Burden of Anemia in Chronic Kidney Disease: Beyond Erythropoietin
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REVIEW
Burden of Anemia in Chronic Kidney Disease: Beyond Erythropoietin Ramy M. Hanna . Elani Streja . Kamyar Kalantar-Zadeh
Received: June 24, 2020 / Accepted: October 3, 2020 Ó The Author(s) 2020
ABSTRACT Anemia is a frequent comorbidity of chronic kidney disease (CKD) and is associated with a considerable burden because of decreased patient health-related quality of life and increased healthcare resource utilization. Based on observational data, anemia is associated with an increased risk of CKD progression, cardiovascular events, and all-cause mortality. The current standard of care includes oral or intravenous iron supplementation, erythropoiesis-stimulating agents, and red blood cell transfusion. However, each of these therapies has its own set of population-specific patient concerns, including increased risk of cardiovascular disease, thrombosis, and mortality. Patients receiving dialysis or those who have concurrent diabetes or high blood pressure may be at greater risk of developing these
complications. In particular, treatment with high doses of erythropoiesis-stimulating agents has been associated with increased rates of hospitalization, cardiovascular events, and mortality. Resistance to erythropoiesis-stimulating agents remains a therapeutic challenge in a subset of patients. Hypoxia-inducible factor transcription factors, which regulate several genes involved in erythropoiesis and iron metabolism, can be stabilized by a new class of drugs that act as inhibitors of hypoxia-inducible factor prolyl-hydroxylase enzymes to promote erythropoiesis and elevate hemoglobin levels. Here, we review the burden of anemia of chronic kidney disease, the shortcomings of current standard of care, and the potential practical advantages of hypoxia-inducible factor prolyl-hydroxylase inhibitors in the treatment of patients with anemia of CKD.
Keywords: Anemia; Burden; Chronic kidney disease; Erythropoietin; Hypoxia-inducible factor; Iron; Nephrology R. M. Hanna Division of Nephrology, Hypertension and Kidney Transplantation, Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California, Irvine School of Medicine, Orange, CA, USA E. Streja K. Kalantar-Zadeh (&) Division of Nephrology and Hypertension, University of California, Irvine School of Medicine, Orange, CA, USA e-mail: [email protected]
Adv Ther
Key Summary Points Anemia is common in patients with chronic kidney disease and has been associated with increased risk of cardiovascular morbidity and mortality in observational studies as well as decreased patient quality of life and increased healthcare utilization. The current standard of care includes supplemental iron, erythropoiesisstimulating agents, and red blood cell transfusions, although each has drawbacks. High doses of erythropoiesis-stimulating agents have been associated with increased cardiovascular complications and mortality. Hypoxia-inducible factor-prolyl hydroxylase inhibitors are novel treatments for anemia of chronic kidney disease that prevent degradation of the t
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