Skip to main content Skip to main navigation menu Skip to site footer

Perbandingan efektivitas dan keamanan antara roxadustat dan epoetin alfa sebagai terapi anemia pada pasien yang menjalani hemodialisis reguler: meta analisis


Introduction: Chronic kidney disease (CKD) is a global health problem. Hemodialysis (HD) is one of the treatment modalities for end-stage renal disease which is commonly used. A complication that is often found in patients undergoing regular HD is anemia. Roxadustat is a prolyl hydroxylase inhibitor (PHI) which has a potential as an alternative therapy for anemia in patients undergoing regular HD. The aim of this meta-analysis was to compare the efficacy and safety of roxadustat and epoetin alfa as anemia management in patients undergoing regular HD.

Methods: We searched the literature sources in the PubMed, MEDLINE, Cochrane, Scopus, Embase, Elsevier, and Proquest databases until June 1, 2021. The search terms used were chronic kidney disease, hemodialysis, dialysis, roxadustat, epoetin alfa, anemia management, incidence of side effects, randomize, and randomization. We excluded the study population with acute kidney injury/dyslipidemia/metabolic syndrome. All analyzes in this meta-analysis were performed using Review Manager version 5.3 (RevMan Cochrane, London, UK).

Result: We have found five eligible studies (2777 patients). Funnel plots and p-Egger were examined to assess publication bias. The results showed a statistically significant difference between roxadustat and epoetin alfa with respect to the mean difference of hemoglobin (Hb) (WMD: 0.31; p<0.05), hepcidin (WMD: -18.94; p<0.05), transferrin (WMD: 67.88; p<0.05), transferrin saturation (WMD: 2.78; p<0.05), iron (WMD: 5.02; p<0.05) and risk of adverse events (OR: 1.25; p<0.05) displayed on the forest plot.

Conclusion: Based on this meta-analysis, it can be concluded that anemia management with roxadustat is better than epoetin alfa in patients undergoing regular HD.


Latar Belakang: Penyakit ginjal kronis (PGK) merupakan masalah kesehatan global. Hemodialisis (HD) merupakan salah satu modalitas terapi PGK stadium akhir yang umum digunakan. Komplikasi yang sering ditemukan pada pasien yang menjalani HD reguler adalah anemia. Roxadustat adalah suatu prolyl hydroxylase inhibitor (PHI) yang memiliki potensi sebagai alternatif terapi anemia pada pasien yang menjalani HD reguler. Tujuan dari meta-analisis ini adalah untuk membandingkan efektivitas dan keamanan antara roxadustat dan epoetin alfa sebagai manajemen anemia pada pasien yang menjalani HD reguler.

Metode: Kami mencari sumber literatur pada database PubMed, MEDLINE, Cochrane, Scopus, Embase, Elsevier, dan Proquest hingga 1 Juni 2021. Istilah pencarian yang digunakan yaitu penyakit ginjal kronis, hemodialisis, dialisis, roxadustat, epoetin alfa, manajemen anemia, kejadian efek samping, acak, dan pengacakan. Kami mengeksklusi populasi penelitian dengan cedera ginjal akut/dislipidemia/sindrom metabolik. Semua analisis dalam meta-analisis ini dilaksanakan dengan menggunakan Review Manager versi 5.3 (RevMan Cochrane, London, UK).

Hasil: Kami menemukan lima studi yang memenuhi syarat (2777 pasien). Funnel plot dan p-Egger diperiksa untuk menilai bias publikasi. Hasil menunjukkan perbedaan signifikan secara statistik antara roxadustat dan epoetin alfa terhadap perbedaan rerata dari hemoglobin (Hb) (WMD: 0,31; p<0,05), hepsidin (WMD: -18,94; p<0,05), transferin (WMD: 67,88; p<0,05), saturasi transferin (WMD: 2,78; p<0,05), zat besi (WMD: 5,02; p<0,05) dan risiko kejadian efek samping (OR: 1,25; p<0,05) yang ditampilkan pada forest plot.

Kesimpulan: Berdasarkan meta-analisis ini, dapat disimpulkan bahwa manajemen anemia dengan roxadustat lebih baik dibandingkan dengan epoetin alfa pada pasien yang menjalani HD reguler.


