Factors associated with acyclovir nephrotoxicity in children: data from 472 pediatric patients from the last 10 years.

Acyclovir may cause acute kidney injury (AKI) due to the accumulation of relatively insoluble acyclovir crystals in renal tubules. The aim of this study was to evaluate risk factors associated with acyclovir-related AKI in children. Between January 2010 and December 2019, pediatric recipients of intravenous (IV) acyclovir were evaluated retrospectively. There were a total of 472 patients [249 (52.7%) boys] of which 32 (6.8%) had AKI [15 (46.8%) boys]. Patients with AKI had greater mean age, baseline creatinine level, and duration of treatment compared to patients without AKI (p<0.001). In the AKI group, concomitant nephrotoxic drug use was more frequent (p=0.032), and the percentage of patients treated with 1500 mg/m2/day dosage was higher (p<0.001). AKI was diagnosed at a mean of 4.3 ± 2.5 days after acyclovir initiation and creatinine levels returned to normal at a mean of 7.3 ± 3.6 days after AKI diagnosis. Only eight patients (25%) had vomiting which led to suspicion of AKI. Being older than 100.5 months (HR: 4.501, 95% CI: 1.802-11.241; p=0.001), use of 1500 mg/m2/day acyclovir (HR: 9.536, 95% CI: 2.157-42.158; p=0.003) and use of concomitant nephrotoxic drugs (HR: 5.043, 95% CI: 2.289-11.109; p<0.001) were the factors that independently increased the likelihood of nephrotoxicity.
Conclusion: Most patients were asymptomatic when they were diagnosed with AKI. Clinicians should be aware of AKI risk in pediatric patients with risk factors (age >100.5 months, 1500 mg/m2/day dosage, concomitant use of nephrotoxic drugs). Acyclovir dosing should be evaluated in prospective, multicenter studies in order to identify the lowest possible therapeutic doses that do not increase AKI risk. What is Known: • Although acyclovir is mostly well tolerated, nephrotoxicity may be seen due to the accumulation of acyclovir crystals in renal tubules. • Older age, obesity, and concomitant use of other nephrotoxic drugs are reported to be risk factors for acyclovir-induced AKI in children. What is New: • In this study, pediatric patients with acyclovir-induced AKI were older, received treatment longer, received concomitant nephrotoxic drugs more commonly, and had higher acyclovir dosage and baseline creatinine levels compared to those without AKI. • Being older than 100.5 months of age, use of 1500 mg/m2/day dosage and use of nephrotoxic drugs concomitantly appear to be the prominent risk factors for AKI development in children treated with acyclovir.