Sclerostin and Vascular Calcification in CKD and Renal Transplant

Sclerostin is a 22-kDa glycoprotein encoded by the SOST gene. This glycoprotein is almost exclusively synthesized by osteocytes that are not present near the bone surface but lie in the mineralized cortical and cancellous bone (3). Sclerostin can exert its inhibitory effects on bone formation by not only inhibiting proliferation, differentiation and function of osteoblast cells but also facilitating their apoptosis(4). Wnt/β-catenin signalling pathway participates in bone homeostasis and diseases.(5,6) But beyond that, many lines of evidence derived from cell cultures and animal studies indicate that this signalling pathway plays a prominent role in the pathogenesis of atherosclerosis and vascular calcification(VC) (7-10). Serum sclerostin levels in CKD patients are remarkably higher than those in the normal population, with their values increasing across the CKD stages(4,11). However; the studies on the association of serum sclerostin with VC and mortality in renal disease patients have yielded conflicting results. Some investigations showed a positive correlation, whereas others suggested no or even negative correlation(12). VC occurs frequently in CKD patients and its incidence increases across the CKD stages (19). Notably, VC is associated with cardiovascular events (CVEs) and poor prognosis in CKD. It is well recognized that VC occurs in the early years of kidney disease patients recently, even prior to the occurrence of disordered phosphate homeostasis.VC is recognized as a pathological process of osteogenesis initiated by inflammatory factors in vessels(20). The upregulation of sclerostin in calcified tissues led researchers and clinicians to come up with a hypothesis that sclerostin may be related to the pathogenic mechanism of VC in renal disease patients, leading to a large number of studies to examine the association between sclerostin and VC in CKD patients. However, these studies reported inconsistent results, with some studies showing positive association between sclerostin and VC in CKD patients,(21-24) whereas others showing negative association (25-28) or no association at all(29). As in CKD patients, kidney transplant recipients' (KTRs') VC strongly predicts cardiovascular events and all-cause mortality over conventional risk factors.