Inhibition of USAG-1 improved delayed graft function in renal transplantation.

Abstract

Delayed graft function (DGF) is a critical complication following kidney transplantation. This study aimed to identify novel biomarkers and therapeutic targets for DGF. Transcriptomic data from the Gene Expression Omnibus (GEO) database were analyzed to screen for DGF-associated core genes. Serum levels of uterine sensitization-associated gene-1 (USAG-1) and kidney injury molecule-1 (KIM-1) were measured one day post-transplantation, and their predictive values for DGF were compared. Mouse models of DGF were established by inducing graded warm ischemia. USAG-1 was identified as a core gene significantly associated with DGF. Multivariate logistic regression identified USAG-1 as an independent risk factor for DGF (P&#xa0;<&#xa0;0.05). Importantly, USAG-1 demonstrated superior diagnostic performance with an area under the curve (AUC) of 0.774 (95% CI: 0.660-0.895), which outperformed the traditional marker KIM-1 (AUC&#xa0;=&#xa0;0.686; 95% CI: 0.559-0.831) (P&#xa0;<&#xa0;0.05). High USAG-1 expression was significantly correlated with prolonged recovery time (P&#xa0;<&#xa0;0.05) and post-transplant dialysis duration (P&#xa0;<&#xa0;0.05). In mouse models, USAG-1 knockout (KO) significantly increased survival (P&#xa0;<&#xa0;0.05), improved renal pathology, and reduced the levels of injury markers (all P&#xa0;<&#xa0;0.01), whereas exogenous USAG-1 supplementation reversed these effects (all P&#xa0;<&#xa0;0.05). In conclusion, USAG-1 is a key regulator in DGF pathogenesis. Early postoperative serum USAG-1 levels can effectively predict DGF, and inhibition of USAG-1 expression may alleviate renal injury and promote functional recovery, offering potential diagnostic and therapeutic value in renal transplantation.