Tổng quan về HIF - PHI trong điều trị thiếu máu ở người bệnh thận mạn tính
Nội dung chính của bài viết
Tóm tắt
Những năm gần đây, các chất ức chế enzym hydroxyl hóa yếu tố cảm ứng thiếu oxy (HIF-PHI) đã thu hút nhiều quan tâm trong điều trị thiếu máu do bệnh thận mạn (CKD). Các thuốc này hoạt động bằng cách ổn định yếu tố cảm ứng thiếu oxy (HIF), từ đó kích thích sản xuất erythropoietin nội sinh và điều hòa chuyển hóa sắt theo cơ chế sinh lý tự nhiên hơn so với erythropoietin tái tổ hợp. Nhờ được sử dụng qua đường uống, thuốc mang lại sự thuận tiện cho người bệnh và góp phần tối ưu hóa quá trình tạo máu. Nhiều thử nghiệm lâm sàng quy mô lớn đã ghi nhận hiệu quả của HIF-PHI trong việc nâng cao nồng độ hemoglobin, giảm nhu cầu sử dụng sắt tĩnh mạch và hạn chế truyền máu. Một số thuốc thuộc nhóm này đã được cấp phép sử dụng tại Nhật Bản, Trung Quốc, Mỹ và các quốc gia châu Âu. Bài tổng quan này nhằm cung cấp thông tin cập nhật về cơ chế tác dụng, hiệu quả lâm sàng và tiềm năng ứng dụng của HIF-PHI trong điều trị thiếu máu ở người bệnh CKD, qua đó mở rộng lựa chọn điều trị và nâng cao chất lượng chăm sóc người bệnh.
Chi tiết bài viết
Từ khóa
Thuốc ức chế HIF-PHI, thiếu máu, bệnh thận mạn tính, erythropoietin
Tài liệu tham khảo
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3. Dasgupta I, Bagnis CI, Floris M, et al. Anaemia and quality of life in chronic kidney disease: a consensus document from the European Anaemia of CKD Alliance. Clin Kidney J. 2024; 17(8): sfae205. doi:10.1093/ckj/sfae205.
4. Portolés J, Martín L, Broseta JJ, Cases A. Anemia in Chronic Kidney Disease: From Pathophysiology and Current Treatments, to Future Agents. Front Med (Lausanne). 2021; 8:642296. doi:10.3389/fmed.2021.642296.
5. Palmer SC, Navaneethan SD, Craig JC, et al. Meta-analysis: erythropoiesis-stimulating agents in patients with chronic kidney disease. Ann Intern Med. 2010; 153(1): 23-33. doi:10.7326/0003-4819-153-1-201007060-00252.
6. Koulouridis I, Alfayez M, Trikalinos TA, Balk EM, Jaber BL. Dose of erythropoiesis-stimulating agents and adverse outcomes in CKD: a metaregression analysis. Am J Kidney Dis. 2013; 61(1): 44-56. doi:10.1053/j.ajkd.2012.07.014.
7. Ogawa T, Nitta K. Erythropoiesis-stimulating agent hyporesponsiveness in end-stage renal disease patients. Contrib Nephrol. 2015; 185: 76-86. doi:10.1159/000380972.
8. Atzinger C, Arens HJ, Neri L, et al. Hyporesponsiveness to Erythropoiesis-Stimulating Agents in Dialysis-Dependent Patients with Anaemia of Chronic Kidney Disease: A Retrospective Observational Study. Adv Ther. 2025; 42(1): 471-489. doi:10.1007/s12325-024-03015-4.
9. Semenza GL. The Genomics and Genetics of Oxygen Homeostasis. Annu Rev Genomics Hum Genet. 2020; 21: 183-204. doi:10.1146/annurev-genom-111119-073356.
10. Del Vecchio L, Locatelli F. Investigational hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHI) for the treatment of anemia associated with chronic kidney disease. Expert Opin Investig Drugs. 2018; 27(7): 613-621. doi:10.1080/13543784.2018.1493455.
11. Haase VH. Hypoxia-inducible factor-prolyl hydroxylase inhibitors in the treatment of anemia of chronic kidney disease. Kidney Int Suppl. 2021; 11(1): 8-25. doi:10.1016/j.kisu.2020.12.002.
12. Ogawa C, Tsuchiya K, Maeda K. Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors and Iron Metabolism. Int J Mol Sci. 2023; 24(3): 3037. doi:10.3390/ijms24033037.
13. Minutolo R, Liberti ME, Simeon V, et al. Efficacy and safety of hypoxia-inducible factor prolyl hydroxylase inhibitors in patients with chronic kidney disease: meta-analysis of phase 3 randomized controlled trials. Clin Kidney J. 2023; 17(1): sfad143. doi:10.1093/ckj/sfad143.
14. Akizawa T, Iwasaki M, Otsuka T, Yamaguchi Y, Reusch M. Phase 3 Study of Roxadustat to Treat Anemia in Non-Dialysis-Dependant CKD. Kidney Int Rep. 2021; 6(7): 1810-1828. doi:10.1016/j.ekir.2021.04.003.
