Risk factors for acute kidney injury associated with intravenous acyclovir in older adults: ACICLOAGED study

Intravenous acyclovir is the recommended treatment for suspected viral meningoencephalitis, but it may induce acute kidney injury. Evidence in very old adults is limited, particularly regarding the role of frailty in renal vulnerability.

We conducted a retrospective cohort study of adults aged 75 years or more who received intravenous acyclovir for suspected meningoencephalitis at a single university hospital between November 2021 and December 2024. Frailty was assessed using the 9-point Clinical Frailty Scale, with frailty defined as a score of 4 or higher. The primary outcome was acute kidney injury occurring within seven days of acyclovir initiation, identified according to international consensus criteria based on changes in serum creatinine levels. Logistic regression models were used to examine factors associated with acute kidney injury.

Among 139 included patients (median age 83 years; 38% women), 31% developed acute kidney injury within seven days. Frailty was present in 60% of the cohort and was more frequent among those who developed acute kidney injury (79% vs. 52%, p = 0.004). Age, sex, comorbidity burden, baseline renal impairment, excessive acyclovir dosing, prolonged treatment, and use of three or more nephrotoxic medications were not significantly associated with the outcome.

In adults aged 75 years or more treated with intravenous acyclovir for suspected meningoencephalitis, frailty was a strong and independent predictor of acute kidney injury, whereas chronological age and baseline renal function were not. Incorporating frailty assessment into clinical decision-making may help identify patients at higher risk and guide preventive strategies.