anuria (< 100 mL/d). the baroreceptor reflexes located in the aortic arch and carotid sinuses are activated. Any form of ARF may be so severe to virtually stop formation. Intrarenal azotemia Intrarenal azotemia. There are several definitions. reducing GFR proportionally. also known as acute renal failure (ARF). the MDRD formula also takes into account the patient's age and race. In prerenal azotemia. Although more accurate. uric acid.[1] It has therefore been argued that the formula should be applied with caution. Renin converts angiotensin I to angiotensin II. decrease in renal flow stimulates salt and water retention to restore volume and pressure. If output falls below 500 mL/d. and postrenal azotemia. in turn. intrarenal azotemia. Increased aldosterone levels results in salt and water absorption in the distal collecting tubule. . as follows: prerenal azotemia.Another formula was derived from data collected in a large study called the Modification of Diet in Renal Disease (MDRD). such as healthy individuals and patients who are anorectic or obese. Delanaye et al have argued that the MDRD formula is not applicable to all persons. It is now widely accepted as more accurate than the Cockroft and Gault formula and is an alternative to radioisotope clearance. A decrease in volume or pressure is a nonosmotic stimulus for antidiuretic hormone production in the hypothalamus. Through unknown mechanisms. it is much more difficult to calculate manually. which. If output is preserved. activation of the sympathetic nervous system leads to enhanced proximal tubular reabsorption of salt and water.

Acute interstitial nephritis is characterized by inflammation and edema. the urinary sediment is active with white or red cell casts. water. hematuria. white cells. and azotemia. Some studies indicate that nonoliguric forms of ARF are associated with less morbidity and mortality than oliguric ARF. The pathophysiology of acute oliguric or nonoliguric ARF depends on the anatomical location of the injury. Patients may still make 1440 mL/d of urine even when the GFR falls to about 1 mL/min because of decreased tubular reabsorption. red cells. low urinary excretion of sodium. or cisplatin nephrotoxicity. edema formation. potent diuretic agents. in the presence of a superimposed prerenal azotemia. scleroderma renal crisis. which has . low specific gravity (< 1. white cell casts with variable eosinophiluria. granular and cellular casts. epithelial damage leads to functional decline in the ability of the tubules to reabsorb salt. Tubular damage is less severe than in oliguric ARF. the tubular lumen is filled with epithelial casts. but increased salt and water retention in glomerulonephritis can lead to hypertension. Nephrotic syndrome usually is not associated with active inflammation and often presents as proteinuria greater than 3. and a variable degree of proteinuria. Some patients with nephrotic syndrome may present with ARF. Acute vascular diseases include vasculitis syndromes. hyperlipidemia. In nephrotic syndrome. Uncontrolled studies also suggest that volume expansion. In nephritic syndrome. all of which cause renal hypoperfusion and ischemia leading to azotemia.015). In ATN. osmolality. Glomerulonephritis or vasculitis is suggested by the presence of hematuria. and hyaline casts. and sodium may be misleading. granular casts. but their presence may indicate advanced disease. resulting in the decline of GFR. lithium toxicity. and other electrolytes. Excretion of acid and potassium also is impaired. Azotemia and hypertension are uncommon initially. the urinary sediment is inactive. the specific gravity. causing intraluminal obstruction. Glomerular diseases may reduce GFR due to changes in basement membrane permeability and because of stimulation of the renin-aldosterone axis.5 g/d). high urinary sodium (>40 mEq/L). Normal output in nonoliguric ARF does not reflect normal GFR. Proteinuria is less obvious. Glomerular diseases often manifest as nephrotic or nephric syndrome. hypoalbuminemia. with low osmolality (usually < 500 mOsm/L). and renal vasodilators can convert oliguric to nonoliguric ARF if administered early. sterile pyuria.The most common causes of nonoliguric ARF are acute tubular necrosis (ATN). aminoglycoside nephrotoxicity. and there is gross proteinuria (>3. However. Chronic vascular diseases are due to hypertensive benign nephrosclerosis. The net effect is a loss of urinary concentrating ability. and occasionally. decreased output.5 g/24 h. and edema. In more severe ATN. malignant hypertension. resulting in azotemia. Impairment of capillary circulation in the kidney due to edema (nephrosarca) and tubular obstruction from protein casts have been proposed as potential mechanisms for the development of ARF in patients with nephrotic syndrome. proteinuria. and thromboembolic disease. and increased specific gravity. hyperkalemia and renal tubular acidosis.

