The research investigated the role of the SLC1A1 protein in renal interstitial fibrosis (RIF) and its effect on glutamate uptake and extracellular ion levels. Renal damage was assessed by tissue microarray analysis and HE staining, while immunohistochemistry confirmed a decrease in SLC1A1 expression in fibrotic tissues, which worsened with the extent of fibrosis. They created an in vitro model of fibrosis on HK-2 cells stimulated with TGF-β1 at a concentration of 15 ng/ml. After 48 hours of exposure, SLC1A1 expression decreased and glutamate uptake significantly decreased compared to the control group. Extracellular sodium (Na+) and chlorine (Cl−) levels increased significantly, aspartic acid (ASP) levels increased, glutamate (Glu) decreased, and cysteine (Cys) remained unchanged. Decreased expression of SLC1A1 in RIF is inversely related to fibrosis severity and affects ion balance, suggesting potential as a therapeutic target.