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Burden of Anemia in Chronic Kidney Disease: Beyond Erythropoietin
Ramy M Hanna1, Elani Streja2, Kamyar Kalantar-Zadeh3
1Division 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.
Insights
Anemia in chronic kidney disease (CKD) reduces quality of life and increases mortality. New hypoxia-inducible factor prolyl-hydroxylase inhibitors offer potential advantages over current treatments for anemia of CKD.
Area of Science:
- Nephrology
- Hematology
- Pharmacology
Background:
- Anemia is a common complication of chronic kidney disease (CKD), negatively impacting patient quality of life and survival.
- Current treatments for CKD anemia, including iron, erythropoiesis-stimulating agents, and transfusions, have significant limitations and risks.
- High-dose erythropoiesis-stimulating agents are linked to increased cardiovascular events, hospitalization, and mortality, with some patients showing resistance.
Purpose of the Study:
- To review the overall burden of anemia in CKD patients.
- To discuss the limitations and risks associated with current anemia management strategies in CKD.
- To explore the potential benefits of hypoxia-inducible factor prolyl-hydroxylase (HIF-PH) inhibitors for treating anemia of CKD.
Main Methods:
- Literature review of observational data and clinical studies on anemia in CKD.
- Analysis of the efficacy and safety profiles of existing anemia treatments.
- Examination of the mechanism of action and potential clinical applications of HIF-PH inhibitors.
Main Results:
- Anemia in CKD is associated with accelerated disease progression, cardiovascular complications, and increased mortality.
- Standard therapies carry risks such as cardiovascular disease, thrombosis, and mortality, particularly in high-risk patient groups.
- HIF-PH inhibitors represent a novel therapeutic approach by stabilizing hypoxia-inducible factor transcription factors to enhance erythropoiesis and iron metabolism.
Conclusions:
- Anemia of CKD poses a significant health burden with suboptimal current treatments.
- HIF-PH inhibitors show promise as a new class of drugs for managing anemia in CKD patients.
- Further research is warranted to fully elucidate the practical advantages and long-term safety of HIF-PH inhibitors in this population.
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.
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