Sclerostin and Vascular Calcification in CKD and Renal Transplant
Study Details
Study Description
Brief Summary
the aim of the research is to determine the degree of vascular calcification in chronic kidney disease and post-transplant and whether there is a correlation with the level of serum sclerostin.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Chronic Kidney Disease (CKD) patients diagnosed as CKD |
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| Renal transplant recipients of renal transplantation |
Outcome Measures
Primary Outcome Measures
- Vascular calcification [3 months]
measurement of carotid intima media thickness (CIMT) as an indicator of vascular calcification for all patients included in both groups and comparison of the mean CIMT between the groups
- Sclerostin [3 months]
measurement of serum sclerostin levels for all patients included in both groups and comparison of the mean sclerostin level between the groups
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Chronic Kidney disease stages 4 and 5
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Renal transplant recipients
Exclusion Criteria:
- Significant co-morbidity: advanced cancer, advanced liver disease, tertiary hyperparathyroidism
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Ahmed Faisal Mohamed Mohamed Saleh
Investigators
- Principal Investigator: Ahmed FMM Saleh, MSc, Assiut University
Study Documents (Full-Text)
None provided.More Information
Publications
- Sclerostin-Vas-CKD