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 complains of 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: 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?

Question

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 complains of 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:  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?

Quizplus · Accepted Answer

11ec25c8_d4d2_46d2_bc81_9d8bea6f2c95_MD0003_00 The patient's presentation is most likely consistent with crystal-induced acute kidney injury (AKI) due to intravenous acyclovir. The kidney rapidly excretes 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. Intravenous acyclovir less commonly causes AKI through acute tubular necrosis or acute interstitial nephritis. Risk factors for crystal-induced AKI include underlying volume depletion or 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 discontinuing the drug and providing volume repletion. Administration of intravenous fluids for adequate hydration while giving the drug can also prevent AKI. (Choice A) Acute interstitial nephritis (AIN) is usually associated with exposure to medications such as beta lactams and proton pump inhibitors. However, AIN usually occurs 7-10 days after drug exposure. Patients can develop findings that include skin rash, eosinophilia, eosinophiluria, and pyuria. This patient's onset of AKI (2 days) makes AIN less likely. (Choice B) Bladder neck obstruction due to conditions including benign prostatic hyperplasia or prostate cancer can cause post-renal 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 C) Glomerular injury is seen in glomerulonephritis, which usually causes an abnormal urinalysis (eg, proteinuria, hematuria, red blood cell casts). 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 D) Pre-renal azotemia is often due to volume depletion with hypoperfusion to 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. 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. References: Acyclovir nephrotoxicity: a case report highlighting the importance of prevention, detection, and treatment of acyclovir-induced nephropathy. (http://www.ncbi.nlm.nih.gov/pubmed/20862348)

A 20-Year-Old Man Is Brought to the Emergency Department with a One-Day