Acute kidney injury after valacyclovir administration for prevention of congenital cytomegalovirus infection.

Abstract

Cytomegalovirus (CMV) is the most common cause of congenital infection, affecting about 0.6% of all live births worldwide1. Congenital CMV infection can have severe consequences, including long-term neurosensory sequelae, with it being the leading cause of congenital deafness of non-genetic origin2. Recently, the use of high-dose oral valacyclovir (an acyclovir prodrug) to prevent vertical transmission of CMV after maternal primary infection during the first trimester has been shown to be beneficial, with a 71% reduction in the congenital infection rate3. This may lead to a change in international recommendations in favor of systematic screening for CMV infection and treatment during pregnancy. We read with great interest the recent study by Faure-Bardon et al., which reported on a longitudinal cohort of 269 cases of maternal primary CMV infection treated with high-dose oral valacyclovir in the first trimester of pregnancy to prevent fetal CMV infection4. One case of acute kidney injury, which resolved within 5 days after valacyclovir discontinuation, was reported. We report here our own experience of a pregnant woman with primary CMV infection who developed acute kidney injury following high-dose valacyclovir administration. The 35-year-old woman had no noteworthy medical history except for two previous normal pregnancies. During her third pregnancy, she was diagnosed with periconceptional primary CMV infection on routine serological screening at 6 + 3 weeks' gestation based on the last menstrual period (both anti-CMV immunoglobulin M and immunoglobulin G were positive, with an avidity index of 37%). At 7 + 1 weeks, the woman was started on oral valacyclovir (4 g per day for 8 days and then 8 g per day thereafter); she was not taking any other medication. She complained of pruritus and asthenia, without skin damage, 1 day after treatment initiation. Laboratory testing revealed KDIGO (Kidney Disease: Improving Global Outcomes) Stage-3 acute kidney injury at 14 days of treatment (serum creatinine, 3.3 mg/dL vs 0.8 mg/dL at 7 days) (Figure 1a). Physical examination was unremarkable, including normal blood pressure. High C-reactive protein level was noted (72 mg/L, normal range < 5 mg/L) without elevation of white-blood-cell count or hypereosinophilia. Liver enzyme levels were normal. Urine laboratory testing showed a protein-to-creatinine ratio of 0.03 g/mmol, with a high level of low-molecular-weight proteins (urine retinol-binding protein-to-creatinine ratio, 0.7 mg/mmol (normal range < 0.08 mg/mmol) and β2-microglobulin-to-creatinine ratio, 1268 µg/mmol (normal range < 32 μg/mmol)). Aseptic leukocyturia was present (white-blood-cell count, 31/mm3, normal range < 10/mm3). Kidney ultrasonography did not demonstrate any abnormalities. Urinalysis using manual microscopy revealed needle-shaped crystals, consistent with acyclovir crystals (crystal count 1.5/mm3) (Figure 1b). Valacyclovir treatment was immediately discontinued. Therapeutic management consisted of intravenous hydration. Kidney function improved rapidly after valacyclovir discontinuation, and the patient experienced full recovery (serum creatinine level was 0.8 mg/dL 14 days after cessation of treatment) (Figure 1a). Kidney biopsy was not performed because renal function improved promptly. Urine acyclovir crystallization is a complication of high-dose acyclovir infusion5 as well as of high-dose valacyclovir administration. The main identified risk factors are rapid intravascular volume depletion and underlying renal insufficiency6. Given its potential benefits, use of valacyclovir is expected to increase rapidly around the world. However, prescribers should be aware of its potential associated risks. In this regard, physicians should prescribe ample hydration when high-dose valacyclovir is required and monitor closely kidney function in order to allow prompt detection of adverse renal effects and discontinuation of valacyclovir. We thank Dr Vincent Frochot for performing photomicrography of acyclovir crystals. Data are available.