*Purpose: The clinicopathological diagnosis of rejection after kidney transplantation (KT) was well defined by Banff classification. In the diagnosis of antibody-mediated rejection (AMR), the presence of C4d and human leukocyte antigen-donor specific antibody (HLA-DSA) are very important. However, clinical significance between C4d and HLA-DSA is uncertain. We investigated the clinical significance of both C4d and HLA-DSA on post-transplant clinical outcomes in kidney transplant recipients (KTRs) with AMR.

*Methods: Our study enrolled 102 KTRs diagnosed to AMR by allograft biopsies between 2006 and 2019. KTRs were divided into C4d (-) and C4d (+) AMR groups, and both groups were subdivided into HLA-DSA (-) and HLA-DSA (+) subgroups. We investigated the clinical characteristics, pathologic findings by allograft biopsies, death-censored allograft survival rates of HLA-DSA (-) and HLA-DSA (+) subgroups within C4d (-) and C4d (+) AMR groups.

*Results: In C4d (-) group, mean age of KTRs was significantly higher in HLA-DSA (+) group than HLA-DSA (-) group (P=0.019), but in C4d (+) group, there was no significant difference between the two groups. There were also no significant differences of mean age of donor, the amount of proteinuria, the proportion of gender, KT type, frequency of KT, the number of HLA mismatches, induction and maintenance immunosuppressants, and delayed graft function between HLA-DSA (-) and HLA-DSA (+) subgroups in C4d (-) or C4d(+) AMR group. In the pathologic findings, microvascular inflammation was significantly higher in HLA-DSA (+) group than HLA-DSA (-) group in C4d (+) group (P=0.05), but there was no significant difference between the two groups in C4d (-) group. There were also no significant differences of transplant glomerulopathy, and interstitial fibrosis/tubular atrophy between the two groups. In Kaplan-Meier analysis, death-censored graft survivals were lower in HLA-DSA (+) subgroup compared to HLA-DSA (-) subgroup, regardless of the presence of C4d. Death-censored graft survival rate was the lowest in the C4d (+) HLA-DSA (+) AMR group compared to C4d (-) HLA-DSA (-), C4d (-) HLA-DSA (+) and C4d (+) HLA-DSA (-) AMR groups.

*Conclusions: Our study showed that C4d (+) HLA-DSA (+) AMR had poor prognosis on post-transplant clinical outcomes. Therefore, aggressive treatment needs in KTRs with C4d (+) HLA-DSA (+) AMR to protect allograft function.

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