Роксадустат: лечение анемии и дополнительные клинические эффекты (обзор литературы)
- Авторы: Михайлова Н.А.1
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Учреждения:
- Российская медицинская академия непрерывного профессионального образования Минздрава России
- Выпуск: Том 16, № 2 (2024)
- Страницы: 68-82
- Раздел: Обзоры литературы
- URL: https://journals.eco-vector.com/2075-3594/article/view/634575
- DOI: https://doi.org/10.18565/nephrology.2024.2.68-82
- ID: 634575
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Аннотация
Статья посвящена имеющемуся на сегодня опыту применения первого препарата для лечения анемии из группы ингибиторов фермента пролилгидроксилазы, индуцируемого гипоксией фактора (Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor [HIF-PHI]), – роксадустату. В обзоре кратко изложены сведения о роли индуцируемого гипоксией фактора (HIF) в поддержании адекватного эритропоэза, механизме действия ROX, обеспечивающего клинический эффект в отношении ренальной анемии. Приведены основные результаты крупных клинических исследований III фазы и мета-анализов, написанных на их основе, касающихся лечения анемии у пациентов с хронической болезнью почек, в т.ч. диабетического генеза, как на додиализном этапе, так и на заместительной почечной терапии. Также представлены выявленные к настоящему времени плейотропные эффекты роксадустата, которые целесообразно учитывать при назначении препарата для лечения анемии и которые в будущем могут быть использованы как новые терапевтические подходы в отношении целого ряда заболеваний.
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Об авторах
Наталья Алексеевна Михайлова
Российская медицинская академия непрерывного профессионального образования Минздрава России
Автор, ответственный за переписку.
Email: natmikhailova@mail.ru
ORCID iD: 0000-0001-5819-4360
к.м.н., доцент кафедры нефрологии и гемодиализа ГБОУ ДПО РМАНПО Минздрава РФ
Россия, МоскваСписок литературы
- Babitt J.L., Eisenga M.F., Haase V.H., et al. Controversies in optimal anemia management: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference. Kidney Int 2021;99:1280–95. doi: 10.1016/j.kint.2021.03.020.
- Kim-Mitsuyama S., Soejima H., Yasuda O., et al. Anemia is an independent risk factor for cardiovascular and renal events in hypertensive outpatients with well-controlled blood pressure: a subgroup analysis of the ATTEMPTCVD randomized trial. Hypertens Res 2019;42:883–91. doi: 10.1038/s41440-019-0210-1.
- Stauffer M.E., and Fan T. Prevalence of anemia in chronic kidney disease in the United States. PLoS ONE/2014;9:e84943. doi: 10.1371/journal.pone.0084943.
- Li Z.-L., Tu Y., Liu B.-C., Treatment of renal anemia with Roxadustat: advantages and achievement, Kidney Dis. 6 (2020) 65–73. doi: 10.1159/000504850.
- Babitt J.L., Lin H.Y. Mechanisms of Anemia in CKD. J. Am. Soc. Nephrol. 2012, 23:1631–34. doi: 10.1681/ASN.2011111078.
- Haase V.H. Regulation of erythropoiesis by hypoxia-inducible factors. Blood Rev 2013;27(1):41–53. doi: 10.1016/j.blre.2012.12.003.
- Fishbane S., Spinowitz B. Update on anemia in ESRD and earlier stages of CKD: core curriculum 2018. Am J Kidney Dis 2018;71(3):423–35. doi: 10.1053/j.ajkd.2017.09.026.
- Semenza G.L., Nejfelt M.K., Chi S.M., Antonarakis S.E. Hypoxia-inducible nuclear factors bind to an enhancer element located 3’ to the human erythropoietin gene. Proc Natl Acad Sci USA 1991;88(13):5680–84. doi: 10.1073/pnas.88.13.5680.
- Kaplan J.M., Sharma N., Dikdan S. Hypoxia-Inducible Factor and Its Role in the Management of Anemia in Chronic Kidney Disease. Int. J. Mol. Sci. 2018, 19:389. doi: 10.3390/ijms19020389.
- Wang G.L., Jiang B.H., Rue E.A., Semenza G.L. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci USA 1995;92(12):5510–14. doi: 10.1073/pnas.92.12.5510.
