Renal tubular endostatin as a histopathological biomarker of allograft rejection

Kidney transplantation provides a survival advantage in patients with kidney failure compared to dialysis; however, allograft rejection continues to be the leading cause of graft failure. Circulating endostatin is implicated in graft loss, but the role of local endostatin expression is unclear. Because of the anti-fibrotic and anti-angiogenic properties, we predicted decreased endostatin in renal proximal tubules to be associated with a higher risk of rejection.

A retrospective study of 67 kidney allograft biopsies was performed, including zero-time (n = 11), non-rejection (n = 23), and rejection (n = 33) groups. Endostatin was quantitatively analyzed using immunohistochemistry on a 2-point scale. After adjustment for clinical and histological covariates, multivariate logistic regression was used to study the association of endostatin and rejection.

Endostatin expression was highest in zero-time biopsies and significantly lower in rejection versus non-rejection cases (P < .001). Low endostatin expression was independently associated with rejection (adjusted OR = 7.47, 95% CI: 1.85-30.23, P = .005).

Reduced endostatin in proximal tubules is strongly associated with rejection. Endostatin may serve as a tissue biomarker for early detection and risk stratification, offering potential to guide early intervention and improve transplant outcomes. Further studies are needed to confirm its clinical utility.