A 44-year-old man is brought to the hospital after being found unresponsive. Temperature is 35.6 C (96.1 F), blood pressure is 120/80 mm Hg, and pulse is 110/min. He is responsive only to pain and has dry mucous membranes. The patient's condition is initially treated with intravenous fluids, and his mental status slowly improves, but urine output decreases and flank pain develops. A renal biopsy reveals marked ballooning and vacuolar degeneration of proximal renal tubules; multiple oxalate crystals are observed in the tubular lumen. Which of the following is most likely responsible for this patient's acute kidney injury?
This patient has altered mental status and acute renal failure. In conjunction with the oxalate crystals noted on renal biopsy, this presentation is consistent with ethylene glycol poisoning. Ethylene glycol is a toxic alcohol found in antifreeze, engine coolants, and brake fluids and may be accidentally or intentionally ingested (used as a substitute for alcohol). Patients initially have symptoms of ethanol intoxication; signs of acute renal failure (oliguria, flank pain) develop approximately 24-72 hours after ingestion. Ethylene glycol itself is relatively nontoxic; however, it is metabolized to glycolic acid and oxalic acid, resulting in its various toxicities.
Acute kidney injury occurs due to both glycolic acid, which causes direct tubular cytotoxicity, and oxalic acid, which crystalizes and causes tubular obstruction. This results in acute tubular necrosis (ATN), demonstrated histologically by proximal tubular cell ballooning and vacuolar degeneration with morphologically normal glomeruli. Urinalysis shows tubular casts and oxalate crystals. Other common laboratory findings include a markedly elevated anion gap metabolic acidosis (due to acid metabolite formation) and an elevated osmolar gap (due to the uncharged parent alcohol).
(Choice B) Multiple myeloma can cause light-chain cast nephropathy due to obstruction of the proximal tubules. This causes ATN, but biopsy demonstrates eosinophilic (light-chain) casts, not oxalate crystals. It also typically occurs in older patients and presents with hypercalcemia and anemia; altered mentation is unexpected.
(Choice C) Hyperparathyroidism causes hypercalcemia, which predisposes patients to calcium stone (eg, calcium oxalate) formation. However, kidney stones typically cause postobstructive nephropathy with cortical atrophy and blunting of calyces; ATN would be unexpected.
(Choice D) Thrombotic microangiopathies (eg, hemolytic uremic syndrome) cause endothelial injury characterized by microthrombi in the glomerular capillaries and fibrinoid necrosis of the arterioles; schistocytes are commonly seen on microscopy. Proximal tubules are typically unaffected, and oxalate crystals would not be seen.
(Choice E) Advanced liver disease with portal hypertension and splanchnic vasodilation may lead to renal failure (hepatorenal syndrome). The hallmark of this condition is renal vasoconstriction, resulting in prerenal azotemia. The kidneys are histologically normal and resume function following liver transplantation.
Educational objective:
Ethylene glycol ingestion causes acute tubular necrosis with vacuolar degeneration and ballooning of the proximal tubular cells. Typical clinical findings include altered mentation, renal failure, high anion gap metabolic acidosis, increased osmolar gap, and calcium oxalate crystals in the urine.