- Semenza G.L. HIF-1 and mechanisms of hypoxia sensing. Curr Opin Cell Biol 2001;13(2):167–71. doi: 10.1016/S0955-0674(00)00194-0.
- Majmundar A.J., Wong W.J., Simon M.C. Hypoxia inducible factors and the response to hypoxic stress. Mol Cell 2010;40:294–309. doi: 10.1016/j.molcel.2010.09.022.
- Del Vecchio L., Minutolo R. ESA, Iron Therapy and New Drugs: Are There New Perspectives in the Treatment of Anaemia? J Clin Med 2021;10:839. doi: 10.3390/jcm10040839.
- Chen X., Yao J. M., Fang X. et al. Hypoxia promotes pulmonary vascular remodeling via HIF-1α to regulate mitochondrial dynamics. J. Geriatr Cardiol.2019,16:855–71. doi: 10.11909/j.issn.1671-5411.2019.12.003.
- 15. Lee J.W., Bae S.H., Jeong J.W., et al. Hypoxia-inducible factor (HIF-1) alpha: its protein stability and biological functions. Exp Mol Med. 2004;36(1):1–12. doi: 10.1038/emm.2004.1.
- 16. Joharapurkar A.A., Pandya V.B., Patel V.J. et al. Prolyl hydroxylase inhibitors: A breakthrough in the therapy of anemia associated with chronic diseases. J. Med. Chem. 2018, 61 (16):6964–82. doi: 10.1021/acs.chem.7b01686.
- Sanghani N.S., Haase V.H. Hypoxia-inducible factor Activators in renal anemia: Current clinical experience. Adv. Chronic Kidney Dis. 2019, 26(4):253–66. doi: 10.1053/j.ackd.2019.04.004.
- Mahajan R., Samanthula G., Srivastava S., Asthana A. A critical review of Roxadustat formulations, solid state studies, and analytical methodology. Heliyon, 2023;9:e16595. doi: 10.1016/j.heliyon.2023.e16595.
- Barratt J., Andric B., Tataradze A. et al. Roxadustat for the treatment of anaemia in chronic kidney disease patients not on dialysis: a Phase 3, randomized, open-label, active-controlled study (DOLOMITES). Nephrol Dial Transplant. 2021, 36(9):1616–28. doi: 10.1093/ndt/gfab191.
- Barratt J., Sulowicz W., Schömig M. et al. Efficacy and cardiovascular safety of roxadustat in dialysis-dependent chronic kidney disease: pooled analysis of four phase 3 studies. Adv Ther. 2021 Oct;38(10):5345–60. doi: 10.1007/s12325-021-01903-7.
- Barratt J., Dellanna F., Portoles J. et al. Safety of roxadustat versus erythropoiesisstimulating agents in patients with anemia of non-dialysis-dependent or incident-to-dialysis chronic kidney disease: pooled analysis of four phase 3 studies. Adv Ther 2023, 40:1546–59. doi: 10.1007/s12325-023-02433-0.
- Provenzano R., Szczech L., Leong R. et al. Efficacy and cardiovascular safety of roxadustat for treatment of anemia in patients with non-dialysis-dependent ckd: pooled results of three randomized clinical trials. Clin J Am Soc Nephrol. 2021,16(8):1190–1200. doi: 10.2215/CJN.16191020.
- Alexandre A.F., Morga A., Thomas C. et al. Preferences for anaemia treatment attributes among patients with non-dialysis-dependent chronic kidney disease. Adv Ther 2023, 40:641–57. doi: 10.1007/s12325-022-02367-z.
- Naganuma Т., Iwai Т., Takemoto Y., Uchida J. Experience With the Use of a Novel Agent, Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor, for Posttransplant Anemia in Renal Transplant Recipients: A Case Report. Transplantation Proceedings 2021, 54:544−48. doi: 10.1016/j.transproceed.2021.10.022.
- DF Diabetes Atlas 10th edition https://diabetesatlas.org/atlas/tenth-edition/
- Ruiz-Ortega M., Rodrigues-Diez R.R., Lavoz C., et al. Special Issue "Diabetic Nephropathy: Diagnosis, Prevention and Treatment". J Clin Med 2020;9:813. doi: 10.3390/jcm9030813.
- Loutradis C., Skodra A., Georgianos P. et al. Diabetes mellitus increases the prevalence of anemia in patients with chronic kidney disease: A nested case-control study. World J Nephrol 2016 Jul 6;5(4):358–66. doi: 10.5527/wjn.v5.i4.358.
