Updates on Novel Erythropoiesis-Stimulating Agents: Clinical and Molecular Approach

  • Zahra Moradi
  • Amirhosein Maali
  • Javad Sadeghi Shad
  • Alireza Farasat
  • Reza Kouchaki
  • Mona Moghadami
  • Mohamad Hosein Ahmadi
  • Mehdi AzadEmail author
Review Article


Erythropoietin (EPO) is an important hormone responsible for the stimulation of hematopoiesis which is impaired in a variety of diseases, such as chronic kidney disease, cancer chemotherapy, and the use of some anti-HIV drugs. Difficulties in the purification of endogenous EPO due to problems such as technical limitations, heterogeneity of target cells, inadequate amount and immunogenicity of the resultant product, had limited the entry of endogenous EPO in the clinical applications. The integration of medical biotechnology and hematology has introduced novel procedures for the production of human recombinant erythropoietin (rHuEPO), and other erythropoiesis-stimulating agents (ESAs). To investigate and produce rHuEPO, the first step is to recognize the molecular biology and functional pathways, structure, metabolism, and basic physiology of EPO. In this review, all clinical indications, side effects, challenges and notable points regarding EPO, rHuEPO, and other ESAs have also been addressed along with its molecular characterization, such as the modifications needed to optimize their rHuEPO biosynthesis.


Erythropoietin Human recombinant erythropoietin Erythropoiesis-stimulating agents 



The authors declare that there are no acknowledgements.

Compliance with Ethical Standards

Conflict of interest

The authors declare that there is no conflict of interests.


  1. 1.
    Elliott S, Lorenzini T, Asher S, Aoki K, Brankow D, Buck L et al (2003) Enhancement of therapeutic protein in vivo activities through glycoengineering. Nat Biotechnol 21(4):414–421CrossRefPubMedGoogle Scholar
  2. 2.
    Lai PH, Everett R, Wang FF, Arakawa T, Goldwasser E (1986) Structural characterization of human erythropoietin. J Biol Chem 261(7):3116–3121PubMedGoogle Scholar
  3. 3.
    Tran AD, Park S, Lisi PJ, Huynh OT, Ryall RR, Lane PA (1991) Separation of carbohydrate-mediated microheterogeneity of recombinant human erythropoietin by free solution capillary electrophoresis. Effects of pH, buffer type and organic additives. J Chromatogr 542(2):459–471CrossRefPubMedGoogle Scholar
  4. 4.
    European Medicines Agency. Silapo: EPAR summary for the public 2007. 4 Mar 2008
  5. 5.
    Morris AL, MacArthur MW, Hutchinson EG, Thornton JM (1992) Stereochemical quality of protein structure coordinates. Proteins 12(4):345–364CrossRefPubMedGoogle Scholar
  6. 6.
    Obara N, Suzuki N, Kim K, Nagasawa T, Imagawa S, Yamamoto M (2008) Repression via the GATA box is essential for tissue-specific erythropoietin gene expression. Blood 111(10):5223–5232CrossRefPubMedGoogle Scholar
  7. 7.
    La Ferla K, Reimann C, Jelkmann W, Hellwig-Burgel T (2002) Inhibition of erythropoietin gene expression signaling involves the transcription factors GATA-2 and NF-kappaB. FASEB J 16(13):1811–1813CrossRefPubMedGoogle Scholar
  8. 8.
    Tarng DC, Huang TP, Chen TW, Yang WC (1999) Erythropoietin hyporesponsiveness: from iron deficiency to iron overload. Kidney Int Suppl 69:S107–S118CrossRefPubMedGoogle Scholar
  9. 9.
    Ng T, Marx G, Littlewood T, Macdougall I (2003) Recombinant erythropoietin in clinical practice. Postgrad Med J 79(933):367–376CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Maxwell PH, Wiesener MS, Chang GW, Clifford SC, Vaux EC, Cockman ME et al (1999) The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399(6733):271–275CrossRefPubMedGoogle Scholar
  11. 11.
    Maynard MA, Evans AJ, Shi W, Kim WY, Liu FF, Ohh M (2007) Dominant-negative HIF-3 alpha 4 suppresses VHL-null renal cell carcinoma progression. Cell Cycle 6(22):2810–2816CrossRefPubMedGoogle Scholar
  12. 12.
