Rossi, G.M.; Ricco, F.; Pisani, I.; Delsante, M.; Maggiore, U.; Fiaccadori, E.; Manenti, L. C3 Hypocomplementemia Predicts the Progression of CKD towards End-Stage Kidney Disease in IgA Nephropathy, Irrespective of Histological Evidence of Thrombotic Microangiopathy. J. Clin. Med.2024, 13, 2594.
Rossi, G.M.; Ricco, F.; Pisani, I.; Delsante, M.; Maggiore, U.; Fiaccadori, E.; Manenti, L. C3 Hypocomplementemia Predicts the Progression of CKD towards End-Stage Kidney Disease in IgA Nephropathy, Irrespective of Histological Evidence of Thrombotic Microangiopathy. J. Clin. Med. 2024, 13, 2594.
Rossi, G.M.; Ricco, F.; Pisani, I.; Delsante, M.; Maggiore, U.; Fiaccadori, E.; Manenti, L. C3 Hypocomplementemia Predicts the Progression of CKD towards End-Stage Kidney Disease in IgA Nephropathy, Irrespective of Histological Evidence of Thrombotic Microangiopathy. J. Clin. Med.2024, 13, 2594.
Rossi, G.M.; Ricco, F.; Pisani, I.; Delsante, M.; Maggiore, U.; Fiaccadori, E.; Manenti, L. C3 Hypocomplementemia Predicts the Progression of CKD towards End-Stage Kidney Disease in IgA Nephropathy, Irrespective of Histological Evidence of Thrombotic Microangiopathy. J. Clin. Med. 2024, 13, 2594.
Abstract
IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. IgAN causes end-stage kidney disease (ESKD) in 20–40% of all cases. The activation of the complement system by pathological circulating IgAs, which is often associated with low serum C3 levels (LowC3), seems to play a crucial role. Previous studies have shown an association between histological evidence of TMA, which is the result of alternative complement activation, and poor outcome. However, it is not known to what extent the decrease in serum C3 levels reflects ongoing TMA injury. Our study aimed at assessing the association of LowC3 and ESKD and whether this association reflects ongoing TMA. We enrolled all patients with biopsy-proven IgAN and followed-up patients until last visit, ESKD or death. Of the 56 patients included in the study, 12 (21%) presented low serum C3 (LowC3) at the time of renal biopsy. TMA was significantly more frequent in the LowC3 group [7/12 (58%) vs 9/44 (20%), p=0.02]. After adjusting for potential confounders, LowC3 was strongly associated with an increased hazard of ESKD (hazard ratio [HR]: 5.84 [95%CI: 1.69,20.15; P=0.005). The association was not affected by adjusting for TMA. The estimated overall proportion of the relation between C3 and ESKD mediated by TMA was low and not statistically significant. Our study provides evidence that C3 hypocomplementemia is associated with an increased risk of ESKD with mechanisms that are largely independent from TMA.
Keywords
IgA Nephropathy; complement; thrombotic microangiopathy; end-stage kidney disease
Subject
Medicine and Pharmacology, Urology and Nephrology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
