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BackgroundRecent studies have demonstrated the key role of the complement alternative pathway (cAP) in the pathophysiology of experimental ANCA-associated vasculitis (AAV). However, in human AAV the role of cAP has not been extensively explored. In the present work, we analysed circulating serum C3 levels measured at AAV onset and their relation to outcomes.MethodsWe conducted a retrospective observational cohort study including 45 consecutive patients with AAV diagnosed between 2000 and 2014 with serum C3 measurement at diagnosis, before immunosuppressive treatment initiation. Two groups were defined according to the median serum C3 level value: the low C3 group (C3<120 mg/dL) and the high C3 level group (C3≥120 mg/dL). Patient and renal survivals, association between C3 level and renal pathology were analysed.ResultsSerum complement C3 concentration remained in the normal range [78–184 mg/dL]. Compared with the high C3 level, the patients in the low C3 level group had lower complement C4 concentrations (P = 0.008) and lower eGFR (P = 0.002) at diagnosis. The low C3 level group had poorer patient and death-censored renal survivals, compared with the high C3 level group (P = 0.047 and P = 0.001, respectively). We observed a significant negative correlation between C3 levels and the percentage of glomeruli affected by cellular crescent (P = 0.017, r = -0.407). According to the Berden et al renal histologic classification, patients in the crescentic/mixed category had low C3 levels more frequently (P<0.01). Interestingly, we observed that when patients with the crescentic/mixed histologic form were analysed according to C3 level, long term renal survival was significantly greater in the high C3 level group than in the low C3 level group (100% vs 40.7% at 6 years, p = 0.046). No relationship between serum C4 and renal outcome was observed.ConclusionA Low C3 serum level in AAV patients at diagnosis is associated with worse long-term patient and renal survival.

SUMMARYThe aim of this study was to compare the outcomes of kidney transplants from uncontrolled DCD (uDCD) with kidney transplants from extended (ECD) and standard criteria donors (SCD). In this multicenter study, we included recipients from uDCD (n = 50), and from ECD (n = 57) and SCD (n = 102) who could be eligible for a uDCD program. We compared patient and graft survival, and kidney function between groups. To address the impact of preservation procedures in uDCD, we compared in situ cold perfusion (ICP) with normothermic regional perfusion (NRP). Patient and graft survival rates were similar between the uDCD and ECD groups, but were lower than the SCD group (P < 0.01). Although delayed graft function (DGF) was more frequent in the uDCD group (66%) than in the ECD (40%) and SCD (27%) groups (P = 0.08 and P < 0.001), graft function was comparable between the uDCD and ECD groups at 3 months onwards post-transplantation. The use of NRP in the uDCD group (n = 19) was associated with a lower risk of DGF, and with a better graft function at 2 years post-transplantation, compared to ICP-uDCD (n = 31) and ECD. In conclusion, the use of uDCD kidneys was associated with post-transplantation results comparable to those of ECD kidneys. NRP preservation may improve the results of uDCD transplantation.