Acute Tubular Necrosis for USMLE Step 2
Acute Tubular Necrosis for the USMLE Step 2 Exam
- Definition:
- Acute tubular necrosis (ATN) is the most common cause of acute kidney injury (AKI), resulting from damage to renal tubular cells due to ischemic or nephrotoxic insults. It leads to decreased glomerular filtration and renal dysfunction.
- Etiology:
- Ischemic ATN:
- Caused by reduced renal perfusion, leading to tubular hypoxia and necrosis. Common causes include:
- Shock: Hypovolemic, septic, or cardiogenic shock, which reduces renal blood flow.
- Surgical Complications: Major surgeries, especially with prolonged hypotension or cardiopulmonary bypass.
- Nephrotoxic ATN:
- Caused by toxic injury to the renal tubules from:
- Medications: Aminoglycosides, NSAIDs, amphotericin B, cisplatin, and radiocontrast agents.
- Endogenous Toxins: Myoglobin (from rhabdomyolysis), hemoglobin (from hemolysis), uric acid (tumor lysis syndrome).
- Exogenous Toxins: Heavy metals (e.g., lead, mercury).
- Pathophysiology:
- Tubular Cell Damage:
- Hypoxia or nephrotoxic agents cause tubular epithelial cell death and sloughing, leading to obstruction and a further reduction in the glomerular filtration rate (GFR).
- Intrarenal Vasoconstriction:
- Ischemia or nephrotoxins trigger vasoconstriction within the kidneys, reducing renal blood flow and worsening hypoxia.
- Backleak of Filtrate:
- Damaged tubular cells allow filtrate to leak back into the interstitium, impairing renal function and causing fluid overload and electrolyte imbalances.
- Clinical Features:
- Oliguria or Non-oliguria:
- Oliguria (<400 mL/day) is common in ischemic ATN, though nephrotoxic ATN can present with normal urine output.
- Volume Overload:
- Edema, pulmonary congestion, and hypertension may occur due to impaired renal excretion of fluids.
- Electrolyte Imbalances:
- Hyperkalemia: Due to impaired potassium excretion.
- Metabolic Acidosis: From reduced excretion of hydrogen ions and bicarbonate loss.
- Hyperphosphatemia: Due to impaired phosphate excretion.
- Phases of ATN:
- Initiation Phase:
- Tubular injury occurs from ischemia or nephrotoxicity, leading to reduced GFR. This phase lasts hours to days.
- Maintenance Phase:
- Persistent oliguria or anuria, with electrolyte imbalances, fluid overload, and uremia. This phase may last 1-3 weeks.
- Recovery Phase:
- Tubular cells regenerate, GFR improves, and urine output increases, often with polyuria. Electrolyte imbalances may occur due to rapid diuresis.
- Diagnosis:
- Urinalysis:
- Granular ("muddy brown") casts: Pathognomonic for ATN, formed from necrotic tubular cells.
- Low Specific Gravity: Indicates impaired urine concentrating ability.
- 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, reflecting impaired sodium reabsorption.
- Imaging:
- Renal ultrasound may show normal kidneys but helps exclude postrenal causes of AKI.
- Management:
- Supportive Care:
- Fluid Management: Ensure adequate hydration in hypovolemic patients. Diuretics (e.g., furosemide) may be used for volume overload.
- Electrolyte Management: Hyperkalemia can be treated with diuretics, insulin with glucose, or calcium gluconate for cardioprotection. Metabolic acidosis may require bicarbonate therapy.
- Avoid Nephrotoxins:
- Discontinue nephrotoxic drugs. Radiocontrast-induced ATN may be prevented with prehydration and the use of agents like N-acetylcysteine.
- Renal Replacement Therapy (RRT):
- Indications for dialysis include refractory hyperkalemia, severe metabolic acidosis, and volume overload unresponsive to diuretics.
- Prognosis:
- Most patients recover renal function within weeks if the underlying cause is addressed, but some may develop chronic kidney disease (CKD) with prolonged or severe injury. Mortality is higher in critically ill patients, especially those with sepsis or multi-organ failure.
Key Points
- Acute tubular necrosis is the most common cause of acute kidney injury in hospitalized patients, caused by ischemic or nephrotoxic insults.
- ATN presents with oliguria, volume overload, hyperkalemia, and metabolic acidosis.
- Diagnosis involves identifying granular ("muddy brown") casts on urinalysis, elevated serum creatinine, and a FeNa >2%.
- Treatment includes supportive care, management of fluid and electrolyte imbalances, and avoidance of nephrotoxic agents. Dialysis may be needed in severe cases.
- Recovery is common with proper treatment, but some patients may progress to chronic kidney disease.