Urinary Dickkopf-3 reflects renal and vascular damage in diabetic kidney disease: A cross-sectional study

Dickkopf-3 (DKK3) is a stress-induced glycoprotein involved in Wnt/β-catenin signaling and has emerged as a marker of renal tubular injury and fibrosis. Although urinary DKK3 has been associated with kidney disease progression independent of albuminuria, its relationship with vascular dysfunction in diabetic kidney disease (DKD) remains unclear. This study aimed to investigate the association between urinary DKK3, albuminuria, and arterial stiffness in patients with DKD.

In this cross-sectional study, 45 patients with DKD and 30 age- and sex-matched healthy controls were enrolled. Urinary DKK3 levels were measured using enzyme-linked immunosorbent assay and normalized to urinary creatinine. Arterial stiffness was assessed by pulse wave velocity (PWV) using an oscillometric device. Correlation and multivariable linear regression analyses were performed to evaluate independent associations among urinary DKK3, albuminuria, and PWV.

Urinary DKK3/creatinine ratios were significantly higher in patients with DKD compared to controls (p < 0.001). In DKD patients, urinary DKK3 showed strong positive correlations with albuminuria (r = 0.785, p < 0.001) and PWV (r = 0.454, p = 0.023). Albuminuria was also significantly correlated with PWV (r = 0.543, p = 0.005). In multivariable regression analysis, urinary DKK3 independently predicted albuminuria (β = 0.546, p = 0.004), whereas albuminuria was the only independent predictor of PWV (β = 0.443, p = 0.026).

Urinary DKK3 is significantly associated with albuminuria and arterial stiffness in DKD. While DKK3 primarily reflects renal tubular stress and fibrotic activation, albuminuria represents systemic endothelial dysfunction and vascular damage. These findings suggest that urinary DKK3 provides complementary information by capturing tubular injury within the cardiorenal axis. If validated in prospective studies, DKK3 may serve as a noninvasive biomarker for early risk stratification of cardiorenal progression.