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Glomerular C4d in Post-Transplant IgA Nephropathy is associated with decreased allograft survival

Abstract : Background: Glomerulonephritis (GN), including post-transplant IgAN (post-Tx IgAN) is an important contributor to decreased long-term allograft survival. The immunopathological detection of the complement degradation product C4d in glomeruli (C4dG) has been recently described as a risk factor in native kidney IgAN, however little is known about C4dG deposition in post-Tx IgAN. We hypothesized that glomerular C4d may indicate a more aggressive disease course and worse allograft survival in patients with post-Tx IgAN. Methods: In this retrospective study we assessed the presence and clinical relevance of C4dG in patients with post-transplant IgAN. We analyzed 885 renal allograft recipients, including 84 patients with post-transplant GN. All patients were transplanted between January 1999 and April 2006 and underwent at least one biopsy for differnt causes. The primary endpoint was death-censored graft survival, with a median follow-up of 9.6 (IQR 3.8–13.2) years. Results: The prevalence of post-Tx GN was 9.5%. Twenty-seven patients with post-Tx IgAN were included. C4dG positive patients (N = 18, 66.7%) had significantly worse allograft survival compared to C4dG negative post-Tx IgAN patients and patients without post-Tx IgAN [C4dG positive: 27.8% vs. 55.6% and 66.0%; log-rank: p = 0.01]. C4dG remained a significant risk factor (HR 2.22, 95% CI 1.27–3.87) for allograft loss even after adjustment for T cell mediated rejection (TCMR) and antibody mediated rejection. Conclusion: Glomerular C4d deposition is an independent risk factor for worse graft-survival in patients with post-Tx IgAN, even after adjusting for other risk factors such as antibody mediated rejection. Assessment of glomerular C4d deposition may provide a valuable prognostic risk assessment tool to identify high risk patients in post-Tx IgAN.
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https://hal.sorbonne-universite.fr/hal-03298497
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Submitted on : Friday, July 23, 2021 - 4:20:01 PM
Last modification on : Friday, August 13, 2021 - 1:30:07 PM

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Michael Eder, Nicolas Kozakowski, Haris Omic, Christof Aigner, Johannes Kläger, et al.. Glomerular C4d in Post-Transplant IgA Nephropathy is associated with decreased allograft survival. Journal of Nephrology, Italian Society of Nephrology/Springer, 2021, 34 (3), pp.839 - 849. ⟨10.1007/s40620-020-00914-x⟩. ⟨hal-03298497⟩

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