Sections

DDx

Diagnostic Considerations

Although acute kidney injury (AKI) is a potentially reversible condition, it can occur in patients with chronic kidney diseae. Every effort should be made to identify reversibility, even if improvement in kidney function is marginal. The best way to identify reversibility is by tracking the rate of deterioration of kidney function. If the rate fo deterioration accelerates, the cause should be sought and treated.

Differentials to consider in AKI include the following:

Abdominal aneurysm
Alcohol toxicity
Alcoholic ketoacidosis
Chronic kidney disease
Dehydration
Diabetic ketoacidosis
Gastrointestinal (GI) bleeding
Heart failure
Metabolic acidosis
Obstructive uropathy
Protein overloading
Renal calculi
Sickle cell anemia
Steroid use
Urinary obstruction
Urinary tract infection

Urine output in differential diagnosis

Changes in urine output generally correlate poorly with changes in the glomerular filtration rate (GFR). Approximately 50-60% of all causes of AKI do not produce oliguria. However, the identification of anuria, oliguria, and nonoliguria may be useful in the differential diagnosis of AKI, as follows:

Anuria (< 100 mL/day) - Urinary tract obstruction, renal artery obstruction, rapidly progressive glomerulonephritis, bilateral diffuse renal cortical necrosis
Oliguria (100-400 mL/day) - Prerenal failure, hepatorenal syndrome, and severe AKI
Nonoliguria (> 400 mL/day) - Acute interstitial nephritis, acute glomerulonephritis, partial obstructive nephropathy, nephrotoxic and ischemic acute tubular necrosis, radiocontrast-induced AKI, and rhabdomyolysis

Differential Diagnoses

Workup

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Pigmented, muddy brown, granular casts are visible in the urine sediment of a patient with acute tubular necrosis (400x magnification).
Photomicrograph of a kidney biopsy specimen shows renal medulla, which is composed mainly of renal tubules. Features suggesting acute tubular necrosis are the patchy or diffuse denudation of the renal tubular cells with loss of brush border (blue arrows); flattening of the renal tubular cells due to tubular dilation (orange arrows); intratubular cast formation (yellow arrows); and sloughing of cells, which is responsible for the formation of granular casts (red arrow). Finally, intratubular obstruction due to the denuded epithelium and cellular debris is evident (green arrow); note that the denuded tubular epithelial cells clump together because of rearrangement of intercellular adhesion molecules.

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Table 1. RIFLE Classification System for Acute Kidney Injury

Stage	GFR Criteria	Urine Output Criteria	Probability
Risk	SCreat increased × 1.5 or GFR decreased >25%	UO < 0.5 mL/kg/h × 6 h	High sensitivity (Risk >Injury >Failure)
Injury	SCreat increased × 2 or GFR decreased >50%	UO < 0.5 mL/kg/h × 12 h
Failure	SCreat increased × 3 or GFR decreased 75% or SCreat ≥4 mg/dL; acute rise ≥0.5 mg/dL	UO < 0.3 mL/kg/h × 24 h (oliguria) or anuria × 12 h
Loss	Persistent acute renal failure: complete loss of kidney function >4 wk		High specificity
ESKD	Complete loss of kidney function >3 mo		High specificity
ESKD—end-stage kidney disease; GFR—glomerular filtration rate; SCreat—serum creatinine; UO—urine output Note: Patients can be classified by GFR criteria and/or UO criteria. The criteria that support the most severe classification should be used. The superimposition of acute on chronic failure is indicated with the designation RIFLE-F_C; failure is present in such cases even if the increase in SCreat is less than 3-fold, provided that the new SCreat is greater than 4.0 mg/dL (350 µmol/L) and results from an acute increase of at least 0.5 mg/dL (44 µmol/L).

Table 2. Acute Kidney Injury Network Classification/Staging System for AKI

Stage	Serum Creatinine Criteria	Urine Output Criteria
1	Increase of ≥0.3 mg/dL (≥26.4 µmol/L) or 1.5- to 2-fold increase from baseline	< 0.5 mL/kg/h for >6 h
2	> 2-fold to 3-fold increase from baseline	< 0.5 mL/kg/h for >12 h
3*	> 3-fold increase from baseline, or increase of ≥ 4.0 mg/dL (≥35.4 µmol/L) with an acute increase of at least 0.5 mg/dL (44 µmol/L)	< 0.3 mL/kg/h for 24 h or anuria for 12 h
*Patients who receive renal replacement therapy (RRT) are considered to have met the criteria for stage 3 irrespective of the stage they are in at the time of RRT.

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Author

Biruh T Workeneh, MD, FASN Professor of Medicine, University of Texas MD Anderson Cancer Center

Biruh T Workeneh, MD, FASN is a member of the following medical societies: American Society of Nephrology, National Kidney Foundation

Disclosure: Nothing to disclose.

Coauthor(s)

Omar Mamlouk, MBBS Instructor, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center

Omar Mamlouk, MBBS is a member of the following medical societies: American Society of Nephrology, American Society of Onconephrology, National Kidney Foundation, Texas Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Eleanor Lederer, MD, FASN Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine; Consulting Staff, Louisville Veterans Affairs Hospital

Eleanor Lederer, MD, FASN is a member of the following medical societies: American Association for the Advancement of Science, 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

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: American Society of Nephrology<br/>Received income in an amount equal to or greater than $250 from: Healthcare Quality Strategies, Inc.

Chief Editor

Vecihi Batuman, MD, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Interim Chair, Deming Department of Medicine, Tulane University School of Medicine

Vecihi Batuman, MD, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, International Society of Nephrology, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

Mahendra Agraharkar, MD, MBBS, FACP, FASN Clinical Associate Professor of Medicine, Baylor College of Medicine; President and 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, National Kidney Foundation

Disclosure: Nothing to disclose.

Rajiv Gupta, MD Assistant Professor, Department of Medicine, Texas A&M University College of Medicine; Consulting Staff, Veterans Affairs Medical Center

Rajiv Gupta, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Cardiology, Society for Cardiovascular Angiography and Interventions

Disclosure: Nothing to disclose.

Acknowledgements

Aruna Agraharkar, MD, FACP Consulting Staff, Department of Gerontology, Space Center Clinic

Aruna Agraharkar, MD, FACP is a member of the following medical societies: American Medical Assocation

Disclosure: Nothing to disclose.

Eleanor Lederer, MD Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine; Consulting Staff, Louisville Veterans Affairs Hospital

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: Dept of Veterans Affairs Grant/research funds Research

Laura Lyngby 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.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Acute Kidney Injury (AKI) Differential Diagnoses

Diagnostic Considerations

Urine output in differential diagnosis

Differential Diagnoses

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