Tubular Necrosis, Acute

Key Features

Essentials of Diagnosis

• Acute kidney injury

• Ischemia or toxic insult or underlying sepsis

• Urine sediment with granular (muddy brown) casts and renal tubular epithelial cells is pathognomonic but not essential

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 with low effective arterial blood flow to the kidney can result in tubular necrosis and apoptosis

• Ischemic acute kidney injury occurs in prolonged hypotension or hypoxemia such as with volume depletion, shock, and sepsis and after major surgical procedures

• 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

• Pigment-containing products (myoglobin and hemoglobin)

• Uric acid

• 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, beta-lactams), infections (eg, Streptococcus), immune (eg, systemic lupus erythematosus)

Diagnosis

Laboratory Tests

• BUN:creatinine ratio < 20:1

• Hyperkalemia and hyperphosphatemia are commonly present

• Urine microscopy may show evidence of acute tubular damage

• In some instances, kidney biopsy is necessary

• 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 three times daily orally

  • Calcium acetate, 667 mg 2–3 tablets orally before meals

  • Sevelamer carbonate, 800–1600 mg three times daily orally

  • Lanthanum carbonate, 1000 mg orally with meals, over longer ...