Circulating levels of sclerostin but not DKK1 associate with laboratory parameters of CKD-MBD

Abstract

Introduction

Mounting evidence indicates that a disturbed Wnt–β-catenin signaling may be involved in the pathogenesis of chronic kidney disease-mineral and bone and mineral disorder (CKD-MBD). Data on the impact of CKD on circulating levels of the Wnt antagonists sclerostin and Dickkopf related protein 1 (DKK1) and the relationship with laboratory parameters of CKD-MBD are incomplete.

Methods

We analyzed serum sclerostin and DKK1 in 308 patients across the stages of chronic kidney disease (kDOQI stage 1–2 n = 41; CKD stage 3 n = 54; CKD stage 4–5 n = 54; hemodialysis n = 100; peritoneal dialysis n = 59) as well as in 49 healthy controls. We investigated associations with demographics, renal function, parameters of mineral metabolism including 25(OH) vitamin D, 1,25(OH) ₂ vitamin D, biointact fibroblast growth factor 23 (FGF23), and parathyroid hormone (PTH), and bone turnover markers.

Results

Serum sclerostin, but not DKK1, increases in more advanced stages of CKD and associates with PTH, phosphate, and 1,25(OH) ₂ vitamin D concentrations. Bone turnover markers are highest in hemodialysis patients presenting the combination of high PTH with low sclerostin level. Serum DKK1 levels are lower in CKD patients than in controls and are not associated with laboratory parameters of mineral metabolism. Interestingly, a direct association between DKK1 and platelet count was observed.

Conclusion

In CKD, serum levels of the Wnt inhibitors DKK1 and sclerostin are unrelated, indicating different sites of origin and/ or different regulatory mechanisms. Sclerostin, as opposed to DKK1, may qualify as a biomarker of CKD-MBD, particularly in dialysis patients. DKK1 serum levels, remarkably, correlate almost uniquely with blood platelet counts.