Partial endothelial-to-mesenchymal transition associates with endothelial human leukocyte antigen II expression and precedes the development of de novo donor-specific anti-human leukocyte antigen antibodies in kidney recipients experiencing a delayed graft function.

There are several stages in kidney transplantation during which epithelial injury and endothelial activation in the graft can occur. When acute tubular necrosis delays recovery of graft function, a biopsy is occasionally taken to estimate the risk of primary nonfunction, adapt immunosuppression, and eliminate acute rejection, a priority in recipients known to have anti-human leukocyte antigen (HLA) antibodies against the donor-specific antibodies (DSAs). We investigated the phenotype of endothelial cells in peritubular capillaries in early biopsy samples from 74 recipients experiencing delayed graft function, paying special attention to markers of partial endothelial-to-mesenchymal transition (pEndMT) and induction of expression of HLA II antigens. We also focused on the presence of preformed DSA and on the development of de novo DSA during the follow-up. The majority of patients with delayed graft function (62%) had pEndMT, which was associated with the endothelial expression of HLA II antigens in peritubular capillaries (detected in 81.8% of pEndMT+ grafts vs 14.3% of pEndMT- ones, P = .005). Early pEndMT was significantly associated with the presence of DSA (57.8% vs 14.8%, P < .001) and with antibody-mediated rejection during follow-up (31.4% vs 7.14%, P = .018), more graft dysfunction (estimated glomerular filtration rate 23.34 ± 22.9 vs 40.2 ± 22.5 mL/min, P = .0064), and more graft loss (51.2% vs 14.8%, P = .002).