eMedicine Specialties > Emergency Medicine > Genitourinary

Renal Failure, Acute: Differential Diagnoses & Workup

Author: Peter R Peacock Jr, MD, Director of Information and Systems, Department of Emergency Medicine, Kings County Hospital; Informatics Director, EM Physicians of Brooklyn
Coauthor(s): Richard H Sinert, DO, Associate Professor of Emergency Medicine, Clinical Assistant Professor of Medicine, Research Director, State University of New York College of Medicine; Consulting Staff, Department of Emergency Medicine, Kings County Hospital Center
Contributor Information and Disclosures

Updated: Aug 8, 2008

Differential Diagnoses

Workup

Laboratory Studies

• Urinalysis: Microscopic examination of urine is essential in establishing differential diagnosis for acute renal failure (ARF).
  • Normal urinary sediment without hemoglobin, protein, cells, or casts generally consistent with prerenal and postrenal failure, HUS/thrombotic thrombocytopenic purpura (TTP), preglomerular vasculitis, or atheroembolism
  • Granular casts - ATN, glomerulonephritis, interstitial nephritis
  • RBC casts - Glomerulonephritis, malignant HTN
  • WBC casts - Pyelonephritis
  • Eosinophiluria - Acute allergic interstitial nephritis, atheroembolism
  • Crystalluria - Acyclovir, sulfonamides, methotrexate, ethylene glycol toxicity, radiocontrast agents (Mild crystalluria can be a normal finding.) 
• BUN: The urea concentration correlates poorly with the GFR. Because urea is highly permeable to renal tubules, urea clearance varies with urine flow rate.
  • Urea is filtered freely, but reabsorption along the tubule is a function of urine flow rate. During antidiuresis with urine flow rates less than 30 mL/h, urea clearance is as low as an estimated 30% of GFR. Under conditions of diuresis, with urine outputs greater than 100 mL/h, urea clearance can increase to 70-100% of GFR.
    • This information can be used clinically to help differentiate prerenal failure from other etiologies of ARF.
    • In prerenal conditions, low urine flow rates favor BUN reabsorption out of proportion to decreases in GFR, resulting in a disproportionate rise of BUN relative to creatinine, creating a serum BUN-creatinine ratio >20 in prerenal failure.
  • BUN concentration is dependent on nitrogen balance and renal function.
    • BUN concentration can rise significantly with no decrement in GFR by increases in urea production with steroids, trauma, or GI bleeding.
    • Tetracycline increases BUN by decreasing tissue anabolic rates.
    • Basal BUN concentration can be depressed severely by malnutrition or advanced liver disease.
    • Always first estimate basal BUN concentration when attempting to correlate changes in BUN with GFR. For example, in a patient with cirrhosis and a BUN of 12 mg/dL, a GFR in the normal range may be assumed. Only with the knowledge of a baseline BUN of 4 mg/dL does the real decrease in GFR become apparent.
• Creatinine: Serum creatinine measurement provides the ED physician with an accurate and consistent estimation of GFR. Correct interpretation of serum creatinine measurement extends beyond just knowing normal values for the specific laboratory.
  • Creatinine measuring methods
    • Serum creatinine level varies by method of measurement, either Jaffe or iminohydrolase. Upper limit of normal creatinine level can be 1.6-1.9 mg/dL or 1.2-1.4 mg/dL, respectively. This becomes important when patients present with changes in creatinine measured in different laboratories.
    • Differing methods report markedly different results when interfacing with certain chemicals.
    • Jaffe method of measuring creatinine reports falsely elevated serum creatinine in the presence of the following noncreatinine chromogens: glucose, fructose, uric acid, acetone, acetoacetate, protein, ascorbic acid, pyruvate, cephalosporin antibiotics. High levels of bilirubin cause reports of falsely low creatinine by the Jaffe method.
    • Extremely high glucose levels and the antifungal agent flucytosine interfere with the iminohydrolase method.
  • Serum creatinine level is a reflection of creatinine clearance.
    • Serum creatinine level is a function of its production and excretion rates.
    • Creatinine production is determined by muscle mass. Serum creatinine level must always be interpreted with respect to patient's weight, age, and sex. The GFR can be estimated by the following formulas: The ADQI consensus committee on ARF favors the Modification of Diet in Renal Disease (MDRD) equation to estimate GFR.
    • Cockcroft-Gault equation: GFR mL/min = (140 - Age y)(Weight kg)(0.85 if female)/(72 X Serum Creatinine mol/L
    • MDRD equation: GFR, in mL/min per 1.73 mm² = 186.3 X ((Serum Creatinine) exp[-1.154]) X (Age exp[-0.203]) X (0.742 if female) X (1.21 if African American
    • For example, GFR decreases by 1% per year after age 40 years, yet serum creatinine level generally remains stable. Balance is achieved via a decrease in muscle mass with age, which matches the fall in GF
    • Men generally have a higher muscle mass per kilogram of body weight and thus a higher serum creatinine level than women.
  • An important consideration and limitation is that significant decrements in GFR can occur while creatinine levels remain in the normal range.
  • Changes in serum creatinine level reflect changes in GFR. Rate of change in serum creatinine level is an important variable in estimating GFR. Stable changes in serum creatinine level correlate with changes in GFR by the following relationships:
    • If creatinine 1 mg/dL is baseline for a given patient with normal GFR
    • Creatinine 2 mg/dL - 50% reduction in GFR
    • Creatinine 4 mg/dL - 70–85% reduction in GFR
    • Creatinine 8 mg/dL - 90–95% reduction in GFR
    • As suggested by these data, knowledge of a patient's baseline creatinine level becomes very important. Small changes with low baseline levels of creatinine may be much more important clinically than large changes with high basal creatinine.
    • Certain diseases and medications can interfere with the correlation of serum creatinine with GFR. Acute glomerulonephritis causes increased tubular secretion of creatinine, falsely depressing the rise in serum creatinine level when ARF occurs in acute glomerulonephritis. Trimethoprim and cimetidine cause decreased creatinine secretion and a falsely elevated creatinine with no change in GFR.
• Cystatin C is emerging as a superior biomarker for early kidney injury. 
  • It is generated at a constant rate by all nucleated cells and is not secreted by the tubules or eliminated by other routes than renal excretion. 
  • It does not appear to be affected by body habitus, nutritional state, or comorbid illness.
  • One of its principal advantages is that it identifies kidney injury while creatinine levels remain in the normal range.
• Complete blood cell count
  • Leukocytosis is common in ARF.
  • Leukopenia and thrombocytopenia suggest SLE or TTP.
  • Anemia and rouleaux formation suggest multiple myeloma.
  • Microangiopathic anemia suggests DIC, TTP, or atheroemboli.
  • Eosinophilia suggests allergic interstitial nephritis, polyarteritis nodosa, or atheroemboli.
  • Coagulation disturbances indicate liver disease, DIC, TTP, or hepatorenal syndrome.
• Blood chemistry
  • Creatine phosphokinase (CPK) elevations are seen in rhabdomyolysis and myocardial infarction.
  • Elevations in liver transaminase levels are seen in rapidly progressive liver failure and hepatorenal syndrome.
  • Hypocalcemia (moderate) is common in ARF; marked hypocalcemia is more typical of chronic renal failure.
  • Hyperkalemia is a common and important complication of ARF.
• Urine chemical indices
  • Differentiation of prerenal azotemia from ATN takes on a special importance in early management of these patients. Aggressive fluid resuscitation is appropriate in prerenal ARF. However, overly aggressive volume resuscitation in a patient with ATN who is unable to excrete the extra fluid can result in volume overload and respiratory embarrassment.
  • To help with the differentiation of prerenal azotemia, analysis of urine may provide important clues. Diuretics interfere with some of these indices, so collect urine prior to any considered administration of diuretics.
  • Urine indices that suggest prerenal ARF include the following:
    • Urine specific gravity >1.018
    • Urine osmolality (mOsm/kg H₂ O) >500
    • Urine sodium (mEq/L) <15-20
    • Plasma BUN-creatinine ratio >20
    • Urine-plasma creatinine ratio >40
  • Urine indices that suggest ATN include the following:
    • Urine specific gravity <1.012
    • Urine osmolality (mOsm/kg H₂ O) <500
    • Urine sodium (mEq/L) >40
    • Plasma BUN/creatinine ratio <10-15
    • Urine-plasma creatinine ratio <20
• Calculation of fractional excretion of sodium (FeNa)
  • FeNa = (urine Na/plasma Na)/(urine creatinine/plasma creatinine)
  • FeNa <1% suggests prerenal ARF
  • FeNa >1% suggests ATN
• Advantages of FeNa compared to other indices
  • Physiologic measure of sodium reabsorption
  • Measured creatinine and sodium clearances, accounting for filtration and reabsorption of sodium
  • FeNa increased before oliguric phase established and predictive of incipient ARF
• Exceptions (intrinsic renal failure with FeNa <1%)
  • Acute glomerulonephritis
  • Hepatorenal syndrome
  • Radiologic contrast–induced ATN
  • Myoglobinuric and hemoglobinuric ARF
  • Renal allograft rejection
  • Drug-related alterations in renal hemodynamics (eg, captopril, NSAIDs)

Imaging Studies

Imaging studies in ARF are most important in the emergent workup of suspected postrenal azotemia. Please refer to Urinary Obstruction for a complete discussion of available imaging studies for this cause of ARF.

• Renal ultrasonography
  • Renal ultrasonography is the test of choice for urologic imaging in the setting of acute renal failure. It has excellent sensitivity and specificity for detecting hydronephrosis due to obstruction, and it can also give valuable information other than ruling obstruction in or out.
  • Bipolar renal length is easy to assess, and kidneys smaller than 9 cm suggest chronic renal failure. 
  • Renal parenchyma should be isoechogenic or hypoechogenic when compared with that of the liver and spleen; hyperechogenicity indicates diffuse parenchymal disease. 
  • Color Doppler allows assessment of renal perfusion and can allow diagnosis of large-vessel etiologies of ARF.
  • In critically ill patients, bedside sonography warrants special consideration as it can quickly diagnose treatable etiologies of the patient’s condition and give guidance for fluid resuscitation. 
• Chest radiography
  • Obtain chest radiographs on a routine basis to look for evidence of volume overload.
  • Findings of lung infiltration can lead to pulmonary/renal syndromes, such as Wegener granulomatosis and Goodpasture syndrome, or evidence of pulmonary emboli from endocarditis or atheroembolic disease.

Other Tests

• Electrocardiography: Obtain routine ECGs to look for manifestations of hyperkalemia and arrhythmias, ischemia, and infarction.

Procedures

• Renal biopsy
  • Renal biopsy is often helpful in finding specific cause of intrinsic renal failure; however, it is not an ED procedure.
  • This is reserved for evaluation of ARF when the cause cannot be determined.
  • Renal biopsy is especially important when glomerular causes of ARF are suspected.
  • It is often helpful in finding a specific cause of renal failure.

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