Tubular Necrosis, Acute

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)

Diagnosis

• 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 FE_Na = clearance of Na⁺/GFR = clearance ...