eMedicine Specialties > Nephrology > Acute Kidney Failure

Acute Renal Failure: Differential Diagnoses & Workup

Author: Mahendra Agraharkar, MD, MBBS, FACP, FASN, Clinical Associate Professor of Medicine, Baylor College of Medicine, President & CEO, Space City Associates of Nephrology
Coauthor(s): Rajiv Gupta, MD, Assistant Professor, Department of Medicine, Texas A & M University Health Science Center; Consulting Staff, Veterans Affairs Medical Center; Biruh T Workeneh, MD, Assistant Professor, Baylor College of Medicine
Contributor Information and Disclosures

Updated: Aug 17, 2009

Differential Diagnoses

Acute Tubular Necrosis
Azotemia
Chronic Renal Failure

Other Problems to Be Considered

Obstructive uropathy
GI bleeding
Protein overloading
Steroid use


Workup

Laboratory Studies

Several laboratory tests are useful for assessing the etiology of AKI, and the findings can aid in proper management. These tests include complete blood cell (CBC) count, serum biochemistries, urine analysis with microscopy, and urine electrolytes.

  • Blood urea nitrogen (BUN) and serum creatinine
    • Although increased levels of BUN and creatinine are the hallmarks of renal failure, the rate of rise is dependent on the degree of renal insult as well as protein intake with respect to BUN.
    • The ratio of BUN to creatinine is an important finding, because the ratio can exceed 20:1 in conditions in which enhanced reabsorption of urea is favored (eg, in volume contraction); this suggests prerenal AKI.
    • BUN may be elevated in patients with GI or mucosal bleeding, steroid treatment, or protein loading. 
    • Assuming no renal function, the rise in BUN over 24 hours can be roughly predicted using the following formula: 24-hour protein intake in milligrams X 0.16 divided by total body water in mg/dL added to the BUN value.
    • Assuming no renal function, the rise in creatinine can be predicted using the following formulas:
      • For males: weight in kilograms X [28 – 0.2(age)] divided by total body water in mg/dL added to the creatinine value
      • For females: weight in kilograms X [23.8 – 0.17(age)] divided by total body water added to the creatinine value
    • As a general rule, if serum creatinine increases to more than 1.5 mg/dL/d, rhabdomyolysis must be ruled out.
  • CBC count, peripheral smear, and serology
    • The peripheral smear may show schistocytes in conditions such as HUS or TTP.
    • A finding of increased rouleaux formation suggests multiple myeloma, and the workup should be directed toward immunoelectrophoresis of serum and urine.
    • The presence of myoglobin or free hemoglobin, increased serum uric acid level, and other related findings may help further define the etiology of AKI.
    • Serologic tests for antinuclear antibody (ANA), ANCA, anti-GBM antibody, hepatitis, and antistreptolysin (ASO) and complement levels may help include and exclude glomerular disease. Although serologic tests can be informative, the costs can be prohibitive if these tests are not ordered judiciously.
  • Urinalysis
    • Findings of granular, muddy-brown casts are suggestive of tubular necrosis. (See image below and Image 5.) The presence of tubular cells or tubular cell casts also supports the diagnosis of ATN. Often, oxalate crystals are observed in cases of ATN.


Sloughing of cells, which is responsible for the ...

Sloughing of cells, which is responsible for the formation of granular casts, is a feature of acute tubular necrosis.

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Sloughing of cells, which is responsible for the ...

Sloughing of cells, which is responsible for the formation of granular casts, is a feature of acute tubular necrosis.

    • Reddish brown or cola-colored urine suggests the presence of myoglobin or hemoglobin, especially in the setting of a positive dipstick for heme and no RBCs on the microscopic examination.
    • The dipstick assay may reveal significant proteinuria, which would suggest glomerular or interstitial disease.
    • The presence of RBCs in the urine is always pathologic. Eumorphic RBCs suggest bleeding along the collecting system. Dysmorphic RBCs or RBC casts indicate glomerular inflammation, suggesting glomerulonephritis is present. 
    • The presence of WBCs or WBC casts suggests pyelonephritis or acute interstitial nephritis. The presence of urine eosinophils is helpful in establishing a diagnosis but is not necessary for allergic interstitial nephritis to be present.
    • The presence of eosinophils, as visualized with Wright stain or Hansel stain, suggests interstitial nephritis but can also be seen in urinary tract infections, glomerulonephritis, and atheroembolic disease.   
    • The presence of uric acid crystals may represent ATN associated with uric acid nephropathy.
    • Calcium oxalate crystals are usually present in cases of ethylene glycol poisoning.
  • Urine electrolytes
    • Urine electrolyte findings also can serve as valuable indicators of functioning renal tubules.
    • The fractional excretion of sodium (FENa) is the commonly used indicator. However, the interpretation of results from patients in nonoliguric states, those with glomerulonephritis, and those receiving or ingesting diuretics can lead to an erroneous diagnosis. FENa can be a valuable test for helping to detect extreme renal avidity for sodium in conditions such as hepatorenal syndrome. The formula for calculating the FENa is as follows:
    • FENa = (UNa/PNa) / (UCr/PCr) X 100
    • Calculating the FENa is useful in AKI only in the presence of oliguria.
    • In patients with prerenal azotemia, the FENa is usually less than 1%. In ATN, the FENa is greater than 1%. Exceptions to this rule are ATN caused by radiocontrast nephropathy, severe burns, acute glomerulonephritis, and rhabdomyolysis.
    • In the presence of liver disease, FENa can be less than 1% in the presence of ATN. On the other hand, because administration of diuretics may cause the FENa to be greater than 1%, these findings cannot be used as the sole indicators in AKI.
    • In patients who are receiving diuretics, a fractional excretion of urea (FEUrea) can be obtained, since urea transport is not affected by diuretics. The formula for calculating the FEUrea is as follows: FEUrea = (Uurea/Purea) / (UCr/PCr) X 100
    • FEUrea of less than 35% is suggestive of a prerenal state.

