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

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art_OLIVEIRA_Disturbances_of_Wnt_beta_catenin_pathway_and_energy_2013.PDF (167.51 KB)
Citações na Scopus
40
Tipo de produção
article
Data de publicação
2013
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
OXFORD UNIV PRESS
Autores
CANCELA, Ana L. E.
CUPPARI, Lilian
CANZIANI, Maria E.
CARVALHO, Aluizio B.
Citação
NEPHROLOGY DIALYSIS TRANSPLANTATION, v.28, n.10, p.2510-2517, 2013
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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.
Palavras-chave
Wnt, beta-catenin signalling, adipokines, fibroblast growth factor-23, phosphate binders
URI
https://observatorio.fm.usp.br/handle/OPI/4376
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Coleções
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/16
Artigos e Materiais de Revistas Científicas - ODS/03