Serum Sclerostin Levels, Cardiovascular Parameters and Carpal Tunnel Syndrome in Maintenance Hemodialysis Patients

NCT ID: NCT01382966

Last Updated: 2011-06-28

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 400 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2011-07-31
• Study Completion Date: 2011-10-31

Brief Summary

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.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.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).

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.

Detailed Description

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.

Conditions

Chronic Kidney Disease; Renal Osteodystrophy; Left Ventricular Hypertrophy

Study Design

• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Single group

Maintenance hemodialysis patients of minimal 6 months of hemodialysis duration; free of malignancy, infection and autoimmune disease; age over 18 years

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Maintenance hemodialysis patients (minimum 6 months of duration)
• Willingness
• Age > 18 years

Exclusion Criteria

• Infection
• Malignancy
• Autoimmune disease

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

RFM Renal Treatment Services

OTHER

Sponsor Role: lead

Responsible Party

RFM RENAL TEDAVİ HİZMETLERİ

Principal Investigators

ALPER KIRKPANTUR, MD

Role: PRINCIPAL_INVESTIGATOR

RFM Renal Treatment Services

Locations

Rfm Renal Tedavi Merkezi

Ankara, Ankara, Turkey (Türkiye)

Countries

Turkey (Türkiye)

Facility Contacts

FAHRİ MANDIROĞLU, MD

Role: primary

fmoglu@hotmail.com

+903123176065

References

Drueke TB, Lafage-Proust MH. Sclerostin: just one more player in renal bone disease? Clin J Am Soc Nephrol. 2011 Apr;6(4):700-3. doi: 10.2215/CJN.01370211. Epub 2011 Mar 24. No abstract available.

Reference Type: BACKGROUND

PMID: 21441122 (View on PubMed)

Cejka D, Herberth J, Branscum AJ, Fardo DW, Monier-Faugere MC, Diarra D, Haas M, Malluche HH. Sclerostin and Dickkopf-1 in renal osteodystrophy. Clin J Am Soc Nephrol. 2011 Apr;6(4):877-82. doi: 10.2215/CJN.06550810. Epub 2010 Dec 16.

Reference Type: BACKGROUND

PMID: 21164019 (View on PubMed)

Cejka D, Jager-Lansky A, Kieweg H, Weber M, Bieglmayer C, Haider DG, Diarra D, Patsch JM, Kainberger F, Bohle B, Haas M. Sclerostin serum levels correlate positively with bone mineral density and microarchitecture in haemodialysis patients. Nephrol Dial Transplant. 2012 Jan;27(1):226-30. doi: 10.1093/ndt/gfr270. Epub 2011 May 25.

Reference Type: BACKGROUND

PMID: 21613383 (View on PubMed)

Kirkpantur A, Balci M, Turkvatan A, Afsar B. Serum sclerostin levels, arteriovenous fistula calcification and 2-years all-cause mortality in prevalent hemodialysis patients. Nefrologia. 2016;36(1):24-32. doi: 10.1016/j.nefro.2015.07.006. Epub 2015 Nov 3.

Reference Type: DERIVED

PMID: 26546060 (View on PubMed)

Other Identifiers

RFM RENAL

Identifier Type: -

Identifier Source: org_study_id