    Hu CJ, Wang LY, Chodosh LA, Keith B, Simon MC (2003) Differential roles of hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha in hypoxic gene regulation. Mol Cell Biol 23(24):9361–9374CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Gruber M, Hu CJ, Johnson RS, Brown EJ, Keith B, Simon MC (2007) Acute postnatal ablation of Hif-2alpha results in anemia. Proc Natl Acad Sci U S A 104(7):2301–2306CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Rankin EB, Biju MP, Liu Q, Unger TL, Rha J, Johnson RS et al (2007) Hypoxia-inducible factor-2 (HIF-2) regulates hepatic erythropoietin in vivo. J Clin Investig 117(4):1068–1077CrossRefPubMedGoogle Scholar
  15. 15.
    Knabe W, Knerlich F, Washausen S, Kietzmann T, Siren AL, Brunnett G et al (2004) Expression patterns of erythropoietin and its receptor in the developing midbrain. Anat Embryol (Berl) 207(6):503–512CrossRefGoogle Scholar
  16. 16.
    Knabe W, Siren AL, Ehrenreich H, Kuhn HJ (2005) Expression patterns of erythropoietin and its receptor in the developing spinal cord and dorsal root ganglia. Anat Embryol (Berl) 210(3):209–219CrossRefGoogle Scholar
  17. 17.
    Shingo T, Sorokan ST, Shimazaki T, Weiss S (2001) Erythropoietin regulates the in vitro and in vivo production of neuronal progenitors by mammalian forebrain neural stem cells. J Neurosci 21(24):9733–9743CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Ehrenreich H, Degner D, Meller J, Brines M, Behe M, Hasselblatt M et al (2004) Erythropoietin: a candidate compound for neuroprotection in schizophrenia. Mol Psychiatry 9(1):42–54CrossRefPubMedGoogle Scholar
  19. 19.
    Ehrenreich H, Hasselblatt M, Knerlich F, von Ahsen N, Jacob S, Sperling S et al (2005) A hematopoietic growth factor, thrombopoietin, has a proapoptotic role in the brain. Proc Natl Acad Sci U S A 102(3):862–867CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Marti HH, Wenger RH, Rivas LA, Straumann U, Digicaylioglu M, Henn V et al (1996) Erythropoietin gene expression in human, monkey and murine brain. Eur J Neurosci 8(4):666–676CrossRefPubMedGoogle Scholar
  21. 21.
    Yu X, Shacka JJ, Eells JB, Suarez-Quian C, Przygodzki RM, Beleslin-Cokic B et al (2002) Erythropoietin receptor signalling is required for normal brain development. Development 129(2):505–516PubMedGoogle Scholar
  22. 22.
    Chong ZZ, Shang YC, Mu Y, Cui S, Yao Q, Maiese K (2013) Targeting erythropoietin for chronic neurodegenerative diseases. Expert Opin Ther Targets 17(6):707–720CrossRefPubMedGoogle Scholar
  23. 23.
    Ribatti D, Presta M, Vacca A, Ria R, Giuliani R, Dell’Era P et al (1999) Human erythropoietin induces a pro-angiogenic phenotype in cultured endothelial cells and stimulates neovascularization in vivo. Blood 93(8):2627–2636CrossRefGoogle Scholar
  24. 24.
    Buemi M, Lacquaniti A, Bolignano D, Maricchiolo G, Favaloro A, Buemi A et al (2009) The erythropoietin and regenerative medicine: a lesson from fish. Eur J Clin Investig 39(11):993–999CrossRefGoogle Scholar
  25. 25.
    Elliott S, Sinclair AM (2012) The effect of erythropoietin on normal and neoplastic cells. Biologics 6:163–189PubMedPubMedCentralGoogle Scholar
  26. 26.
    Konishi Y, Chui DH, Hirose H, Kunishita T, Tabira T (1993) Trophic effect of erythropoietin and other hematopoietic factors on central cholinergic neurons in vitro and in vivo. Brain Res 609(1–2):29–35CrossRefPubMedGoogle Scholar
  27. 27.
    Sinclair AM, Coxon A, McCaffery I, Kaufman S, Paweletz K, Liu L et al (2010) Functional erythropoietin receptor is undetectable in endothelial, cardiac, neuronal, and renal cells. Blood 115(21):4264–4272CrossRefPubMedGoogle Scholar
  28. 28.
    Elliott S, Busse L, Swift S, McCaffery I, Rossi J, Kassner P et al (2012) Lack of expression and function of erythropoietin receptors in the kidney. Nephrol Dial Transplant 27(7):2733–2745CrossRefPubMedGoogle Scholar
  29. 29.
