The evolution of histological changes suggestive of antibody-mediated injury, in the presence and absence of donor-specific anti-HLA antibodies.

The interplay between donor-specific anti-HLA antibodies (HLA-DSA), histology of active antibody-mediated rejection (aABMRh ), transplant glomerulopathy (cg) and graft failure in kidney transplantation remains insufficiently understood. We performed a single-center cohort study (n=1000) including 2761 protocol and 833 indication biopsies. Patients with pre-transplant HLA-DSA were more prone to develop aABMRh (OR 22.7, 95% CI, 11.8 - 43.7, p<0.001), cg (OR 5.76, 95% CI, 1.67 - 19.8, p=0.006) and aABMRh/cg (OR 19.5, 95% CI, 10.6 - 35.9, p<0.001). The negative impact of pre-transplant HLA-DSA on graft survival (HR 2.12, 95% CI, 1.41 - 3.20, p<0.001) was partially mediated through aABMRh and cg occurrence. When adjusted for time-dependent HLA-DSA (HR 4.03, 95% CI, 2.21 - 7.15, p=0.002), graft failure was only affected by aABMRh when cg was evident. In HLA-DSA negative patients, aABMRh was associated with impaired graft outcome only when evolving to cg (HR 1.32, 95% CI, 1.07 - 1.61, p=0.008). We conclude that the kinetics of HLA-DSA are important to estimate the rate of graft failure, and that histological follow-up is necessary to discover, often subclinical, ABMR and cg. In the absence of HLA-DSA, patients experience similar histological lesions and the evolution to transplant glomerulopathy associates with impaired graft outcome. This article is protected by copyright. All rights reserved.