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Войти в исследования Current opinion in nephrology and hypertension · 2020
Hypoxia-inducible factor prolyl hydroxylase inhibitor in the treatment of anemia in chronic kidney disease.
СтатьяПоддержка исследования: вне правительства СШАОбзорНазвание и аннотация: Перевод в очереди
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Kurata Yu, Tanaka Tetsuhiro, Nangaku Masaomi
Аннотация
PURPOSE OF REVIEW: Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are orally active small molecules and are launched as novel therapeutic agents for anemia in chronic kidney disease (CKD). In contrast to conventional exogenous erythropoietin (EPO) administration, HIF-PHIs stimulate endogenous EPO production and improve iron metabolism via stabilization of hypoxia-inducible factor (HIF). This review summarizes the mechanism of action, the results of clinical trials, and future perspectives of HIF-PHIs.
RECENT FINDINGS: Six HIF-PHIs are currently under phase III studies, some of which have been already completed. According to the results of clinical trials, HIF-PHIs increased and maintained hemoglobin levels in both nondialysis-dependent and dialysis-dependent CKD patients with physiological EPO concentrations. HIF-PHIs also improved iron utilization and were comparably effective regardless of underlying inflammation and iron status.
SUMMARY: HIF-PHIs have several advantages including oral administration, physiological EPO secretion, and improved iron utilization. Undoubtedly, HIF-PHIs will pave the new way in the field of treatment of anemia in CKD, but it should be noted that HIFs have pleiotropic effects on a plethora of cellular functions, which might lead to either beneficial or undesirable off-target effects. Intensive postmarketing surveillance is crucially important to identify unexpected consequences.
RECENT FINDINGS: Six HIF-PHIs are currently under phase III studies, some of which have been already completed. According to the results of clinical trials, HIF-PHIs increased and maintained hemoglobin levels in both nondialysis-dependent and dialysis-dependent CKD patients with physiological EPO concentrations. HIF-PHIs also improved iron utilization and were comparably effective regardless of underlying inflammation and iron status.
SUMMARY: HIF-PHIs have several advantages including oral administration, physiological EPO secretion, and improved iron utilization. Undoubtedly, HIF-PHIs will pave the new way in the field of treatment of anemia in CKD, but it should be noted that HIFs have pleiotropic effects on a plethora of cellular functions, which might lead to either beneficial or undesirable off-target effects. Intensive postmarketing surveillance is crucially important to identify unexpected consequences.