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

J Nephrol. 2021 Jun;34(3):839-849. doi: 10.1007/s40620-020-00914-x. Epub 2020 Dec 11.


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.

Keywords: C4d; Glomerulonephritis; Glomerulus; Graft loss; IgA Nephropathy; IgAN; Kidney allograft.

MeSH terms

  • Adult
  • Allografts
  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Biopsy
  • Complement C4b* / immunology
  • Female
  • Glomerulonephritis, IGA* / immunology
  • Graft Rejection
  • Graft Survival*
  • Humans
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Retrospective Studies


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Complement C4b