. Hydronephrosis may be absent if obstruction is mild or acute or if the collecting system is encased by retroperitoneal tumor or fibrosis. and hyperkalemia. converting enzyme inhibitors and receptor blockers are contraindicated in bilateral renal artery stenosis. salt. With relief of complete ureteral obstruction within 48 hours of onset. which leads to increased bleeding tendencies. and water excretion (causing acidosis. reduction in acid. hyperphosphatemia. phenols. maintenance of adequate intraglomerular pressure for filtration greatly depends on efferent arteriolar vasoconstriction. community-acquired ARF occurred in about 1% of all hospital admissions. hyperkalemia. secondary hyperparathyroidism. Epidemiology Frequency United States Considerable variability exists in reports about the incidence of hospital or community-acquired ARF. thereby decreasing intraglomerular pressure and filtration. guanidines) have been identified. urea. In one report. creatinine. and renal osteodystrophy).not been conclusively associated with end-stage renal disease and ischemic renal disease from bilateral renal artery stenosis. and platelet dysfunction. while little or no further recovery occurs after 12 weeks. there is evidence that relatively complete recovery of GFR can be achieved within a week. Therefore. hypertension. a substantial reduction in GFR in CKD results in decreased production of erythropoietin (causing anemia) and vitamin D-3 (causing hypocalcemia. potassium. Postrenal azotemia Postrenal azotemia refers to elevation in BUN and creatinine levels because of obstruction in the collecting system. Obstruction to flow leads to a reversal of Starling forces responsible for glomerular filtration. Some of the uremic toxins (ie. Progressive bilateral obstruction causes hydronephrosis with an increase in the Bowman capsular hydrostatic pressure and tubular blockage resulting in progressive decline and ultimate cessation in glomerular filtration. and edema). The syndrome associated with the signs and symptoms of accumulation of toxic waste products (uremic toxins) is termed uremia and often occurs at a GFR of about 10 mL/min. Complete or prolonged partial obstruction can lead to tubular atrophy and irreversible renal fibrosis. In addition to accumulation of urea creatinine and other waste products. azotemia. acidosis. Azotemia sets in when angiotensinconverting enzyme (ACE) inhibitors or angiotensin type 2 receptor blockers cause efferent arteriolar dilatation. Unilateral obstruction rarely causes azotemia.[2] In bilateral renal artery stenosis. fluid overload. but none has been found responsible for all the manifestations of uremia.

prerenal (21%). the mortality in the patient in the intensive care unit on mechanical ventilation is as high as 80%. large-vessel arterial occlusive disease) tend to have progressive azotemia resulting in end-stage renal disease.Overall. About 50% of patients with polycystic kidney disease progress to end-stage renal disease by the fifth or sixth decade of life. differences exist in ARF occurring in the intensive care unit (about 15%) and in the coronary care unit (about 4%).000 patients with end-stage renal disease were receiving dialysis or a kidney transplant in the United States. glomerulonephritis (15%).0% and female frequency is 44. Patients with diabetic kidney disease. American Indian (1. whereas others have rapid progression to end-stage renal disease within months. Different types of glomerulonephritis have major differences in prognosis. urinary tract obstruction (10%).0%). uncertain (5%). International A report from Madrid evaluated 748 cases of ARF at 13 tertiary hospital centers. Race In the 2008 annual report of the United States Renal Data System (USRDS).0%).0%. Etiologies of CKD differ around the world. cystic kidney disease (4%).6%). hypertensive nephrosclerosis. . However. Diabetic nephropathy as a cause of CKD is on the rise in developed and developing countries. and atheroemboli (1%). more than 500. While mortality rate in simple ARF without other underlying disease is 7-23%. and other/unknown (0. mostly due to ATN and prerenal disease (13%). hypertension (24%).3%). In CKD. and all other known miscellaneous renal disorders (15%). with some being quite benign and rarely progressing to end-stage renal disease. Racial distribution was reported as Asian/Pacific Islander (4. ARF occurs in about 5% of all hospital admissions. acute interstitial nephritis (2%). glomerulonephritis or vasculitis (4%). male frequency is 56. progressive azotemia leading to end-stage renal disease requiring dialysis or kidney transplantation occurs in a number of chronic diseases with frequencies for diabetes (36%). white (61. The prognosis of patients with CKD depends on the etiology of the failure.7%). The most frequent causes were ATN (45%). Mortality/Morbidity   Prognosis in ARF generally is poor and depends on the severity of the underlying disease and the number of failed organs. black (32. and ischemic nephropathy (ie. acute or chronic renal failure. Sex Of the patients reported in the 2008 annual report of the USRDS.

