Active vitamin D treatment in CKD patients raises serum sclerostin and this effect is modified by circulating pentosidine levels.
Nutr Metab Cardiovasc Dis
; 27(3): 260-266, 2017 Mar.
Article
em En
| MEDLINE
| ID: mdl-28017524
ABSTRACT
BACKGROUND AND AIMS:
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. METHODS ANDRESULTS:
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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Arginina
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Distúrbio Mineral e Ósseo na Doença Renal Crônica
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Vitaminas
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Ergocalciferóis
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Proteínas Morfogenéticas Ósseas
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Insuficiência Renal Crônica
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Lisina
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article