Prognostic value of cystatin C for chronic kidney disease in pediatric urologic malformations

Background: To assess the prognostic value of serum cystatin C for predicting 10-year major adverse kidney events (MAKE) in pediatric patients with urologic malformations (UTMs). Methods: This retrospective cohort study used the TriNetX global federated research network of electronic health records. Children aged 0–18 years with UTMs (including congenital urinary tract anomalies, vesicoureteral reflux, obstructive uropathy, neurogenic bladder, and spina bifida) and available serum cystatin C measurements were included. The primary outcome was MAKE, defined as the first occurrence of dialysis initiation, kidney transplantation, chronic kidney disease, albuminuria, or an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m² within 10 years. Secondary outcomes were the individual components of MAKE. Results: After 1:1 propensity score matching, 2062 patients were analyzed (mean follow-up 1025 days). Elevated cystatin C (≥1.3 mg/L) was associated with higher MAKE incidence (39.3% vs 29.2%; HR 2.5, 95% CI 2.00–3.12, p < 0.001). Significant risks were observed for CKD (HR 3.55), dialysis (HR 9.09), and albuminuria (HR 1.83). No significant differences were found for renal transplantation (HR 0.52) or eGFR decline <60 (HR 1.48). Conclusions: High cystatin C independently predicts MAKE and CKD in children with UTMs. Routine testing may enable early risk stratification and guide long-term renal surveillance. Impact: Pediatric patients with urologic malformations have increased chronic kidney disease risk, often requiring dialysis with a significant healthcare and quality-of-life burden. Traditional markers like serum creatinine and eGFR have limitations in detecting early renal impairment in growing children. Serum cystatin C, unaffected by muscle mass or growth, offers superior kidney function assessment but has not been evaluated for predicting long-term outcomes in pediatric urinary tract malformations. This study is the first to evaluate cystatin C’s prognostic value for Major Adverse Kidney Events in this population. Incorporating cystatin C into routine monitoring may improve early risk stratification and guide surveillance strategies.