Determinants of aciclovir-induced nephrotoxicity in children

Background: Aciclovir is the drug of choice for severe systemic herpes virus infections. Nephrotoxicity is one of the clinically significant adverse effects of this drug, but studies examining nephrotoxicity in children are scarce. Objective: To identify risk factors for aciclovir-associated nephrotoxicity in the pediatric population. Patients and methods: A retrospective review was conducted on all children (mean age 81 months; n = 126 [74 boys]) who were treated with aciclovir in a tertiary center between July 2005 and January 2006 and who met our inclusion criteria. Glomerular filtration rate (GFR) was calculated on the first day of treatment and at the peak measured creatinine level while on therapy, using Schwartz's method. Results: Aciclovir therapy was associated with a significant increase in serum creatinine levels and a parallel decrease in GFR (n = 93; both p ≤ 0.0001). Children with immunosuppression who received a variety of other nephrotoxic drugs exhibited more severe nephrotoxicity than those not receiving nephrotoxic drugs. In multiple regression analysis, the use of nephrotoxic drugs (p = 0.02) and impaired GFR at baseline (p = 0.04) were predictive for nephrotoxicity. Conclusions: Within the recommended age-dependent dosage schedule of aciclovir there was no effect of dose per kg, age, or sex on nephrotoxicity. The predictors of aciclovir nephrotoxicity were the concomitant use of nephrotoxic drugs and impaired GFR at baseline.