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.


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 <or= 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.
Schreiber
Ruth
R
Division of Clinical Pharmacology/Toxicology, Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.
Wolpin
Jacob
J
Koren
Gideon
G
D000212:Acyclovir / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007223:Infant; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D015999:Multivariate Analysis; D051437:Renal Insufficiency / Q000139:chemically induced*; D012189:Retrospective Studies; D012307:Risk Factors
D000998:Antiviral Agents; D003404:Creatinine; D000212:Acyclovir