Mechanism of disease
Anemia due to CKD is multifactorial, and the HIF pathway plays an important role1-6
HIF is a transcription factor that activates genes for EPO production and iron metabolism, which can result in erythropoiesis5,7
In healthy kidneys, the HIF pathway helps regulate the body’s response to hypoxia5,7
HIF is regulated by oxygen-dependent PHD enzymes.1,5,7
In normoxia, PHD enzymes are active1,2,5,7
In hypoxia, PHD enzymes are less active1,2,5,7
Insufficient activation of the HIF pathway can directly
contribute to the development of anemia due to CKD2,6
contribute to the development of anemia due to CKD2,6
Anemia due to CKD is multifactorial
- Damage to kidney cells impairs oxygen sensing and reduces EPO production2,6
- Anemia also develops due to chronic inflammation, which can lead to increased hepcidin,* impairing iron metabolism3,4
* Hepcidin is a hormone produced by the liver that plays a key role in regulating iron metabolism.4
CKD=chronic kidney disease; EPO=erythropoietin; Hb=hemoglobin; HIF=hypoxia-inducible factor; OH=hydroxyl; PHD=prolyl hydroxylase domain.
Unmet need
Suboptimal management of anemia due to chronic kidney disease (CKD) can negatively impact patient health8,9
of the ~550,000‡ adult patients with ESRD on dialysis developed anemia10-13
adult patients with ESRD on dialysis fell below target Hb range10,14,15,§
of adult patients with ESRD on dialysis received blood transfusions in 2022 despite most of them being on anemia treatment, which may jeopardize their ability to receive a kidney transplant10,16
Patients on dialysis with anemia due to CKD may be at an increased risk of clinical complications and higher rates of hospitalization8,9
† Based on the 2023 Dialysis Outcomes and Practice Patterns Study Practice Monitor in which patients on dialysis had Hb ≤12.9 g/dL (from a sample of over 11,000 patients in more than 200 hemodialysis facilities in the US).11
‡ From the United States Renal Data System (USRDS) 2024 report with data from 2021-2023, N=815,896.10
§ Data were based on mean hemoglobin in ESRD patients receiving dialysis from 2013-2023. Below target Hb level is defined as 10 g/dL.10,14,15
CKD=chronic kidney disease; ESRD=end-stage renal disease; Hb=hemoglobin.
References: 1. Bhoopalan SV, Huang LJ, Weiss MJ. Erythropoietin regulation of red blood cell production: from bench to bedside and back. F1000Res. 2020;9(Faculty Rev):1153. doi:10.12688/f1000research.26648 2. Haase VH. Therapeutic targeting of the HIF oxygen-sensing pathway: lessons learned from clinical studies. Exp Cell Res. 2017;356(2):160-165. doi:10.1016/j.yexcr.2017.05.004 3. Brugnara C, Eckardt K-U. Hematologic aspects of kidney disease. In: Taal MW, Chertow GM, Marsden PA, Skorecki K, Yu ASL, Brenner BM, eds. Brenner and Rector’s the Kidney. 9th ed. Saunders; 2012:2081-2120 4. Wang Y, Yu X. Stabilizing hypoxia-inducible factor to manage anemia in chronic kidney disease: from basic theory to clinical study. Kidney Dis. 2024;10(2):132-142. doi:10.1159/000536039 5. Gupta N, Wish JB. Hypoxia-inducible factor prolyl hydroxylase inhibitors: a potential new treatment for anemia in patients with CKD. Am J Kidney Dis. 2017;69(6):815-826. doi:10.1053/j.ajkd.2016.12.011 6. Portolés J, Martín L, Broseta JJ, Cases A. Anemia in chronic kidney disease: from pathophysiology and current treatments, to future agents. Front Med. 2021;8:642296. doi:10.3389/fmed.2021.642296 7. Watts D, Gaete D, Rodriguez D, et al. Hypoxia pathway proteins are master regulators of erythropoiesis. Int J Mol Sci. 2020;21(21):8131. doi:10.3390/ijms21218131 8. Young EW, Wang D, Kapke A, et al. Hemoglobin and clinical outcomes in hemodialysis: an analysis of US Medicare data from 2018 to 2020. Kidney Med. 2022;5(2):100578. doi:10.1016/j.xkme.2022.100578 9. Pisoni RL, Bragg-Gresham JL, Young EW, et al. Anemia management and outcomes from 12 countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis. 2004;44(1):94-111. doi:10.1053/j.ajkd.2004.03.023 10. United States Renal Data System. 2024 USRDS Annual Data Report: Epidemiology of Kidney Disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2024 11. Hemoglobin (3 month average), categories. The Dialysis Outcomes and Practice Patterns Study Practice Monitor. Accessed March 20, 2024. https://www.dopps.org/DPM-PD/Files/meanhgbgdl1_c_overallTAB.ht 12. Gender. The Dialysis Outcomes and Practice Patterns Study Practice Monitor. Accessed May 21, 2025. https://www.dopps.org/DPM-HD/Files/gender_c_overallTAB.htm 13. Hemoglobin (most recent), categories. The Dialysis Outcomes and Practice Patterns Study Practice Monitor. Accessed March 20, 2024. https://www.dopps.org/DPM-HD/Files/hgbgdl_c_overallTAB.htm 14. Bazeley J, Wish JB. The evolution of target hemoglobin levels in anemia of chronic kidney disease. Adv Chronic Kidney Dis. 2019;26(4):229-236. doi:10.1053/j.ackd.2019.06.001 15. Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO clinical practice guideline for anemia in chronic kidney disease. Kidney Int Suppl. 2012;2(4):279-335 16. Orbrador G, Macdougall C. Effect of red cell transfusions on future kidney transplantation. Am Society of Nephrology. 2013;(8):852-860. doi:10.2215/CJN.00020112.