A 38-year-old man is brought to the emergency department due to vomiting blood. After appropriate resuscitation measures, he undergoes upper gastrointestinal endoscopy, which reveals a bleeding duodenal ulcer. During hospital day 2, the patient develops decreased urine output. Serum creatinine rises to 3.0 mg/dL from a baseline of 1.2 mg/dL. Renal biopsy shows patchy epithelial necrosis of the tubules, tubulorrhexis, and intratubular casts. Supportive care is provided. Several days later, his urine output significantly increases and serum creatinine levels decline. Over the next few days, this patient is at highest risk for which of the following complications?
Stages of acute tubular necrosis | |
Initiation stage (24-36 hours) |
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Maintenance stage (days to weeks) |
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Recovery stage (weeks to months) |
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BUN = blood urea nitrogen; GFR = glomerular filtration rate; K = potassium; PO4 = phosphate. | |
This patient developed acute renal failure following gastrointestinal hemorrhage; renal biopsy showing tubular epithelial necrosis, tubulorrhexis (ie, cell rupture with loss of the basement membrane), and intratubular casts is consistent with acute tubular necrosis (ATN). ATN is characterized by tubular injury due to renal ischemia (eg, shock) or direct cytotoxicity (eg, radiologic contrast agents, aminoglycosides).
The clinical course of ATN takes place in 3 stages. The initiation stage is marked by the inciting event (eg, hemorrhage, as in this patient) and the onset of tubular injury. If significant tubular damage occurs, the maintenance stage (oliguric stage) follows in 24-36 hours. During this stage, urine output decreases and patients may develop volume overload. Renal tubular dysfunction results in characteristic low urinary osmolality (<350 mOsm/kg), high urinary sodium (>30 mEq/L), and high urinary fractional sodium excretion (>2%).
Despite the seemingly profound damage that occurs to nephrons in ATN, tubular epithelial cells have excellent regenerative capacity. If the patient survives the maintenance stage (via conservative management or dialysis), the recovery stage follows in several days or up to several weeks. Glomerular filtration rate often improves before renal tubular resorptive function is restored, so patients can develop transient polyuria (sometimes >3 L/day) with significant electrolyte wasting. During this time, patients are at high risk for developing clinically significant electrolyte imbalances, particularly hypokalemia, which can be life threatening. Low serum concentrations of magnesium, phosphorus, and calcium may also develop. Depending on the magnitude of the initial injury, most patients eventually recover both glomerular filtration and tubular resorptive function.
(Choices A, C, and E) Hyperphosphatemia, anion gap metabolic acidosis, and volume overload occur in the maintenance stage of ATN. This patient's spontaneous diuresis and falling creatinine are more consistent with the recovery phase.
(Choice D) Protein-losing nephropathies (eg, nephrotic syndrome) occur due to significant glomerular damage. Because the destruction in ATN is largely tubular, protein loss is unexpected. Patients with nephrotic syndrome typically develop progressive renal dysfunction, which is not expected to improve after several days.
Educational objective:
Acute tubular necrosis is characterized by tubular injury due to renal ischemia or direct cytotoxicity. The course of the disease takes place in 3 stages: initiation (initial insult), maintenance (oliguric renal failure), and recovery. During the recovery stage, glomerular filtration rate improves prior to restoration of renal tubular resorptive capacity, so transient polyuria and electrolyte wasting (eg, hypokalemia) can occur.