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Peer-reviewedCC BYFrontiers in nephrology

Clinical significance of persistent C4d deposition on sequential protocol biopsies in ABO-incompatible kidney transplantation.

  1. 1Department of Urology, Tokyo Women's Medical University Hospital, Shinjuku-ku, Tokyo, Japan.
  2. 2Department of Organ Transplant Medicine, Tokyo Women's Medical University Hospital, Shinjuku-ku, Tokyo, Japan.

Abstract

Introduction

C4d deposition is common after ABO-incompatible (ABOi) kidney transplantation and, unlike ABO-compatible grafts, is not necessarily indicative of antibody-mediated injury.Methods

Between 2015 and 2022, 254 ABOi kidney transplantations were performed at our center, and 69 recipients with paired 3-month and 1-year protocol biopsies were classified as persistently C4d-positive (n = 54) or C4d-negative/nonpersistent (n = 15). Pre-transplant background, cellular infiltration, chronic Banff lesions according to the Banff 2019 classification, graft function, and graft survival were compared.Results

Baseline anti-A/B titers, ABO combination, donor age, and donor relationship did not differ between the groups, whereas donor sex differed significantly (P = 0.014). Microvascular inflammation, defined as glomerulitis plus peritubular capillaritis ≥2, was observed in 6/54 recipients (11.1%) versus 1/15 (6.7%), and chronic changes, defined as interstitial fibrosis score ≥1, were observed in 27/54 (50.0%) versus 6/15 (40.0%); none of these differences reached statistical significance. Graft function and survival also did not differ significantly, although all four graft losses occurred in the persistent C4d-positive group. Three of these losses were attributable to chronic active antibody-mediated rejection, diagnosed at the 1-year biopsy in one recipient and later in two recipients.Discussion

Given the selected cohort and limited statistical power, these findings represent a failure to detect an association rather than evidence of equivalence. They are consistent with accommodation but require confirmation in larger, less-selected cohorts.

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BibTeX
@article{kijima2026clinical,
  title = {{Clinical significance of persistent C4d deposition on sequential protocol biopsies in ABO-incompatible kidney transplantation.}},
  author = {Yu Kijima and Hideki Ishida and Takafumi Yagisawa and Toshihito Hirai and Kohei Unagami and Tomokazu Shimizu and Toshio Takagi},
  journal = {Frontiers in nephrology},
  year = {2026},
  month = oct,
  doi = {10.3389/fneph.2026.1940137},
  url = {https://europepmc.org/article/MED/42903221},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Clinical significance of persistent C4d deposition on sequential protocol biopsies in ABO-incompatible kidney transplantation.
AU  - Yu Kijima
AU  - Hideki Ishida
AU  - Takafumi Yagisawa
AU  - Toshihito Hirai
AU  - Kohei Unagami
AU  - Tomokazu Shimizu
AU  - Toshio Takagi
PY  - 2026
DA  - 2026/10/06
JO  - Frontiers in nephrology
DO  - 10.3389/fneph.2026.1940137
UR  - https://europepmc.org/article/MED/42903221
AB  - Introduction  C4d deposition is common after ABO-incompatible (ABOi) kidney transplantation and, unlike ABO-compatible grafts, is not necessarily indicative of antibody-mediated injury.Methods  Between 2015 and 2022, 254 ABOi kidney transplantations were performed at our center, and 69 recipients with paired 3-month and 1-year protocol biopsies were classified as persistently C4d-positive (n = 54) or C4d-negative/nonpersistent (n = 15). Pre-transplant background, cellular infiltration, chronic Banff lesions according to the Banff 2019 classification, graft function, and graft survival were compared.Results  Baseline anti-A/B titers, ABO combination, donor age, and donor relationship did not differ between the groups, whereas donor sex differed significantly (P = 0.014). Microvascular inflammation, defined as glomerulitis plus peritubular capillaritis ≥2, was observed in 6/54 recipients (11.1%) versus 1/15 (6.7%), and chronic changes, defined as interstitial fibrosis score ≥1, were observed in 27/54 (50.0%) versus 6/15 (40.0%); none of these differences reached statistical significance. Graft function and survival also did not differ significantly, although all four graft losses occurred in the persistent C4d-positive group. Three of these losses were attributable to chronic active antibody-mediated rejection, diagnosed at the 1-year biopsy in one recipient and later in two recipients.Discussion  Given the selected cohort and limited statistical power, these findings represent a failure to detect an association rather than evidence of equivalence. They are consistent with accommodation but require confirmation in larger, less-selected cohorts.
SN  - 2813-0626
ER  -