and edema o Personal or family history of congenital or systemic diseases. The presence of uremic pericarditis requires immediate dialysis. and older than 75 years. diastolic BP drop of >10 mm Hg or more from the supine to standing position).    Prerenal azotemia: Look for tachycardia. Intrarenal azotemia: Look for hypertension and its end organ effects. NSAIDs. hepatitis C (HCV). hesitancy. chemical exposure.6%. joint swelling or tenderness. diabetes. vomiting. hypertension. proteinuria. or postrenal causes. History It is necessary to quickly establish if azotemia is acute or chronic and whether it is due to prerenal.    Prerenal azotemia: History of diarrhea.0%. signs of dehydration. urinalysis. hearing abnormality.7%. 44. abdominal bruits. physical examination. caused by lithium intoxication. especially diabetes. . polyuria. orthostatic hypotension (systolic BP drop of >20 mm Hg. and benign prostatic hypertrophy Physical Physical examination should be detailed but focused on signs of high diagnostic yield. if indicated. pelvic malignancy or irradiation. dysuria. and AIDS o Detailed medication history (looking for nephrotoxic medications. hepatitis B (HBV). multiple myeloma. and polyuria (eg. pericardial rub. and HCV infections) Postrenal azotemia: Renal colic. Clinical evaluation requires a thorough history. such as hypertensive retinopathy and left ventricular hypertrophy (apical impulse displaced lateral to midclavicular line). frequencies for patients aged 019 years is 1. palpable kidneys. syphilis. and herbal remedies). and. excessive sweat loss. intrarenal. rash. and specific laboratory tests. concurrent illness that impairs patient's ability to eat and drink adequately. hypotension. frequency. and signs of congestive heart failure or hepatic insufficiency. loss of skin turgor. The latter 2 signs are suggestive of uremia. This is vital in initiating treatment and in preventing progression. aged 20-44 years. especially antibiotics. diuretics. congestive heart failure. aged 65-74 years. Postrenal azotemia: A palpable bladder that is dull to percussion and a rectal or pelvic mass on digital examination is suggestive of postrenal azotemia (obstruction). shock. including dry mucous membranes. Tests include serologies. and intravenous drug abuse (exposure to HIV. radiologic studies and kidney biopsy. and asterixis. needle tracks. aged 45-64 years.1%. ACE inhibitors. 19. diabetes insipidus) Intrarenal azotemia o History of nocturia. HBV.5%. diuretics. profound heat exhaustion. and loss of axillary sweat. urgency incontinence.Age Of the patients reported in the 2008 annual report of the USRDS. liver disease. 15. other collagen vascular diseases. 19. hemorrhage. systemic lupus erythematosus.

Interstitial Obstructed Megaureter Uremia Laboratory Studies Obtain CBC count. acute nonoliguric. decreased effective arterial volume from sepsis or hepatorenal syndrome. decreased systemic vascular resistance. o It may be superimposed on a background of chronic renal failure. intrarenal. retroperitoneal fibrosis. Intrarenal azotemia o Intrarenal azotemia occurs as a result of injury to the glomeruli. proteinuria. and postrenal. Acute Glomerulonephritis. clues for the origin of azotemia may emerge from these tests. decreased cardiac output (congestive heart failure). tubules. should be ruled out. urinalysis. In addition to establishing the presence of systemic disease. Diagnostic indices commonly used to differentiate prerenal from intrarenal or postrenal azotemia are summarized in the image below. o It is observed in bilateral ureteral obstruction from tumors or stones. nocturia. biochemical profile. such as excessive diuresis and treatment with ACE inhibitors. or small vessels. and renal artery abnormalities.    Prerenal azotemia o Prerenal azotemia occurs as a result of impaired renal blood flow or decreased perfusion resulting from decreased blood volume. Differentials        Acute Tubular Necrosis Chronic Renal Failure Glomerulonephritis. o The presence of systemic disease. . loss of urinary concentrating ability (low urine specific gravity). o Iatrogenic causes of prerenal azotemia. Chronic Nephritis. anemia. and hypocalcemia are suggestive of chronic intrarenal azotemia. Postrenal azotemia o Postrenal azotemia occurs when an obstruction to urine flow is present. o It may be acute oliguric. or chronic. and bladder neck obstruction from prostatic hypertrophy or carcinoma and posterior urethral valves. interstitium. and urine electrolytes for the initial evaluation.Causes Causes are broadly classified as prerenal. o It may be superimposed on a background of chronic renal failure. neurogenic bladder.

