Active vitamin D is cardioprotective in experimental uraemia but not in children with CKD Stages 3-5
© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:36 |
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| Enthalten in: |
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association - 36(2021), 3 vom: 20. Feb., Seite 442-451 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Schön, Anne [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 17.05.2021 Date Revised 04.12.2021 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/ndt/gfaa227 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM318078619 |
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| 100 | 1 | |a Schön, Anne |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Active vitamin D is cardioprotective in experimental uraemia but not in children with CKD Stages 3-5 |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 17.05.2021 | ||
| 500 | |a Date Revised 04.12.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a chronic kidney disease | |
| 650 | 4 | |a fibroblast growth factor 23 | |
| 650 | 4 | |a left ventricular hypertrophy | |
| 650 | 4 | |a renin–angiotensin system | |
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| 650 | 7 | |a Calcitriol |2 NLM | |
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| 700 | 1 | |a Fischer, Dagmar-Christiane |e verfasserin |4 aut | |
| 700 | 1 | |a Bayazit, Aysun K |e verfasserin |4 aut | |
| 700 | 1 | |a Obrycki, Lukasz |e verfasserin |4 aut | |
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| 700 | 1 | |a Bulut, Ipek Kaplan |e verfasserin |4 aut | |
| 700 | 1 | |a Azukaitis, Karolis |e verfasserin |4 aut | |
| 700 | 1 | |a Yilmaz, Alev |e verfasserin |4 aut | |
| 700 | 1 | |a Mir, Sevgi |e verfasserin |4 aut | |
| 700 | 1 | |a Yalcinkaya, Fatos |e verfasserin |4 aut | |
| 700 | 1 | |a Soylemezoglu, Oguz |e verfasserin |4 aut | |
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| 700 | 1 | |a Shroff, Rukshana |e verfasserin |4 aut | |
| 700 | 1 | |a Bacchetta, Justine |e verfasserin |4 aut | |
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