A 23-year-old man is hospitalized for fever, headache, and confusion. He does not use tobacco or illicit drugs and is monogamous with his wife. The patient's cerebrospinal fluid analysis reveals lymphocytic pleocytosis, and a PCR is positive for herpesvirus. The patient is treated with intravenous high-dose acyclovir. Fever and mental status gradually improve, but on the third day of hospitalization the patient's serum creatinine level increases to 3.4 mg/dL from a baseline of 0.9 mg/dL at admission. The observed finding could have been prevented by which of the following?

Question

A 23-year-old man is hospitalized for fever, headache, and confusion.  He does not use tobacco or illicit drugs and is monogamous with his wife.  The patient's cerebrospinal fluid analysis reveals lymphocytic pleocytosis, and a PCR is positive for herpesvirus.  The patient is treated with intravenous high-dose acyclovir.  Fever and mental status gradually improve, but on the third day of hospitalization the patient's serum creatinine level increases to 3.4 mg/dL from a baseline of 0.9 mg/dL at admission.  The observed finding could have been prevented by which of the following?

Quizplus · Accepted Answer

The acute elevation of this patient's serum creatinine on the third day of hospitalization is likely due to acyclovir nephrotoxicity, which occurs in 5%-10% of patients who receive the drug intravenously. Acyclovir is excreted principally in the urine via glomerular filtration and tubular secretion. When the acyclovir concentration in the collecting duct exceeds its solubility, crystallization, crystalluria, and renal tubular damage can occur. In most cases, this toxic complication is transient and can be prevented (as well as treated) with adequate hydration and a reduction in the rate of drug infusion. (Choice B) Acute interstitial nephritis (AIN) is an allergic inflammation of the kidney that is most commonly triggered by medications and is often associated with fever, rash, and eosinophilia. However, acyclovir is not a common cause of AIN; common causes include nonsteroidal anti-inflammatory drugs, penicillins, cephalosporins, diuretics, and allopurinol. (Choice C) Monitoring of acyclovir blood levels is not always effective in preventing nephrotoxicity. During states of low intravascular volume (eg, dehydration), nephrotoxicity can develop secondary to increased urinary concentration even when acyclovir blood levels are not within the established toxic range. (Choice D) Allopurinol blocks xanthine oxidase, which reduces the formation of uric acid. Pretreatment with allopurinol is often used in patients with lymphoma and leukemia to prevent urate crystal nephropathy due to tumor lysis syndrome. Acyclovir nephrotoxicity is mediated by the formation of acyclovir crystals, not urate crystals, so allopurinol pretreatment would be ineffective. (Choice E) Pretreatment with prednisone can help prevent radiocontrast-induced allergic reactions. Prednisone does not prevent the formation of acyclovir crystals. Educational objective: Intravenous acyclovir can cause crystalline nephropathy if adequate hydration is not also provided.

A 23-Year-Old Man Is Hospitalized for Fever, Headache, and Confusion