C4d, rather than C3d and C5b-9, Is Associated with Graft Loss in Recurrent IgA Deposition after Kidney Transplantation.

Publisher: Karger Country of Publication: Switzerland NLM ID: 8109361 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1421-9670 (Electronic) Linking ISSN: 02508095 NLM ISO Abbreviation: Am J Nephrol Subsets: MEDLINE

Original Publication: Basel ; New York : Karger, [1981-

Kidney Transplantation*/adverse effects ; Glomerulonephritis, IGA*/immunology ; Glomerulonephritis, IGA*/pathology ; Glomerulonephritis, IGA*/surgery ; Complement C4b*/immunology ; Complement C4b*/analysis ; Complement C3d*/analysis ; Complement C3d*/immunology ; Complement C3d*/metabolism ; Recurrence* ; Graft Rejection*/immunology ; Graft Rejection*/etiology ; Peptide Fragments*/immunology ; Peptide Fragments*/analysis ; Immunoglobulin A*/immunology ; Immunoglobulin A*/metabolism; Humans ; Male ; Adult ; Middle Aged ; Female ; Graft Survival/immunology ; Complement Membrane Attack Complex/metabolism ; Complement Membrane Attack Complex/analysis ; Complement Membrane Attack Complex/immunology ; Retrospective Studies ; Biopsy

Introduction: Recurrent IgA deposition is common after kidney transplantation. However, it is difficult to define whether IgA deposition is innocuous or contributes to organ damage. Next, although complement is known to be involved in the pathogenesis of IgA nephropathy (IgAN), its involvement has not been studied systematically in kidney transplant recipients (KTRs).
Methods: KTRs with biopsy-proven native IgAN who underwent kidney biopsy after transplantation between 1995 and 2020 were included. Recurrent IgA deposition was defined as IgA deposit in the glomerulus. Staining of complement factors C4d, C3d, and C5b-9 was quantitatively evaluated using ImageScope.
Results: Sixty-seven KTRs (85% male, 46 ± 13 years old, 12 [6-24] months after transplantation, 58% with indication biopsy) were included in the analyses. Of them, 25 (37%) had recurrent IgA deposition. There were no clinical differences between KTR with and without recurrent IgA deposition. C3d and C5b-9 were always present in biopsies with IgA deposition, while C4d was present in 48% of the biopsies. During a median follow-up of 9.6 [4.8-14] years, 18 (27%) KTRs developed death-censored graft failure. Recurrent IgA deposition was not associated with graft failure. Of the evaluated complement factors, only C4d staining was associated with graft failure in KTR with recurrent IgA deposition (hazard ratio = 2.55, 95% confidence interval = 1.07-6.03, p = 0.034).
Conclusions: Recurrent IgA deposition was not associated with graft failure in itself. C4d, when present, is strongly associated with graft loss in KTR with recurrent IgA deposition, suggesting a pathogenic role for the lectin pathway in recurrent IgAN.
(© 2024 The Author(s). Published by S. Karger AG, Basel.)

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Keywords: Complement; Graft survival; Iga nephropathy; Kidney transplantation; Renal biopsy

80295-50-7 (Complement C4b)
80295-52-9 (complement C4d)
80295-45-0 (Complement C3d)
0 (Peptide Fragments)
0 (Immunoglobulin A)
0 (Complement Membrane Attack Complex)

Date Created: 20240818 Date Completed: 20241216 Latest Revision: 20250104

20250104

PMC11651231

10.1159/000540986

39154645