15. Shutov E, Sułowicz W, Esposito C, et al. Roxadustat for the treatment of anemia in chronic kidney disease patients not on dialysis: a Phase 3, randomized, double-blind, placebo-controlled study (ALPS). Nephrol Dial Transplant. 2021; 36(9): 1629-1639. doi:10.1093/ndt/gfab057.
16. Singh AK, Carroll K, McMurray JJV, et al. Daprodustat for the Treatment of Anemia in Patients Not Undergoing Dialysis. N Engl J Med. 2021; 385(25): 2313-2324. doi:10.1056/NEJMoa2113380.
17. Gang S, Khetan P, Varade D, et al. Desidustat in Anemia due to Dialysis-Dependent Chronic Kidney Disease: A Phase 3 Study (DREAM-D). Am J Nephrol. 2022; 53(5): 343-351. doi:10.1159/000523949.
18. Agrawal D, Varade D, Shah H, et al. Desidustat in Anemia due to Non-Dialysis-Dependent Chronic Kidney Disease: A Phase 3 Study (DREAM-ND). Am J Nephrol. 2022; 53(5): 352-360. doi:10.1159/000523961.
19. Akizawa T, Nangaku M, Yamaguchi T, et al. A Phase 3 Study of Enarodustat (JTZ-951) in Japanese Hemodialysis Patients for Treatment of Anemia in Chronic Kidney Disease: SYMPHONY HD Study. Kidney Dis (Basel). 2021; 7(6): 494-502. doi:10.1159/000517053.
20. Akizawa T, Nangaku M, Yamaguchi T, et al. A Phase 3 Study of Enarodustat in Anemic Patients with CKD not Requiring Dialysis: The SYMPHONY ND Study. Kidney Int Rep. 2021; 6(7): 1840-1849. doi:10.1016/j.ekir.2021.04.037.
21. Eckardt KU, Agarwal R, Farag YM, et al. Global Phase 3 programme of vadadustat for treatment of anaemia of chronic kidney disease: rationale, study design and baseline characteristics of dialysis-dependent patients in the INNO2VATE trials. Nephrol Dial Transplant. 2021; 36(11): 2039-2048. doi:10.1093/ndt/gfaa204.
22. Akizawa T, Yamada T, Nobori K, et al. Molidustat for Japanese Patients With Renal Anemia Receiving Dialysis. Kidney Int Rep. 2021; 6(10): 2604-2616. doi:10.1016/j.ekir.2021.07.015.
23. Stoumpos S, Crowe K, Sarafidis P, et al. Hypoxia-inducible factor prolyl hydroxylase inhibitors for anaemia in chronic kidney disease: a clinical practice document by the European Renal Best Practice board of the European Renal Association. Nephrol Dial Transplant. 2024; 39(10): 1710-1730. doi:10.1093/ndt/gfae075.
24. Macdougall IC. Hypoxia-inducible factor prolyl hydroxylase enzyme inhibitors: ready for primetime?. Curr Opin Nephrol Hypertens. 2022; 31(5): 399-405. doi:10.1097/MNH.0000000000000813.
25. Charytan C, Manllo-Karim R, Martin ER, et al. A Randomized Trial of Roxadustat in Anemia of Kidney Failure: SIERRAS Study. Kidney Int Rep. 2021; 6(7): 1829-1839. Published 2021 Apr 17. doi:10.1016/j.ekir.2021.04.007.
26. Chen N, Hao C, Peng X, et al. Roxadustat for Anemia in Patients with Kidney Disease Not Receiving Dialysis. N Engl J Med. 2019; 381(11): 1001-1010. doi:10.1056/NEJMoa1813599.
27. Pergola PE, Charytan C, Little DJ, et al. Changes in Iron Availability with Roxadustat in Nondialysis- and Dialysis-Dependent Patients with Anemia of CKD. Kidney360. 2022; 3(9): 1511-1528. doi:10.34067/KID.0001442022.
28. Singh AK, Cizman B, Carroll K, et al. Efficacy and Safety of Daprodustat for Treatment of Anemia of Chronic Kidney Disease in Incident Dialysis Patients: A Randomized Clinical Trial. JAMA Intern Med. 2022; 182(6): 592-602. doi:10.1001/jamainternmed.2022.0605.
29. Baker DE. Daprodustat. Hosp Pharm. 2023; 58(6): 530-543. doi:10.1177/00185787231172382.
30. Joharapurkar A, Pandya V, Patel H, Jain M, Desai R. Desidustat: a novel PHD inhibitor for the treatment of CKD-induced anemia. Front Nephrol. 2024; 4: 1459425. doi:10.3389/fneph.2024.1459425.
31. Akizawa T, Nangaku M, Yamaguchi T, et al. Two long-term phase 3 studies of enarodustat (JTZ-951) in Japanese anemic patients with chronic kidney disease not on dialysis or on maintenance hemodialysis: SYMPHONY ND-Long and HD-Long studies. Ther Apher Dial. 2022; 26(2): 345-356. doi:10.1111/1744-9987.13724.
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