Acute Tubular Necrosis for USMLE Step 1
Acute Tubular Necrosis for the USMLE Step 1 Exam
- Definition:
- Acute tubular necrosis (ATN) is a form of acute kidney injury (AKI) caused by damage to the renal tubular cells, leading to impaired renal function. It is the most common cause of AKI in hospitalized patients and is usually reversible with appropriate treatment.
- Etiology:
- Ischemic ATN:
- Caused by reduced renal perfusion from prolonged or severe hypotension, which leads to tubular cell injury. Common causes include:
- Shock: Hypovolemic (e.g., hemorrhage, dehydration), septic, or cardiogenic shock (e.g., heart failure).
- Surgery: Prolonged surgeries, especially with cardiopulmonary bypass, may reduce renal blood flow.
- Nephrotoxic ATN:
- Caused by toxic injury to the renal tubules from:
- Medications: Aminoglycosides, NSAIDs, cisplatin, amphotericin B, and radiocontrast agents.
- Endogenous Toxins: Myoglobin (rhabdomyolysis), hemoglobin (hemolysis), uric acid (tumor lysis syndrome).
- Exogenous Toxins: Heavy metals like lead and mercury.
- Pathophysiology:
- Tubular Cell Injury:
- Hypoxia or toxins damage the tubular epithelial cells, causing cell death and sloughing into the lumen, leading to obstruction and further reduction in the glomerular filtration rate (GFR).
- Intrarenal Vasoconstriction:
- Hypoxia or nephrotoxins induce vasoconstriction within the kidneys, further reducing blood flow to the renal tubules.
- Backleak of Filtrate:
- Damaged tubular cells allow filtrate to leak back into the interstitium, further impairing renal function.
- Clinical Features:
- Oliguria or Non-oliguria:
- Decreased urine output (<400 mL/day in oliguria) is common in ischemic ATN. Non-oliguric ATN (normal urine output) can occur in nephrotoxic cases.
- Volume Overload:
- Edema, pulmonary congestion, and hypertension due to fluid retention.
- Electrolyte Imbalances:
- Hyperkalemia: Impaired potassium excretion.
- Metabolic Acidosis: Due to decreased excretion of hydrogen ions and reduced bicarbonate reabsorption.
- Hyperphosphatemia: Reduced phosphate excretion.
- Phases of ATN:
- Initiation Phase:
- The initial insult (ischemia or nephrotoxicity) leads to tubular cell injury and reduced GFR. This phase lasts hours to days.
- Maintenance Phase:
- Ongoing oliguria or anuria, with electrolyte disturbances and fluid overload. This phase can last 1 to 3 weeks.
- Recovery Phase:
- Tubular cells regenerate, GFR improves, and urine output increases. Polyuria may occur, with a risk of dehydration and electrolyte imbalances.
- Diagnosis:
- Urinalysis:
- Granular ("muddy brown") casts: Pathognomonic for ATN, consisting of sloughed tubular cells.
- Low Specific Gravity: Reflects impaired ability to concentrate urine.
- Blood Tests:
- Elevated serum creatinine and blood urea nitrogen (BUN), hyperkalemia, and metabolic acidosis.
- Fractional Excretion of Sodium (FeNa):
- FeNa >2% suggests ATN, reflecting impaired sodium reabsorption.
- Imaging:
- Renal ultrasound is often normal but helps rule out obstruction.
- Management:
- Supportive Care:
- Fluid Management: Ensure adequate volume resuscitation in hypovolemic patients. In cases of volume overload, diuretics (e.g., furosemide) may be used cautiously.
- Electrolyte Management: Correct hyperkalemia with diuretics, insulin with glucose, or calcium gluconate for cardioprotection. Treat acidosis with bicarbonate if severe.
- Avoid Nephrotoxins:
- Discontinue nephrotoxic drugs. Radiocontrast-induced ATN can be prevented with prehydration and possibly N-acetylcysteine.
- Renal Replacement Therapy (RRT):
- Indicated for refractory hyperkalemia, severe acidosis, or volume overload unresponsive to medical therapy.
- Prognosis:
- Most patients recover renal function within weeks, though some may develop chronic kidney disease (CKD) if there is prolonged ischemia or nephrotoxic exposure. 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.
- Clinical features include oliguria, volume overload, hyperkalemia, and metabolic acidosis.
- Diagnosis is supported by granular casts in the urine, elevated creatinine, and a FeNa >2%.
- Management is supportive, including fluid management, electrolyte correction, and avoidance of nephrotoxins. Dialysis may be required in severe cases.
- Most patients recover with appropriate care, but chronic kidney disease may develop in severe cases.