albumin). total protein. poor nutritional state (BUN. and hematocrit levels from their baselines. o When volume depletion is predominant. patients exhibit edema. When hypoperfusion due to decreased cardiac output or effective arterial volume is present. anuria (< 100 mL/d). hypernatremia. total protein. hemoconcentration results in elevation of hematocrit. normal urinary sediment. liver disease (BUN. . it is not necessary to perform all these tests on a particular patient. while hemoconcentration results in the elevation of total protein. FEUrea and FELi appear to be better in assessing prerenal status in patients on diuretics. elevated levels of calcium. and bicarbonate. such as in anemia (hematocrit). It should be noted that use of some of these indices may be limited in certain clinical conditions. exaggerated proximal tubular reabsorption results in azotemia. decreased mucle mass (serum creatinine). high urine specific gravity (>1. Comparison should always be made with the patients baseline values to identify trends consistent with increase or decrease in effective circulating volume.0%) are seen. and low urinary sodium (< 20 fractional excretion of sodium [FENa] < 1.  Prerenal azotemia o In prerenal azotemia. calcium.Diagnostic Images in Azotemia: Although these indices are helpful. and uric acid from their baselines. albumin. uric acid. o Oliguria (urine volume is < 500 mL/d). total protein/albumin. albumin) and use of diuretics (urine Na).015). bicarbonate. hypocalcemia (serum calcium).

Urine output still may be present if overflow (in bladder outlet obstruction) or partial ureteral obstruction is present. Since the FENa is based on the fact that sodium reabsorption is enhanced in the setting of volume depletion.015). perfusion pressure flow studies). papillary necrosis. a renal sonogram usually shows small. and bicarbonate levels vary widely in this category. a renal biopsy should be considered. o For patients with long-standing CKD. they may exhibit an increase in size or pressure of the collecting system or experience pain. such as HIV nephropathy. When patients are subjected to maneuvers that increase urinary flow (eg. The prima facie finding here is anuria and. Renal sonogram is the test of choice to rule out obstructive uropathy. An FENa below 1% is suggestive of a prerenal cause (eg. FENa (>5%). because urea and uric acid excretion are not influenced by diuretics. and renal amyloidosis. active use of diuretics may elevate the FENa even when volume depletion is present. retroperitoneal process. high urinary sodium (>40 mEq/L). may be clues to postrenal azotemia. diabetes. while an FENa above 2% is suggestive of ATN. hypocalcemia. The hematocrit.  hyponatremia.[3] Intrarenal azotemia o Anemia. or hematoma). The renal sonogram usually is diagnostic for patients with polycystic kidney disease. active urinary sediment (see Pathophysiology). hypertension. o A Foley catheter should be inserted as part of the initial evaluation to rule out obstruction below the bladder outlet. uric acid. thrombocytopenia. o In addition to azotemia. a Lasix washout scan. . producing hydronephrosis. volume depletion). should be performed. and hypoalbuminemia. while an FEUrea of more than 50% or an FEUA above 25% suggests ATN. hypercalcemia from metastatic pelvic tumor. Consultation with a nephrologist is imperative in all such patients. o The FENa has traditionally been used to differentiate prerenal azotemia from ATN. plasma BUN–creatinine ratio (< 20). polyuria due to loss of concentrating ability and type 1 renal tubular acidosis. progressive azotemia. These patients often are critically ill. o Bilateral partial obstruction may be associated with azotemia in the presence of normal urine output. diuretic renogram. occasionally. In patients with active urinary sediment. proteinuria. and low urine osmolality may suggest intrarenal azotemia. Postrenal azotemia o Urinary indices in postrenal azotemia due to complete bilateral obstruction are usually nondiagnostic. If renal sonogram is equivocal. or the fractional excretion of uric acid (FEUA). producing renal colic. it occurs acutely (due to obstruction from calculi. Some causes of CKD can be associated with normal or large-sized kidneys. and high anion gap metabolic acidosis may suggest intrarenal azotemia. o Low urine specific gravity (< 1. and/or normal-sized kidneys on sonogram. with hyperkalemia. The fractional excretion of urea or fractional excretion of urea nitrogen (FEUrea). Hydronephrosis in the absence of hydroureter may be seen in early (< 3 d) obstruction. and elevated prostate-specific antigen (PSA). or partial obstruction. An FEUrea of less than 35% or an FEUA of less than 25% is suggestive of a prerenal etiology of ARF. contracted kidneys. calcium. are the alternatives. as discussed below in Imaging Studies. Unilateral ureteral obstruction rarely leads to azotemia. or may be chronic and asymptomatic.

