Association of AT1R expression with transplant glomerulopathy and interstitial fibrosis in kidney transplant...

Chronic allograft dysfunction (CAD) remains a major cause of late kidney transplant failure and is driven by both immune and non-immune mechanisms. Transplant glomerulopathy (TG) and interstitial fibrosis (IF) are key histopathological features associated with chronic antibody-mediated injury and long-term graft loss. Experimental and clinical data suggest that angiotensin II type 1 receptor (AT1R) signaling, including activation by anti-AT1R antibodies, may contribute to fibrotic processes within the kidney.

In this longitudinal study, 77 kidney transplant recipients who underwent indication biopsies within 60 months post-transplantation were analyzed. AT1R expression in allograft tissue was assessed by immunohistochemistry, and serum anti-AT1R antibody levels were measured using ELISA. Histopathological findings and long-term graft outcomes were evaluated over a median follow-up of 126 months.

AT1R expression in tubular epithelium was observed in 44.2% of patients. TG and IF were significantly more frequent in patients with positive AT1R expression compared to those without (24% vs. 7%, p=0.042; 56% vs. 27%, p=0.011, respectively), and IF severity was higher in the AT1R-positive group (p=0.028). Anti-AT1R antibody levels did not differ between groups. In survival analyses, neither AT1R expression nor anti-AT1R antibodies alone were associated with allograft survival. However, the presence of multiple risk factors, including AT1R expression, anti-AT1R antibodies, and histopathological lesions, was associated with significantly worse long-term graft survival.

AT1R expression is associated with the presence and severity of interstitial fibrosis and transplant glomerulopathy in kidney transplant recipients. While AT1R-related markers alone did not predict graft survival, their combination with histopathological abnormalities identifies patients at higher risk of long-term allograft loss. These findings support a potential role of AT1R-mediated pathways in chronic allograft injury.