Association of Xanthine Oxidase Activity, Oxidative Stress and Early Tubular Kidney Injury in Children with Type 1 Diabetes

Background: Xanthine oxidase (XO) is an important source of reactive oxygen species (ROS) and may be involved in oxidative stress-related renal injury. However, the relationship between XO activity, oxidative stress and early renal tubular injury in children with type 1 diabetes (T1D) and early diabetic nephropathy (DN) remains insufficiently studied. Methods: This cross-sectional study included 150 participants aged 10–18 years: 50 children with T1D without DN, 50 with with T1D and DN and 50 healthy controls. Plasma XOR and XDH activities were determined spectrophotometrically, and XO activity was calculated as the difference between XOR and XDH activities. Superoxide production was assessed spectrophotometrically by monitoring cytochrome c reduction. The Urinary Kidney Injury Molecule (KIM-1) was assessed as a marker of tubular injury. Associations between oxidative stress markers, KIM-1 and DN were examined using correlation and multivariable regression analyses. Results: Plasma XO activity increased progressively across the study groups, from 10.25 (9.49–11.12) μU/mL in controls to 27.95 (26.31–29.29) μU/mL in children with T1D and 54.79 (52.62–57.73) μU/mL in those with DN (p < 0.0001). Principal component analysis showed clustering of oxidative stress and tubular injury biomarkers distinct from conventional renal function measures. Multivariable regression identified XO and superoxide production as independently associated with urinary KIM-1 levels in the DN group. T1D duration, BMI, KIM-1, XO and superoxide production were independently associated with DN. The combined model demonstrated excellent discrimination (AUC = 0.933). Conclusions: Increased XO activity is associated with oxidative stress and urinary KIM-1 in children with T1D, with the highest levels observed in DN group. The combined associations of XO, superoxide, KIM- and clinical factors with DN suggest a potential link between oxidative stress and early tubular injury in pediatric T1D. These biomarkers may be associated with early involvement and require further investigation as potential indicators of kidney injury in children with T1D.