Active vitamin D is cardioprotective in experimental uraemia but not in children with CKD Stages 3-5.
Nephrol Dial Transplant
; 36(3): 442-451, 2021 02 20.
Article
em En
| MEDLINE
| ID: mdl-33241290
ABSTRACT
BACKGROUND:
Uraemic cardiac remodelling is associated with vitamin D and Klotho deficiency, elevated fibroblast growth factor 23 (FGF23) and activation of the renin-angiotensin system (RAS). The cardioprotective properties of active vitamin D analogues in this setting are unclear.METHODS:
In rats with 5/6 nephrectomy (5/6Nx) treated with calcitriol, the cardiac phenotype and local RAS activation were investigated compared with controls. A nested case-control study was performed within the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study, including children with chronic kidney disease (CKD) Stages 3-5 [estimated glomerular filtration rate (eGFR) 25 mL/min/1.73 m2] treated with and without active vitamin D. Echocardiograms, plasma FGF23 and soluble Klotho (sKlotho) were assessed at baseline and after 9 months.RESULTS:
In rats with 5/6Nx, left ventricular (LV) hypertrophy, LV fibrosis and upregulated cardiac RAS were dose-dependently attenuated by calcitriol. Calcitriol further stimulated FGF23 synthesis in bone but not in the heart, and normalized suppressed renal Klotho expression. In the 4C study cohort, treatment over a mean period of 9 months with active vitamin D was associated with increased FGF23 and phosphate and decreased sKlotho and eGFR compared with vitamin D naïve controls, whereas LV mass index did not differ between groups.CONCLUSIONS:
Active vitamin D ameliorates cardiac remodelling and normalizes renal Klotho expression in 5/6Nx rats but does not improve the cardiac phenotype in children with CKD Stages 3-5. This discrepancy may be due to further enhancement of circulating FGF23 and faster progression of CKD associated with reduced sKlotho and higher serum phosphate in vitamin D-treated patients.Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Uremia
/
Vitaminas
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Calcitriol
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Hipertrofia Ventricular Esquerda
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Insuficiência Renal Crônica
Tipo de estudo:
Etiology_studies
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Observational_studies
/
Risk_factors_studies
Limite:
Animals
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Child
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Female
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Humans
/
Male
Idioma:
En
Revista:
Nephrol Dial Transplant
Assunto da revista:
NEFROLOGIA
/
TRANSPLANTE
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Alemanha