Фармакологическое действие эпоэтина бета при лечении анемии у пациентов с заболеваниями почек

Хроническая болезнь почек является одной из наиболее быстрорастущих причин смертности во всем мире. Анемия, осложняющая хроническую болезнь почек, не только ухудшает качество жизни пациентов, но и является независимым фактором риска неблагоприятных сердечно-сосудистых исходов. Внедрение в клиническую практику рекомбинантного человеческого эритропоэтина значительно изменило методы лечения анемии у пациентов с хронической болезнью почек. Достижение целевых цифр уровня гемоглобина с помощью рекомбинантного человеческого эритропоэтина значительно улучшает качество жизни и снижает смертность у пациентов. Эпоэтин бета наряду с другими эритропоэтинами является одним из стимулирующих эритропоэз средств, доступных в настоящее время на отечественном фармацевтическом рынке. Различные исследования показали, что введение эпоэтина бета пациентам, находящимся на заместительной почечной терапии, 1 раз в неделю так же эффективно, как и трехкратное введение эпоэтина альфа в эквивалентных недельных дозах для достижения целевых показателей уровня гемоглобина. С одной стороны, это повышает приверженность пациентов к лечению. С другой стороны, снижение частоты назначения терапии рекомбинантного человеческого эритропоэтина сокращает время и затраты на лечение почечной анемии, что в конечном счете позволяет лучше адаптировать терапию к потребностям пациентов. Доказанная эффективность и профиль безопасности эпоэтина бета в сочетании с повышенным удобством менее частого введения делают эпоэтин бета безопасным и эффективным вариантом терапии, который может помочь большему числу пациентов с хронической болезнью почек достичь целевых значений уровня гемоглобина.

1. Foreman KJ, Marquez N, Dolgert A, Fukutaki K, Fullman N, McGaughey M et al. Forecasting life expectancy, years of life lost, and all-cause and cause-specific mortality for 250 causes of death: reference and alternative scenarios for 2016-40 for 195 countries and territories. Lancet. 2018;392(10159): 2052–2090. https://doi.org/10.1016/s0140-6736(18)31694-5.

2. Eisenga MF, Nolte IM, van der Meer P, Bakker SJL, Gaillard CAJM. Association of different iron deficiency cutoffs with adverse outcomes in chronic kidney disease. BMC Nephrol. 2018;19(1):225. https://doi.org/10.1186/s12882-018-1021-3.

3. Stauffer ME, Fan T. Prevalence of anemia in chronic kidney disease in the United States. PLoS ONE. 2014;9(1):e84943. https://doi.org/10.1371/journal.pone.0084943.

4. Locatelli F, Marcelli D, Conte F, D’Amico M, Del Vecchio L, Limido A et al. Cardiovascular disease in chronic renal failure: the challenge continues. Registro Lombardo Dialisi e Trapianto. Nephrol Dial Transplant. 2000;15(Suppl. 5):69–80. https://doi.org/10.1093/ndt/15.suppl_5.69.

5. Collins AJ, Kasiske B, Herzog C, Chavers B, Foley R, Gilbertson D et al. Excerpts from the United States Renal Data System 2004 annual data report: atlas of end-stage renal disease in the United States. Am J Kidney Dis. 2005;45(Suppl. 1):A5–А7. https://doi.org/10.1053/j.ajkd.2004.10.009.

6. Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis. 1998;32(5 Suppl 3): S112–S119. https://doi.org/10.1053/ajkd.1998.v32.pm9820470.

7. Keith DS, Nichols GA, Gullion CM, Brown JB, Smith DH. Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization. Arch Intern Med. 2004;164(6):659–663. https://doi.org/10.1001/archinte.164.6.659.

8. Foley RN, Murray AM, Li S, Herzog CA, McBean AM, Eggers PW, Collins AJ. Chronic kidney disease and the risk for cardiovascular disease, renal replacement, and death in the United States Medicare population, 1998 to 1999. J Am Soc Nephrol. 2005;16(2):489–495. https://doi.org/10.1681/ASN.2004030203.