    Bartels C, Spate K, Krampe H, Ehrenreich H (2008) Recombinant human erythropoietin: novel strategies for neuroprotective/neuro-regenerative treatment of multiple sclerosis. Ther Adv Neurol Disord 1(3):193–206CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Miyake T, Kung CK, Goldwasser E (1977) Purification of human erythropoietin. J Biol Chem 252(15):5558–5564PubMedGoogle Scholar
  31. 31.
    Sahmani M, Vatanmakanian M, Goudarzi M, Mobarra N, Azad M (2016) Microchips and their significance in isolation of circulating tumor cells and monitoring of cancers. Asian Pac J Cancer Prev 17(3):879–894CrossRefPubMedGoogle Scholar
  32. 32.
    Winearls CG, Oliver DO, Pippard MJ, Reid C, Downing MR, Cotes PM (1986) Effect of human erythropoietin derived from recombinant DNA on the anaemia of patients maintained by chronic haemodialysis. Lancet 2(8517):1175–1178CrossRefPubMedGoogle Scholar
  33. 33.
    Eschbach JW, Abdulhadi MH, Browne JK, Delano BG, Downing MR, Egrie JC et al (1989) Recombinant human erythropoietin in anemic patients with end-stage renal disease. Results of a phase III multicenter clinical trial. Ann Intern Med 111(12):992–1000CrossRefPubMedGoogle Scholar
  34. 34.
    Eschbach JW, Egrie JC, Downing MR, Browne JK, Adamson JW (1987) 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 316(2):73–78CrossRefPubMedGoogle Scholar
  35. 35.
    Elliott S, Tomita D, Endre Z (2017) Erythropoiesis stimulating agents and reno-protection: a meta-analysis. BMC Nephrol 18(1):14CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Mc Causland FR, Claggett B, Burdmann EA, Chertow GM, Cooper ME, Eckardt KU et al (2018) Treatment of anemia with darbepoetin prior to dialysis initiation and clinical outcomes: analyses from the trial to reduce cardiovascular events with Aranesp therapy (TREAT). Am J Kidney Dis 73:309–315CrossRefPubMedGoogle Scholar
  37. 37.
    Locatelli F, Covic A, Eckardt KU, Wiecek A, Vanholder R, ERA-EDTA ERBP Advisory Board (2009) Anaemia management in patients with chronic kidney disease: a position statement by the Anaemia Working Group of European Renal Best Practice (ERBP). Nephrol Dial Transplant 24(2):348–354CrossRefPubMedGoogle Scholar
  38. 38.
    Egrie JC, Dwyer E, Browne JK, Hitz A, Lykos MA (2003) Darbepoetin alfa has a longer circulating half-life and greater in vivo potency than recombinant human erythropoietin. Exp Hematol 31(4):290–299CrossRefPubMedGoogle Scholar
  39. 39.
    Patton J, Kuzur M, Liggett W, Miranda F, Varsos H, Porter L (2004) Epoetin alfa 60,000 U once weekly followed by 120,000 U every 3 weeks increases and maintains hemoglobin levels in anemic cancer patients undergoing chemotherapy. Oncologist 9(1):90–96PubMedGoogle Scholar
  40. 40.
    Jelkmann W (2013) Physiology and pharmacology of erythropoietin. Transfus Med Hemother 40(5):302–309CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Roger SD (2006) Biosimilars: how similar or dissimilar are they? Nephrology (Carlton) 11(4):341–346CrossRefGoogle Scholar
  42. 42.
    Khalili H, Dashti S, Seifi S, Hadjibabaie M, Shafiei S (2006) Erythropoietin utilization evaluation and two brand products comparison, eprex and eposim. Tehran Univ Med J 64(2):1–2Google Scholar
  43. 43.
    Omrani H, Bashiri H, Reissi Dastgerdi D, Najafi F, Shafiezadeh S, Izadi N (2014) Comparison of the effect of various products of erythropoietin on hemoglobin level in hemodialysis patients. J Babol Univ Med Sci 16(2):23–28Google Scholar
  44. 44.
    Harzallah A, Zouaghi K, Dridi A, Boubaker K, Beji S, Ayari M et al (2015) Therapeutic efficacy of a biosimilar epoetin alfa in hemodialysis patients. Saudi J Kidney Dis Transplant 26(1):78–82CrossRefGoogle Scholar
  45. 45.
    Macdougall IC, Robson R, Opatrna S, Liogier X, Pannier A, Jordan P et al (2006) Pharmacokinetics and pharmacodynamics of intravenous and subcutaneous continuous erythropoietin receptor activator (C.E.R.A.) in patients with chronic kidney disease. Clin J Am Soc Nephrol. 1(6):1211–1215CrossRefPubMedGoogle Scholar
  46. 46.
