Serum Sclerostin and Adverse Outcomes in Nondialyzed Chronic Kidney Disease Patients

Kanbay, Mehmet; Siriopol, Dimitrie; Sağlam, Mutlu; Kurt, Yasemin Gülcan; Gök, Mahmut; Çetinkaya, Hakkı; Karaman, Murat; Ünal, Hilmi Umut; Oğuz, Yusuf; Sarı, Sebahattin; Eyıleten, Tayfun; Goldsmith, David; Vural, Abdülgaffar; Veisa, Gabriel; Covic, Adrian; Yılmaz, Mahmut İlker

doi:10.1210/jc.2014-2042

Cited by 108 publications

(88 citation statements)

References 38 publications

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“…Interestingly, we found sclerostin levels in hemodialysis patients to be considerably higher than in the control group, which is in line with previous results [15,16,24].This phenomenon could be explained not only by reduced clearance in impaired kidney function, but also by an enhanced production in uremia. Cejka et al were the first to document increased renal sclerostin elimination with declining kidney function suggesting an increased sclerostin production in uremia [22] .…”

Section: Discussionsupporting

confidence: 92%

“…A study by Viaene et al found a trend towards survival benefit with higher circulating sclerostin levels in 100 hemodialysis patients after a median follow-up time of 637 days [15], suggesting that sclerostin might be a calcification inhibitor. In contrast, Kanbay et al found higher sclerostin values to be associated with fatal and non-fatal cardiovascular events in 173 non-dialyzed patients with CKD stages 3-5 after a mean follow-up of 26 months [16]. A very recent study by Drechsler et al found high sclerostin levels to be protective for cardiovascular mortality in 673 incident dialysis patients [17].…”

Section: Sclerostin In Controls Versus Hemodialysis Patientsmentioning

confidence: 95%

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Sclerostin Quo Vadis? - Is This a Useful Long-Term Mortality Parameter in Prevalent Hemodialysis Patients?

Nowak

Artunc

Serra

et al. 2015

Kidney Blood Press Res

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Background/Aims: Cardiovascular calcification contributes to the increased mortality in hemodialysis patients. Sclerostin was identified as an antianabolic bone factor causing soft tissue calcification. Data on prospective large-scale studies associating sclerostin with mortality in hemodialysis patients are so far inconsistent. Methods: In our multicenter prospective longitudinal study following hemodialysis patients, we assessed the associations of sclerostin and bone remodeling markers with long-term mortality. We evaluated the relationship between circulating sclerostin, Fibroblast growth factor 23 (FGF23) and traditional bone remodeling markers. Sclerostin levels in hemodialysis patients were compared with healthy controls. Results: We enrolled 239 hemodialysis patients with a median follow up of 1461 days. In Cox regression analysis, FGF23 (HR 1.40;95%CI 1.11-1.76), parathyroid hormone (PTH) (HR 1.80;95%CI 1.44-2.26) and alkaline phosphatase (AP) (HR 1.50;95%CI 1.10-2.04) per SD, 25(OH)vitamin D (HR 0.42;95%CI 0.23-0.76) per natural log but not sclerostin (HR 1.02;95%CI 0.75-1.38) per SD increase were associated with mortality. FGF23, PTH and AP were negatively associated with sclerostin. Among control and hemodialysis females, sclerostin levels were lower than in men. Conclusion: Higher FGF23, PTH, AP and lower 25(OH)vitamin D but not sclerostin predict long-term mortality. Sclerostin was negatively associated with FGF23, PTH and AP and lower in females than in males.

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Section: Discussionsupporting

confidence: 92%

Section: Sclerostin In Controls Versus Hemodialysis Patientsmentioning

confidence: 95%

Sclerostin Quo Vadis? - Is This a Useful Long-Term Mortality Parameter in Prevalent Hemodialysis Patients?

