*Purpose: Transplant glomerulopathy (TG) is established as a hallmark of chronic antibody-mediated rejection in kidney transplant patients with donor-specific HLA antibodies (HLA-DSA). The clinical importance of TG in the absence of HLA-DSA is not well established.

*Methods: Patients who underwent kidney transplantation between 2004-2013 were included in this study (N=954 with 3744 biopsies). We investigated the risk factors, histopathological appearance and prognosis of cases with TG in the absence of HLA-DSA, compared to cases of TG with HLA-DSA, and we evaluated the impact of the PIRCHE-II score and eplet mismatches, determined using high-resolution HLA genotyping, on TG development.

*Results: In this cohort, 98 patients (10.3%) developed TG, on average at 3.2 years posttransplant. At the time of TG, 23 patients (23.5%) had persistent pretransplant or de novo HLA-DSA (HLA-DSA_posTG group), while 75 patients (76.5%) were HLA-DSA negative (HLA-DSA_negTG). Only HLA-DSA were identified as risk factor for TG development; HLA molecular mismatches, eplet mismatches and PIRCHE-II scores did not associate with TG. The HLA-DSA_negTG biopsies had less interstitial inflammation, less glomerulitis and less C4d deposition in peritubular capillaries compared to the HLA-DSA_posTG biopsies. While graft function was comparable between the two groups, HLA-DSA_posTG was associated with a higher risk of graft failure compared to HLA-DSA_negTG (HR=3.84; 95%CI 1.94-7.59; p=0.0001). Landmark analysis at 3-year post-transplant showed that HLA-DSA_negTG patients still had an increased risk of graft failure compared to TG-negative patients (HR=2.62; 95%CI 1.46-4.72; p=0.001).

*Conclusions: In conclusion, TG often occurs in the absence of HLA-DSA, independently of HLA molecular mismatches, and represents a different phenotype with less concomitant inflammation and better graft survival compared to TG developed in the presence of HLA-DSA.

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