Immune Sensitization and Mortality On the Waiting List for Kidney Transplantation.

Abstract

Purpose: Cardiovascular mortality is the leading cause of death in end-stage renal disease (ESRD) patients. Inflammation has been shown to play a role in cardiovascular disease. Anti-HLA antibodies, measured as panel reactive antibodies (PRA), may also be a marker of inflammation. PRA is routinely monitored in ESRD patients on the waiting list to facilitate transplantation with a compatible donor. Whether PRA is a risk factor for cardiovascular mortality in ESRD is unknown. Methods: Using the Scientific Registry of Transplant Recipients, we conducted a retrospective cohort study in first-time adult kidney transplant candidates. The relationship between PRA modeled as a time-varying categorical variable (PRA 0%, PRA 1-19%, PRA 20-79%, and PRA 80-100%) and cardiovascular mortality was assessed in Cox proportional hazards models. All-cause mortality was a secondary endpoint. The analysis was repeated in a subcohort of transplant candidates at low risk for significant comorbidity. Competing risk analyses evaluating the effect of time-fixed PRA category upon activation on study endpoints were also conducted. In these analyses, transplantation and non-cardiovascular mortality were considered competing events. Results: Among 161,308 kidney transplant candidates, Cox models showed an increase in the hazard ratio (HR [95% confidence interval]) for cardiovascular mortality (HR 1.04 [0.95, 1.13], 1.23 [1.12, 1.36], and 1.45 [1.28, 1.65]) and all-cause mortality (HR 1.01 [0.95, 1.08], 1.11 [1.02, 1.21], and 1.17 [1.05, 1.31]) in PRA 1-19%, PRA 20-79%, and PRA 80-100% categories compared with PRA 0%, respectively. The relationship was accentuated in patients at low risk for significant comorbidity (cardiovascular mortality: HR 1.14 [0.64, 2.06], 1.85 [1.07, 3.21], and 3.90 [2.21, 6.90]; all-cause mortality: HR 0.97 [0.78, 1.20], 1.25 [1.01, 1.56], and 1.53 [1.18, 2.00]) and in the competing risks models (cardiovascular mortality: HR 1.03 [0.94, 1.12], 1.22 [1.09, 1.36], and 1.58 [1.37, 1.84]; all-cause mortality: HR 1.05 [1.01, 1.08], 1.20[1.15, 1.25], and 1.52 [1.44, 1·62]). Conclusion: Our findings suggest that PRA may be an independent risk factor for mortality on the waiting list for kidney transplantation. Current organ allocation schemes may need to consider this additional risk of mortality in sensitized candidates awaiting kidney transplantation. Whether transplantation modifies the risk of cardiovascular mortality in sensitized patients requires further study.