Imaging Studies

In some cases, renal imaging is useful, especially if renal failure is secondary to obstruction. The American College of Radiology recommends ultrasonography, preferably with Doppler methods, as the most appropriate imaging method in AKI.5

  • Ultrasonography
    • Renal ultrasonography is useful for evaluating existing renal disease and obstruction of the urinary collecting system. The degree of hydronephrosis does not necessarily correlate with the degree of obstruction. Mild hydronephrosis may be observed with complete obstruction if found early. 
    • Obtaining images of the kidneys can be technically difficult in patients who are obese or in those with abdominal distension due to ascites, gas, or retroperitoneal fluid collection.
    • Ultrasonographic scans or other imaging studies showing small kidneys suggest chronic renal failure.
  • Doppler ultrasonography
    • Doppler scans are useful for detecting the presence and nature of renal blood flow.
    • Because renal blood flow is reduced in prerenal or intrarenal AKI, test findings are of little use in the diagnosis of AKI.
    • Doppler scans can be quite useful in the diagnosis of thromboembolic or renovascular disease.
    • Increased resistive indices can be observed in patients with hepatorenal syndrome.
  • Nuclear scans
    • Radionuclide imaging with technetium-99m-mercaptoacetyltriglycine (99m Tc-MAG3),99m Tc-diethylenetriamine pentaacetic acid (99m Tc-DTPA), or iodine-131 (131 I)–hippurate can be used to assess renal blood flow and tubular functions.
    • Because of a marked delay in tubular excretion of radionuclide in prerenal disease and intrarenal disease, the value of these scans is limited.
  • Aortorenal angiography can be helpful in establishing the diagnosis of renal vascular diseases, including renal artery stenosis, renal atheroembolic disease, atherosclerosis with aortorenal occlusion, and in certain cases of necrotizing vasculitis (eg, polyarteritis nodosa).

Procedures

  • Renal biopsy
    • A renal biopsy can be useful in establishing the diagnosis of intrarenal causes of AKI and can be justified if it will change management (eg, initiation of immunosuppressive medications). A renal biopsy may also be indicated when renal function does not return for a prolonged period and a prognosis is required to develop long-term management.
    • In as many as 40% of cases, renal biopsy results reveal an unexpected diagnosis.
    • Acute cellular or humoral rejection in a transplanted kidney can be definitively diagnosed only by performing a renal biopsy.

More on Acute Renal Failure

Overview: Acute Renal Failure
Differential Diagnoses & Workup: Acute Renal Failure
Treatment & Medication: Acute Renal Failure
Follow-up: Acute Renal Failure
Multimedia: Acute Renal Failure
References
Further Reading
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References

  1. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. Aug 2004;8(4):R204-12. [Medline]. [Full Text].

  2. [Best Evidence] Kheterpal S, Tremper KK, Heung M, Rosenberg AL, Englesbe M, Shanks AM, et al. Development and validation of an acute kidney injury risk index for patients undergoing general surgery: results from a national data set. Anesthesiology. Mar 2009;110(3):505-15. [Medline].

  3. Goldberg R, Dennen P. Long-term outcomes of acute kidney injury. Adv Chronic Kidney Dis. Jul 2008;15(3):297-307. [Medline].

  4. Feest TG, Mistry CD, Grimes DS, Mallick NP. Incidence of advanced chronic renal failure and the need for end stage renal replacement treatment. BMJ. Oct 20 1990;301(6757):897-900. [Medline]. [Full Text].

  5. American College of Radiology. ACR Appropriateness Criteria® renal failure. National Guideline Clearinghouse. Available at http://www.guideline.gov/summary/summary.aspx?doc_id=8283&nbr=004615. Accessed May 20, 2009.

  6. [Best Evidence] Ho KM, Morgan DJ. Meta-analysis of N-acetylcysteine to prevent acute renal failure after major surgery. Am J Kidney Dis. Jan 2009;53(1):33-40. [Medline].

  7. [Best Evidence] Zacharias M, Conlon NP, Herbison GP, Sivalingam P, Walker RJ, Hovhannisyan K. Interventions for protecting renal function in the perioperative period. Cochrane Database Syst Rev. Oct 8 2008;CD003590. [Medline].

