Association of Excessive Polypharmacy with Clinical Outcomes Following Kidney Transplantation

Background: Polypharmacy (PP), the use of multiple medications, is common among kidney transplant recipients (KTRs) owing to lifelong immunosuppressive therapy and comorbidity management. However, its impact on clinical outcomes remains unclear. In this study, we examine the association between PP and adverse outcomes in KTRs. Methods: We analyzed the data of 972 KTRs from the Korean Cohort Study for Outcomes in Patients with Kidney Transplantation (KNOW-KT). Excessive PP (ePP) was defined as ≥10 medications at 1-year post-transplant. The outcomes included all-cause mortality, graft failure, and cardiovascular events. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. Results: At one year post-transplant, 49% of patients were classified as having ePP, with a mean of 9.8 medications. After IPTW, no significant differences were observed between groups in terms of all-cause mortality (HR 1.3, 95% CI 0.78–2.02) or graft failure (HR 1.0, 95% CI 0.73–1.30). However, ePP was significantly associated with an increased risk of CV events (HR 1.8, 95% CI 1.07–2.96, P = 0.026). The incidence rate of CV events was 11.7 per 1,000 person-years in the ePP group versus 7.1 in the non-ePP group. Kaplan–Meier curves and weighted log-rank tests confirmed a significantly lower CV event-free survival in the ePP group (P < 0.001). Sensitivity analysis using Winsorization and competing risk models yielded consistent results, with the ePP group showing a 74% increased risk of CV events (HR 1.74, 95% CI 1.05–2.90, P = 0.033), even after accounting for death as a competing event. Conclusion: These findings suggest that while ePP may not directly affect patient or graft survival, it significantly increases the long-term cardiovascular burden in KTRs. Given that CV disease remains a leading cause of morbidity and mortality post-transplant, our results highlight the importance of structured medication review and risk-based deprescribing strategies.