Mediation analysis identifies causal factors that lead to increased rates of kidney transplant failure in patients with peripheral vascular disease

Background: This study aims to identify causal mediators of one-year kidney transplant failure in patients with peripheral vascular disease. Methods: Standard Transplant Analysis and Research database was queried for adults who underwent kidney transplantation from 1987 to 2021. Multi-organ transplant, prior transplant, and living donor kidneys were excluded. Causal mediation analysis with 2000 percentile bootstrapping interactions identified mediators of oneyear kidney transplant failure. Results: 212,259 patients were included: 16,215 with and 196,044 without peripheral vascular disease. Causal mediators of one-year kidney transplant failure are Kidney Donor Profile Index (proportionate mediation [PM] 17 %, p < 0.01, E-value = 1.20), pre-transplant dialysis (PM 19%, p < 0.001, E-value = 1.17), recipient total serum albumin (PM 2 %, p = 0.003, E-value = 1.05), and donor hypertension (PM 1 %, p = 0.017, E-value = 1.04). Conclusions: Several causal mediators increase rates of one-year kidney transplant failure in patients with peripheral vascular disease. Understanding these mediators can improve pre-transplant assessments and post- transplant outcomes.