renal infarction. particularly in younger patients. but radiolucent ones. a plain film of the abdomen is performed to screen for presence of a radiopaque stone. Renal sonogram is the most commonly used renal imaging study because of its ease of use and broad application for the following: o Renal sonogram can determine renal size. o It is the preferred technique in the evaluation and diagnosis of certain structural disorders. o It can provide data on the degree of obstruction. Doppler renal ultrasonography can be used to evaluate renal vascular flow (eg. o They are used in the evaluation of renal cell carcinoma and renal artery stenosis or vasculitis. Magnetic resonance imaging (MRI) or magnetic resonance angiography (MRA) o MRI or MRA is used only when CT scanning and ultrasonography are nondiagnostic. . especially when the diagnosis is uncertain. o Intravenous pyelogram can provide detailed information concerning calyceal anatomy and the size and shape of the kidney. Small kidneys (< 9 cm) may be suggestive of scarring from advanced renal disease. whereas normal or large kidneys with smooth contours may indicate a potentially reversible process. o It can be used to evaluate and stage renal cell carcinoma and to diagnose renal vein thrombosis. such as chronic pyelonephritis. which is important when considering renal biopsy. o It is a test of choice for diagnosing urinary tract obstruction. Renal arteriography o The availability of procedures not requiring contrast material (ie. will be missed. and papillary necrosis. o Renal sonogram can detect kidney stones. It can diagnose polycystic kidney disease with higher sensitivity than ultrasonography. struvite. Computed tomography (CT) scanning[4] is complementary to ultrasonography. renal vein thrombosis. o It is extremely useful for detecting renal stones. o It can differentiate cystic lesions from solid lesions. o They are the criterion standard for diagnosis of renal vein thrombosis. such as uric acid stones. MRA) and the risk of contracting contrast nephrotoxicity have reduced use of this test. o Renal arteriography is used in polyarteritis nodosa and renal artery stenosis to demonstrate multiple aneurysms and/or stenoses. CT scanning does the following: o It can be used to distinguish (in most cases) neoplastic lesions from simple cyst and is the criterion standard for radiologic diagnosis of renal stone disease. MRI. o Calcium-containing. sonography. and cystine stones can be identified. renal artery stenosis).Imaging Studies        Plain film of abdomen o If symptoms suggest nephrolithiasis. including radiolucent stones. Intravenous pyelogram o The risk of contrast nephrotoxicity should be weighed against the benefits of making a diagnosis that will not change management. Contrast nephrotoxicity should be weighed against the benefits. medullary sponge kidney.