- Li Y., Shi H., Wang W.M., et al. Prevalence, awareness, and treatment of anemia in Chinese patients with nondialysis chronic kidney disease: First multicenter, cross-sectional study. Medicine (Baltimore) 2016;95:e3872. doi: 10.1097/MD.0000000000003872.
- Bosman D.R., Winkler A.S., Marsden J.T., et al. Anemia with erythropoietin deficiency occurs early in diabetic nephropathy. Diabetes Care 2001;24:495–99. doi: 10.2337/diacare.24.3.495.
- Ito K., Yokota S., Watanabe M., et al. Anemia in Diabetic Patients Reflects Severe Tubulointerstitial Injury and Aids in Clinically Predicting a Diagnosis of Diabetic Nephropathy. Intern Med 2021;60:1349–57. doi: 10.2169/internalmedicine.5455-20.
- Li Vecchi M., Fuiano G., Francesco M., et al. Prevalence and severity of anaemia in patients with type 2 diabetic nephropathy and different degrees of chronic renal insufficiency. Nephron Clin Pract 2007;105:c62–7. doi: 10.1159/000097600. Epub 2006 Nov 29.
- Provenzano R., Singh A.K. Hemoglobin maintenance with use of extended dosing of epoetin alfa in patients with diabetes and anemia of chronic kidney disease. Endocr Pract 2007;13:251–59. doi: 10.4158/EP.13.3.251.
- AkizawaТ., Tanaka-Amino К., Otsuka Т., Yamaguchi Y. Clinical parameters among patients in Japan with anemia and non-dialysis-dependent chronic kidney disease with and without diabetes mellitus who received roxadustat. Clinical and Experimental Nephrology 2022, 26:843–50. doi: 10.1007/s10157-022-02225-w.
- Akizawa Т., Iwasaki М., Otsuka Т. et al. Phase 3 study of roxadustat to treat anemia in non-dialysis-dependant CKD. Kidney Int Rep. 2021 Apr 17;6(7):1810–28. doi: 10.1016/j.ekir.2021.04.003.
- Zhang L., Liu Y., Huang Y. et al. Effect of Roxadustat versus erythropoietin (EPO) for treating anemia in patients with diabetic kidney disease: a retrospective cohort study. Ann Transl Med 2022;10(22):1224. doi: 10.21037/atm-22-4344.
- Ito H., Araki R., Mori T., et al. Relationship Between the Effect of Roxadustat and Comorbid Diabetes in Non-dialyzed Chronic Kidney Disease Patients: A Retrospective Observational Study. Cureus 2023, 15(5): e39543. doi: 10.7759/cureus.39543.
- Catrina S.B., Zheng X. Hypoxia and hypoxia-inducible factors in diabetes and its complications. Diabetologia 2021, 64:709–16. doi: 10.1007/s00125-021-05380-z.
- Bai T., Wang F., Mellen N. et al. Diabetic cardiomyopathy:Role of the E3 ubiquitin ligase. Am. J. Physiol. Endocrinol. Metab 2016. 310:E473–83. doi: 10.1152/ajpendo.00467.2015.
- Evangelista I., Nuti R., Picchioni T. et al. Molecular dysfunction and phenotypic derangement in diabetic cardiomyopathy. Int. J. Mol. Sci. 2019, 20, 3264. doi: 10.3390/ijms20133264.
- Bayeva M., Sawicki K.T., and Ardehali H. Taking diabetes to heartderegulation of myocardial lipid metabolism in diabetic cardiomyopathy. J. Am. Heart Assoc.2013, 2, e000433. doi: 10.1161/JAHA.113.000433.
- Mansor L.S., Mehta K., Aksentijevic D. et al. Increased oxidative metabolism following hypoxia in the type 2 diabetic heart, despite normal hypoxia signalling and metabolic adaptation. J. Physiol 2016, 594:307–20. doi: 10.1113/JP271242.
- Jia G., DeMarco V.G., and Sowers J.R. Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy. Nat. Rev. Endocrinol 2016;12:144–53. doi: 10.1038/nrendo.2015.216.
