Background and Objective: Few reports assessed biomarkers of endothelial activation in kidney allograft biopsies using immunohistochemistry (IHC). This study aimed to analyze the IHC expression of Caveolin-1 (Cav), Von Willebrand Factor (Vwf), and T-Cadherin (Cad) in for-cause allograft biopsies diagnosed as Interstitial Fibrosis and Tubular Atrophy (IF/TA) of unknown etiology and evaluate its association with graft loss.

Methods: This was a retrospective single-center cohort study including kidney biopsies performed in a single center between January 2013 and December 2017, whose histological, laboratory and clinical analysis concluded for IF/TA of unknown etiology. Samples with antibody-mediated changes were excluded. Patients were followed for three years after the biopsy or until graft loss/death.

Results: Seventy-one (71) samples from 66 patients were included. Eighteen (25.4%) patients lost their grafts, mainly due to chronic rejection (33.3%). Cav and Cad were not associated with graft loss. Vwf had good accuracy to predict graft failure (AUC 0.637, 95%CI 0.486-0.788, p = 0.101). The presence of more than 10% of Vwf positivity in the microvasculature (Vwf > 10%) was associated with reduced death-censored graft survival (58.2% versus 85.4%, p = 0.006). The multivariate analysis showed that Vwf > 10% was an independent risk factor for graft loss (HR = 2.88, 95%CI 1.03-8.02, p = 0.043).

Conclusion: Vwf might be an additional tool to predict allograft outcomes in kidney transplant recipients with IF/TA of unknown etiology, probably reflecting immune endothelial activation.