9. Babitt JL, Lin HY. Mechanisms of anemia in CKD. J Am Soc Nephrol. 2012;23(10):1631–1634. https://doi.org/10.1681/ASN.2011111078.

10. Kular D, Macdougall IC. HIF stabilizers in the management of renal anemia: from bench to bedside to pediatrics. Pediatr Nephrol. 2019;34(3):365–378. https://doi.org/10.1007/s00467-017-3849-3.

11. Tsukamoto T, Matsubara T, Akashi Y, Kondo M, Yanagita M. Annual Iron Loss Associated with Hemodialysis. Am J Nephrol. 2016;43(1):32–38. https://doi.org/10.1159/000444335.

12. Levin A. Prevalence of cardiovascular damage in early renal disease. Nephrol Dial Transplant. 2001;16(Suppl. 2):7–11. https://doi.org/10.1093/ndt/16.suppl_2.7.

13. Astor BC, Muntner P, Levin A, Eustace JA, Coresh J. Association of kidney function with anemia: the Third National Health and Nutrition Examination Survey (1988–1994). Arch Intern Med. 2002;162(12):1401–1408. https://doi.org/10.1001/archinte.162.12.1401.

14. Tsai SF, Tarng DC. Anemia in patients of diabetic kidney disease. J Chin Med Assoc. 2019;82(10):752–755. https://doi.org/10.1097/JCMA.0000000000000175.

15. Luthi JC, Flanders WD, Burnier M, Burnand B, McClellan WM. Anemia and chronic kidney disease are associated with poor outcomes in heart failure patients. BMC Nephrol. 2006;7:3. https://doi.org/10.1186/1471-2369-7-3.

16. Al-Ahmad A, Rand WM, Manjunath G, Konstam MA, Salem DN, Levey AS, Sarnak MJ. Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction. J Am Coll Cardiol. 2001;38(4):955–962. https://doi.org/10.1016/s0735-1097(01)01470-x.

17. McClellan WM, Flanders WD, Langston RD, Jurkovitz C, Presley R. Anemia and renal insufficiency are independent risk factors for death among patients with congestive heart failure admitted to community hospitals: a population-based study. J Am Soc Nephrol. 2002;13(7):1928–1936. https://doi.org/10.1097/01.asn.0000018409.45834.fa.

18. Cai A, Wu Z, Xu L, Xia S, He X, Zhang Y et al. Association of anaemia and allcause mortality in patients with ischaemic heart failure varies by renal function status. ESC Heart Fail. 2021;8(3):2270–2281. https://doi.org/10.1002/ehf2.13325.

19. Lee G, Choi S, Kim K, Yun JM, Son JS, Jeong SM et al. Association of Hemoglobin Concentration and Its Change With Cardiovascular and AllCause Mortality. J Am Heart Assoc. 2018;7(3):e007723. https://doi.org/10.1161/JAHA.117.007723.

20. Hörl WH. Anaemia management and mortality risk in chronic kidney disease. Nat Rev Nephrol. 2013;9(5):291–301. https://doi.org/10.1038/nrneph.2013.21.

21. Tanaka S, Kamiya K, Saito H, Saito K, Ogasahara Y, Maekawa E et al. Prevalence and prognostic value of the coexistence of anaemia and frailty in older patients with heart failure. ESC Heart Fail. 2021;8(1):625–633. https://doi.org/10.1002/ehf2.13140.

22. Goh VJ, Tromp J, Teng TK, Tay WT, Van Der Meer P, Ling LH et al. Prevalence, clinical correlates, and outcomes of anaemia in multi-ethnic Asian patients with heart failure with reduced ejection fraction. ESC Heart Fail. 2018;5(4):570–578. https://doi.org/10.1002/ehf2.12279.