- Sousa Fialho M.D.L., Abd Jamil A.H., Stannard G.A., Heather L.C. Hypoxia-inducible factor 1 signalling, metabolism and its therapeutic potential in cardiovascular disease. Biochim. Biophys. Acta Mol. Basis Dis 2019, 1865:831–43. doi: 10.1016/j.bbadis.2018.09.024.
- Ma X., Dong Z., Liu J. et al. β-Hydroxybutyrate exacerbates hypoxic injury by inhibiting HIF-1α-Dependent glycolysis in cardiomyocytes-adding fuel to the fire? Cardiovasc Drugs Ther 2021, 36 (3):383–97. doi: 10.1007/s10557-021-07267-y.
- Yu J., Wang S., Shi W. et al. Roxadustat prevents Ang II hypertension by targeting angiotensin receptors and eNOS. JCI Insight 2021;6:e133690. doi: 10.1172/jci.insight.133690.
- Nakanishi N., Kaikita K., Ishii M., et al. Erratum: Cardioprotective Effects of Rivaroxaban on Cardiac Remodeling After Experimental Myocardial Infarction in Mice. Circ Rep. 2020, 10;2(11):705. doi: 10.1253/circrep.CR-66-0007. PMID: 33981907.
- Fang Т., Ma С., Zhang Z. et al. Roxadustat, a HIF-PHD inhibitor with exploitable potential on diabetes-related complications. Front. Pharmacol.2023, 14:1088288. doi: 10.3389/fphar.2023.1088288.
- Kim A., Nemeth E. New insights into iron regulation and erythropoiesis. Curr Opin Hematol 2015; May;22(3):199-205. doi: 10.1097/MOH.0000000000000132.
- Xu M.M., Wang J., Xie J.X. Regulation of iron metabolism by hypoxia-inducible factors. Acta Physiologica Sinica 2017;69(5):598–610. doi: 10.13294/j.aps.2017.0054.
- Ward D.M., Kaplan J. Ferroportin-mediated Iron Transport: Expression and Regulation. Biochim. Biophys. Acta. 2012, 1823:1426–33. doi: 10.1016/j.bbamcr.2012.03.004.
- Camaschella C., Nai A., Silvestri L. Iron Metabolism and Iron Disorders Revisited in the Hepcidin Era. Haematologica. 2020;105:260–72. Doi.org/10.3324/haematol.2019.232124.
- Zou L.X., Sun L., Hua R.X., Wu, Y. Serum Hepcidin-25 and All-Cause Mortality in Patients Undergoing Maintenance Hemodialysis. Int. J. Gen. Med. 2021;14:3153–62. doi.org/10.2147/IJGM.S313777
- Wagner М., Ashby D.R., Kurtz C. et al. Hepcidin-25 in diabetic chronic kidney disease is predictive for mortality and progression to end stage renal disease. PLoS One 2015, 10:e0123172. doi: 10.1371/journal.pone.0123072
- Locatelli, F., Fishbane S., Block G.A., Macdougall, I.C. Targeting Hypoxia-Inducible Factors for the Treatment of Anemia in Chronic Kidney Disease Patients. Am. J. Nephrol. 2017, 45, 187–199. https://doi.org/10.1159/000455166
- Hasegawa S, Tanaka Т, Nangaku M. Hypoxia-inducible factor stabilizers for treating anemia of chronic kidney disease. Current Opinion in Nephrology and Hypertension 2018, 27(5):331-338, doi: 10.1097/MNH.0000000000000431
- Wish, J.B. Assessing iron status: Beyond Serum Ferritin and Transferrin Saturation. Clin. J. Am. Soc. Nephrol. 2006, 1 (Suppl. S1), S4–S8. doi: 10.2215/CJN.01490506
- Dignass, A., Farrag K., Stein J. Limitations of Serum Ferritin in Diagnosing Iron Deficiency in Inflammatory Conditions. Int. J.Chronic. Dis. 2018, 2018, 9394060. doi: 10.1155/2018/9394060
- Hou Y-P, Wang C, Mao X-Y et al. Roxadustat regulates iron metabolism in dialysis-dependent and non-dialysis-dependent chronic kidney disease patients: A meta-analysis. Journal of the Formosan Medical Association 2022, 121:2288-2299. doi.org/10.1016/j.jfma.2022.06.008
- Pergola P.E., Charytan C., Little D.J., et al. Changes in Iron Availability with Roxadustat in Non-Dialysis-Dependent and Dialysis-Dependent Patients with Anemia of CKD. Kidney 2022, 360, 3:1511–1528. doi: 10.34067/KID.0001442022
