Erythropoietin and a hypoxia ‐inducible factor prolyl hydroxylase inhibitor (HIF‐PHDi) lowers FGF23 in a model of chronic kidney disease (CKD)

Iron ‐deficiency anemia is a potent stimulator of the phosphaturic hormone FGF23, and anemia, elevated FGF23, and serum phosphate are all significant risk factors for chronic kidney disease (CKD) patient death; however, the contribution of anemia to circulating FGF23 in CKD is not understood. We found that a CKD mouse model treated with EPO or a HIF‐PHDi to restore proper iron utilization had a 70% reduction of circulating iFGF23, normalization of vitamin D metabolic enzymes, and no exacerbation of hyperphosphatemia. In summary, our work demonstrated that the major portion of elevated iFGF23 in CKD is likely due to the associated anemia/iron deficiency, is therapeutically responsive to the control of iron utilization, and may thus provide modifiable patient benefit for mineral handling during CKD. AbstractIron ‐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 ci rculating 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 produc tion of, and outcomes associated with, changes in bioactive, intact FGF2...
Source: Physiological Reports - Category: Physiology Authors: Tags: ORIGINAL RESEARCH Source Type: research