4.6 Article

Disturbances of Wnt/β-catenin pathway and energy metabolism in early CKD: effect of phosphate binders

期刊

NEPHROLOGY DIALYSIS TRANSPLANTATION
卷 28, 期 10, 页码 2510-2517

出版社

OXFORD UNIV PRESS
DOI: 10.1093/ndt/gft234

关键词

Wnt; beta-catenin signalling; adipokines; chronic kidney disease; fibroblast growth factor-23; phosphate binders

资金

  1. Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES, Brazil)
  2. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ, Brazil)
  3. Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Brazil)
  4. CNPQ

向作者/读者索取更多资源

Mineral bone disorder (MBD) is an early complication of chronic kidney disease (CKD), with complex interactions in the bonekidneyenergy axis. These events lead to impaired bone remodelling, which in turn is associated with cardiovascular disease. Recently, we reported on a positive effect of phosphate binder treatment on bone remodelling markers and a reduction in serum FGF-23 levels in predialysis-CKD patients. The goal of the present study of this trial was to examine the effects of phosphate binders on energy-regulating hormones and Wnt pathway. In this present post hoc analysis of the above randomized, open-label, 8-week trial, which compared the effects of increasing doses of sevelamer-HCl or calcium acetate on various CKD-MBD parameters in 40 normophosphatemic CKD Stage 34 patients, we measured serum sclerostin, Dickkopf-1, leptin, adiponectin and serotonin concentrations. Serum sclerostin, Dickkopf-1 and leptin were elevated at baseline despite normal calcium, phosphorus levels and daily urinary phosphorus excretion. There were significant and positive correlations between sclerostin and FGF-23, as well between leptin and Dickkopf-1. Treatment with both phosphate binders led to a significant decrease in phosphate overload. However, sevelamer-HCl, but not with calcium acetate, led to a significant decrease in serum FGF-23, sclerostin and leptin, and to a significant increase in bone alkaline phosphatase levels. Early stages of CKD are associated with an impairment of the Wnt pathway, as reflected by elevated sclerostin, and a dysregulation of energy-regulating hormones. Many of these disturbances can be ameliorated by phosphate binder treatment, more with sevelamer-HCl than with calcium acetate.

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