  8. Agraharkar M, Safirstein RL. Pathophysiology of acute renal failure. In: Greenberg A, Coffman T, eds. Primer on Kidney Diseases. 3rd ed. San Diego, Calif: Academic Press; 2001:243-86.

  9. Chertow GM, Christiansen CL, Cleary PD, et al. Prognostic stratification in critically ill patients with acute renal failure requiring dialysis. Arch Intern Med. Jul 24 1995;155(14):1505-11. [Medline].

  10. Donohoe JF, Venkatachalam MA, Bernard DB, Levinsky NG. Tubular leakage and obstruction after renal ischemia: structural-functional correlations. Kidney Int. Mar 1978;13(3):208-22. [Medline].

  11. [Best Evidence] Marenzi G, Assanelli E, Marana I, et al. N-acetylcysteine and contrast-induced nephropathy in primary angioplasty. N Engl J Med. Jun 29 2006;354(26):2773-82. [Medline].

  12. Merten GJ, Burgess WP, Gray LV, et al. Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial. JAMA. May 19 2004;291(19):2328-34. [Medline].

  13. Mitch WE, Klahr S. Handbook of Nutrition and the Kidney. 4th ed. Philadelphia: Lippincott Williams & Wilkins.

  14. Safirstein R, Bonventre JV. Molecular response to ischemic and nephrotoxic acute renal failure. In: Schlondorff D, Bonventre JV, eds. Molecular Nephrology. New York: Marcel Dekker; 1995:839-54.

  15. Schrier RW, Wang W, Poole B, Mitra A. Acute renal failure: definitions, diagnosis, pathogenesis, and therapy. J Clin Invest. 114(1):5-14. [Medline].

  16. Solomon R, Werner C, Mann D, et al. Effects of saline, mannitol, and furosemide to prevent acute decreases in renal function induced by radiocontrast agents. N Engl J Med. Nov 24 1994;331(21):1416-20. [Medline].

  17. Thadhani R, Pascual M, Bonventre JV. Acute renal failure. N Engl J Med. May 30 1996;334(22):1448-60. [Medline].

  18. Tonelli M, Manns B, Feller-Kopman D. Acute renal failure in the intensive care unit: a systematic review of the impact of dialytic modality on mortality and renal recovery. Am J Kidney Dis. Nov 2002;40(5):875-85. [Medline].

  19. van Bommel E, Bouvy ND, So KL, et al. Acute dialytic support for the critically ill: intermittent hemodialysis versus continuous arteriovenous hemodiafiltration. Am J Nephrol. 1995;15(3):192-200. [Medline].

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Keywords

acute renal failure, kidney disease, renal failure, kidney failure, renal disease, acute renal, glomerulonephritis, dialysis renal, oliguria, anuria, hypotension, acute kidney failure, acute tubular necrosis, chronic renal failure, tumor lysis syndrome, ethylene glycol poisoning, vasculitis, intrinsic renal failure, interstitial renal disease, renal dysfunction, renal artery occlusion, urethral stricture, bladder outlet obstruction, prostate enlargement, interstitial nephritis, renovascular disease, bladder cancer, epigastric bruit, diabetic ketoacidosis, pancreatitis, hypercalcemia, prostaglandin inhibition, ischemic tubular necrosis, crescentic glomerulonephritis, postinfective glomerulonephritis, lupus nephritis, hepatitis, vasculitis-associated glomerulonephritides, prostatic hypertrophy

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Contributor Information and Disclosures

Author

Mahendra Agraharkar, MD, MBBS, FACP, FASN, Clinical Associate Professor of Medicine, Baylor College of Medicine, President & CEO, Space City Associates of Nephrology
Mahendra Agraharkar, MD, MBBS, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Nephrology, and National Kidney Foundation
Disclosure: South Shore DaVita Dialysis Center  Ownership interest Other

Coauthor(s)

Rajiv Gupta, MD, Assistant Professor, Department of Medicine, Texas A & M University Health Science Center; Consulting Staff, Veterans Affairs Medical Center
Rajiv Gupta, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Cardiology, and Society of Cardiac Angiography and Interventions
Disclosure: Nothing to disclose.

Biruh T Workeneh, MD, Assistant Professor, Baylor College of Medicine
Biruh T Workeneh, MD is a member of the following medical societies: American Medical Association, American Society of Nephrology, and Texas Medical Association
Disclosure: Nothing to disclose.

Medical Editor

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

Pharmacy Editor

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

Managing Editor

Eleanor Lederer, MD, Consulting Staff, Louisville VA Hospital; Professor of Medicine; Interim Chief of Nephrology; Director of Nephrology Training Program; Director, Metabolic Stone Clinic; Director of Outpatient Clinics, Kidney Disease Program, University of Louisville School of Medicine
Eleanor Lederer, MD is a member of the following medical societies: American Association for the Advancement of Science, American Federation for Medical Research, American Society for Biochemistry and Molecular Biology, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney Foundation, and Phi Beta Kappa
Disclosure: Nothing to disclose.

CME Editor

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

Chief Editor

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

 
 
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