Intravenous acyclovir and renal dysfunction in children: a matched case control study
Suchitra Rao1, Mark J Abzug1, Phyllis Carosone-Link1
1Department of Pediatrics (Infectious Diseases and Hospital Medicine), University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO.
Insights
Intravenous acyclovir can cause acute kidney injury in children, with higher doses and certain co-medications increasing risk. Monitoring renal function is crucial, and doses should be kept below established thresholds to minimize nephrotoxicity.
Area of Science:
- Pediatric Nephrology
- Infectious Diseases
- Clinical Pharmacology
Background:
- A cluster of acute renal failure cases in children treated with intravenous acyclovir prompted this investigation.
- Intravenous acyclovir is a critical antiviral medication for treating serious infections like meningoencephalitis in children.
Purpose of the Study:
- To determine the incidence and risk factors of acute kidney injury (AKI) associated with intravenous acyclovir in pediatric patients.
- To identify specific patient and treatment parameters that increase the risk of nephrotoxicity.
Main Methods:
- A retrospective case-control study design was employed.
- Renal function was assessed using modified Pediatric Risk Injury, Failure, Loss, End-Stage Renal Disease criteria based on creatinine measurements.
- Univariate and multivariate analyses identified risk factors for nephrotoxicity.
Main Results:
- Nephrotoxicity occurred in 35% of treatment courses, with 22% classified as risk, 9.7% as injury, and 3.8% as failure.
- Higher acyclovir doses (>15 mg/kg), cumulative exposure exceeding 500 mg/m²/dose, older age (>8 years), and coadministration with ceftriaxone were significant risk factors.
- Most renal dysfunction developed within 48 hours of initiating acyclovir treatment.
Conclusions:
- Acute kidney injury from intravenous acyclovir is common in children and requires vigilant renal function monitoring.
- Key risk factors include higher drug dosage, older age, and concurrent use of ceftriaxone.
- Optimizing acyclovir dosing below 500 mg/m²/dose or 15 mg/kg/dose, especially in older children, may reduce the incidence of nephrotoxicity.
Objectives:
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.
Study Design:
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.
