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For further information, see CMDT Part 22-06: Acute Tubular Necrosis

Key Features

Essentials of Diagnosis

  • Acute kidney injury (AKI)

  • Ischemia or toxic insult or underlying sepsis

  • Pigmented granular casts and renal tubular epithelial cells in urine sediment are pathognomonic but not always present

General Considerations

  • AKI as a result of tubular damage is termed acute tubular necrosis (ATN)

  • Accounts for approximately 85% of intrinsic acute kidney injury

  • Two major causes are ischemia and nephrotoxin exposure

  • Renal tubular damage can be caused by low effective arterial blood flow to the kidneys in the setting of prolonged hypotension or hypoxemia, such as volume depletion or shock

  • Underlying sepsis is an independent risk factor for acute tubular necrosis, even in the absence of hemodynamic compromise

  • Prolonged periods of renal hypoperfusion can occur with major surgical procedures, and may be exacerbated by vasodilating anesthetic agents

  • Exogenous nephrotoxins more commonly cause damage than endogenous nephrotoxins

Exogenous nephrotoxins

  • Aminoglycosides: cause ATN in up to 25% of hospitalized patients receiving therapeutic levels of the drugs

  • Amphotericin B

  • Vancomycin, intravenous acyclovir, cephalosporins

  • Radiographic contrast media

  • Calcineurin inhibitors (tacrolimus, cyclosporine)

  • Antineoplastics, such as cisplatin and organic solvents (eg, etoposides, paclitaxel), and heavy metals (mercury, cadmium, and arsenic)

  • Some herbal medicine

  • ACE inhibitors and angiotensin receptor blockers (at times of prolonged hypotension or volume depletion)

Endogenous nephrotoxins

  • Myoglobin (eg. from rhabdomyolysis)

  • Hemoglobin (eg. from massive intravascular hemolysis)

  • Hyperuricemia (eg. from tumor lysis)

  • Paraproteins (from plasma cell myeloma)

Clinical Findings

Symptoms and Signs

  • See Kidney Injury, Acute

  • Three phases of the clinical course of ATN: Initial injury, Maintenance, and Recovery

  • Maintenance phase

    • Either oliguric (urinary output < 500 mL/day) or nonoliguric

    • Average duration is 1–3 weeks, but some cases last several months

  • Recovery phase

    • Can be heralded by diuresis from inability of recovering renal tubules to reabsorb salt and water appropriately and to solute-induced diuresis from accumulated BUN

    • As GFR begins to rise, BUN and serum creatinine fall

Differential Diagnosis

  • Prerenal azotemia (eg, dehydration)

  • Postrenal azotemia (eg, benign prostatic hyperplasia)

  • Renal causes of acute kidney injury

    • Acute glomerulonephritis: immune complex (eg, IgA nephropathy), pauci-immune (eg, granulomatosis with polyangiitis), antiglomerular basement membrane disease

    • Acute interstitial nephritis: drugs (eg, β-lactams), infections (eg, Streptococcus), immune (eg, systemic lupus erythematosus)


  • BUN:creatinine ratio < 20:1

  • Hyperkalemia and hyperphosphatemia are commonly present

  • Urine microscopy may show evidence of acute tubular damage

    • Presence of two or more granular casts or renal tubular epithelial cells

      • Strongly predictive of ATN

      • Low negative predictive value

  • Kidney biopsy is sometimes helpful in cases of diagnostic uncertainty

  • Fractional excretion of sodium or FENa = clearance of Na+/GFR = clearance ...

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