23. Harnett JD, Kent GM, Foley RN, Parfrey PS. Cardiac function and hematocrit level. Am J Kidney Dis. 1995;25(4 Suppl. 1):S3–7. https://doi.org/10.1016/0272-6386(95)90673-8.

24. Parfrey PS, Foley RN, Harnett JD, Kent GM, Murray DC, Barre PE. Outcome and risk factors for left ventricular disorders in chronic uraemia. Nephrol Dial Transplant. 1996;11(7):1277–1285. https://doi.org/10.1093/ndt/11.7.1277.

25. Levin A. The role of anaemia in the genesis of cardiac abnormalities in patients with chronic kidney disease. Nephrol Dial Transplant. 2002;17(2):207–210. https://doi.org/10.1093/ndt/17.2.207.

26. Madore F, Lowrie EG, Brugnara C, Lew NL, Lazarus JM, Bridges K, Owen WF. Anemia in hemodialysis patients: variables affecting this outcome predictor. J Am Soc Nephrol. 1997;8(12):1921–1929. https://doi.org/10.1681/ASN.V8121921.

27. Ma JZ, Ebben J, Xia H, Collins AJ. Hematocrit level and associated mortality in hemodialysis patients. J Am Soc Nephrol. 1999;10(3):610–319. https://doi.org/10.1681/ASN.V103610.

28. Kovesdy CP, Trivedi BK, Kalantar-Zadeh K, Anderson JE. Association of anemia with outcomes in men with moderate and severe chronic kidney disease. Kidney Int. 2006;69(3):560–564. https://doi.org/10.1038/sj.ki.5000105.

29. Levin A, Djurdjev O, Duncan J, Rosenbaum D, Werb R. Haemoglobin at time of referral prior to dialysis predicts survival: an association of haemoglobin with long-term outcomes. Nephrol Dial Transplant. 2006;21(2):370–377. https://doi.org/10.1093/ndt/gfi209.

30. Rossert J, McClellan WM, Roger SD, Verbeelen DL. Epoetin treatment: what are the arguments to expect a beneficial effect on renal disease progression? Nephrol Dial Transplant. 2002;17(3):359–362. https://doi.org/10.1093/ndt/17.3.359.

31. Kuriyama S, Tomonari H, Yoshida H, Hashimoto T, Kawaguchi Y, Sakai O. Reversal of anemia by erythropoietin therapy retards the progression of chronic renal failure, especially in nondiabetic patients. Nephron. 1997;77(2):176–185. https://doi.org/10.1159/000190270.

32. Jungers P, Choukroun G, Oualim Z, Robino C, Nguyen AT, Man NK. Beneficial influence of recombinant human erythropoietin therapy on the rate of progression of chronic renal failure in predialysis patients. Nephrol Dial Transplant. 2001;16(2):307–312. https://doi.org/10.1093/ndt/16.2.307.

33. Erslev A. Humoral regulation of red cell production. Blood. 1953;8(4):349–357. https://doi.org/10.1182/blood.V8.4.349.349.

34. Jacobson LO, Goldwasser E, Fried W, Plzak LF. Studies on erythropoiesis. VII. The role of the kidney in the production of erythropoietin. Trans Assoc Am Physicians. 1957;70:305–317. Available at: https://pubmed.ncbi.nlm.nih.gov/13496139/.

35. Miyake T, Kung CK, Goldwasser E. Purification of human erythropoietin. J Biol Chem. 1977;252(15):5558–5564. https://doi.org/10.1016/S0021-9258(19)63387-9.

36. Lin FK, Suggs S, Lin CH, Browne JK, Smalling R, Egrie JC et al. Cloning and expression of the human erythropoietin gene. Proc Natl Acad Sci U S A. 1985;82(22):7580–7584. https://doi.org/10.1073/pnas.82.22.7580.

37. Winearls CG, Oliver DO, Pippard MJ, Reid C, Downing MR, Cotes PM. Effect of human erythropoietin derived from recombinant DNA on the anaemia of patients maintained by chronic haemodialysis. Lancet. 1986;2(8517): 1175–1178. https://doi.org/10.1016/s0140-6736(86)92192-6.

