Jan Yuan-Sheng Hsu, Jian‐Ri Li, Chuan-Shu Chen, Che-Jui Yang
PURPOSE: Phosphodiesterase type 5 (PDE5) inhibitors are commonly prescribed for erectile dysfunction (ED) and benign prostatic hyperplasia (BPH) in kidney transplant recipients (KTRs), but their cardiovascular and renal associations in this population remain unexamined. This study evaluated these associations in male KTRs with ED or BPH. METHODS: This retrospective cohort study used TriNetX Global Collaborative Network data (January 2015-December 2023). Male KTRs ≥ 40 years with ED or BPH were identified using a unified diagnosis index date in both arms, with PDE5 inhibitor exposure bounded to days 0-365. Three drug strata (tadalafil 5 mg daily, tadalafil, sildenafil) were propensity-matched 1:1 against controls on thirty covariates. Balance was assessed by standardized mean differences. Primary outcomes (all-cause mortality, MACE excluding death, MAKE excluding death) were analyzed by Cox regression and Kaplan-Meier methods. Secondary outcomes comprised individual components (AMI, stroke, and dialysis initiation). RESULTS: All-cause mortality was inversely associated with PDE5 inhibitor exposure across all six strata (HR 0.574-0.697). MACE excluding death was inversely associated in the ED cohort for tadalafil 5 mg daily (HR 0.527) and tadalafil all doses (HR 0.620), but not sildenafil; no composite associations reached significance in the BPH cohort. Two secondary outcomes survived Benjamini-Hochberg correction: MACE excluding death and AMI in the ED tadalafil all-doses stratum (q = 0.023 and q = 0.041). Negative control outcomes near unity supported propensity score balance. CONCLUSION: PDE5 inhibitor exposure was associated with lower all-cause mortality in male KTRs with ED or BPH. Composite cardiovascular and renal associations were stratum-dependent. These findings are hypothesis-generating and require prospective evaluation.