title: Active vitamin D treatment in CKD patients raises serum sclerostin and this effect is modified by circulating pentosidine levels.
abstract: OBJECTIVE
  1,25(OH)2Vitamin D increases the expression of the sclerostin gene. Whether vitamin D receptor activation (VDRA) influences serum sclerostin in CKD and whether compounds interfering with VDRA like Advanced Glycosylation End Products (AGEs) may alter the sclerostin response to VDRA is unknown.
  
  
  RESULTS
  Eighty-eight stage G3-4 CKD patients randomly received 2 μg paricalcitol (PCT)/day (n = 44) or placebo (n = 44) for 12 weeks. Sclerostin, a major AGE compound like pentosidine, and bone mineral disorder biomarkers were measured at baseline, at 12 weeks and 2 weeks after stopping the treatments. At baseline, in the whole study population sclerostin correlated with male gender (P = 0.002), BMI (P < 0.001), waist circumference (P < 0.001), serum pentosidine (P = 0.002) and to a weaker extent, with diabetes (P = 0.04), 1,25(OH)2Vitamin D (r = 0.22, P = 0.04) and serum phosphate (r = -0.26, P = 0.01). Sclerostin increased during PCT treatment (average + 15.7 pg/ml, 95% CI: -3.0 to +34.3) but not during placebo (P = 0.03) and the PCT effect was abolished 2 weeks after stopping this drug. The increase in sclerostin levels induced by PCT was modified by prevailing pentosidine levels (P = 0.01) and was abolished by statistical adjustment for simultaneous changes in PTH but not by FGF23 changes.
  
  
  CONCLUSIONS
  VDRA by paricalcitol causes a moderate increase in serum sclerostin in CKD patients. Such an effect is abolished by adjustment for PTH, suggesting that it may serve to counter PTH suppression. The sclerostin rise by PCT is attenuated by pentosidine, an observation in keeping with in vitro studies showing that AGEs alter the functioning of the VDRA.
authors.affiliation: CNR-IFC & Nephrology and Renal Transplantation Unit, Reggio Calabria, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Torino
authors.affiliation: CNR-IFC & Nephrology and Renal Transplantation Unit, Reggio Calabria, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Pizzini
authors.affiliation: CNR-IFC & Nephrology and Renal Transplantation Unit, Reggio Calabria, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Cutrupi
authors.affiliation: CNR-IFC & Nephrology and Renal Transplantation Unit, Reggio Calabria, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Tripepi
authors.affiliation: CNR-IFC & Nephrology and Renal Transplantation Unit, Reggio Calabria, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Mallamaci
authors.affiliation: Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, USA.
authors.forename: R
authors.initials: R
authors.lastname: Thadhani
authors.affiliation: CNR-IFC & Nephrology and Renal Transplantation Unit, Reggio Calabria, Italy. Electronic address: carmine.zoccali@tin.it.
authors.forename: C
authors.initials: C
authors.lastname: Zoccali
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D004311:Double-Blind Method; D004872:Ergocalciferols / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005819:Genetic Markers; D006801:Humans; D007558:Italy; D008239:Lysine / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D008875:Middle Aged; D018167:Receptors, Calcitriol / Q000819:agonists / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation; D014815:Vitamins / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D004872:Ergocalciferols; C000717427:FGF23 protein, human; D005819:Genetic Markers; D018167:Receptors, Calcitriol; C422903:SOST protein, human; C579457:VDR protein, human; D014815:Vitamins; C084656:paricalcitol; D000089703:Fibroblast Growth Factor-23; D001120:Arginine; C062187:pentosidine; D008239:Lysine
keywords: Chronic Kidney Disease; Pentosidine; Sclerostin; Vitamin D