Microvasculature partial endothelial mesenchymal transition in early post-transplant biopsy with acute tubular necrosis identifies poor recovery renal allografts.

Acute tubular necrosis (ATN), a frequent histopathological feature in the early post-renal transplant biopsy, affects long-term graft function. Appropriate markers to identify patients at risk of no or incomplete recovery after delayed graft function are lacking. In this study, we first included 41 renal transplant patients whose biopsy for cause during the first month after transplantation showed ATN lesions. Using partial microvasculature endothelial (fascin, vimentin) and tubular epithelial (vimentin) to mesenchymal transition markers, detected by immunohistochemistry, we found a significant association between partial endothelial to mesenchymal transition (pEndMT) and poor graft function recovery (Spearman's rho= -0.55, P=0.0005). Transforming growth factor-beta1 was strongly expressed in these phenotypic changed endothelial cells. Extent of ATN was also correlated with short- and long-term graft dysfunction. However, the association of extensive ATN with long-term graft dysfunction (24 months posttransplant) was observed only in patients with pEndMT marker expression in their grafts (Spearman's rho= -0.64, P=0.003), but not in those without. The association of pEndMT with worse renal graft outcome was confirmed on 34 other early biopsies with ATN from a second transplant center. Our results suggest endothelial cell activation at the early phase of renal transplantation plays a detrimental role.