- Akizawa T., Yamaguchi Y., Majikawa Y., Reusch M. Factors Affecting the Doses of Roxadustat vs Darbepoetin Alfa for Anemia Treatment in Hemodialysis Patients. Ther. Apher. Dial. 2021, 25:575–585. doi.org/10.1111/1744-9987.13609
- Zhao X-N, Liu S-X, Wang Z-Z et al. Roxadustat alleviates the infammatory status in patients receiving maintenance hemodialysis with erythropoiesis-stimulating agent resistance by increasing the short-chain fatty acids producing gut bacteria. European Journal of Medical Research 2023, 28:230. doi: 10.1186/s40001-023-01179-3
- Fan D, Coughlin LA, Neubauer MM, et al. Activation of HIF-1α and LL-37 by commensal bacteria inhibits Candida albicans colonization. Nat Med. 2015, 21(7):808–14
- Das N K, Schwartz A J, Barthel G et al. Microbial metabolite signaling is required for systemic iron homeostasis. Cell Metab. 2020, 31(1):115–30
- Taylor M, Qu A, Anderson E R, et al. Hypoxia-inducible factor-2α mediates the adaptive increase of intestinal ferroportin during iron defciency in mice. Gastroenterology. 2011, 140(7):2044–55
- Chapter 4: Other complications of CKD: CVD, medication dosage, patient safety, infections, hospitalizations, and caveats for investigating complications of CKD. Kidney Int Suppl (2011) 2013 Jan;3(1):91-111. doi: 10.1038/kisup.2012.67.
- 66. Eleftheriadis T., Pissas G., Liakopoulos V., and Stefanidis I. On the increased event rate of urinary tract infection and pneumonia in CKD patients treated with roxadustat for anemia,” Journal of the American Society of Nephrology, 2021, 32(6):1537, doi: 10.1681/ASN.2021020204
- Chong S, Xie Q, Ma T et al. Risk of infection in roxadustat treatment for anemia in patients with chronic kidney disease: A systematic review with meta-analysis and trial sequential analysisFront. Pharmacol. 2022, 13:967532, doi: 10.3389/fphar.2022.967532
- Takada A, Shibata T, Shiga T et al. Pharmacokinetic/pharmacodynamic modeling of roxadustat's effect on LDL cholesterol in patients in Japan with dialysis-dependent chronic kidney disease and anemia. Drug Metab Pharmacokinet.2022, 46:100461. doi: 10.1016/j.dmpk.2022.100461
- Chen N., Hao C., Liu B. et al. Roxadustat treatment for anemia in patients undergoing long-term dialysis. N. Engl. J. Med. 2019;381(11):1011–22. doi: 10.1056/NEJMoa1901713.
- Del Vecchio L., Locatelli F. Roxadustat in the treatment of anaemia in chronic kidney disease. Expert Opin. Investig. Drugs 2018, 27(1):125–33. doi: 10.1080/13543784.2018.1417386.
- Kassimatis T., Goldsmith D. Statins in chronic kidney disease and kidney transplantation. Pharmacol. Res. 2014;88:62–73. doi: 10.1016/j.phrs.2014.06.011.
- Mi X., Li Z., Yan J. et al. Activation of HIF-1signaling meliorates liver steatosis in zebrafish atp7b deficiency (Wilson’s disease) models. Biochim. Biophys. Acta. Mol. Basis Dis. 2020, 1866 (10), 165842. doi: 10.1016/j.bbadis.2020.165842.
- Hirai K., Kaneko S., Minato S. et al. Effects of roxadustat on anemia, iron metabolism, and lipid metabolism in patients with non-dialysis chronic kidney disease. Front. Med.2023, 10:1071342. doi: 10.3389/fmed.2023.1071342.
- Hasegawa S., Tanaka T., Saito T. et al. The oral hypoxia-inducible factor prolyl hydroxylase inhibitor enarodustat counteracts alterations in renal energy metabolism in the early stages of diabetic kidney disease. Kidney Int 2020, 97 (5):934–50. doi: 10.1016/j.kint.2019.12.007.
- Kaplan J. Roxadustat for anemia in patients with chronic kidney disease. Reply. N. Engl. J. Med.2020; 383(1):e3. doi: 10.1056/NEJMc1913712.
