Non-HLA Autoantibodies at 1 Year Negatively Affect 5-Year Native Renal Function in Liver Transplant Recipients

Background: Angiotensin II type-1 receptor (AT₁R) and endothelin-1 type A receptor (ET_AR) autoantibodies, in addition to allograft injury, can bind native endothelial cells and cause vascular vasoconstriction and fibrosis progression in nontransplanted organs. Therefore, we investigated long-term native renal function in liver transplant (LT) recipients with and without anti-AT₁R-Abs and/or anti-ET_AR-Abs present in serum. Methods: Primary LT recipients at our single center from January 2000 to April 2009 had their prospectively collected pre-LT (1269 patients) and year 1 post-LT (795 patients) serum tested retrospectively for anti-AT₁R-Abs and/or anti-ET_AR-Abs. Anti-AT₁R-Abs and anti-ET_AR-Abs testing was accomplished with a standardized solid phase assay in which >10 U was considered positive. Results: Pretransplant anti-AT₁R-Abs and/or anti-ET_AR-Abs did not change the median delta creatinine from pretransplant to 1 year post-transplant. In multivariable analysis controlling for diabetes (DM) and calcineurin inhibitor (CNI) use, anti-AT₁R-Abs and/or anti-ET_AR-Abs at 1-year remained statistically significantly associated with a decline in GFR (measured by Modification of Diet in Renal Disease-6) from years 1-5 post-LT (P = .04). In diabetic patients the association with a decline in renal function was more pronounced with (-9.29 mL/min) vs without (-2.28 mL/min) anti-AT₁R-Abs and/or anti-ET_AR-Abs at year 1, respectively (P = .004). Conclusion: At 1-year post-LT, the autoantibodies anti-AT₁R-Abs and/or anti-ET_AR-Abs are associated in multivariable analysis with an increased risk of native renal function decline especially in diabetic patients.