History

The patient’s history is very important in the diagnosis of acute tubular necrosis (ATN), as it can establish the risk factors for the development of ATN. A careful historical timeline of events leading to acute kidney injury (AKI) can frequently identify the underlying cause.

The history commonly reveals recent surgery, hypotension, sepsis, muscle necrosis, or volume depletion, as well as exposure to nephrotoxic agents. Several of those may be present simultaneously, which increases the risk and severity of ATN.

In addition, pre-existing medical conditions or medication use (eg, diabetes mellitus, multiple myeloma, nonsteroidal anti-inflammatory drugs) may contribute to the worsening of renal function. Hence, a thorough medical and medication history can also be key to the diagnosis.

Physical Examination

Physical examination findings are often unremarkable and acute kidney injury (AKI) is incidentally detected on routine laboratory studies (ie, elevated blood urea nitrogen [BUN] and creatinine levels).

Findings may suggest hypovolemia (eg, low jugular venous pressure, loss of skin turgor, orthostatic hypotension, dry mucous membranes, tachycardia) as a cause. Abdominal distension may raise the concern of intra-abdominal hypertension and compartment syndrome as a potential cause of ATN. Muscle tenderness could potentially be due to rhabdomyolysis, which can lead to ATN.

Differential Diagnoses

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Media Gallery

Acute tubular necrosis. Pigmented, muddy brown, granular casts are visible in the urine sediment of a patient with acute tubular necrosis (400x magnification).
Acute tubular necrosis. 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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Author

Sangeeta Mutnuri, MBBS Nephrologist, Space City Associates of Nephrology

Sangeeta Mutnuri, MBBS is a member of the following medical societies: American Society of Nephrology

Disclosure: Nothing to disclose.

Coauthor(s)

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.

Edgar V Lerma, MD, FACP, FASN, FAHA, FASH, FNLA, FNKF Clinical Professor of Medicine, Section of Nephrology, Department of Medicine, University of Illinois at Chicago College of Medicine; Research Director, Internal Medicine Training Program, Advocate Christ Medical Center; Consulting Staff, Associates in Nephrology, SC

Edgar V Lerma, MD, FACP, FASN, FAHA, FASH, FNLA, FNKF is a member of the following medical societies: American Heart Association, American Medical Association, American Society of Hypertension, American Society of Nephrology, Chicago Medical Society, Illinois State Medical Society, National Kidney Foundation, Society of General Internal Medicine

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Astra Zeneca<br/>Author for: UpToDate, ACP Smart Medicine, Elsevier, McGraw-Hill, Wolters Kluwer.

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

Brent Kelly, MD Assistant Professor, Department of Dermatology, University of Texas Medical Branch, Galveston, Texas

Brent Kelly, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association

Disclosure: Nothing to disclose.

Nikhil A Shah, MBBS, DNB(Neph) Clinical Research Fellow in Home Dialysis, Nephrologist, University of Alberta Faculty of Medicine and Dentistry, Canada

Nikhil A Shah, MBBS, DNB(Neph) is a member of the following medical societies: American Society of Nephrology, American Society of Transplantation, Canadian Medical Protective Association, Canadian Society of Nephrology, Indian Society of Nephrology, International Society of Nephrology

Disclosure: Nothing to disclose.

Acknowledgements

George R Aronoff, MD Director, Professor, Departments of Internal Medicine and Pharmacology, Section of Nephrology, Kidney Disease Program, University of Louisville School of Medicine

George R Aronoff, MD is a member of the following medical societies: American Federation for Medical Research, American Society of Nephrology, Kentucky Medical Association, and National Kidney Foundation

Disclosure: Nothing to disclose.

F John Gennari, MD Associate Chair for Academic Affairs, Robert F and Genevieve B Patrick Professor, Department of Medicine, University of Vermont College of Medicine

F John Gennari, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Federation for Medical Research, American Heart Association, American Physiological Society, American Society for Clinical Investigation, American Society of Nephrology, and International Society of Nephrology

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

Finding	Prerenal Azotemia	ATN and/or Intrinsic Renal Disease
Urine osmolarity (mOsm/kg)	>500	< 350
Urine sodium (mmol/d)	< 20	>40
Fractional excretion of sodium (FENa) (%)	< 1	>2
Fractional excretion of urea (%)	< 35	>50
Urine sediment	Bland and/or nonspecific	May show muddy brown granular casts

Acute Tubular Necrosis Clinical Presentation

History

Physical Examination

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