Age-dependent Association Between Dickkopf-1 and Calcium-containing Urolithiasis

Objective To evaluate the serum Dickkopf-1 (DKK1) level in patients with calcium-containing upper urinary tract stones (Ca-UUTS). Methods The study retrospectively enrolled 184 patients with Ca-UUTS and 46 age-matched controls. The serum DKK1 level and urine calcium/creatinine ratio were detected in both groups. Results The mean serum DKK1 level in the controls was 321.7 ± 284.1 pg/mL, which was significantly lower than that of the patients with calcium oxalate and calcium phosphate (CaOx + CaP), CaOx, and CaP stones (687.8 ± 600.2, 640.5 ± 721.5, and 857.9 ± 913.2 pg/mL, respectively). The mean urine calcium/creatinine ratio, an indicator of hypercalciuria, was higher in the Ca-UUTS patients with CaOx + CaP (0.10 ± 0.06), CaOx (0.13 ± 0.07), and CaP (0.12 ± 0.07) stones than in the controls (0.08 ± 0.04). Statistical significance was noted only in the patients with CaOx ( P  = .005) and CaP ( P  = .037) stones. A significant positive association was found between the serum DKK1 level and age in the control group but not in the Ca-UUTS patients. In subjects aged younger than 50 years, the serum DKK1 level in the Ca-UUTS group was significantly higher than in the control group (605.3 ± 514.4 vs 274 ± 229.8 pg/mL, P  = .0003). The serum DKK1 level was not associated with stone size. Conclusion Serum DKK1, an inhibitor of the Wnt signaling pathway, was positively associated with the formation of Ca-UUTS, especially in patients aged younger than 50 years.