Early glomerular capillary C4d is associated with poor graft function in kidney transplant recipients with preformed...

The role of positive glomerular capillary C4d (C4dglom) in chronic antibody-mediated rejection (ABMR) has been examined. However, the role of C4dglom in the development of transplant glomerulopathy (TG) and graft outcomes in the early phase after kidney transplantation (KT) among patients with preformed donor-specific antibodies (preDSAs) remains undetermined.

In this single-center, retrospective cohort study, we included 110 kidney transplant recipients (KTRs) with preDSAs (2008-2024, median follow-up: 7.8 years). Overall, 325 index and indication biopsies were performed within 1 year post-KT. All biopsy specimens were stained with immunofluorescent C4d. C4dglom was defined as global, moderate to severe, pseudolinear glomerular capillary wall staining, and peritubular capillary C4d (C4dptc), as described in Banff 2019. Patients were divided into two groups, with or without C4dglom, within 1 year post-KT. The association between C4dglom and TG was evaluated. Further, among KTRs with ABMR or TG, the incidence of a 30% decline in estimated glomerular filtration rate (eGFR) within 1 year post-KT and eGFR at 1 year post-KT were compared according to the presence or absence of C4dglom or C4dptc.

Twenty-two cases of C4dglom and 26 cases of TG were identified within 1 year post-KT. C4dglom was associated with TG development. In the TG group, C4dglom positivity was associated with a significantly lower 30% decline in eGFR-free survival than C4dglom negativity (45.7% vs 92.9%, p = 0.036), whereas C4dptc positivity was not (71.4% vs 70.3%, p = 0.979).

C4dglom was associated with subsequent TG and even poor graft function.