Kidney Week

Abstract: FR-PO0521

Urinary Dickkopf-3 Concentration and Kidney Function Decline in Adults with Type 2 Diabetes: A Prospective Cohort Study

Session Information

• CKM: Clinical - Trials, Epidemiology, and Biomarkers
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Cardiovascular-Kidney-Metabolic Health

• 602 Cardiovascular-Kidney-Metabolic Health: Clinical

Authors

• Dervan, Louise, School of Medicine, University of Galway,, Galway, Ireland

Louise Dervan, MBChB

• Islam, Nahidul, Department of Applied Science, Technological University of Shannon Midwest,, Limerick, Ireland

Nahidul Islam, MD, PhD

• Griffin, Tomas P., Department of Endocrinology and Diabetes, University Hospital Galway, Galway, Ireland

Tomas P. Griffin, MBChB, MSc, PhD

• Griffin, Matthew D., Department of Nephrology, University Hospital Galway, Galway, Ireland

Matthew D. Griffin, MBChB

• O'Shea, Paula Mary/m, Department of Clinical Chemistry, Mater Misericordiae University Hospital, Dublin, Ireland

Paula Mary/m O'Shea, PhD

Background

In 2024,the International Diabetes Federation estimated that 589million adults aged 20-79 have diabetes,projected to rise to 853 million by 2050.Diabetic kidney disease(DKD) affects 30-40% and is associated with high mortality;10-year all-cause mortality of 31.1%,compared with 11.5% in diabetes without CKD and 7.7% in unaffected people.

Current monitoring with eGFR and albuminuria,vary between individuals and often detect disease late.Novel biomarkers could identify patients at risk of rapid decline,enabling early introduction of renoprotective therapies.Renal fibrosis and tubular atrophy are key features of CKD progression.Urinary Dickkopf-3(uDKK3),released by stressed tubular cells,promotes fibrosis through Wnt/β-catenin signalling and may improve risk stratification.

Methods

BIOmarkers in Diabetes in Galway(Bio-DIG) is a prospective cohort study of adults with type2 diabetes across a spectrum of DKD attending Galway University Hospital.Participants underwent structured phenotyping,serial biospecimen collection,and longitudinal follow-up.

uDKK3 was measured using the BioHIT ReFiNE® DKK3 ELISA.The study evaluated if uDKK3 predicts rapid decline and improves prediction beyond the Kidney Failure Risk Equation(KFRE).

Results

Of 148 participants,142 had biobanked urine available. Median age was 67.4 years(range 23.2-94),70.3%(n=104) were male,median HbA1c was 57.5 mmol/mol(range 33-134),BMI 31 kg/m²(range 20.9-51.2),and eGFR(CKD-EPI 2009)65.4 mL/min/1.73 m²(range 13-127).

Individual eGFR slopes were estimated using linear mixed-effects models with random intercepts and slopes.Rapid progression was defined as >3 mL/min/1.73 m²/year.

Higher uDKK3 levels were associated with greater annual renal decline on univariate analysis(β=−0.888,95% CI −1.61 - −0.162),although variance explained was modest (R²=0.04).After adjustment for baseline eGFR,albuminuria,age,and sex,uDKK3 was no longer independently associated with renal decline(adjusted p=0.289-0.314),while baseline eGFR remained significant(p<0.001).

Addition of uDKK3 to the 4-parameter KFRE produced minimal improvement in prediction of rapid progression(AUC 0.779vs0.780;Δχ²=0.213,p=0.645).Similar findings were observed with the 8-parameter KFRE(AUC 0.807vs0.813; Δχ²=0.416,p=0.519).

Conclusion

Although uDKK3 showed only modest added value beyond KFRE, it may have utility as a complementary biomarker for progressive DKD risk.