- Linkermann A., Chen G., Dong G. et al. Regulated cell death in AKI. J Am Soc Nephrol 2014, 25(12):2689–701. doi: 10.1681/ASN.2014030262.
- Zhang M., Dong R., Yuan J. et al. Roxadustat (FG4592) protects against ischaemia/reperfusion-induced acute kidney injury through inhibiting the mitochondrial damage pathway in mice. Clin Exp Pharmacol Physiol. 2021;49(2):311–18. doi: 10.1111/1440-1681.13601.
- Yang Y., Yu X., Zhang Y. et al. HypoxiaInducible Factor Prolyl Hydroxylase Inhibitor Roxadustat (Fg-4592) Protects against Cisplatin-Induced Acute Kidney Injury. Clin. Sci. 2018, 132 (7):825–38. doi: 10.1042/CS20171625.
- Li X., Zou Y., Xing J. et al. Pretreatment with Roxadustat (FG-4592) Attenuates Folic Acid-Induced Kidney Injury through Antiferroptosis via Akt/GSK-3β/Nrf2 Pathway. Oxid Med. Cell Longev 2020, 6286984–6287017. doi: 10.1155/2020/6286984.
- Miao A.-F., Liang J.-X., Yao L. et al. Hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) protects against renal ischemia/reperfusion injury by inhibiting inflammation. Ren Fail 2021;43(1):803–10. doi: 10.1080/0886022X.2021.1915801.
- Li X., Zhang X., Xia J. et al. Macrophage HIF-2α suppresses NLRP3 inflammasome activation and alleviates insulin resistance. Cell Rep 2021;36(8):109607. doi: 10.1016/j.celrep.2021.109607.
- Wu M., Chen W., Miao M. et al. Anti-anemia drug FG4592 retards the AKI-to-CKD transition by improving vascular regeneration and antioxidative capability. Clin Sci 2021;135(14):1707–26. doi: 10.1042/CS20210100.
- Yu Y., Cui H., Chen C.. et al. Hypoxia inducible factor-1alpha directs renal regeneration induced by decel lularized scaffolds. Biomaterials 2018,165:48–55. doi: 10.1016/j.biomaterials.2018.02.045.
- Kushida N., Nomura S., Mimura I. et al. Hypoxia-inducible factor-1alpha activates the transforming growth factor-beta/SMAD3 pathway in kidney tubular epithelial cells. Am J Nephrol 2016, 44(4):276–85. doi: 10.1159/000449323
- Raptis V., Bakogiannis C., Loutradis C. et al. Levels of endocan, angiopoietin-2, and hypoxia-inducible factor-1a in patients with autosomal dominant polycystic kidney disease and different levels of renal function. Am J Nephrol 2018;47(4):231–38. doi: 10.1159/000488115.
- Kenkre JS, Bassett J. The bone remodelling cycle. Ann Clin Biochem. 2018, 55(3):308–27. doi: 10.1177/0004563218759371.
- Yi L., Ju Y., He Y. et al. Intraperitoneal injection of Desferal(R) alleviated the age-related bone loss and senescence of bone marrow stromal cells in rats. Stem Cell Res Ther. 2021;12(1):45. doi: 10.1186/s13287-020-02112-9.
- Liu X., Tu Y., Zhang L. et al. Prolyl hydroxylase inhibitors protect from the bone loss in ovariectomy rats by increasing bone vascularity. Cell Biochem Biophys. 2014;69(1):141–49. doi: 10.1007/s12013-013-9780-8.
- Karner C.M., Long F. Wnt signaling and cellular metabolism in osteoblasts. Cell Mol Life Sci. 2017;74(9):1649–57. doi: 10.1007/s00018-016-2425-5.
- Genetos D.C., Toupadakis C.A., Raheja L.F. et al. Hypoxia decreases sclerostin expression and increases Wnt/signaling in osteoblasts. J Cell Biochem. 2010;110(2):457–67. doi: 10.1002/jcb.22559.Chen C, Yan S, Qiu S et al. HIF/Ca(2+)/NO/ROS is critical in roxadustat treating bone fracture by stimulating the proliferation and migration of BMSCs. Life Sci. 2021;264: 118684. doi: 10.1016/j.lfs.2020.118684
- Hulley P.A., Papadimitriou-Olivgeri I., Knowles H.J. Osteoblast-osteoclast coculture amplifes inhibitory efects of FG-4592 on human osteoclastogenesis and reduces bone resorption. JBMR Plus. 2020;4(7):e10370. doi: 10.1002/jbm4.10370.
