Urinary DKK3 as a Novel Biomarker for Kidney Function Decline in Children with Alport Syndrome

Background: CKD progression in children with Alport syndrome (AS), a common genetic kidney disease, is hard to predict. DKK3 predicts declining kidney function in adults and advanced CKD children, but its usefulness in early AS detection is unknown. Methods: Urine samples from 50 children enrolled in the EARLY PRO-TECT Alport trial were analyzed to address this hypothesis. Results: DKK3 levels were higher than those of the general population reported in the literature. DKK3 levels were also higher elevated in patients with later AS stages. Furthermore, children, who were not treated with RASi, had higher DKK3 levels compared to treated children. Children with above-average DKK3 levels were more likely to experience increased albuminuria compared to children with below-average DKK3 levels after 2 years of follow-up. Conclusion: This study demonstrated that urinary DKK3, a biomarker for CKD progression, is significantly increased in children at very early stages of AS. Children with above-average DKK3 had higher risk of disease progression. - Age (years) 9.0±4.2 Male no. (%) 49 (98) Mode of inheritance - X-linked 44 (88) Autosomal 5 (10) Unknown 1 (2) BMI (kg/m2) 18±4 Systolic/diastolic blood pressure (mmHg) 105±13/60±9 Creatinine (mg/dl) 0.5±0.2 eGFR (ml/min/1.73 m2) 127±25 Albuminuria (mg/g creatinine) 54 (160) RASi 42 (84) AS stage - 0 22 (44) I 19 (38) II 9 (18)