Urinary DKK3 as a biomarker for pediatric CKD progression: a review of current evidence
Jan Boeckhaus1, Christoph Licht2,3, Matthew Hall4
1Clinic of Nephrology and Rheumatology, University Medical Center Goettingen, Goettingen, Germany.
Insights
Urinary Dickkopf-3 (uDKK3) shows promise as a biomarker for early detection and risk assessment in pediatric chronic kidney disease (CKD). This could enable personalized monitoring beyond traditional measures like estimated glomerular filtration rate (eGFR).
Area of Science:
- Nephrology
- Biomarker Discovery
- Pediatric Medicine
Background:
- Pediatric chronic kidney disease (CKD) presents significant long-term health challenges.
- Early detection and accurate risk stratification are crucial for effective management and preventing disease progression.
- Current biomarkers like estimated glomerular filtration rate (eGFR) and albuminuria have limitations in early detection and prognosis.
Purpose of the Study:
- To review the potential of Dickkopf-3 (DKK3) as a biomarker for pediatric CKD.
- To explore DKK3's role in renal fibrosis and its association with disease progression.
- To highlight urinary DKK3 (uDKK3) as a tool for early detection and risk stratification in pediatric CKD.
Main Methods:
- This is a narrative review examining existing research on DKK3 in the context of pediatric CKD.
- Literature search focused on experimental models and clinical evidence of DKK3's role in renal pathophysiology.
- Analysis of DKK3's function in WNT/β-catenin signaling and its impact on tubulointerstitial fibrosis.
Main Results:
- DKK3 is a pro-fibrotic protein released by renal tubular cells under stress.
- Experimental models show DKK3 drives renal tubulointerstitial fibrosis via WNT/β-catenin pathway.
- Emerging evidence suggests uDKK3 levels correlate with CKD progression risk in pediatric patients.
Conclusions:
- Urinary DKK3 (uDKK3) may serve as a valuable, early biomarker for pediatric CKD.
- uDKK3 has the potential to identify patients at high risk for rapid disease progression, irrespective of etiology.
- uDKK3 could facilitate a personalized approach to monitoring pediatric CKD, complementing eGFR and albuminuria.
Abstract:
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.
Related Concept Videos
02:55The Evidence for Evolution
01:10Review and Preview
Percentiles are a type of fractile that partition data into...
01:13Review and Preview
02:07Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
01:13Introduction to Urinary System
The kidneys are bean-shaped organs located in the retroperitoneal space, on either side of the vertebral column, between the T12 and L3 vertebrae. They are partially protected by the rib cage and surrounded by perirenal fat, which provides cushioning. They are responsible for urine formation and play critical roles in regulating blood pressure, electrolyte levels, and hormone production. The ureters...
01:23Urinary Bladder
In males, the bladder is situated in front of the rectum, while in females, it is positioned anterior to the vagina and uterus. The bladder floor contains an inverted triangular area called the trigone, defined by the two ureteric...