in the presence of obstruction. of greater than 20 minutes is considered obstruction. o The half life or clearance of the radioisotope is plotted on a curve. if needed. and. Lasix is used as a part of the renogram to separate nonobstructive hydronephrosis from obstructive hydronephrosis. In patients with a megaureter. Then.    Renal venography o Risk of contrast nephrotoxicity is present. Because it is heavily filtered. and excretion. as the Lasix should be administered when it is thought that the renal pelvis is full. To overcome the problem of poor renal function or relative hypovolemia if a patient has been fasting. flow induced by Lasix and containing little or no radionuclide will fill the collecting system. o The test also is operator dependent. in patients with renal disease. o It may be used in patients with a high index of suspicion for hydronephrosis for whom sonogram results are normal. A full bladder also delays washout of isotope. For the same reason. to assess the 3 aspects of function. Therefore. o Conditions that can make it difficult to interpret the Lasix washout curve include a megaureter or pelvis that accepts a large bolus of urine and poor renal function. . it is also used concomitantly with Lasix washout scan (see below) for assessing functional obstruction of the collecting system. and excretion). 99m o Technetium diethylenetriamine pentaacetic acid ( Tc DTPA) is heavily filtered at first pass and therefore is best for qualitative assessment of renal function (filtration. If there is no obstruction. it is most sensitive in detecting urine leaks after renal transplant. the radionuclide is not washed out as quickly. o Mercaptoacetyltriglycine (MAG3) scan is evenly distributed at first pass in the kidney and so is best for qualitative assessment of perfusion. to detect vesicoureteral reflux. o Renal venography is the criterion standard for diagnosis of renal vein thrombosis. It is the preferred test after renal transplantation. washing out urine that contains radionuclide from the system. and of between 10-20 minutes is subject to further interpretation. the patient's bladder needs to be catheterized before the study can be performed. the Lasix washout is performed after the radionuclide has accumulated in the collecting system. Retrograde or anterograde pyelography o This test has limited use because of the availability of sonography. filtration. such as in retroperitoneal fibrosis. A half life of less than 10 minutes is considered normal. the renal scan is performed first. it can be difficult to determine when the renal pelvis is full. It can be used to detect urine leaks or functional obstruction with Lasix. although99m Tc DTPA scan remains the test of choice for these conditions. Radionuclide studies 99m o Technetium dimercaptosuccinic acid ( Tc DMSA) distributes heavily within the renal parenchyma at first pass and so is best for detecting renal parenchymal scarring. Voiding cystourethrogram can be performed with a radionuclide study. Lasix onset of action may be prolonged. o Usually. However. the patient should be well hydrated with IV fluids prior to the study. Lasix washout scan 99m o The 2 agents used in performing Lasix washout renal scans are Tc DTPA and MAG3.

multiple bilateral cysts or renal tumor.1-0. hydronephrosis. occasionally. Medical Care  Prerenal azotemia o If volume depletion is due to free water loss. and fluid replacement should be adjusted to avoid a precipitous decline. active renal or perirenal infection. NSAIDs should be stopped at least 1 week prior to a scheduled elective biopsy. partial thromboplastin time. otherwise. small kidneys. Percutaneous renal biopsy contraindications o Contraindications include uncorrectable bleeding diathesis. a transvenous transjugular renal core biopsy can be performed.7 mEq/h (17 mEq/24 h) to avoid brain edema. interstitial nephritis are suspected to establish correct diagnosis and to guide therapy. The rate of decrease in serum sodium should be no more than 0. free water can be administered via a nasogastric tube. Serum sodium should be measured every 6-8 hours. prothrombin time.3% of patients. When percutaneous biopsy is contraindicated but a diagnosis is necessary.[5] With this approach. vasculitis.5 X weight in kg). Patients on Coumadin should be started on heparin at least 3 days prior to renal biopsy. o Bleeding requiring transfusion occurs in about 0. such as 0. o Percutaneous biopsy may be performed in selected patients with a solitary kidney because of the generally low risk of bleeding. Bleeding complications can be minimized by data obtained from tests for bleeding time. Patients on heparin for other reasons should be stopped for at least 1 day. the serum sodium is often greater than 10 mEq/L. The amount of fluid replacement in liters (free water deficit) can be estimated from serum sodium (patients Na-140/140 X 0. The following are common indications for renal biopsy: o Isolated glomerular proteinuria or hematuria o Nephrotic syndrome o Acute nephritic syndrome o Unexplained acute or subacute renal failure Percutaneous renal biopsy complications o Severe bleeding causing hypotension occurs in 1-2% of patients. Volume depletion due to blood loss requires IV saline and transfusion to maintain pressure (as well as interventions to halt further loss). and.5% NaCl or D5W. Alert patients should be encouraged to drink free water as much as tolerated. Open renal biopsy may be performed if a percutaneous attempt either is unsuccessful or contraindicated and if the benefits of diagnosis outweigh the risks. severe hypertension. and platelet count.Procedures      Renal biopsy is indicated when glomerulonephritis. thereby reducing the risk of hematoma. bleeding occurs intravascularly. . and uncooperative patient. The free water deficit should be administered intravenously over 2-8 hours and should consist of hypotonic solutions.

