ORIGINAL ARTICLE
Microvasculature partial endothelial mesenchymal transition in early posttransplant biopsy with acute tubular necrosis identifies poor recovery renal allografts

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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 and poor graft function recovery (Spearman’s rho = −0.55, P = .0005). Transforming growth factor–β1 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 partial endothelial to mesenchymal transition marker expression in their grafts (Spearman’s rho = −0.64, P = .003), but not in those without. The association of partial endothelial to mesenchymal transition with worse renal graft outcome was confirmed on 34 other early biopsies with ATN from a second transplant center. Our results suggest that endothelial cell activation at the early phase of renal transplantation plays a detrimental role.

KEYWORDS

biomarker
clinical research / practice
delayed graft function (DGF)
ischemia/reperfusion injury (IRI)
kidney transplantation/nephrology
pathology/histopathology
rejection: antibody-mediated (ABMR)
translational research/science
vascular biology

Abbreviations

ABMR
antibody-mediated rejection
ATN
acute tubular necrosis
DGF
delayed graft function
DSA
donor-specific antibodies
eGFR
estimated glomerular filtration rate
EndMT
endothelial to mesenchymal transition
I/R
ischemia/reperfusion
IF/TA
interstitial fibrosis and tubular atrophy
KIM-1
kidney injury molecule-1
MFI
mean fluorescence intensity
pEMT
partial epithelial to mesenchymal transition
pEndMT
partial endothelial to mesenchymal transition
TGFβ1
transforming growth factor-β1
TNFα
tumor necrosis factor α
αSMA,
α smooth muscle actin

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Yi-Chun Xu-Dubois and Pedram Ahmadpoor contributed equally to this article.