Hyperpolypharmacy in patients with chronic kidney disease and its impact on clinical outcomes

Hyperpolypharmacy (≥ 10 daily medications) is frequent in patients with chronic kidney disease (CKD), but its impact remains poorly characterized. This study, based on 3,011 non-dialyzed, non-transplant CKD outpatients from the CKD-REIN cohort (eGFR < 60 mL/min/1.73 m²) aimed to describe drug burden and assess associations between hyperpolypharmacy and adverse outcomes. Drug prescription, kidney function, adverse drug reactions (ADRs), hospitalizations, kidney replacement therapy and deaths before KRT were prospectively recorded over five years. Median age was 69 years and mean eGFR was 34 mL/min/1.73 m². At baseline, 80% of the cohort had polypharmacy (≥ 5 daily medications), and 33% had hyperpolypharmacy. These rates remained stable over time. Diabetes, dyslipidemia, and a history of cardiovascular and respiratory diseases were the main contributors to hyperpolypharmacy status. Hyperpolypharmacy was associated with greater likelihoods of an ADR (hazard ratio (HR) [95% confidence interval (CI)] 1.21 [1.04-1.40]), hospitalization (HR [95%CI] 1.34 [1.18-1.51]) and death before KRT (HR [95%CI] 1.46 [1.17-1.82]). Among patients with eGFR ≥ 30 mL/min/1.73m², hyperpolypharmacy also raised the risk of KRT initiation (HR [95%CI] 1.46 [1.00-2.13]), but not in those with eGFR < 30 (HR [95%CI] 0.94 [0.78-1.14]). These results identify hyperpolypharmacy as a significant concern in CKD and underscore the importance of regular medication reviews to reduce adverse outcomes.