title: Disturbances of Wnt/β-catenin pathway and energy metabolism in early CKD: effect of phosphate binders.
abstract: BACKGROUND
  Mineral bone disorder (MBD) is an early complication of chronic kidney disease (CKD), with complex interactions in the bone-kidney-energy 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.
  
  
  METHODS
  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 3-4 patients, we measured serum sclerostin, Dickkopf-1, leptin, adiponectin and serotonin concentrations.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Nephrology Department, University of São Paulo (USP), São Paulo, Brazil.
authors: Rodrigo B
authors: RB
authors: de Oliveira
authors: Fabiana G
authors: FG
authors: Graciolli
authors: Luciene M
authors: LM
authors: dos Reis
authors: Ana L E
authors: AL
authors: Cancela
authors: Lilian
authors: L
authors: Cuppari
authors: Maria E
authors: ME
authors: Canziani
authors: Aluizio B
authors: AB
authors: Carvalho
authors: Vanda
authors: V
authors: Jorgetti
authors: Rosa M A
authors: RM
authors: Moysés
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D048868:Adaptor Proteins, Signal Transducing; D052242:Adiponectin / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D015519:Bone Density / Q000187:drug effects; D001847:Bone Diseases / Q000188:drug therapy / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins / Q000097:blood; D017610:Calcium Compounds / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005819:Genetic Markers; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D011073:Polyamines / Q000494:pharmacology*; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy / Q000378:metabolism*; D012701:Serotonin / Q000097:blood; D000069603:Sevelamer; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C499918:ADIPOQ protein, human; D000085:Acetates; D048868:Adaptor Proteins, Signal Transducing; D052242:Adiponectin; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; C495270:CTNNB1 protein, human; D017610:Calcium Compounds; D002614:Chelating Agents; C501126:DKK1 protein, human; C000717427:FGF23 protein, human; D005819:Genetic Markers; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D011073:Polyamines; C422903:SOST protein, human; D051153:Wnt Proteins; D051176:beta Catenin; D012701:Serotonin; D000089703:Fibroblast Growth Factor-23; D000069603:Sevelamer; C120662:calcium acetate
keywords: Wnt/β-catenin signalling; adipokines; chronic kidney disease; fibroblast growth factor-23; phosphate binders.