Evaluation of Aciclovir-Induced Nephrotoxicity in Critically Ill Patients: A Propensity-Matched Cohort Study

<b>Background/Objectives:</b> Aciclovir is a widely used antiviral agent. Since aciclovir is primarily eliminated through the kidneys, maintaining renal function is crucial to avoid toxicity. Although mitigating strategies are introduced in the standard of care, nephrotoxicity is still a major concern during treatment, especially for critically ill intensive care unit (ICU) patients. Therefore, risk factors for the development of nephrotoxicity during aciclovir therapy should be addressed. This study aimed to evaluate if aciclovir in combination with therapeutic drug monitoring (TDM) and additional nephrotoxicity-mitigating strategies is associated with a decrease in renal function in critically ill ICU patients. <b>Methods:</b> In a cohort of ICU patients with or without intravenous aciclovir treatment (including standard of care mitigating strategies) propensity score matching was applied to balance baseline characteristics between aciclovir-treated and untreated groups. Aciclovir was monitored by measuring serum levels and the dose was adjusted when needed. Renal function was primarily assessed through serum creatinine. Univariate and multivariate regression analyses were used to identify risk factors for nephrotoxicity during ICU admission. <b>Results</b>: After propensity score matching, the study included 518 ICU patients, of whom 259 received aciclovir. Aciclovir was not associated with a significant decrease in renal function during admission. In fact, renal function appeared to improve in the aciclovir-treated group compared to the control group (beta-coefficient: -14.5 (95% confidence interval: -28.3 to -0.68), <i>p = 0.04</i>). Median aciclovir concentrations remained within the exploratory therapeutic range. <b>Conclusions</b>: Aciclovir therapy, at least when appropriately monitored, does not independently induce nephrotoxicity in critically ill ICU patients. TDM may further enhance safety by preventing supratherapeutic drug exposures. The results are significant as they provide evidence supporting the safe use of aciclovir in a vulnerable patient population. Future studies should focus on establishing therapeutic and toxic concentration thresholds for aciclovir and assessing the clinical utility of TDM in this context.