    Piotr B, Mariusz S, Jacek R (2017) Methoxy polyethylene glycol-epoetin beta as a novel erythropoiesis stimulating agent with possible nephroprotective and cardiovascular protective effects in non-dialysis chronic kidney disease patients. Curr Pharm Biotechnol 18(4):303–308CrossRefPubMedGoogle Scholar
  47. 47.
    Macdougall IC, Eckardt K-U (2006) Novel strategies for stimulating erythropoiesis and potential new treatments for anaemia. Lancet 368(9539):947–953CrossRefPubMedGoogle Scholar
  48. 48.
    Macdougall IC (2001) An overview of the efficacy and safety of novel erythropoiesis stimulating protein (NESP). Nephrol Dial Transplant 16(Suppl 3):14–21CrossRefPubMedGoogle Scholar
  49. 49.
    Locatelli F, Olivares J, Walker R, Wilkie M, Jenkins B, Dewey C et al (2001) Novel erythropoiesis stimulating protein for treatment of anemia in chronic renal insufficiency. Kidney Int 60(2):741–747CrossRefPubMedGoogle Scholar
  50. 50.
    Egrie JC, Dwyer E, Browne JK, Hitz A, Lykos MA (2003) Darbepoetin alfa has a longer circulating half-life and greater in vivo potency than recombinant human erythropoietin. Exp Hematol 31(4):290–299CrossRefPubMedGoogle Scholar
  51. 51.
    Egrie J (1997) Novel erythropoiesis stimulating protein (NESP) has a longer serum half-life and greater in vivo biological activity compared to recombinant human erythropoietin (rHuEPO). Blood 90:56aGoogle Scholar
  52. 52.
    Smith RE Jr, Jaiyesimi IA, Meza LA, Tchekmedyian NS, Chan D, Griffith H et al (2001) Novel erythropoiesis stimulating protein (NESP) for the treatment of anaemia of chronic disease associated with cancer. Br J Cancer 84(Suppl 1):24–30CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Egrie JC, Browne JK (2002) Development and characterization of darbepoetin alfa. Oncology (Williston Park) 16(10 Suppl 11):13–22Google Scholar
  54. 54.
    Desai J, Demetri GD (2005) Recombinant human erythropoietin in cancer-related anemia: an evidence-based review. Best Pract Res Clin Haematol 18(3):389–406CrossRefPubMedGoogle Scholar
  55. 55.
    Joy MS (2002) Darbepoetin alfa: a novel erythropoiesis-stimulating protein. Ann Pharmacother 36(7–8):1183–1192CrossRefPubMedGoogle Scholar
  56. 56.
    Seastone DJ, Gerds AT (2015) Darbepoetin alfa for anemia with myelodysplastic syndrome. Expert Rev Hematol 8(2):139–146CrossRefPubMedGoogle Scholar
  57. 57.
    Hermanson T, Bennett CL, Macdougall IC (2016) Peginesatide for the treatment of anemia due to chronic kidney disease—an unfulfilled promise. Expert Opin Drug Saf 15(10):1421–1426CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    US Food and Drug Administration (2013) Affymax and takeda announce a nationwide voluntary recall of all lots of OMONTYS® (peginesatide) injection, 23 FebGoogle Scholar
  59. 59.
    Kamioner D (2012) Erythropoietin biosimilars currently available in hematology-oncology. Target Oncol 7(1):25–28CrossRefGoogle Scholar
  60. 60.
    Molineux G, Kinstler O, Briddell B, Hartley C, McElroy P, Kerzic P et al (1999) A new form of Filgrastim with sustained duration in vivo and enhanced ability to mobilize PBPC in both mice and humans. Exp Hematol 27(12):1724–1734CrossRefPubMedGoogle Scholar
  61. 61.
    Wang YS, Youngster S, Bausch J, Zhang R, McNemar C, Wyss DF (2000) Identification of the major positional isomer of pegylated interferon alpha-2b. Biochemistry 39(35):10634–10640CrossRefPubMedGoogle Scholar
  62. 62.
    Schriebl K, Trummer E, Lattenmayer C, Weik R, Kunert R, Muller D et al (2006) Biochemical characterization of rhEpo-Fc fusion protein expressed in CHO cells. Protein Expr Purif 49(2):265–275CrossRefPubMedGoogle Scholar
  63. 63.
