Urinary DKK3 as a biomarker for pediatric CKD progression: a review of current evidence

Chronic kidney disease (CKD) is a significant challenge in pediatric care, as it can lead to substantial long-term comorbidities, reduced quality of life and reduced lifetime. Early detection of pediatric CKD is vital for preventive care and maintaining organ function. Therefore, there is a critical need for biomarkers that should ideally offer early detection (before glomerular filtration rate (GFR) decline), possess high specificity for the underlying renal disease process (e.g. tubular or glomerular damage), and show strong prognostic value for predicting disease progression. This narrative review examines the role of Dickkopf-3 (DKK3), a pro-fibrotic protein released by renal tubular cells during pathophysiological stress, in the context of pediatric CKD. In experimental models, DKK3 has been shown to drive renal tubulointerstitial fibrosis by modulating the WNT/β-catenin signaling pathway. There is increasing evidence suggesting that urinary DKK3 (uDKK3) levels could serve as a valuable biomarker for identifying pediatric CKD patients at high risk for rapid disease progression, regardless of the underlying etiology. This review highlights uDKK3 as a potential marker for the early detection and risk stratification of pediatric patients with CKD, which could lead to a personalized approach to monitor CKD beyond estimated GFR and albuminuria.