C5b-9 Deposition in Renal Transplant Biopsies Associates With Prolonged Delayed Graft Function in Kidneys Donated After Circulatory Death

BACKGROUND: Ischemia-reperfusion injury is a risk factor for delayed graft function (DGF). During reperfusion, the damaged tissues and cells are exposed to blood, thereby contributing to complement activation. The aim of this study was to investigate if complement activation correlates with the duration of DGF in donation after circulatory death (DCD) kidney transplants and whether it provides additional information beyond regular histology. METHODS: In day-10 protocol, biopsies from 64 DCD recipients, complement deposition (C4d, C3d, C5b-9) was assessed by immunohistochemistry, quantified and correlated with fDGF duration (early graft function [≤7 d], intermediate [8-20 d], and prolonged duration [≥21 d]), as well as with Banff classification. RESULTS: C4d and C3d deposition was not different between fDGF durations. In contrast, C5b-9 deposition was higher in recipients with prolonged DGF (median 8.1%) compared with those with early graft function (median 5.6%) and intermediate DGF (median 5.6%). Kidneys from expanded criteria donors exhibited significantly higher C5b-9 deposition compared with standard criteria donors (P = 0.001), but no correlation with warm or cold ischemia times. Banff classification scores showed only significant associations of C4d with interstitial inflammation (i), total inflammation (ti), and arteriolar hyalinosis (ah). Similar results were found with semiquantitative complement scoring in specific kidney compartments. No significant associations were observed between C5b-9 deposition and any of the Banff scores. CONCLUSIONS: C5b-9 deposition is increased in DCD kidneys with prolonged fDGF, representing a marker not reflected by Banff scoring. Higher C5b-9 levels in expanded criteria donors kidneys suggest that intrinsic donor factors contributes to early complement activation after transplantation.