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


BACKGROUND
Complement activation plays a central pathogenetic role in idiopathic membranous nephropathy (IMN). Urinary excretion of C5b-9 correlates to the immunologic activity of this disease. Recently, renal cortical C3 gene expression has been described in several nephropathies.


METHODS
The aim of this study was to investigate the renal C3 gene expression by in situ hybridization in IMN and to correlate it with histopathologic, pathophysiologic, and immunologic (urinary C5b-9) indices of disease activity.


RESULTS
C3 was expressed in 77% of 22 renal biopsies of IMN patients, mainly at the cortical tubular and glomerular parietal epithelial cell levels. C3 protein synthesis by tubular cells was demonstrated by immunofluorescence. The intensity of C3 gene expression by both glomerular and tubulointerstitial compartments correlated with the glomerular stage of disease (P = 0. 0023 and P = 0.0214, respectively). Although no correlation was found with proteinuria, serum creatinine at renal biopsy time was strongly associated with renal C3 expression. IMN patients showed a trend of increased urinary C5b-9 levels, which correlated to C3 at the tubulointerstitial level (P = 0.0143).


CONCLUSIONS
Renal C3 production, mainly at the tubular level, may be induced 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.
Montinaro
V
V
Division of Nephrology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy. v.montinaro@nephro.uniba.it
Lopez
A
A
Monno
R
R
Cappiello
V
V
Manno
C
C
Gesualdo
L
L
Schena
F P
FP
D000328:Adult; D000368:Aged; D003176:Complement C3 / Q000096:biosynthesis* / Q000235:genetics; D015938:Complement Membrane Attack Complex / Q000652:urine*; D005260:Female; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D015433:Glomerulonephritis, Membranous / Q000378:metabolism* / Q000652:urine; D006801:Humans; D017403:In Situ Hybridization; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics
D003176:Complement C3; D015938:Complement Membrane Attack Complex; D012333:RNA, Messenger