when indicated. decreased salt and water retention. These patients often pose a management problem because of severe edema. Postischemic polyuria can be seen in the recovery phase and represents an attempt to excrete excess water and solute. the diagnosis of ischemic nephropathy or atheroembolic disease should be entertained when renal function continues to worsen despite optimization of cardiac function. Diarrhea often causes isotonic volume loss requiring replacement with normal saline. The treatment of choice is normal saline infusion and correction of hypokalemia. however. o Decreased effective arterial volume due to systemic shunting can result from sepsis or liver failure (hepatorenal syndrome [HRS]). shift the Starling forces toward formation of interstitial fluid. Although this approach is widely used. an ACE inhibitor. the combination of nitrates and hydralazine offers an alternative. o Diuretic induced volume depletion. Saline may be replaced (75% of output) as maintenance fluid because of salt wasting during this o . especially in the elderly. The administration of albumin in this setting is not for volume expansion. Decreased oncotic pressure and increased vascular permeability. renal function is advanced. Normal anion gap metabolic acidosis occurring with diarrhea requires bicarbonate in 0. If oliguria persists.5% normal saline infusion. albumin in combination with high-dose furosemide should be tried. the average survival is 1-2 weeks. hyponatremia. there is evidence that the kidneys will recover with early liver transplantation. Occasionally. The renal failure phase usually lasts 7-21 days if the primary insult can be corrected. Adequate nutrition and effective treatment of sepsis may improve oncotic pressure and normalize vascular permeability. o For the severely hypoalbuminemic patient. but there is no conclusive evidence of benefit. thereby decreasing the systemic shunting.  Other approaches that have no conclusive benefit include renal dose dopamine and synthetic atrial natriuretic peptide. Effective treatment of sepsis with the appropriate antibiotics and hypotension with dopamine and norepinephrine is mandated. and hypoalbuminemia. improved output. as well as exaggerated salt and water retention. thereby allowing more Lasix to enter the tubule than would otherwise enter it. hyponatremia. Intrarenal azotemia o Acute renal failure (acute kidney injury)  Ischemic or nephrotoxic ATN  The initial approach is to restore pressure (with fluid replacement) and to withdraw nephrotoxic drugs. Crystalloid replacement can be tried. and. positive inotropic agents (including dobutamine). but it often leads to more edema. manifests as dehydration. o Decreased cardiac output requires optimizing cardiac performance by careful use of diuretics. specific therapy for the cause of impaired cardiac function. there is no supporting evidence for it. requiring replacement therapy. The net result is improved renal perfusion. and edema. As these patients tend to have risk factors for macrovascular disease.[6] and. The use of albumin in this context allows more Lasix to be bound to albumin for delivery to the organic anion transporter in the kidney. In the HRS. salt-poor albumin infusion can be undertaken. When ACE inhibitors are contraindicated because of hyperkalemia. hypokalemia. nitrates. occasionally. beta-blockers.

