INTRODUCTION

Polypharmacy, typically defined as the use of five or more medications, has become increasingly common among older adults due to the rising prevalence of multimorbidity. While polypharmacy can be clinically necessary, it poses substantial risks for adverse drug events, including acute kidney injury (AKI). Drug-induced AKI accounts for a significant proportion of hospital-acquired cases and can result in prolonged hospitalization, increased healthcare costs, and higher mortality. Despite growing concern over these risks, the incidence of AKI associated with polypharmacy and the specific clinical and pharmacological factors contributing to this risk remain poorly quantified across different populations and setting.

AIM

To estimate the incidence of AKI among adults exposed to polypharmacy and identify key drug-related and clinical risk factors.

METHOD

A systematic review and meta-analysis were conducted and reported following PRISMA guidelines. We searched eight international and Chinese databases from inception to April 2025 for observational studies involving adults (≥ 18 years) receiving polypharmacy that reported AKI incidence or related risk factors. Eligible studies were assessed using the Newcastle-Ottawa Scale. Random-effects meta-analysis was used to calculate pooled AKI incidence. A narrative synthesis summarized the definitions of polypharmacy and identified associated risk factors.

RESULTS

Ten studies comprising over 302,000 participants were included; six studies provided data suitable for meta-analysis. The pooled incidence of AKI among patients exposed to polypharmacy was 18% (95% CI 2%, 45%). Key risk factors included high medication burden (≥ 5 or ≥ 10 medications), cardiovascular drug combinations, use of nephrotoxic agents, pre-existing renal impairment, frailty, and exposure to intensive care. Definitions of polypharmacy varied substantially across studies, including count-based thresholds, class-specific definitions, and risk-based exposure models.

CONCLUSION

Polypharmacy is significantly associated with an increased incidence of AKI, particularly among hospitalized and clinically vulnerable individuals. The lack of standardized definitions for polypharmacy complicates evidence synthesis and cross-study comparisons. Standardized terminology and risk-adjusted prescribing practices are essential to improve medication safety and renal outcomes in at-risk populations.