Tubular Necrosis, Acute

Key Features

Essentials of Diagnosis

• Acute kidney injury

• 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

• Acute kidney injury as a result of tubular damage

• 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, which are exacerbated by vasodilating anesthetic agents

• Exogenous nephrotoxins more commonly cause damage than endogenous nephrotoxins

Exogenous nephrotoxins

• Aminoglycosides

• Vancomycin, intravenous acyclovir, several cephalosporins

• Radiographic contrast media

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

Endogenous nephrotoxins

• Myoglobinuria as a consequence of rhabdomyolysis

• Hemoglobinuria as a consequence of massive intravascular hemolysis

• Hyperuricemia

• Bence Jones proteinuria, paraproteins

Clinical Findings

Symptoms and Signs

• See Kidney Injury, Acute

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

• Kidney biopsy is sometimes helpful in cases of diagnostic uncertainty

• Fractional excretion of sodium or FE_Na = clearance of Na⁺/GFR = clearance of Na⁺/creatinine clearance

• FE_Na = (urine_Na/serum_Na)/(urine_Cr/serum_Cr) × 100%

• FE_Na is high (> 1%) in acute tubular necrosis

Treatment

Medications

• Stop offending agent and correct ischemia

• Furosemide

  • Intravenous use can minimize disabling side effects of supranormal dosing

  • Starting dose of 0.1–0.3 mg/kg/h is appropriate

    • Increase to a maximum of 0.5–1 mg/kg/h

    • A bolus of 1–1.5 mg/kg should be administered with each dose escalation

• Thiazide diuretics can be used to augment urinary output; reasonable choices include

  • Metolazone: 2.5–5 mg orally every 12–24 hours

    • Less expensive than intravenous chlorothiazide

    • Reasonable bioavailability

  • Chlorothiazide at doses of 250–500 mg intravenously every 8–12 hours

• Phosphate-binding agents

  • Aluminum hydroxide, 500 mg orally with meals

  • Calcium carbonate, 500–1500 mg ...