Objectives: C4d staining in the peritubular capillaries (C4d-PTC) is often observed without evidence of rejection in ABO-incompatible kidney transplantation (ABOI-KTx), and this phenomenon is generally thought to indicate graft accommodation. C4d staining in the glomerular capillaries (C4d-GC) is not included in the current diagnostic criteria, and the significance of C4d-GC is not clearly understood. This study assessed the clinical relevance of C4d-GC as well as that of C4d-PTC in early allograft biopsies without histological evidence of rejection in ABOI-KTx.

Methods: Of the 121 recipients who underwent living ABOI-KTx in our department between 2005 and 2012, 79 recipients without histologic evidence of antibody-mediated rejection or acute T-cell mediated rejection (Banff 1A or greater or borderline change) on biopsy results for biopsy performed within three months after transplant were eligible for this study. C4d staining was performed via indirect immunofluorescence on cryostat sections. C4d-PTC was considered positive if focal-to-diffuse (Banff ptc2-3) staining was observed according to the Banff 2013 criteria. C4d-GC was defined positive if a bright linear pattern was identified in more than 50% of the total tufts in a glomerulus.

Results: The positivity of C4d-PTC and C4d-GC was 72% and 65%, respectively. All C4d-GC-positive biopsy samples were positive for C4d-PTC. There was no significant difference in serum creatinine level according to C4d-PTC at the time of the biopsy and at one year after transplant (at Bx: C4d+: 1.36 ± 0.49, C4d-: 1.25 ± 0.33 mg/dl; at 1 year: C4d+: 1.22 ± 0.36, C4d-: 1.22 ± 0.37 mg/dl). The serum creatinine level was significantly higher in C4d-GC-positive recipients than in C4d-GC-negative recipients (at Bx: C4d+: 1.58 ± 0.61, C4d-: 1.22 ± 0.33 mg/dl, p=0.019; at 1 year: C4d+: 1.38 ± 0.43, C4d-: 1.17 ± 0.31 mg/dl; p=0.021). In the follow-up biopsy, incidence of interstitial fibrosis was higher in C4d-GC-positive recipients than in C4d-GC-negative recipients (71% vs. 31%, p=0.013).

Conclusions: C4d-PTC does not appear to affect graft function as previously reported. In contrast, C4d-GC without evidence of rejection was significantly associated with worse graft function and development of interstitial fibrosis in ABOI-KTx.

CITATION INFORMATION: Toki D, Inui M, Okumi M, Ishida H, Setoguchi K, Shimizu T, Unagami K, Tanabe K. Glomerular Capillary C4d Staining without Evidence of Rejection Is Associated with Worse Graft Function in ABO-Incompatible Kidney Transplantation. Am J Transplant. 2016;16 (suppl 3).

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