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Urinary Dickkopf-3 Predicts GFR Loss in the General Population
Jon Viljar Norvik1,2, Danilo Fliser3, Bjørn Odvar Eriksen1,2
1Metabolic and Renal Research Group, Institute of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
Kidney International Reports
|October 27, 2025
Summary
Elevated urinary Dickkopf-3 (uDKK3) levels predict faster kidney function decline in adults. This finding highlights uDKK3 as a potential biomarker for early detection of chronic kidney disease (CKD) progression.
Area of Science:
- Nephrology
- Biomarker Discovery
- Epidemiology
Background:
- Chronic kidney disease (CKD) affects over 800 million people globally, with increasing prevalence necessitating improved early detection and management.
- Urinary Dickkopf-3 (uDKK3), a protein linked to kidney injury and fibrosis, is being investigated for its role in CKD progression.
Purpose of the Study:
- To evaluate urinary Dickkopf-3 (uDKK3) as a predictive biomarker for glomerular filtration rate (GFR) decline in the general adult population.
- To assess the association between uDKK3 levels and the rate of GFR decline, independent of established CKD risk factors.
Main Methods:
- A prospective cohort study of 1316 adults (aged 55-69) with 5.3 years of follow-up and multiple GFR measurements using iohexol clearance.
- Participants were categorized based on urinary Dickkopf-3 normalized to creatinine (uDKK3/Cr) levels: undetectable, low (<400 pg/mg), and high (≥400 pg/mg).
- Statistical analyses included linear mixed models for GFR decline rate and logistic regression for accelerated GFR decline.
Main Results:
- Higher baseline uDKK3/Cr levels were significantly associated with a faster annual GFR decline rate (-0.63 ml/min/1.73 m² faster in the high uDKK3/Cr group).
- Individuals with high uDKK3/Cr levels demonstrated a 2.68-fold increased odds of experiencing accelerated GFR decline compared to those with undetectable levels (P=0.03).
- The association between elevated uDKK3/Cr and GFR decline persisted independently of traditional CKD risk factors such as blood pressure and medication use.
Conclusions:
- Elevated urinary Dickkopf-3 (uDKK3) levels are a significant independent predictor of accelerated glomerular filtration rate (GFR) decline.
- uDKK3 shows promise as a valuable biomarker for the early identification of individuals at higher risk of progressive kidney function loss.
- Further research can explore uDKK3's utility in clinical settings for CKD risk stratification and management.
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