*Purpose: After kidney transplantation, the occurrence of ABMRh (=histological picture of antibody-mediated rejection) and transplant glomerulopathy (cg) has been reported, both in the presence and absence of donor-specific HLA antibodies (HLA-DSA). In patients with HLA-DSA, ABMRh is a confirmed risk factor for development of transplant glomerulopathy (cg) and graft failure. In patients without HLA-DSA, ABMRh is an unclear phenotype with unclear outcomes. We investigated the occurrence and impact of ABMRh and ABMRh/cg after kidney transplantation, in patients with and without HLA-DSA.

*Methods: In this single-center prospective cohort study, 926 individual renal allograft recipients were included, with histological data of 3361 renal allograft biopsies obtained up to 5 years after transplantation. We studied the effect of presence and absence of pre- and post-transplant HLA-DSA, determined using Luminex SAB and high-resolution donor-recipient HLA genotyping, on the occurrence of post-transplant histological phenotypes and on graft survival using mixed and joint models.

*Results: Prior to transplantation, HLA-DSA were present in 95/926 (10.3%) renal allograft recipients. These patients had a worse graft survival (HR 1.85, 95% CI, 1.10 – 3.11, p=0.021) and increased risk of ABMRh (OR 28.65, 95% CI, 13.98 – 58.85, p<0.001), ABMRh/cg (OR, 21.75, 95% CI, 11.48 - 41.21, p<0.001) and T-cell mediated rejection (TCMR) (OR 2.74, 95% CI, 1.58 - 4.77, p<0.001). The increased risk of TCMR was solely due to its co-occurrence with ABMRh (mixed rejection). There was no increased risk for isolated TCMR (OR 0.66, 95 CI, 0.35 - 1.25, p=0.20). Despite the lower risk, ABMRh and ABMRh/cg occurred also in patients without HLA-DSA. When jointly modelling the longitudinal evolution of ABMRh and ABMRh/cg with the survival model for graft failure, the hazardous effect of pre-transplant DSA disappeared, indicating mediation by the occurrence of both phenotypes. When taking into account the time-dependent nature of DSA (including resolution and de novo occurrence of HLA-DSA), the effect of ABMRh lost its significance, while ABMRh/cg (HR 1.22, 95% CI, 1.06 - 1.41, p=0.006) remained independently associated with graft survival. Also in the patients without HLA-DSA, ABMRh and ABMRh/cg increased the risk for graft failure (HR 1.31, 95% CI, 1.09 - 1.62, p=0.002 and HR 1.46, 95% CI, 1.22 - 1.80, p<0.001 respectively).

*Conclusions: The effect of HLA-DSA on impaired graft survival is largely mediated through ABMRh and ABMRh/transplant glomerulopathy, but not through TCMR lesions. In the absence of HLA-DSA, the same histology can be observed, and is also associated with an increased risk of graft failure.

« Back to 2020 American Transplant Congress