38. Eschbach JW, Egrie JC, Downing MR, Browne JK, Adamson JW. Correction of the anemia of end-stage renal disease with recombinant human erythropoietin. Results of a combined phase I and II clinical trial. N Engl J Med. 1987;316(2):73–78. https://doi.org/10.1056/NEJM198701083160203.

39. Park H, Liu X, Henry L, Harman J, Ross EA. Trends in anemia care in nondialysis-dependent chronic kidney disease (CKD) patients in the United States (2006–2015). BMC Nephrol. 2018;19(1):318. https://doi.org/10.1186/s12882-018-1119-7.

40. De Cock E, Dellanna F, Khellaf K, Klatko W, Maduell F, Raluy-Callado M, Villa G. Time savings associated with C.E.R.A. once monthly: a time-andmotion study in hemodialysis centers in five European countries. J Med Econ. 2013;16(5):648–656. https://doi.org/10.3111/13696998.2013.775133.

41. Halstenson CE, Macres M, Katz SA, Schnieders JR, Watanabe M, Sobota JT, Abraham PA. Comparative pharmacokinetics and pharmacodynamics of epoetin alfa and epoetin beta. Clin Pharmacol Ther. 1991;50(6):702–712. https://doi.org/10.1038/clpt.1991.210.

42. Besarab A, Flaharty KK, Erslev AJ, McCrea JB, Vlasses PH, Medina F et al. Clinical pharmacology and economics of recombinant human erythropoietin in end-stage renal disease: the case for subcutaneous administration. J Am Soc Nephrol. 1992;2(9):1405–1416. https://doi.org/10.1681/ASN.V291405.

43. Kaufman JS, Reda DJ, Fye CL, Goldfarb DS, Henderson WG, Kleinman JG, Vaamonde CA. Subcutaneous compared with intravenous epoetin in patients receiving hemodialysis. Department of Veterans Affairs Cooperative Study Group on Erythropoietin in Hemodialysis Patients. N Engl J Med. 1998;339(9):578–583. https://doi.org/10.1056/NEJM199808273390902.

44. Locatelli F, Pisoni RL, Combe C, Bommer J, Andreucci VE, Piera L et al. Anaemia in haemodialysis patients of five European countries: association with morbidity and mortality in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Nephrol Dial Transplant. 2004;19(1):121–132. https://doi.org/10.1093/ndt/gfg458.

45. Abraham PA, Macres MG. Blood pressure in hemodialysis patients during amelioration of anemia with erythropoietin. J Am Soc Nephrol. 1991;2(4):927–936. https://doi.org/10.1681/ASN.V24927.

46. Bennett WM. A multicenter clinical trial of epoetin beta for anemia of endstage renal disease. J Am Soc Nephrol. 1991;1(7):990–998. https://doi.org/10.1681/ASN.V17990.

47. Kaizu K, Uriu K, Eto S. Effects of recombinant human erythropoietin (EPOCH) on the coagulation and fibrinolytic systems and platelet function in pre-dialysis patients with chronic renal failure. Nihon Jinzo Gakkai Shi. 1993;35(8):989–997. https://doi.org/10.14842/jpnjnephrol1959.35.989.

48. Weiss LG, Clyne N, Divino Fihlho J, Frisenette-Fich C, Kurkus J, Svensson B. The efficacy of once weekly compared with two or three times weekly subcutaneous epoetin beta: results from a randomized controlled multicentre trial. Nephrol Dial Transplant. 2000;15(12):2014–2019. https://doi.org/10.1093/ndt/15.12.2014.

49. Locatelli F, Baldamus CA, Villa G, Ganea A, Martín de Francisco AL. Onceweekly compared with three-times-weekly subcutaneous epoetin beta: results from a randomized, multicenter, therapeutic-equivalence study. Am J Kidney Dis. 2002;40(1):119–125. https://doi.org/10.1053/ajkd.2002.33920.