  1. Control UC for Diseases. National Chronic Kidney Disease Fact Sheet. CDC. Published 2014. Accessed June 18, 2021.
  2. Hemmelgarn BR, Zhang J, Manns BJ, et al. Progression of kidney dysfunction in the community-dwelling elderly. Kidney Int. 2006;69(12):2155-2161. doi:10.1038/
  3. Roderick PJ, Atkins RJ, Smeeth L, et al. Detecting chronic kidney disease in older people; what are the implications? Age Ageing. 2008;37(2):179-186. doi:10.1093/ageing/afm180
  4. Dipiro JT. Pharmacoterapy Handbook 9th Edition. Mc Graw Hill; 2015.
  5. Suyatno FE, Rotty LWA, Moeis ES. Gambaran anemia defisiensi besi pada pasien penyakit ginjal kronik stadium V yang menjalani hemodialisis di instalasi tindakan hemodialisis RSUP PROF. DR. R.D. Kandou Manado. e-CliniC. 2016;4(1). doi:10.35790/ecl.4.1.2016.10948
  6. McClellan W, Aronoff SL, Bolton WK, et al. The prevalence of anemia in patients with chronic kidney disease. Curr Med Res Opin. 2004;20(9):1501-1510. doi:10.1185/030079904x2763
  7. Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood. 2004;104(8):2263-2268. doi:10.1182/blood-2004-05-1812
  8. Adiatma D, Tobing M. Prevalensi Dan Jenis Anemia Pada Pasien Penyakit Ginjal Kronik Yang Menjalani Hemodialisis Reguler (Studi Di Rsup Dr. Kariadi Semarang). J Kedokt Diponegoro. 2014;3(1):137839.
  9. Collins AJ. The hemoglobin link to adverse outcomes. Adv Stud Med. 2003;3:194-197.
  10. 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. doi:10.1097/01.asn.0000018409.45834.fa
  11. Sarnak MJ, Tighiouart H, Manjunath G, et al. Anemia as a risk factor for cardiovascular disease in the atherosclerosis risk in communities (aric) study. J Am Coll Cardiol. 2002;40(1):27-33. doi:10.1016/s0735-1097(02)01938-1
  12. 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. doi:10.1038/kisup.2012.40
  13. Gill KS, Muntner P, Lafayette RA, et al. Red blood cell transfusion use in patients with chronic kidney disease. Nephrol Dial Transplant. 2013;28(6):1504-1515. doi:10.1093/ndt/gfs580
  14. Besarab A, Bolton WK, Browne JK, et al. The Effects of Normal as Compared with Low Hematocrit Values in Patients with Cardiac Disease Who Are Receiving Hemodialysis and Epoetin. N Engl J Med. 1998;339(9):584-590. doi:10.1056/nejm199808273390903
  15. Singh AK, Szczech L, Tang KL, et al. Correction of Anemia with Epoetin Alfa in Chronic Kidney Disease. N Engl J Med. 2006;355(20):2085-2098. doi:10.1056/nejmoa065485
  16. Drüeke TB, Locatelli F, Clyne N, et al. Normalization of Hemoglobin Level in Patients with Chronic Kidney Disease and Anemia. N Engl J Med. 2006;355(20):2071-2084. doi:10.1056/nejmoa062276
  17. Pfeffer MA, Burdmann EA, Chen C-Y, et al. A Trial of Darbepoetin Alfa in Type 2 Diabetes and Chronic Kidney Disease. N Engl J Med. 2009;361(21):2019-2032. doi:10.1056/nejmoa0907845
  18. Szczech LA, Barnhart HX, Inrig JK, et al. Secondary analysis of the CHOIR trial epoetin-? dose and achieved hemoglobin outcomes. Kidney Int. 2008;74(6):791-798. doi:10.1038/ki.2008.295
  19. Zhang Y, Thamer M, Stefanik K, Kaufman J, Cotter DJ. Epoetin requirements predict mortality in hemodialysis patients. Am J Kidney Dis. 2004;44(5):866-876. doi:10.1016/s0272-6386(04)01086-8
  20. Koury MJ, Haase VH. Anaemia in kidney disease: harnessing hypoxia responses for therapy. Nat Rev Nephrol. 2015;11(7):394-410. doi:10.1038/nrneph.2015.82
