A 20-year-old man is brought to the emergency department with a one-day history of fever, headache, and altered mental status. He has no history of medical illness. Cerebral spinal fluid analysis shows lymphocytic pleocytosis, elevated protein level, and normal glucose level. The patient is started on high-dose intravenous acyclovir. Two days later, his neurologic status improves. Polymerase chain reaction assay for herpes simplex virus DNA comes back positive. However, the patient reports new onset nausea and abdominal discomfort. He is afebrile, normotensive without orthostasis, and has normal oxygen saturation. The rest of the physical examination is unremarkable. Laboratory results are as follows:
| Sodium | 140 mEq/L |
| Potassium | 4.5 mEq/L |
| Creatinine | 2.8 mg/dL |
| Blood urea nitrogen | 38 mg/dL |
His admission creatinine level was 0.8 mg/dL. Which of the following is the most likely cause of acute kidney injury in this patient?
Clinical features of crystal-induced acute kidney injury | |
Common etiologies |
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Clinical presentation |
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Management |
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AKI = acute kidney injury; CKD = chronic kidney disease; UA = urinalysis. | |
The patient's presentation is most consistent with crystal-induced acute kidney injury (AKI) due to intravenous acyclovir. The kidneys rapidly excrete acyclovir into the urine, but the drug has low urine solubility. As a result, it easily precipitates in renal tubules, causing intratubular obstruction and direct renal tubular toxicity. Crystal-induced AKI is more common with large intravenous doses of acyclovir and occurs only rarely with oral acyclovir.
Risk factors for crystal-induced AKI include volume depletion and underlying chronic kidney disease. Most patients develop AKI within 24-48 hours after drug exposure and can be asymptomatic or develop nonspecific symptoms (eg, nausea, flank/abdominal pain). Urinalysis can show hematuria, pyuria, and crystals visualized with a polarizing microscope. Treatment involves holding or discontinuing the drug (if possible) and providing volume repletion. A loop diuretic (eg, furosemide) may be given concurrently with volume repletion to help flush the renal tubules. Preemptive administration of intravenous fluids while giving the drug can help prevent AKI.
(Choice A) Bladder neck obstruction due to conditions including benign prostatic hyperplasia or prostate cancer can cause postrenal AKI. However, this occurs more commonly in older men and presents with obstructive voiding symptoms. This patient's younger age and absence of symptoms of urinary obstruction make this unlikely.
(Choice B) Glomerulonephritis can occur after certain infections (eg, streptococcal) but is not usually associated with viral meningitis. In addition, acyclovir is more commonly associated with renal tubular than glomerular injury.
(Choice C) Prerenal azotemia is often due to volume depletion with hypoperfusion of the kidneys. Laboratory studies typically show a blood urea nitrogen to creatinine ratio >20:1. This patient's normal blood pressure without orthostasis and ratio <20:1 make this less likely.
(Choice E) The ureters are relatively large in diameter compared to the renal tubules, and they rarely become obstructed with crystal-induced AKI. Ureteral obstruction must be bilateral to cause AKI.
Educational objective:
High-dose intravenous acyclovir can cause crystalluria with renal tubular obstruction. Administering intravenous fluids concurrently with the drug can help reduce the risk of acute kidney injury.