Reduced Renal Calcium Excretion in the Absence of Sclerostin Expression

Kumar, Rajiv; Vallon, Volker

doi:10.1681/asn.2014020166

Cited by 23 publications

(14 citation statements)

References 125 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…FGF‐23 has recently been implicated to be more strongly associated with myocardial than vascular toxicity . Sclerostin has not been studied extensively and may be considered to be a new link to both bone and vessel disease in HD patients . Vascular inflammation may be one of the mechanisms to consider; an important morbidity and mortality factor in HD patients .…”

Section: Discussionmentioning

confidence: 99%

Sclerostin, TNF‐alpha and Interleukin‐18 Correlate and are Together with Klotho Related to Other Growth Factors and Cytokines in Haemodialysis Patients

et al. 2015

View full text Add to dashboard Cite

Patients with chronic renal failure are known to have renal osteodystrophy (bone disease) and increased calcification of vessels. A new marker of bone disease, sclerostin, the two pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-18 (IL-18), and the fibroblast growth factor-23 (FGF-23) receptor-associated marker Klotho were tested in 84 haemodialysis (HD) patients and in healthy controls. The patients had significantly higher levels of the three former markers than of the controls while Klotho was significantly higher in the controls. Low level, but significant, correlations were observed in the patient group when the levels of these four markers were compared to each other and to those of 5 cytokines and growth factors tested earlier; high-sensitive CRP (hsCRP), interleukin-6 (IL-6), hepatocyte growth factor (HGF), fibroblast growth factor-23 (FGF-23) and soluble urokinase plasminogen activator (suPAR). Ln sclerostin correlated positively to Ln hsTNFalpha, Ln HGF and Ln suPAR. Ln hsTNF-alpha correlated positively to Ln sclerostin, Ln hsCRP, Ln IL-6, Ln FGF-23, Ln suPAR and Ln IL-18. Ln IL-18 correlated positively to Ln suPAR and Ln TNF-alpha. Ln Klotho correlated negatively to Ln hsCRP but did not correlate to Ln FGF-23. The markers studied here may be involved in the calcification of vessels seen in HD patients due to a combination of inflammation and bone disease. The mechanisms are still not fully known but may be of importance for future therapeutic possibilities in this group of patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Sclerostin, TNF‐alpha and Interleukin‐18 Correlate and are Together with Klotho Related to Other Growth Factors and Cytokines in Haemodialysis Patients

et al. 2015

View full text Add to dashboard Cite

show abstract

“…To date, the effects of sclerostin overexpression on mineral metabolism remain to be determined, and many outstanding questions remain regarding potential renal actions of sclerostin ( 127 ). For example, does FGF-23 act independently of sclerostin or mediate its effects on 1α,25(OH) 2 D synthesis?…”

Section: Sclerostin In Mineral Metabolismmentioning

confidence: 99%

Sclerostin and Osteocalcin: Candidate Bone-Produced Hormones

2021

View full text Add to dashboard Cite

In addition to its structural role, the skeleton serves as an endocrine organ that controls mineral metabolism and energy homeostasis. Three major cell types in bone - osteoblasts, osteoclasts, and osteocytes – dynamically form and maintain bone and secrete factors with systemic activity. Osteocalcin, an osteoblast-derived factor initially described as a matrix protein that regulates bone mineralization, has been suggested to be an osteoblast-derived endocrine hormone that regulates multiple target organs including pancreas, liver, muscle, adipose, testes, and the central and peripheral nervous system. Sclerostin is predominantly produced by osteocytes, and is best known as a paracrine-acting regulator of WNT signaling and activity of osteoblasts and osteoclasts on bone surfaces. In addition to this important paracrine role for sclerostin within bone, sclerostin protein has been noted to act at a distance to regulate adipocytes, energy homeostasis, and mineral metabolism in the kidney. In this article, we aim to bring together evidence supporting an endocrine function for sclerostin and osteocalcin, and discuss recent controversies regarding the proposed role of osteocalcin outside of bone. We summarize the current state of knowledge on animal models and human physiology related to the multiple functions of these bone-derived factors. Finally, we highlight areas in which future research is expected to yield additional insights into the biology of osteocalcin and sclerostin.

show abstract

“…Indeed, hypercalciuric effect in T2DM could be due to the osmotic effect [26] or decreased renal alpha-Klotho expression [15]. In addition, sclerostin was considered to increase renal Ca excretion by downregulation of vitamin D activity [27]. Therefore, the inverse relationship between serum sclerostin and FeCa in our T2DM patients with or without CKD may reflect a possible new negative feedback of FeCa on sclerostin, which has not yet been described before.…”

Section: Discussionmentioning

confidence: 97%

The Association of Urinary Sclerostin and Renal Magnesium Handling in Type 2 Diabetic Patients with Chronic Kidney Disease

Liou

Kuo

et al. 2021

Kidney Blood Press Res

View full text Add to dashboard Cite

Introduction: Sclerostin could enhance renal excretion of calcium (Ca) and phosphate (P). The association between sclerostin and magnesium (Mg) has not yet discovered. In patients with type 2 diabetes mellitus (T2DM) or chronic kidney disease (CKD), higher serum sclerostin and altered renal excretion of Ca, P, and Mg were detected. Therefore, we tried to evaluate if there was any association between sclerostin and fractional excretion of Ca, P, and Mg (FeCa, FeP, and FeMg) in T2DM with CKD. Methods: In this prospective cohort study, 43 T2DM patients without CKD or with CKD stage 1–5 were enrolled. Values of parameters, including serum and urine sclerostin, were collected at baseline and 6 months later. For baseline data, the Mann-Whitney U test, χ2 test, or Spearman’s correlation were used. For multivariate repeated measurement analysis, generalized estimating equation (GEE) model was utilized. Results: Patients with lower estimated glomerular filtration rate had higher serum sclerostin, FeP, FeMg, and lower FeCa. By correlation analysis, serum sclerostin was negatively associated with FeCa (p = 0.02) and positively associated with FeP (p = 0.002). The urine sclerostin to creatinine ratio (Uscl/Ucre) was positively correlated with FeP (p = 0.007) and FeMg (p = 0.005). After multivariate analyses by GEE model, serum sclerostin was still inversely associated with FeCa, while Uscl/Ucre was significantly associated with FeMg. On the other hand, FeP lost its associations with serum sclerostin or Uscl/Ucre. Conclusion: In our study population of T2DM patients with or without CKD, the inverse correlation between serum sclerostin and FeCa could not be explained by the calciuric effect of sclerostin. In addition, a newly discovered positive association between urinary sclerostin and FeMg indicated a possible role of urinary sclerostin in regulating renal Mg handling especially over distal convoluted tubules.

show abstract

Reduced Renal Calcium Excretion in the Absence of Sclerostin Expression

Cited by 23 publications

References 125 publications

Sclerostin, TNF‐alpha and Interleukin‐18 Correlate and are Together with Klotho Related to Other Growth Factors and Cytokines in Haemodialysis Patients

Sclerostin, TNF‐alpha and Interleukin‐18 Correlate and are Together with Klotho Related to Other Growth Factors and Cytokines in Haemodialysis Patients

Sclerostin and Osteocalcin: Candidate Bone-Produced Hormones

The Association of Urinary Sclerostin and Renal Magnesium Handling in Type 2 Diabetic Patients with Chronic Kidney Disease

Contact Info

Product

Resources

About