Cystatin C: Not Only a Kidney Marker but Also a Potential Early Indicator of Metabolic Alterations in Childhood Obesity

Background: Pediatric obesity is associated with early metabolic and kidney alterations, and identifying high-risk children remains challenging. Cystatin C may reflect both kidney and metabolic dysfunction. Objectives: To assess the relationship between cystatin C and measures of adiposity, insulin resistance (IR), and cardiometabolic risk in children with overweight and obesity. Methods: In this retrospective cross-sectional study, 169 children with overweight and obesity were analyzed. Anthropometric, blood pressure, kidney (serum creatinine, cystatin C), glucose/insulin, and lipid parameters were collected. Participants were stratified by cystatin C tertiles, and variables were compared across groups. Stepwise regression identified independent predictors of cystatin C. Results: Children in the highest cystatin C tertile had higher SDS-BMI, waist circumference (WC), systolic and diastolic BP SDS, and iCARE index—developed within the Improving Renal Complications in Adolescents With Type 2 Diabetes Through the REsearch (iCARE) Cohort Study as a marker of IR and metabolic risk. They also showed elevated HOMA-IR, fasting glucose-to-insulin ratio (FGIR) and TG:HDL ratio, while glucose excursion did not differ. Stepwise regression identified WC and HOMA-IR as independent predictors of cystatin C. Conclusion: Elevated cystatin C in children with overweight and obesity is independently associated with central adiposity and IR, supporting its potential as an integrated early marker of metabolic and kidney risk.