The relationship of diabetic kidney disease with Caveolin-1, Activin A, and Follistatin levels

Objective: Diabetic kidney disease (DBH) is one of the most serious microvascular complications of diabetes and represents the leading cause of end-stage renal disease in developed countries. Current therapeutic strategies, including strict glycemic control and inhibition of the renin–angiotensin–aldosterone system, can only partially delay disease progression. Therefore, identifying novel biomarkers involved in DBH pathogenesis is crucial for early diagnosis and the development of targeted treatment approaches. This study aimed to investigate the relationship between serum levels of Caveolin-1, Activin A, Follistatin, and transforming growth factor-β (TGF-β) in patients with diabetic kidney disease. Materials and Methods: A total of 176 individuals were included in the study: 39 healthy controls, 18 patients with type 2 diabetes mellitus (DM) without nephropathy, 87 diabetic patients with pre-dialysis chronic kidney disease, and 32 diabetic patients undergoing hemodialysis. Biochemical, hemogram, hormonal, and spot urine parameters, as well as HbA1c levels, were obtained from the laboratory automation system. Serum levels of Caveolin-1, Activin A, Follistatin, and TGF-β were analyzed using the ELISA method. Results: Caveolin-1 levels were found to be significantly lower in the pre-dialysis group (p<0.001), while Follistatin levels were significantly decreased in the hemodialysis group (p<0.001). Although there was no statistically significant difference in TGF-β levels among the groups, Activin A levels were found to be higher in diabetic individuals without proteinuria compared to the other groups (p=0.014). A significant positive correlation was observed between TGF-β and Caveolin-1 levels across all groups (r=0.456–0.738, p<0.001). Conclusion: This study demonstrated that alterations in Caveolin-1 and Follistatin levels are associated with different stages of DBH. The strong positive correlation between TGF-β and Caveolin-1 suggests a potential interactive role of these molecules in the pathogenesis of diabetic nephropathy. Caveolin-1 and Follistatin may serve as promising biomarkers for the early detection and monitoring of disease progression in DBH. Further large-scale and longitudinal studies are warranted to confirm these findings and clarify their clinical implications. Keywords: Diabetic kidney disease; diabetes; Caveolin-1; Activin A, Follistatin; TGF-β