title: Uremic toxicity and sclerostin in chronic kidney disease patients.
abstract: OBJECTIVE
  Sclerostin is a circulating inhibitor of the Wnt/β-catenin pathway and may have a role in chronic kidney disease (CKD)-mineral and bone disorder. Blood sclerostin levels are known to be elevated in patients undergoing maintenance dialysis. The aims of the present study were to evaluate sclerostin levels in patients at different CKD stages and study potential associations between sclerostin levels and (i) biochemical parameters that are disturbed in CKD, (ii) markers of vascular disease and (iii) mortality.
  
  
  METHODS
  One hundred and forty patients at CKD stages 2-5D were included in the present study. Routine clinical biochemistry tests and assays for sclerostin, protein-bound uremic toxins (indoxylsulphate [IS] and p-cresyl sulphate [PCS]) and the toxin β2 microglobulin (β2M) were performed. Aortic and coronary calcification and arterial stiffness were assessed by multislice spiral computed tomography and pulse wave velocity measurements. The enrolled patients were prospectively monitored for mortality.
  
  
  RESULTS
  Sclerostin levels were found to be elevated in CKD patients (especially those on hemodialysis). Furthermore, sclerostin levels were positively correlated with inflammation markers, phosphate, fibroblast growth factor 23, IS, PCS, β2M and arterial stiffness. A multivariate linear regression analysis indicated that sclerostin levels were independently associated with IS, PCS and β2M levels. Elevated serum sclerostin appeared to be associated with mortality (independently of age and inflammation). However, this association disappeared after adjustment for a propensity score including age, phosphate, interleukin-6, CKD stage and PCS.
  
  
  CONCLUSIONS
  Our results indicate that sclerostin levels are elevated in CKD patients and are associated with inflammation, vascular lesions, uremia and (potentially) mortality.
authors: Inserm U1088, UFR de médecine et pharmacie, Jules Verne university of Picardy, 1, rue des Louvels, 80037 Amiens cedex 1, France; Clinical research centre, division of clinical pharmacology, Amiens university hospital, avenue Lænnec, 80054 Amiens cedex, France; The Jules Verne university of Picardy, 1, rue des Louvels, 80037 Amiens cedex 1, France.
authors: Lucie
authors: L
authors: Desjardins
authors: Inserm U1088, UFR de médecine et pharmacie, Jules Verne university of Picardy, 1, rue des Louvels, 80037 Amiens cedex 1, France; Clinical research centre, division of clinical pharmacology, Amiens university hospital, avenue Lænnec, 80054 Amiens cedex, France; The Jules Verne university of Picardy, 1, rue des Louvels, 80037 Amiens cedex 1, France.
authors: Sophie
authors: S
authors: Liabeuf
authors: Inserm U1088, UFR de médecine et pharmacie, Jules Verne university of Picardy, 1, rue des Louvels, 80037 Amiens cedex 1, France.
authors: Rodriguo B
authors: RB
authors: Oliveira
authors: Inserm U1088, UFR de médecine et pharmacie, Jules Verne university of Picardy, 1, rue des Louvels, 80037 Amiens cedex 1, France.
authors: Loïc
authors: L
authors: Louvet
authors: Inserm U1088, UFR de médecine et pharmacie, Jules Verne university of Picardy, 1, rue des Louvels, 80037 Amiens cedex 1, France.
authors: Saïd
authors: S
authors: Kamel
authors: EXcorLab, GmbH, industrie Center Obernburg D, 63784 Obernburg, Germany.
authors: Horst-Dieter
authors: HD
authors: Lemke
authors: Nephrology section, department of internal medicine, university hospital, De Pintelaan 185, 9000 Ghent, Belgium.
authors: Raymond
authors: R
authors: Vanholder
authors: Inserm U1088, UFR de médecine et pharmacie, Jules Verne university of Picardy, 1, rue des Louvels, 80037 Amiens cedex 1, France; Division of nephrology, Amiens university hospital, avenue Laennec, 80034 Amiens cedex, France.
authors: Gabriel
authors: G
authors: Choukroun
authors: Inserm U1088, UFR de médecine et pharmacie, Jules Verne university of Picardy, 1, rue des Louvels, 80037 Amiens cedex 1, France; Division of nephrology, Ambroise-Paré hospital, 9, avenue Charles-de-Gaulles, 92100 Boulogne-Billancourt, France. Electronic address: ziad.massy@apr.aphp.fr.
authors: Ziad A
authors: ZA
authors: Massy
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D001027:Aortography; D001161:Arteriosclerosis / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D002114:Calcinosis / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology; D003408:Cresols / Q000097:blood; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D005500:Follow-Up Studies; D005819:Genetic Markers; D006801:Humans; D007200:Indican / Q000097:blood; D007249:Inflammation / Q000097:blood; D008297:Male; D008875:Middle Aged; D063177:Pulse Wave Analysis; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000150:complications; D013463:Sulfuric Acid Esters / Q000097:blood; D016019:Survival Analysis; D036542:Tomography, Spiral Computed; D014511:Uremia / Q000097:blood; D059289:Vascular Stiffness; D001613:beta 2-Microglobulin / Q000032:analysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D003408:Cresols; D005819:Genetic Markers; C422903:SOST protein, human; D013463:Sulfuric Acid Esters; D001613:beta 2-Microglobulin; C408690:4-cresol sulfate; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D007200:Indican
keywords: Chronic kidney disease; Mortality; Sclerostin; Uremic toxins