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C5b-9 Glomerular Deposits Are Associated With Poor Renal Survival in Membranous Nephropathy
Maxime Teisseyre1,2, Anaïs Beyze1,2, Hélène Perrochia3
1Department of Nephrology, Dialysis and Transplantation, Lapeyronie Hospital, Montpellier University Hospital, University of Montpellier, Montpellier, France.
Introduction:
Membranous nephropathy (MN) is the first cause of nephrotic syndrome in patients without diabetes. Its prognosis is variable, and treatment remains controversial because of potential toxicity. Currently, there is no reliable prognostic marker common to all etiologies of MN and routinely available to predict the disease course and guide therapeutic management. Despite the major role of complement in the glomerular damage of MN, its prognostic impact has never been studied. We investigated the frequency and prognostic impact of glomerular deposition of C5b-9 in MN.
Methods:
We retrospectively selected adults diagnosed with MN (primary or secondary) at Montpellier University Hospital between December 2004 and December 2015. To be included, all patients were required to have complete medical data and a kidney tissue sample for further immunohistochemistry. We performed PLA2R1, C4d, and C5b-9 staining by immunohistochemistry.
Results:
Sixty-four adults were included: 45 with primary MN and 19 with secondary MN. C4d was positive in the glomeruli of 61 adults (95.3%). Twenty-nine adults (45.3%) had glomerular deposition of C5b-9. Patients with glomerular deposition of C5b-9 had more severe nephrotic syndrome on diagnosis and lower remission and renal survival rates than adults without.
Conclusion:
C5b-9 glomerular staining is a powerful and easily accessible tool for stratifying adults according to their renal prognosis. The efficacy of complement inhibitors should be tested in adults with glomerular deposition of C5b-9.
Insights
Glomerular C5b-9 deposition in membranous nephropathy (MN) indicates a poorer prognosis and lower survival rates. This finding highlights C5b-9 staining as a valuable prognostic marker for MN patients.
Area of Science:
- Nephrology
- Immunology
- Pathology
Background:
- Membranous nephropathy (MN) is a leading cause of nephrotic syndrome in non-diabetic adults.
- Current prognostic markers for MN are limited, hindering effective treatment strategies.
- The role of complement, particularly C5b-9, in MN pathogenesis and prognosis remains understudied.
Purpose of the Study:
- To investigate the frequency and prognostic significance of glomerular C5b-9 deposition in adult patients with MN.
- To evaluate C5b-9 as a potential biomarker for predicting MN disease course and outcomes.
Main Methods:
- Retrospective analysis of 64 adult MN patients diagnosed between 2004 and 2015.
- Immunohistochemistry performed on kidney tissue samples for C5b-9, PLA2R1, and C4d staining.
- Correlation of C5b-9 deposition with clinical data, including nephrotic syndrome severity, remission rates, and renal survival.
Main Results:
- Glomerular C5b-9 deposition was observed in 45.3% of MN patients.
- Patients with C5b-9 deposition presented with more severe nephrotic syndrome at diagnosis.
- C5b-9 positive patients exhibited significantly lower remission and renal survival rates compared to C5b-9 negative patients.
Conclusions:
- Glomerular C5b-9 staining is an accessible and powerful tool for stratifying MN patients based on renal prognosis.
- The findings suggest that C5b-9 deposition is associated with adverse outcomes in MN.
- Further research should explore the efficacy of complement inhibitors in MN patients with glomerular C5b-9 deposition.
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