Impact of kidney dysfunction on outcomes in peripheral artery disease: A multi-database cohort study

Peripheral artery disease (PAD) and kidney dysfunction frequently coexist, worsening clinical outcomes. This study aimed to clarify the relationship between PAD and kidney dysfunction, including their co-occurrence, impact on outcomes, and potential causal links. Analyzing GBD 2021 data, we identified a global PAD prevalence of 1,326.45 per 100,000, with renal impairment as a primary mortality driver. CDC WONDER data ranked renal disease 8th in PAD-related deaths (AAMR 0.22). In MIMIC-IV (n = 2,133), AKI significantly raised 30-day mortality (21.01% vs. 7.23%; HR = 3.21), while CKD stage 4-5 increased 365-day mortality risk (HR = 2.20). 2H-SXMU clinical cohort (n = 200) showed lower eGFR (74.9 vs. 84.6 mL/min/1.73 m²) associated with increased major adverse limb events. Mendelian randomization confirmed a negative causal effect of PAD on eGFR (OR = 0.997, p = 1.75e^-3), with no reverse causation found. These findings demonstrate that PAD contributes to declining renal function, highlighting the need for integrated nephrology vascular care and routine renal monitoring in PAD management.