*Purpose: ABO incompatible (ABOi) kidney transplantation (KT) has been increasing due to severe organ shortages. Pathologic diagnosis of antibody-mediated rejection (ABMR) in ABOi patients is often challeging because of frequent immunopositivity of C4d in these patients without ABMR. This study aimed providing a description of C4d staining in for-cause biopsies in clinical practice, and determining whether C4d-positivity with MVI and no detectable DSA in ABOi patients should be considered as ABMR.

*Methods: We reviewed 214 for-cause biopsies from 126 ABOi KT patients. Patients with microvascular inflammation (MVI) ≥2 and g≥1 were divided into the absolute ABMR group (MVI ≥2, g≥1, and donor specific antibody (DSA) positive), C4d-positive, MVI≥2 group (MVI≥2, g≥1, C4d-positive, and DSA negative), and compared for Banff scores, estimated glomerular filtration rate (eGFR) and graft failure.

*Results: C4d-positive biopsies showed higher g, ptc, and MVI scores than C4d-negative biopsies. The C4d-positive, MVI≥2 group showed no significant difference in eGFR and graft survival compared to the absolute ABMR group.

*Conclusions: Our results suggest that C4d-positive, MVI ≥2 & g≥1 in ABOi allograft biopsy should be considered and treated as antibody-mediated rejection.

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