Combined morphologic and immunohistochemical assessment of KIM-1-positive proximal tubular vacuolation in one-hour kidney allograft biopsies.

backgroundEarly kidney allograft injury immediately after reperfusion remains incompletely characterized, particularly before overt hypoxic or transcriptional responses develop. Kidney injury molecule-1 (KIM-1) is rapidly induced in injured proximal tubular epithelial cells; however, the significance of morphological changes within KIM-1-positive epithelium during the ultra-early post-transplant period remains unclear. This study aimed to characterize early epithelial instability in one-hour kidney allograft biopsies and assess associations with ischemic stress and early graft function.

methodsWe retrospectively analyzed one-hour post-reperfusion kidney allograft biopsies from 51 adult recipients who underwent living-donor kidney transplantation. KIM-1 immunohistochemistry was used to identify injured proximal tubules in morphologically non-atrophic cortical regions. Detectable staining in a subset of proximal tubular epithelial cells was used to identify evaluable tubules. Within these KIM-1-positive tubules, epithelial changes including cytoplasmic vacuolation, brush border loss, and focal epithelial detachment were semi-quantitatively graded as a KIM-1-associated vacuolation score (range 0-3), designed to reflect epithelial structural instability rather than the extent of KIM-1 expression. Digital image analysis quantified KIM-1-positive tubular area and hypoxia-inducible factor-1α (HIF-1α) nuclear staining. Associations with cold ischemia time and early post-transplant estimated glomerular filtration rate were assessed using correlation analyses and multivariable linear regression models.

resultsKIM-1-positive proximal tubules were identified in morphologically preserved cortical regions one hour after reperfusion. The KIM-1-associated vacuolation score showed a weak positive trend with cold ischemia time, whereas KIM-1-positive tubular area did not. Higher vacuolation scores tended to be associated with lower estimated glomerular filtration rate at one week, although the association was not statistically significant. In contrast, HIF-1α nuclear accumulation was minimal at this ultra-early time point and showed no association with the vacuolation score, suggesting a dissociation between early epithelial instability and hypoxia-driven transcriptional responses.

conclusionsCombined assessment of KIM-1 expression and proximal tubular vacuolation in one-hour reperfusion biopsies captured morphologic features occurring during the ultra-early phase after kidney transplantation, when overt HIF-1α activation was minimal. Although no significant associations with early graft function were observed, this proof-of-concept approach may provide a framework for future studies investigating ultra-early epithelial stress responses in kidney transplantation.