- Li L., Li A., Zhu L. et al. Roxadustat promotes osteoblast diferentiation and prevents estrogen defciency-induced bone loss by stabilizing HIF-1α and activating the Wnt/β-catenin signaling pathway. Journal of Orthopaedic Surgery and Research 2022, 17:286. doi: 10.1186/s13018-022-03162-w.
- Li L., Li А., Gan L., Zuo L. Roxadustat improves renal osteodystrophy by dual regulation of bone remodeling. Endocrine. 2023 79(1):180–89. doi: 10.1007/s12020-022-03199-1.
- Fishbane S., El-Shahawy M.A., Pecoits-Filho R. et al. Roxadustat for treating anemia in patients with CKD not on dialysis: results from a randomized phase 3 study J Am Soc Nephrol 2021;32(3):737–55. https://doi.org/10.1681/ASN. 2020081150
- Provenzano R., Shutov E., Eremeeva L. et al. Roxadustat for anemia in patients with end-stage renal disease incident to dialysis. Nephrol Dial Transplant 2021;36(9):1717–30. doi: 10.1093/ndt/gfab051.
- Chen N., Hao C., Liu B.C. et al. Roxadustat treatment for anemia in patients undergoing long-term dialysis. N Engl J Med 2019;381(11):1011–22. doi: 10.1056/NEJMoa1901713.
- 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):1629–39. doi: 10.1093/ndt/gfab057.
- Zhao J., Xu Y., Xie J. et al. Roxadustat does not affect platelet production, activation, and thrombosis formation. Arterioscler Thromb Vasc Biol 2021;41(10):2523–37. doi: 10.1161/ATVBAHA.121.316495.
- Cygulska K., Wejner-Mik P., Plewka M. et al. Roxadustat: another drug that causes pulmonary hypertension? Report of first human case. Pol Arch Intern Med 2019;129(5):344–45. doi: 10.20452/pamw.4445.
- Veith C., Schermuly R.T., Brandes R.P., Weissmann N. Molecular mechanisms of hypoxia-inducible factor-induced pulmonary arterial smooth muscle cell alterations in pulmonary hypertension. J Physiol 2016; 594(5):1167–77. doi: 10.1113/JP270689.
- Uchida L., Tanaka T., Saito H. et al. Effects of a prolyl hydroxylase inhibitor on kidney and cardiovascular complications in a rat model of chronic kidney disease. Am J Physiol Renal Physiol 2020;318(2):F388–401. doi: 10.1152/ajprenal.00419.2019.
- Demer L.L., Tintut Y. Vascular calcification. Pathobiology of a Multifaceted Disease. Сirculation 2008, 117(22):2938–48. doi: 10.1161/CIRCULATIONAHA.107.743161.
- Demer L.L., Tintut Y. Vascular calcification. Pathobiology of a Multifaceted Disease. Сirculation 2008,117(22):2938–48. doi: 10.1161/CIRCULATIONAHA.107.743161.
- Neven E., Dauwe S., De Broe M.E. et al. Endochondral bone formation is involved in media calcification in rats and in men. Kidney Int 2007, 72;574–81. doi: 10.1038/sj.ki.5002353.
- Chaturvedi P., Chen N.X., O’Neill K. et al. Differential miRNA expression in cells and matrix vesicles in vascular smooth muscle cells from rats with kidney disease. PLoS One 2015;10:e0131589. doi: 10.1371/journal.pone. 0131589.
- Kapustin A.N., Chatrou M.L., Drozdov I. et al. Vascular smooth muscle cell calcification is mediated by regulated exosome secretion. Circ Res 2015;116:1312–23. doi: 10.1161/CIRCRESAHA.116.305012.
- Wolf D., Muralidharam A., Mohan S. Role of prolyl hydroxylase domain proteins in bone metabolism. Osteoporos Sarcopenia 2022, 8:1–10. doi: 10.1016/j.afos.2022.03.001.
- Shomento S.H., Wan C., Cao X. et al. Hypoxia-inducible factors 1alpha and 2alpha exert both distinct and overlapping functions in long bone development. J Cell Вiochem. 2010, 109:196–204. Doi:.10.1002/jcb.22396.