50. Lui SF, Law CB, Ting SM, Li P, Lai KN. Once weekly versus twice weekly subcutaneous administration of recombinant human erythropoietin in patients on continuous ambulatory peritoneal dialysis. Clin Nephrol. 1991;36(5):246–251. Available at: https://pubmed.ncbi.nlm.nih.gov/1752075.

51. Saleh A, Krane NK, Caballero M, Starks E. Once weekly subcutaneous erythropoietin is an effective maintenance therapy in the treatment of anemia of end stage renal disease in patients on CAPD. Adv Perit Dial. 1991;7: 288–291. Available at: https://pubmed.ncbi.nlm.nih.gov/1680448/.

52. Nomoto Y, Kawaguchi Y, Kubota M, Tagawa H, Kubo K, Ogura Y et al. A multicenter study with once a week or once every two weeks high-dose subcutaneous administration of recombinant human erythropoietin in continuous ambulatory peritoneal dialysis. Perit Dial Int. 1994;14(1):56–60. https://doi.org/10.1177/089686089401400111.

53. Frifelt JJ, Tvedegaard E, Bruun K, Steffensen G, Cintin C, Breddam M et al. Efficacy of recombinant human erythropoietin administered subcutaneously to CAPD patients once weekly. Perit Dial Int. 1996;16(6):594–598. https://doi.org/10.1177/089686089601600608.

54. Koch KM, Koene RA, Messinger D, Quarder O, Scigalla P. The use of epoetin beta in anemic predialysis patients with chronic renal failure. Clin Nephrol. 1995;44(3):201–208. Available at: https://pubmed.ncbi.nlm.nih.gov/8556837.

55. Albertazzi A, Di Liberato L, Daniele F, Battistel V, Colombi L. Efficacy and tolerability of recombinant human erythropoietin treatment in pre-dialysis patients: results of a multicenter study. Int J Artif Organs. 1998;21(1):12–18. Available at: https://pubmed.ncbi.nlm.nih.gov/9554820/.

56. Navarro JF, Teruel JL, Marcén R, Ortuño J. Improvement of erythropoietininduced hypertension in hemodialysis patients changing the administration route. Scand J Urol Nephrol. 1995;29(1):11–14. https://doi.org/10.3109/00365599509180532.

57. Besarab A, Reyes CM, Hornberger J. Meta-analysis of subcutaneous versus intravenous epoetin in maintenance treatment of anemia in hemodialysis patients. Am J Kidney Dis. 2002;40(3):439–446. https://doi.org/10.1053/ajkd.2002.34881.

58. Hynes DM, Stroupe KT, Greer JW, Reda DJ, Frankenfield DL, Kaufman JS et al. Potential cost savings of erythropoietin administration in end-stage renal disease. Am J Med. 2002;112(3):169–175. https://doi.org/10.1016/s0002-9343(01)01103-2.

59. Casadevall N, Nataf J, Viron B, Kolta A, Kiladjian JJ, Martin-Dupont P et al. Pure red-cell aplasia and antierythropoietin antibodies in patients treated with recombinant erythropoietin. N Engl J Med. 2002;346(7):469–475. https://doi.org/10.1056/NEJMoa011931.

60. Bennett CL, Luminari S, Nissenson AR, Tallman MS, Klinge SA, McWilliams N et al. Pure red-cell aplasia and epoetin therapy. N Engl J Med. 2004;351(14):1403–1408. https://doi.org/10.1056/NEJMoa040528.

61. Locatelli F, Aljama P, Barany P, Canaud B, Carrera F, Eckardt KU et al. Erythropoiesis-stimulating agents and antibody-mediated pure red-cell aplasia: here are we now and where do we go from here? Nephrol Dial Transplant. 2004;19(2):288–293. https://doi.org/10.1093/ndt/gfg489.