title: Intravenous acyclovir and renal dysfunction in children: a matched case control study.
abstract: OBJECTIVE
  A cluster of children receiving intravenous (IV) acyclovir for meningoencephalitis developed acute renal failure in April-May 2008, which prompted a retrospective case-control study to determine the rate of and risk factors for acute nephrotoxicity during IV acyclovir treatment in children.
  
  
  METHODS
  The percentage decrease in glomerular filtration rate in children receiving IV acyclovir who had ≥ 1 creatinine measurement after acyclovir initiation from October 2006 to January 2009 was classified as renal risk, injury, or failure according to modified Pediatric Risk Injury, Failure, Loss, End-Stage Renal Disease criteria. Univariate and multivariate matched analyses were conducted to identify risk factors contributing to nephrotoxicity.
  
  
  RESULTS
  In the selected study group, renal dysfunction was seen in 131 of 373 (35%) treatment courses studied: 81 of 373 (22%) risk, 36 of 373 (9.7%) injury, and 14 of 373 (3.8%) failure. Most renal dysfunction occurred within 48 hours of the initiation of acyclovir. Renal function returned to the normal range but not to baseline in most cases during the follow-up period. Risk factors for renal dysfunction included acyclovir dose >15 mg/kg (OR 3.81, 95% CI 1.55-9.37) for risk; cumulative exposure greater than calculated cumulative exposure based on 500 mg/m(2)/dose (OR 6.00, 95% CI 1.95-18.46) for injury; and age >8 years (OR 21.5, 95% CI 2.2, >1000) and ceftriaxone coadministration (OR 19.3, 95% CI 1.8, >1000) for failure.
  
  
  CONCLUSIONS
  Nephrotoxicity associated with IV acyclovir is common and necessitates renal function monitoring. Risk factors include greater dose, older age, and concomitant ceftriaxone administration. Outside the neonatal period, renal dysfunction may be minimized by dosing IV acyclovir below thresholds associated with nephrotoxicity (ie, ≤ 500 mg/m(2)/dose or ≤ 15 mg/kg/dose), particularly in older patients.
authors.affiliation: Department of Pediatrics (Infectious Diseases and Hospital Medicine), University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO. Electronic address: suchitra.rao@childrenscolorado.org.
authors.forename: Suchitra
authors.initials: S
authors.lastname: Rao
authors.affiliation: Department of Pediatrics (Infectious Diseases and Hospital Medicine), University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Abzug
authors.affiliation: Department of Pediatrics (Infectious Diseases and Hospital Medicine), University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO.
authors.forename: Phyllis
authors.initials: P
authors.lastname: Carosone-Link
authors.affiliation: Department of Pharmacy, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO.
authors.forename: Tori
authors.initials: T
authors.lastname: Peterson
authors.affiliation: Department of Pharmacy, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO.
authors.forename: Jason
authors.initials: J
authors.lastname: Child
authors.affiliation: Department of Clinical Informatics, Children's Hospital of Colorado, Aurora, CO.
authors.forename: Georgette
authors.initials: G
authors.lastname: Siparksy
authors.affiliation: Section of Nephrology, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO.
authors.forename: Danielle
authors.initials: D
authors.lastname: Soranno
authors.affiliation: Section of Nephrology, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Cadnapaphornchai
authors.affiliation: Department of Pediatrics (Infectious Diseases and Hospital Medicine), University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO; Department of Epidemiology, Colorado School of Public Health and Children's Hospital Colorado, Aurora, CO.
authors.forename: Eric A F
authors.initials: EA
authors.lastname: Simões
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000453:epidemiology*; D000212:Acyclovir / Q000008:administration & dosage*; D000293:Adolescent; D000998:Antiviral Agents / Q000008:administration & dosage*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D020803:Encephalitis, Herpes Simplex / Q000188:drug therapy; D020804:Encephalitis, Varicella Zoster / Q000188:drug therapy; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D000212:Acyclovir