Hypoxia-inducible factor stabilizers for treating anemia of chronic kidney disease

Purpose of review Small-molecule inhibitors of prolyl hydroxylase domain enzymes (PHD inhibitors) are novel renal anemia therapies that increase endogenous erythropoietin (EPO) production by stabilizing hypoxia-inducible factor (HIF). This review summarizes recent findings and future perspectives of PHD inhibitors (HIF stabilizers) in chronic kidney disease (CKD)-associated anemia. Recent findings Clinical trials have demonstrated that HIF stabilizers effectively increase hemoglobin levels of both nondialysis and dialysis CKD patients without causing serious adverse effects. HIF stabilizers not only restore EPO production but also optimize iron metabolism by reducing hepcidin levels. Considering the pleiotropic roles of the PHD–HIF pathway, HIF stabilizers might have both advantageous and disadvantageous effects in humans, in addition to erythropoiesis. Results of studies in animal models have suggested that HIF stabilizers alleviate ischemia–reperfusion injury and play protective roles against metabolic diseases. In contrast, a theoretical concern exists regarding the potential for tumorigenesis due to HIF stabilization. Summary At least five HIF stabilizers are now in phase III trials and may appear on the market in 1–2 years. The long-term effects and safety of HIF stabilization should be carefully examined in future basic and clinical studies.
Source: Current Opinion in Nephrology and Hypertension - Category: Urology & Nephrology Tags: PHARMACOLOGY AND THERAPEUTICS: Edited by Sankar D. Navaneethan Source Type: research

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Publication date: October 2018Source: American Journal of Kidney Diseases, Volume 72, Issue 4Author(s): Yoshio N. HallThere is ongoing recognition that a wide array of social, economic, and environmental factors influence individuals’ opportunities to engage in health care and healthy behaviors. Despite spending $34 billion annually on the care of patients with end-stage renal disease, the American public and nephrology community remain remarkably complacent about addressing “upstream” factors that influence the prevention, progression, and treatment of chronic kidney diseases. Recently, a growing number ...
Source: American Journal of Kidney Diseases - Category: Urology & Nephrology Source Type: research
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Source: Contributions to Nephrology - Category: Urology & Nephrology Tags: Contrib Nephrol Source Type: research
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Source: American Journal of Kidney Diseases - Category: Urology & Nephrology Source Type: research
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