Isolated dyslipidemia triggers early kidney injury through fibrotic remodeling, subcellular lipid accumulation, and AMPK overexpression.

Abstract

Dyslipidemia is increasingly recognized as a potential driver of chronic kidney disease, independent of other components of the metabolic syndrome. This study aimed to investigate the direct impact of isolated dyslipidemia on kidney structure and function in dyslipidemic().animals were fed either a low-energy diet (LED) or high-energy diet (HED) for 12 weeks. Renal tissues were analyzed for fibrosis, inflammation and lipid droplet accumulation, using Masson's trichrome staining and reticulin fiber staining. Protein expression of AMPK, eNOS, and TGF-β was assessed by Western blot and densitometry analysis. The HED exerted a distinctly pronounced hyperlipidemic effect, as evidenced by increased levels of total cholesterol, LDL-C, and triglycerides, without affecting glycemia. Animals fed a HED showed significant perivascular and interstitial fibrosis, tubular atrophy, tubular necrosis, and inflammation. Lipid droplets were notably observed within podocytes in the glomeruli of dyslipidemic animals. Western blot analysis revealed increased AMPK expression and TGF-β, along with altered levels of eNOS, indicating activation of metabolic stress and fibrotic pathways in HED group. Dyslipidemicdisplay significant kidney injury marked by lipid accumulation in podocytes, AMPK overexpression, and progressive fibrosis. These results highlight the direct renal impact of dyslipidemia in the absence of other metabolic stressors.