Tubular Necrosis, Acute

KEY FEATURES

Essentials of Diagnosis

• Acute kidney injury (AKI)

• Ischemia or toxic insult or underlying sepsis

• Urine sediment may reveal granular (muddy brown) casts, renal tubular epithelial cells, or both

General Considerations

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

• Accounts for approximately 85% of intrinsic AKI and the majority of hospitalized cases

• May be caused by prolonged kidney ischemia, nephrotoxin exposure, or sepsis (even in patients who are normotensive)

• 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: common cause of ATN even when therapeutic levels are not exceeded

• Amphotericin B typically nephrotoxic after a total dose of 2–3 g

• Vancomycin, intravenous acyclovir, cephalosporins

• Radiographic contrast media

• Calcineurin inhibitors (tacrolimus, cyclosporine) toxicity usually dose-dependent

• Chemotherapeutic agents (eg, cisplatin), organic solvents, and heavy metals (mercury, cadmium, and arsenic)

• Some herbal medicines

• Angiotensin-converting enzyme (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/d) 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 blood urea nitrogen (BUN)

Differential Diagnosis

• Prerenal azotemia (eg, dehydration)

• Postrenal azotemia (eg, benign prostatic hyperplasia)

• Renal causes of AKI

  • 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 not performed in cases of suspected ATN but is sometimes helpful in cases of diagnostic ...