The Association of Serum Sclerostin Levels,Echocardiographic Parameters, Arteriovenous Fistula Thrombosis and Carpal Tunnel Syndrome in Maintenance Hemodialysis Patients
Sclerostin, the product of the SOST gene, located on chromosome 17, locus q11.2 in humans,
was originally believed to be a non-classical Bone morphogenetic protein (BMP)
antagonist.More recently Sclerostin has been identified as binding to LRP5/6 receptors and
inhibiting the Wnt signalling pathway .Wnt activation under these circumstances is
antagonistic to bone formation. Although the underlying mechanisms are unclear, it is
believed that the antagonism of BMP-induced bone formation by sclerostin is mediated by Wnt
signalling, but not BMP signalling pathways.
Sclerostin is produced by the osteocyte and has catabolic effects on bone formation. This
protein, with a length of 113 residues, has a dssp secondary structure that is 28% beta
sheet (6 strands; 32 residues. Sclerostin has an inhibitory effect on the lifetime of the
osteoblast. Sclerostin production by osteocytes is inhibited by parathyroid hormone,
mechanical loading and cytokines including oncostatin M, cardiotrophin-1 and leukemia
inhibitory factor. Sclerostin production is increased by calcitonin. Thus, osteoblast
activity is self regulated by a negative feedback system.Sclerostin was recently identified
as a component of parathyroid hormone (PTH) signal transduction.
Chronic kidney disease (CKD) is associated with abnormalities in bone and mineral
metabolism.Renal osteodystrophy (ROD) is one of the three components of chronic kidney
disease-mineral and bone disorder (CKD-MBD. Patients with CKD may develop various types of
bone disease, spanning the spectrum of extreme situations such as severe osteitis fibrosa,
osteomalacia, mixed osteopathy, and adynamic bone disease. In addition, patients may have
osteoporosis, which increases the risk for fractures, both in advanced and in less severe
CKD stages (2- 4),which, in turn, result in excess mortality New advances in the
pathogenesis of renal osteodystrophy (ROD) change the perspective from which many of its
features and treatment are viewed. Calcium, phosphate, parathyroid hormone (PTH), and
vitamin D have been shown to be important determinants of survival associated with kidney
diseases. Now ROD dependent and independent of these factors is linked to survival more than
just skeletal frailty.Furthermore, ROD is shown to be an underappreciated factor in the
level of the serum phosphorus in CKD. The discovery and the elucidation of the mechanism of
hyperphosphatemia as a cardiovascular risk in CKD change the view of ROD. Emerging current
data suggests a promising role for serum measurements of sclerostin in addition to iPTH in
the diagnosis of high bone turnover in chronic kidney disease-5D patients (dialysis
patients).
The demonstration that the level of serum sclerostin,which is directly produced by
osteocytes, is a good predictor for bone formation in patients with CKD may be of clinical
interest.Because of the close relationship between ROD and cardiovascular disease, the aim
of this study is to investigate the association between sclerostin, arteriovenous fistula
thrombosis, echocardiography and carpal tunnel syndrome in maintenance hemodialysis
patients.
Observational
Time Perspective: Cross-Sectional
Number of Participants with left ventricular hypertrophy or left ventricular dysfunction according to tertiles of the serum sclerostin levels
3 months
Yes
ALPER KIRKPANTUR, MD
Principal Investigator
RFM Renal Treatment Services
Turkey: Ethics Committee
RFM RENAL
NCT01382966
July 2011
October 2011
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