- Regan J.N., Lim J., Shi Y. et al. Up-regulation of glycolytic metabolism is required for HIF1alpha-driven bone formation. Proc Natl Acad Sci USA 2014, 111:8673–78. doi: 10.1073/pnas.1324290111.
- Merceron C. Ranganathan K., Wang E. et al. Hypoxia-inducible factor 2α is a negative regulator of osteoblastogenesis and bone mass accrual. Bone Res 2019, 7:7. doi: 10.1038/s41413-019-0045-z.
- Mokas S., Lariviere R., Lamalice L. et al. Hypoxia-inducible factor-1 plays a role in phosphate-induced vascular smooth muscle cell calcification. Kidney Int 2016, 90(3):x2003598–609. doi: 10.1016/j.kint.2016.05.020.
- Balogh E., Tóth A., Méhes G. et al. Hypoxia triggers osteochondrogenic differentiation of vascular smooth muscle cells in an HIF-1 (Hypoxia-Inducible Factor 1)-dependent and reactive oxygen species-dependent manner. Arterioscler Thromb Vasc Biol 2019, 39:1088–99. doi: 10.1161/ATVBAHA.119.312509.
- Ward J.P. A twist in the tail: synergism between mitochondria and NADPH oxidase in the hypoxia-induced elevation of reactive oxygen species in pulmonary artery. Free Radic Biol Med 2008;45:1220–22. doi: 10.1016/j.freeradbiomed.2008.08.015.
- Li G., Lu W.H., Ai R. et al. The relationship between serum hypoxia-inducible factor 1α and coronary artery calcification in asymptomatic type 2 diabetic patients. Cardiovasc Diabetol 2014, 13:52. doi: 10.1186/1475-2840-13-52).
- Luo Dю, Li Wю Xie Cю et al. Capsaicin attenuates arterial calcification through promoting SIRT6-mediated deacetylation and degradation of Hif1α (Hypoxic-Inducible Factor-1 alpha). Hypertension 2022, 79:906–17. doi: 10.1161/HYPERTENSIONAHA.121.18778.
- Negri A.L. Role of prolyl hydroxylase/HIF-1 signaling in vascular calcification Clinical Kidney Journal 2023;16(2):205–209. doi.org/10.1093/ckj/sfac224
- Yao B., Wei Y., Zhang S. et al. Revealing a mutant-induced receptor allosteric mechanism for the thyroid hormone resistance. iScience 2019, 20:489–96. doi: 10.1016/j.isci.2019.10.002.
- Ichii M., Mori K., Miyaoka D. et al. Suppression of thyrotropin secretion during Roxadustat treatment for renal anemia in a patient undergoing hemodialysis. BMC Nephrol 2021;22(1):104. doi: 10.1186/s12882-021-02304-2.
- Kouki Y., Okada N., Saga К. et al. Disproportionality Analysis on Hypothyroidism With Roxadustat Using the Japanese Adverse Drug Event Database. PMID: 37408303. doi: 10.1002/jcph.2300.
- Park S., Greenberg P., Yucel A. et al. Clinical effectiveness and safety of erythropoietin-stimulating agents for the treatment of low and intermediate-1− risk myelodysplastic syndrome: a systematic literature review. Br J Haematol 2019, 184:134–60. doi: 10.1111/bjh.15707.
- Ikenoue Т, Furumatsu Y, Kitamura T. Transfusion-dependent anaemia treatment using continuous erythropoietin receptor activator (epoetin β pegol) and roxadustat after darbepoetin treatment failure in low-risk myelodysplastic syndrome: a case report. Oxford Medical Case Reports, 2021;5:177–79. doi: 10.1093/omcr/omab026.
- Еnry D.H., Glaspy J., Harrup R. et al. Roxadustat for the treatment of anemia in patients with lower-risk myelodysplastic syndrome: open-label, dose-selection, lead-in stage of a phase 3 study. Am J Hematol 2022, 97(2):174–84. doi: 10.1002/ajh.26397.
- Wan K., Yin Y., Luo Z., Cheng J. Remarkable response to roxadustat in a case of anti-erythropoietin antibody-mediated pure red cell aplasia. Ann Hematol 2021, 100(2):591–93. doi: 10.1007/s00277-020-04269-y.
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