PROGRESS Study: Longitudinal analysis of antioxidant status and its relationship with heat shock proteins in children with chronic kidney disease

Background: Chronic kidney disease (CKD) progresses via complex mechanisms, including oxidative stress and impaired antioxidant defenses. We aimed to investigate longitudinal changes in serum and urinary levels of superoxide dismutase (SOD), catalase, and glutathione in children with CKD, and to assess their relationship with heat shock proteins (HSPs), which we have previously reported to be altered in this population. Methods: A total of 117 children with CKD and 56 healthy children were enrolled in the study. The CKD group was followed prospectively for 24 months. Serum and urinary levels of SOD, catalase, and glutathione were measured using ELISA at baseline, 12 months, and 24 months. Longitudinal changes and associations with kidney outcomes and CKD progression were analyzed using mixed-effects and logistic regression models. Results: Serum SOD and catalase levels, as well as urinary SOD, catalase, and glutathione levels were higher in the CKD group than in the control group. Serum and urinary SOD and catalase levels steadily decreased over time, similarly to urinary HSP levels. Most antioxidant biomarkers were not significantly associated with longitudinal kidney outcomes. However, higher longitudinal urinary catalase levels were modestly associated with better kidney function over time, and higher baseline urinary catalase was independently associated with a lower risk of CKD progression. In contrast, higher baseline serum SOD levels were associated with an increased risk of progression. Antioxidant biomarkers showed strong correlations with serum and urinary HSP levels. Conclusion: Although urinary catalase consistently associates with kidney function and CKD progression, most antioxidant biomarkers alone have limited predictive value. Children with CKD show altered antioxidant defenses that decline over time, and their correlations with HSPs suggest that they may act together in response to oxidative stress.