  21. Suttorp MM, Hoekstra T, Mittelman M, et al. Treatment with high dose of erythropoiesis-stimulating agents and mortality: analysis with a sequential Cox approach and a marginal structural model. Pharmacoepidemiol Drug Saf. 2015;24(10):1068-1075. doi:10.1002/pds.3855
  22. Busti F, Marchi G, Ugolini S, Castagna A, Girelli D. Anemia and Iron Deficiency in Cancer Patients: Role of Iron Replacement Therapy. Pharmaceuticals. 2018;11(4):94. doi:10.3390/ph11040094
  23. Ratcliffe LEK, Thomas W, Glen J, et al. Diagnosis and Management of Iron Deficiency in CKD: A Summary of the NICE Guideline Recommendations and Their Rationale. Am J Kidney Dis. 2016;67(4):548-558. doi:10.1053/j.ajkd.2015.11.012
  24. Kaelin WG, Ratcliffe PJ. Oxygen Sensing by Metazoans: The Central Role of the HIF Hydroxylase Pathway. Mol Cell. 2008;30(4):393-402. doi:10.1016/j.molcel.2008.04.009
  25. Semenza GL, Agani F, Booth G, et al. Structural and functional analysis of hypoxia-inducible factor 1. Kidney Int. 1997;51(2):553-555. doi:10.1038/ki.1997.77
  26. Peyssonnaux C, Nizet V, Johnson RS. Role of the hypoxia inducible factors HIF in iron metabolism. Cell Cycle. 2008;7(1):28-32. doi:10.4161/cc.7.1.5145
  27. Ganz T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood. 2003;102(3):783-788. doi:10.1182/blood-2003-03-0672
  28. Atanasiu V, Manolescu B, Stoian I. Hepcidin ? central regulator of iron metabolism. Eur J Haematol. 2007;78(1):1-10. doi:10.1111/j.1600-0609.2006.00772.x
  29. Nemeth E, Ganz T. Regulation of Iron Metabolism by Hepcidin. Annu Rev Nutr. 2006;26(1):323-342. doi:10.1146/annurev.nutr.26.061505.111303
  30. Bernhardt WM, Câmpean V, Kany S, et al. Preconditional Activation of Hypoxia-Inducible Factors Ameliorates Ischemic Acute Renal Failure. J Am Soc Nephrol. 2006;17(7):1970-1978. doi:10.1681/asn.2005121302
  31. Akizawa T, Iwasaki M, Yamaguchi Y, Majikawa Y, Reusch M. Phase 3, Randomized, Double-Blind, Active-Comparator (Darbepoetin Alfa) Study of Oral Roxadustat in CKD Patients with Anemia on Hemodialysis in Japan. J Am Soc Nephrol. 2020;31(7):1628-1639. doi:10.1681/asn.2019060623
  32. Akizawa T, Ueno M, Shiga T, Reusch M. Oral roxadustat three times weekly in ESA?naïve and ESA?converted patients with anemia of chronic kidney disease on hemodialysis: Results from two phase 3 studies. Ther Apher Dial. 2020;24(6):628-641. doi:10.1111/1744-9987.13468
  33. 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):1011-1022. doi:10.1056/nejmoa1901713
  34. Besarab A, Chernyavskaya E, Motylev I, et al. Roxadustat (FG-4592): Correction of Anemia in Incident Dialysis Patients. J Am Soc Nephrol. 2015;27(4):1225-1233. doi:10.1681/asn.2015030241
  35. Nangaku N, Kojima I, Tanaka T, Ohse T, Kato H, Fujita F. Novel Drugs and the Response to Hypoxia: HIF Stabilizers and Prolyl Hydroxylase. Recent Pat Cardiovasc Drug Discov. 2006;1(2):129-139. doi:10.2174/157489006777442522
  36. Besarab A, Provenzano R, Hertel J, et al. Randomized placebo-controlled dose-ranging and pharmacodynamics study of roxadustat (FG-4592) to treat anemia in nondialysis-dependent chronic kidney disease (NDD-CKD) patients. Nephrol Dial Transplant. 2015;30(10):1665-1673. doi:10.1093/ndt/gfv302
  37. Provenzano R, Besarab A, Sun CH, et al. Oral Hypoxia–Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat (FG-4592) for the Treatment of Anemia in Patients with CKD. Clin J Am Soc Nephrol. 2016;11(6):982-991. doi:10.2215/cjn.06890615
  38. Green S, Higgins JPT. Preparing a Cochrane Review. Cochrane Handb Syst Rev Interv.:11-30. doi:10.1002/9780470712184.ch2
