Erythropoietin and a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHDi) lowers FGF23 in a model of chronic kidney disease (CKD).
Physiol Rep
; 8(11): e14434, 2020 06.
Article
en En
| MEDLINE
| ID: mdl-32476270
ABSTRACT
Iron-deficiency anemia is a potent stimulator of the phosphaturic hormone Fibroblast growth factor-23 (FGF23). Anemia, elevated FGF23, and elevated serum phosphate are significant mortality risk factors for patients with chronic kidney disease (CKD). However, the contribution of anemia to overall circulating FGF23 levels in CKD is not understood. Our goal was to investigate the normalization of iron handling in a CKD model using the erythropoiesis stimulating agents (ESAs) Erythropoietin (EPO) and the hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHDi) FG-4592, on the production of, and outcomes associated with, changes in bioactive, intact FGF23 ("iFGF23"). Our hypothesis was that rescuing the prevailing anemia in a model of CKD would reduce circulating FGF23. Wild-type mice were fed an adenine-containing diet to induce CKD, then injected with EPO or FG-4592. The mice with CKD were anemic, and EPO improved red blood cell indices, whereas FG-4592 increased serum EPO and bone marrow erythroferrone (Erfe), and decreased liver ferritin, bone morphogenic protein-6 (Bmp-6), and hepcidin mRNAs. In the mice with CKD, iFGF23 was markedly elevated in control mice but was attenuated by >70% after delivery of either ESA, with no changes in serum phosphate. ESA treatment also reduced renal fibrosis markers, as well as increased Cyp27b1 and reduced Cyp24a1 mRNA expression. Thus, improvement of iron utilization in a CKD model using EPO and a HIF-PHDi significantly reduced iFGF23, demonstrating that anemia is a primary driver of FGF23, and that management of iron utilization in patients with CKD may translate to modifiable outcomes in mineral metabolism.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Eritropoyetina
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Insuficiencia Renal Crónica
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Factores de Crecimiento de Fibroblastos
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Prolina Dioxigenasas del Factor Inducible por Hipoxia
/
Inhibidores de Prolil-Hidroxilasa
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Physiol Rep
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos