Acute Tubular Necrosis for USMLE Step 3
Acute Tubular Necrosis for the USMLE Step 3 Exam
- Definition:
- Acute tubular necrosis (ATN) is a common cause of acute kidney injury (AKI), characterized by damage to the renal tubular epithelial cells. ATN results from ischemia or exposure to nephrotoxic substances, leading to impaired renal function.
- Etiology:
- Ischemic ATN:
- Occurs when renal perfusion is severely reduced, leading to tubular hypoxia and necrosis. Causes include:
- Shock: Hypovolemic, septic, or cardiogenic shock leading to hypotension.
- Surgery: Major surgeries, especially with prolonged hypotension or cardiopulmonary bypass, reduce renal perfusion.
- Nephrotoxic ATN:
- Results from toxic injury to the renal tubules from:
- Medications: Aminoglycosides, NSAIDs, radiocontrast agents, amphotericin B, and cisplatin.
- Endogenous Toxins: Myoglobin (rhabdomyolysis), hemoglobin (hemolysis), uric acid (tumor lysis syndrome).
- Exogenous Toxins: Heavy metals (e.g., lead, mercury).
- Pathophysiology:
- Tubular Cell Injury:
- Hypoxia or nephrotoxins cause tubular cell necrosis and sloughing into the lumen, leading to obstruction and reduced glomerular filtration rate (GFR).
- Intrarenal Vasoconstriction:
- Ischemia or toxins trigger vasoconstriction within the kidneys, reducing blood flow and worsening tubular ischemia.
- Backleak of Filtrate:
- Damaged tubular cells allow filtrate to leak back into the interstitium, impairing renal function and contributing to fluid and electrolyte imbalances.
- Clinical Features:
- Oliguria or Non-oliguria:
- Oliguria (<400 mL/day) is common, particularly in ischemic ATN. Non-oliguric ATN, with normal urine output, is more likely in nephrotoxic ATN.
- Volume Overload:
- Edema, pulmonary congestion, and hypertension result from impaired fluid excretion.
- Electrolyte Imbalances:
- Hyperkalemia: Due to decreased potassium excretion.
- Metabolic Acidosis: From impaired hydrogen ion excretion and bicarbonate loss.
- Hyperphosphatemia: From reduced phosphate excretion.
- Phases of ATN:
- Initiation Phase:
- The insult (ischemia or toxin) damages tubular cells and reduces GFR. This phase lasts hours to days.
- Maintenance Phase:
- Oliguria, electrolyte imbalances, and uremia are common. This phase typically lasts 1 to 3 weeks.
- Recovery Phase:
- Tubular cells regenerate, GFR improves, and polyuria may occur. Polyuria may lead to dehydration and electrolyte imbalances.
- Diagnosis:
- Urinalysis:
- Granular ("muddy brown") casts: Indicative of tubular damage.
- Low Specific Gravity: Reflects impaired ability to concentrate urine.
- Blood Tests:
- Elevated serum creatinine and blood urea nitrogen (BUN) due to decreased GFR.
- Hyperkalemia, metabolic acidosis, and hyperphosphatemia.
- Fractional Excretion of Sodium (FeNa):
- FeNa >2% suggests ATN, indicating impaired sodium reabsorption.
- Imaging:
- Renal ultrasound is often normal but helps rule out postrenal causes of AKI.
- Management:
- Supportive Care:
- Fluid Management: Ensure adequate volume resuscitation in hypovolemic patients. Diuretics (e.g., furosemide) may be used for fluid overload.
- Electrolyte Management: Hyperkalemia may be treated with diuretics, insulin with glucose, or calcium gluconate for cardioprotection. Severe metabolic acidosis may require bicarbonate therapy.
- Nephrotoxin Avoidance:
- Discontinue nephrotoxic medications. Prevent radiocontrast-induced ATN with prehydration and N-acetylcysteine.
- Renal Replacement Therapy (RRT):
- Dialysis is indicated for refractory hyperkalemia, severe acidosis, or volume overload unresponsive to medical management.
- Prognosis:
- Most patients recover renal function within weeks, but some may develop chronic kidney disease (CKD) if injury is severe or prolonged. Mortality is higher in critically ill patients, particularly those with sepsis or multi-organ failure.
Key Points
- Acute tubular necrosis is the leading cause of acute kidney injury in hospitalized patients and results from ischemic or nephrotoxic insults.
- Clinical features include oliguria, volume overload, hyperkalemia, and metabolic acidosis.
- Diagnosis involves identifying granular casts on urinalysis, elevated serum creatinine, and a FeNa >2%.
- Management includes supportive care, fluid and electrolyte management, nephrotoxin avoidance, and dialysis in severe cases.
- Recovery is common with appropriate treatment, but severe cases may progress to chronic kidney disease.