Acute Kidney Injury Induced by Oral Acyclovir Therapy

A 37-year-old male with no previous comorbid illnesses presented with oliguria and raised creatinine. He had had genital herpes 1 month back and had been prescribed tablet acyclovir 800 mg thrice a day for 1 week, later reduced to 400 mg thrice a day for 2 months. Baseline renal function tests were not available. Toward the end of the 1-month course, he felt weak and had oliguria and discolored urine. His vital signs and clinical examination were normal. Laboratory investigations revealed hemoglobin 13.5 g%, blood urea – 90 mg/dl; serum creatinine – 3.3 mg/dl; normal serum electrolytes with Na – 142, K – 3.8, Cl – 102 mmol/L, and bicarbonate – 22 mmol/L. Liver function test and lipid profile were normal. An ultrasonogram of the abdomen revealed normal-sized kidneys with grade one increased cortical echogenicity. Urine examination showed pH – 6; specific gravity – 1025; proteinuria – 1+; plenty of red blood cells (RBCs) and 5–6 pus cells; and few needle-shaped crystals. Phase-contrast microscopy of urine revealed RBCs, leukocytes, and refractile needle-shaped crystals [Figure 1], which were birefringent under polarized light [Figure 2] and confirmed to be acyclovir crystals. The patient was managed conservatively. Serum creatinine rapidly decreased from 3.3 mg% to 0.9 mg% within 1 week of stopping acyclovir and maintaining adequate hydration.Figure 1: Urine wet mount – Phase-contrast microscopy – needle-shaped crystals on the background of nonspecific particles – ×40Figure 2: Urine sediment – Polarizer – Birefringent needle-shaped crystals (on a background of nonspecific particles) – ×40Acyclovir is a widely used anti-viral drug. Oral bioavailability is 10%–30%. Approximately 15% is metabolized in the liver, while 85% of acyclovir is excreted unchanged by the kidney through glomerular filtration and tubular secretion. Half-life is 2–6 h, but it is prolonged to more than 20 h in renal failure. Peak plasma levels are very high in renal dysfunction.[1] Acute crystalline nephropathy is a reversible acute kidney injury due to intratubular acyclovir crystal precipitation and obstruction; histology may show crystals in the distal tubule with patchy interstitial infiltration without tubular necrosis.[2] Acute tubular necrosis has also been reported.[3] The risk factors are rapid intravascular infusion, elderly patients, volume depletion, preexisting renal disease, and concomitant nephrotoxic drug administration. Crystal nephropathy usually develops in about 12%–48% of patients within 24–48 h of rapid intravenous infusion, which has now decreased to 5% due to slowing of infusion to more than 1 h. Hemodialysis clears up to 60% of acyclovir in a single session of 4 h, while clearance on peritoneal dialysis is <10%.[4] This case highlights the rare occurrence of acute kidney injury following oral intake of acyclovir.[5,6] In every patient with acute kidney injury, a history of drug intake likely to produce a renal failure to be taken, and prompt stoppage of the offending drug may lead to improvement of renal function. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.