  39. Chen N, Qian J, Chen J, et al. Phase 2 studies of oral hypoxia-inducible factor prolyl hydroxylase inhibitor FG-4592 for treatment of anemia in China. Nephrol Dial Transplant. 2017;32(8):1373-1386. doi:10.1093/ndt/gfx011
  40. Provenzano R, Besarab A, Wright S, et al. Roxadustat (FG-4592) versus epoetin alfa for anemia in patients receiving maintenance hemodialysis: A phase 2, randomized, 6- to 19-week, open-label, active-comparator, dose-ranging, safety and exploratory efficacy study. Am J Kidney Dis. 2016;67(6):912-924. doi:10.1053/j.ajkd.2015.12.020
  41. Provenzano R, Fishbane S, Szczech L, et al. Pooled Analysis of Roxadustat for Anemia in Patients With Kidney Failure Incident to Dialysis. Kidney Int Reports. 2021;6(3):613-623. doi:10.1016/j.ekir.2020.12.018
  42. Charytan C, Manllo-Karim R, Martin ER, et al. A Randomized Trial of Roxadustat in Anemia of Kidney Failure: SIERRAS Study. Kidney Int Reports. Published online 2021. doi:10.1016/j.ekir.2021.04.007
  43. Zheng Q, Yang H, Fu X, et al. The efficacy and safety of roxadustat for anemia in patients with chronic kidney disease: a meta-analysis. Nephrol Dial Transplant. Published online 2020. doi:10.1093/ndt/gfaa110
  44. Jia L, Dong X, Yang J, Jia R, Zhang H. Effectiveness of hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat on renal anemia in non-dialysis-dependent chronic kidney disease: a systematic review and meta-analysis. Ann Transl Med. 2019;7(23):720. doi:10.21037/atm.2019.12.18
  45. Provenzano R, Goodkin D, Klaus S, et al. 253 Evaluation of FG-4592, a Novel Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor, to Treat Anemia in Hemodialysis Patients. Am J Kidney Dis. 2011;57(4):B80. doi:10.1053/j.ajkd.2011.02.256
  46. Bailie GR, Larkina M, Goodkin DA, et al. Data from the Dialysis Outcomes and Practice Patterns Study validate an association between high intravenous iron doses and mortality. Kidney Int. 2015;87(1):162-168. doi:10.1038/ki.2014.275
  47. Karaboyas A, Zee J, Morgenstern H, et al. Understanding the Recent Increase in Ferritin Levels in United States Dialysis Patients: Potential Impact of Changes in Intravenous Iron and Erythropoiesis-Stimulating Agent Dosing. Clin J Am Soc Nephrol. 2015;10(10):1814-1821. doi:10.2215/cjn.02600315
  48. Macdougall IC, Tucker B, Thompson J, Tomson CR V, Baker LRI, Raine AEG. A randomized controlled study of iron supplementation in patients treated with erythropoietin. Kidney Int. 1996;50(5):1694-1699. doi:10.1038/ki.1996.487
  49. Wang H, Huang K, Wang C, Chen C, Fang H, Cao J. Effectiveness and safety of roxadustat in the treatment of anemia of kidney disease: a systematic review and meta-analysis. Ann Palliat Med. 2021;10(4):4736-4746. doi:10.21037/apm-21-456
  50. Pfeffer MA, Burdmann EA, Chen C-Y, et al. Baseline Characteristics in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT). Am J Kidney Dis. 2009;54(1):59-69. doi:10.1053/j.ajkd.2009.04.008

How to Cite

Karya, K. W. S., Praptika, N. L. P., Nurbudhi, N. Y. T., & Kandarini, Y. (2021). Perbandingan efektivitas dan keamanan antara roxadustat dan epoetin alfa sebagai terapi anemia pada pasien yang menjalani hemodialisis reguler: meta analisis. Intisari Sains Medis, 12(3), 768–776.




Search Panel

Kadek Wisnu Segara Karya
Google Scholar
ISM Journal

Ni Luh Parameswari Praptika
Google Scholar
ISM Journal

Nyoman Yudia Trianadewi Nurbudhi
Google Scholar
ISM Journal

Yenny Kandarini
Google Scholar
ISM Journal