but renal function may be severely impaired. phase. o Chronic kidney disease  It is important that patients with CKD be referred early to a nephrologist for the management of complications and for the transition to renal replacement therapy (ie.  Anemia. a trial of oral prednisone (starting at 1 mg/kg/d and tapering over 6 wk) or intravenous pulse methylprednisolone (1 g for 3 d) in severe cases can be considered. Surgical Care  Unilateral or bilateral percutaneous nephrostomy o If hydronephrosis is due to ureteral obstruction. therapy should be started. 8. hypertension. The creatinine level begins to improve within 3-5 days. and hypocalcemia should be aggressively managed prior to renal replacement therapy. A postvoid residual volume of 100 mL or more is suggestive of obstructive uropathy. matching the hourly output with intravenous replacement is not recommended. It is best prevented with adequate hydration with half-normal saline at 1 mL/kg/h 12 hours prior to administration of contrast and the use of smaller amounts of contrast. If the patient is a poor candidate for biopsy but the diagnosis is strongly suspected. unilateral or bilateral stents or percutaneous nephrostomy is performed. requiring dialysis until such time that partial recovery is adequate for withdrawal of dialysis. The benefits of N -acetylcysteine and sodium bicarbonate are still being debated. Clearly explain the risks of such procedures to the patient.  Disease progression can be slowed by various maneuvers. . Hypokalemia may result from the saline diuresis. avoidance of further nephrotoxic exposure. hemodialysis. and the cause should be further investigated. hyperphosphatemia. o In anuria. catheterization should be done after the patient has voided to determine the postvoid residual volume. bladder catheterization is mandatory to rule out bladder neck obstruction. whereas in progressive azotemia. However. 9] Until further evidence is derived from clinical trials.  Acute interstitial nephritis: Management is by withdrawal of the offending nephrotoxin. There is some evidence that early referral of patients with CKD improves short-term outcome. Recovery is marked by the return of BUN and creatinine levels to near baseline values.[7. Recovery of renal function takes 7-10 days. there are no contraindications for using these agents to help prevent contrast-induced nephropathy. acidosis. Postrenal azotemia o Relief of the obstruction is the mainstay of therapy. and dietary protein and phosphate restriction. as well as specific therapies for some of the glomerular diseases. Once the diagnosis is confirmed. such as aggressive control of diabetes. Renal biopsy may be indicated if renal failure is severe or azotemia is not improving. peritoneal dialysis. and dehydration. renal transplantation). such as lupus.  Radiocontrast-induced azotemia: This becomes evident 3-5 days after exposure. and proteinuria.

Because of salt wasting during this phase. two thirds of the urine output should be replaced with half-normal saline and potassium chloride if hypokalemic. potassium. Matching the hourly urine output with intravenous fluids is not recommended since excess water retention during the period of obstruction cannot be lost if hourly urine output is matched.o o o Up to 500-1000 mL/min of postobstructive polyuria can be seen with relief of obstruction. Inhibits sodium chloride reabsorption in the thick ascending limb of the loop of Henle. which is appropriate and represents an attempt to excrete the excess fluid during the period of obstruction. treat edema and hypertension. . Zaroxolyn) Adjunct to furosemide in severe edematous states or when furosemide alone does not achieve adequate diuresis. Specific therapy for various systemic conditions affecting the kidney is discussed in other articles. Increases excretion of sodium. Metolazone may be more effective in impaired renal function. water.[10] Diuretics Class Summary To induce urine output in ATN. View full drug information Metolazone (Mykrox. and hydrogen ions by inhibiting reabsorption of sodium in distal tubules. Thus. Close monitoring is indicated to prevent hypotension and prerenal azotemia. dehydration and hypokalemia are likely. View full drug information Furosemide (Lasix) Drug of choice as a diuretic. These drugs increase urine excretion by inhibiting sodium and chloride reabsorption at different sites in the nephron. Medication Summary The goals of therapy are to increase renal perfusion and to maintain urine output.

thereby reducing inflammation. View full drug information Prednisone (Sterapred) Used commonly for many forms of glomerulonephritis and interstitial nephritis . Enhance delivery of furosemide to distal tubule.Adrenergic agents Class Summary These agents stimulate vasodilation of the renal vasculature and enhance perfusion. Suppresses humoral and cellular response to tissue injury. Not used for nutritional supplementation. Albutein) Supplied as a 5% solution in 250 mL or 25% in 50 mL. Plasma volume expanders Class Summary Increase plasma oncotic pressure and mobilize fluid from the interstitial space into the intravascular space in hypoalbuminemic patients. View full drug information Dopamine (Intropin) Above a critical dose (renal dose). Renal dose dopamine is used widely. Preference is based on whether patient requires additional fluid replacement. thus. this drug becomes a potent vasoconstrictor. View full drug information Albumin (Albuminar. attempts should be made to improve patient's nutrition. Albumisol. Corticosteroids Class Summary Potent anti-inflammatory agent and immunosuppressant. but benefit has not been established clearly. Albunex.

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