Serum Soluble Klotho as an Early Biomarker for Diabetic Nephropathy in Children with Type 1 Diabetes Mellitus

Background:In pediatric patients with type 1 diabetes mellitus (T1DM), early stages of diabetic nephropathy (DN) are frequently asymptomatic and elude detection by standard diagnostic tools like microalbuminuria. Soluble Klotho (s-Klotho), a renal-derived protein with antioxidative and anti-inflammatory properties, is increasingly being investigated as a potential early biomarker of renal injury.Objective:This study aims to assess serum soluble Klotho levels in children with T1DM and explore their associations with glycemic control and renal function parameters.Methods:A case–control study was conducted involving 70 children: 35 with T1DM (duration ≥ 1 year) and 35 healthy controls. All participants underwent clinical evaluations, and blood samples were analyzed for HbA1c, serum creatinine, albumin, creatinine clearance (via Cockcroft–Gault formula), and serum s-Klotho (measured using ELISA). Correlation analyses were performed using Pearson and Spearman tests.Results:Children with T1DM exhibited significantly reduced mean serum s-Klotho levels compared to controls (1.5 ± 0.9 ng/mL vs 3.5 ± 3.4 ng/mL; p = 0.001). A significant positive correlation was observed between s-Klotho and HbA1c (r = 0.39; p = 0.021), while a moderate inverse correlation was found with the renal resistive index (r = –0.57; p < 0.001). Creatinine clearance was also significantly lower among diabetic children.Conclusion:Declining serum s-Klotho levels may serve as an early indicator of renal tubular dysfunction in children with T1DM, preceding the development of microalbuminuria. Its correlation with Doppler-based renal resistive index suggests that s-Klotho may function as a dual biochemical and imaging biomarker for the early detection of DN.