Tubular Necrosis, Acute

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

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)

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

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 periods

Therapeutic Procedures

• Dietary protein restriction of 0.6 g/kg/day helps prevent metabolic acidosis

• Nutritional support

• Avoid volume overload

• Avoid potassium-containing foods, salt substitutes, and medications known to cause hyperkalemia (ACE inhibitors, ARBs, spironolactone, eplerenone, triamterene, NSAIDs)

• Avoid magnesium-containing antacids and laxatives

• Indications for dialysis in acute kidney injury from acute tubular necrosis or other intrinsic disorders include

  • Life-threatening electrolyte disturbances (such as marked hyperkalemia)

  • Volume overload unresponsive to diuresis

  • Refractory acidosis

  • Uremic complications (eg, encephalopathy, pericarditis, and seizures)

  • In gravely ill patients, less severe but worsening abnormalities may also be indications for dialytic support

Complications

• Loop diuretics (furosemide) in large doses may cause hearing loss and cerebellar dysfunction

Prognosis

• Nonoliguric acute tubular necrosis has a better outcome

• Mortality from acute kidney injury is 20–50% in hospitalized settings and up to 70% with additional comorbid illnesses

• Increased mortality with advanced age, severe underlying disease, and multisystem organ failure

• Leading causes of death are

  • Infections

  • Fluid and electrolyte disturbances

  • Worsening of underlying disease

Prevention

• Monitor closely patients who exhibit rising serum creatinine after radiographic contrast media

When to Refer

• When uncertainty exists as to the cause of or treatment for AKI

• For fluid, electrolyte, and acid-base abnormalities that are recalcitrant to interventions

• Nephrology referral improves outcomes in AKI

When to Admit

• When a patient has symptoms or signs of acute kidney injury that require immediate intervention, such as administration of intravenous fluids, dialytic therapy, or a team approach that cannot be coordinated in the outpatient setting