Renal C3 synthesis in idiopathic membranous nephropathy: Correlation to urinary C5b-9 excretion

Background. Complement activation plays a central pathogenetic role in idio pathic membranous nephropathy (IMN). Urinary excretion of C5b-9 correlates to the immunologic activity of this disease. Recently, renal cortical C3 ge ne expression has been described in several nephropathies. Methods. The aim of this study was to investigate the renal C3 gene express ion by in situ hybridization in IMN and to correlate it with histopathologi c, pathophysiologic, and immunologic (urinary C5b-9) indices of disease act ivity. Results. C3 was expressed in 77% of 22 renal biopsies of IMN patients, main ly at the cortical tubular and glomerular parietal epithelial cell levels. C3 protein synthesis by tubular cells was demonstrated by immunofluorescenc e. The intensity of C3 gene expression by both glomerular and tubulointerst itial compartments correlated with the glomerular stage of disease (P = 0.0 023 and P = 0.0214, respectively). Although no correlation was found with p roteinuria, serum creatinine at renal biopsy time was strongly associated w ith renal C3 expression. IMN patients showed a trend of increased urinary C 5b-9 levels, which correlated to C3 at the tubulointerstitial level (P = 0. 0143). Conclusion. Renal C3 production, mainly at the tubular level, may be induce d by urinary excretion of C5b-9 in IMN and may have a pathogenetic role in the tubulointerstitial damage that can be associated with this disease.