FP721COMPLOSOME AFFECTS THE OUTCOME AFTER INCIDENT KIDNEY TRANSPLANTATION

Abstract

Introduction and Aims:The complement system has recentlybeen recognized as a crucial pathogenic mediator of various kidney diseases and after kidney transplantation. Activation of the complement cascades cumulates into the generation of ana-phylatoxins (e.g., C3a and C5a), opsonins (e.g., C3b), and pore-forming membrane attack complex (i.e., C5b-9). The objective was to investigate whether the complosome including plasma complement factors obtained at the first postoperative days predicted the allograft function after kidney transplantation. Methods: We prospective investigated a total of 181 incident kidney transplant recipients. We analyzed plasma complosome in individual samples by quantitative pro-teomics using stable isotope labeling of plasma samples with isobaric tags for relative and absolute quantitation (iTRAQ) combined with nano-Liquid-Chromatography-Tandem Mass-Spectrometry (nano-LC-MSMS). Estimated glomerular filtration rate (eGFR) in kidney recipients was determined four weeks after transplantation using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Results: 30 complement factors and regulatory proteins were simultaneously quanti-fied in 181 incident kidney transplant recipients. Recipients from deceased donors showed significantly higher complement factor C3 levels (Median, 1.08; IQR, 1.00 to 1.21 compared to AB0-incompatible living donors (Median, 0.97; IQR, 0.90 to 1.04; p<0.0001) or AB0-compatible living donors (Median, 1.01; IQR, 0.93 to 1.11; p<0.001 by Kruskal-Wallis test with Dunn's multiple comparisons test). Deceased donors also showed significantly higher complement factor C9 levels (Median, 1.18; IQR, 0.97 to 1.34) compared to AB0-incompatible living donors (Median, 0.89; IQR, 0.82 to 0.95; p<0.0001) or AB0-compatible living donors (Median, 0.99; IQR, 0.87 to 1.13; p<0.001 by Kruskal-Wallis test with Dunn's multiple comparisons test). Conclusions: Increased complement factor levels are associated with worse outcome after kidney transplantation.