Nowak

Artunc

Serra

et al. 2015

Kidney Blood Press Res

View full text Add to dashboard Cite

show abstract

“…63,64 As with subjects having normal renal function, higher concentrations of sclerostin occurs in men, which can be explained by a higher bone mass and indirectly a greater number of osteocytes. 65 The relationship between the concentration of phosphorus and sclerostin (independent from GFR) indicates its potential contribution to the regulation of its secretion by osteocytes. 66 Ishimura et al showed that serum sclerostin was significantly and independently associated with BMD.…”

Section: Sclerostin In Chronic Kidney Diseasementioning

confidence: 99%

Sclerostin: Intracellular mechanisms of action and its role in the pathogenesis of skeletal and vascular disorders

Pietrzyk¹,

Smertka²,

Chudek³

2017

Adv Clin Exp Med

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Sclerostin is a glycoprotein involved in the regulation of bone metabolism, exclusively secreted by osteocytes. It affects the activity of bone morphogenetic proteins (BMPs) and is an inhibitor of the Wnt/β-catenin metabolic pathway in bone cells. Osteocytes reduce the release of sclerostin in response to mechanical stimuli acting on bone, and thus promote the activation of osteogenic pathway Wnt/β-catenin in osteoblasts. This signaling pathway plays a key role in osteogenesis and bone turnover. Loss of sclerostin gene function is related to 3 different craniotubular hyperostosis processes: sclerosteosis, craniodiaphyseal dysplasia, and van Buchem disease. Additionally, experimental and clinical studies suggest that sclerostin may promote vascular calcification. Antibodies directed against sclerostin stimulate bone formation and represent a new therapeutic option in the treatment of diseases with increased bone resorption, such as osteoporosis and inflammatory diseases where there is generalized bone loss, periarticular osteoporosis, and cartilage damage, such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), and glucocorticoid-induced osteoporosis (GIO). Antibody use has the potential to offer new therapeutic approaches in the therapy of mineral and bone disorders resulting from chronic kidney disease (CKD-MBD) and vascular calcifications.

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“…In particular, serum sclerostin was described in patients with chronic kidney disease and uremic patients, underlying its high levels, closely related to mortality risk. 8 The aim of this study was to evaluate the role of serum sclerostin in uremic patients, analyzing its behavior during a single hemodialysis session, through Acetate Free Bio-filtration (AFB) and high-efficiency convective technique. Moreover, we investigated the possible correlations between serum levels of sclerostin and different markers of uremic osteodystrophy and vascular calcification.…”

Section: Introductionmentioning

confidence: 99%

Sclerostin levels in uremic patients: a link between bone and vascular disease

et al. 2016

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Sclerostin is a marker of low-turnover bone disease in end stage renal disease patients. The aim of this study was to evaluate serum sclerostin in uremic patients, analyzing its behavior during a single hemodialysis session. Twenty-one adult patients on intermittent hemodialysis treatment were enrolled. Acetate Free Bio-filtration (AFB) was the technique employed. Uremic patients were characterized by higher levels of serum sclerostin when compared with values observed in healthy subjects. Sclerostin assessed in pre-dialysis samples was 1.4 6 1.02 ng/mL, whereas, in post dialysis samples, a reduction of sclerostin values was observed (0.8 6 0.6 ng/mL; p: 0.008). Sclerostin correlated with parameters of dialysis adequacy, such as creatinine levels and Kt/V values, and it was significantly associated with atherosclerotic disease. Receiver operating characteristics analysis revealed a good diagnostic profile in identifying atherosclerotic disease. Sclerostin, a full dialyzable substance during AFB dialysis, is closely associated with atherosclerotic disease. Its reduction obtained through AFB could represent a defensive mechanism, improving vascular disease and renal osteodystrophy. ARTICLE HISTORY

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Serum Sclerostin and Adverse Outcomes in Nondialyzed Chronic Kidney Disease Patients

Abstract: This is the first study that shows that serum sclerostin values are associated, even after multiple adjustments, with fatal and nonfatal CVEs in a nondialyzed CKD population.

Cited by 108 publications

References 38 publications

Sclerostin Quo Vadis? - Is This a Useful Long-Term Mortality Parameter in Prevalent Hemodialysis Patients?

Sclerostin Quo Vadis? - Is This a Useful Long-Term Mortality Parameter in Prevalent Hemodialysis Patients?

Sclerostin: Intracellular mechanisms of action and its role in the pathogenesis of skeletal and vascular disorders

Sclerostin levels in uremic patients: a link between bone and vascular disease

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