    Eskandari F, Allahverdi A, Nasiri H, Azad M, Kalantari N, Soleimani M et al (2015) Nanofiber expansion of umbilical cord blood hematopoietic stem cells. Iran J Pediatr Hematol Oncol 5(4):170–178Google Scholar
  64. 64.
    Matsushita S, Chuang VT, Kanazawa M, Tanase S, Kawai K, Maruyama T et al (2006) Recombinant human serum albumin dimer has high blood circulation activity and low vascular permeability in comparison with native human serum albumin. Pharm Res 23(5):882–891CrossRefPubMedGoogle Scholar
  65. 65.
    Bai Y, Shen W-C (2006) Improving the oral efficacy of recombinant granulocyte colony-stimulating factor and transferrin fusion protein by spacer optimization. Pharm Res 23(9):2116–2121CrossRefPubMedGoogle Scholar
  66. 66.
    Evers TH, van Dongen EM, Faesen AC, Meijer E, Merkx M (2006) Quantitative understanding of the energy transfer between fluorescent proteins connected via flexible peptide linkers. Biochemistry 45(44):13183–13192CrossRefPubMedGoogle Scholar
  67. 67.
    Joung CH, Shin JY, Koo JK, Lim JJ, Wang JS, Lee SJ et al (2009) Production and characterization of long-acting recombinant human albumin-EPO fusion protein expressed in CHO cell. Protein Expr Purif 68(2):137–145CrossRefPubMedGoogle Scholar
  68. 68.
    Vijayakumar S, Thilaka GK (2014) Synthetic human erythropertin gene-construction, cloning and sequencing. Int J Pharm Sci Rev Res 26:75–78Google Scholar
  69. 69.
    Fishbane S, Spinowitz B (2018) Update on anemia in ESRD and earlier stages of CKD: core curriculum 2018. Am J Kidney Dis 71(3):423–435CrossRefPubMedGoogle Scholar
  70. 70.
    Ma JZ, Ebben J, Xia H, Collins AJ (1999) Hematocrit level and associated mortality in hemodialysis patients. J Am Soc Nephrol 10(3):610–619PubMedGoogle Scholar
  71. 71.
    Greenbaum LA (2005) Anemia in children with chronic kidney disease. Adv Chronic Kidney Dis 12(4):385–396CrossRefPubMedGoogle Scholar
  72. 72.
    Atkinson MA, Furth SL (2011) Anemia in children with chronic kidney disease. Nat Rev Nephrol 7(11):635CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Koury MJ, Haase VH (2015) Anaemia in kidney disease: harnessing hypoxia responses for therapy. Nat Rev Nephrol 11(7):394–410CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Macdougall IC (1998) Meeting the challenges of a new millennium: optimizing the use of recombinant human erythropoietin. Nephrol Dial Transplant 13(Suppl 2):23–27CrossRefPubMedGoogle Scholar
  75. 75.
    Bolanos L, Castro P, Falcon TG, Mouzo R, Varela JM (2002) Continuous intravenous sodium ferric gluconate improves efficacy in the maintenance phase of EPOrHu administration in hemodialysis patients. Am J Nephrol 22(1):67–72CrossRefPubMedGoogle Scholar
  76. 76.
    Wang H, Fan J, Chen M, Yao Q, Gao Z, Zhang G et al (2017) rhEPO enhances cellular anti-oxidant capacity to protect long-term cultured aging primary nerve cells. J Mol Neurosci 62(3–4):291–303CrossRefPubMedGoogle Scholar
  77. 77.
    Rizzo JD, Brouwers M, Hurley P, Seidenfeld J, Arcasoy MO, Spivak JL et al (2010) American Society of Clinical Oncology/American Society of Hematology clinical practice guideline update on the use of epoetin and darbepoetin in adult patients with cancer. J Clin Oncol 28(33):4996–5010CrossRefPubMedGoogle Scholar
  78. 78.
    Greenberg PL, Attar E, Bennett JM, Bloomfield CD, Borate U, De Castro CM et al (2013) Myelodysplastic syndromes: clinical practice guidelines in oncology. J Natl Compr Cancer Netw 11(7):838–874CrossRefGoogle Scholar
  79. 79.
    Burstein SA, Boyd CN, Dale GL (1985) Quantitation of megakaryocytopoiesis in liquid culture by enzymatic determination of acetylcholinesterase. J Cell Physiol 122(1):159–165CrossRefPubMedGoogle Scholar
  80. 80.
    Levine RF, Hazzard KC, Lamberg JD (1982) The significance of megakaryocyte size. Blood 60(5):1122–1131CrossRefGoogle Scholar
  81. 81.
    Ishibashi T, Koziol J, Burstein S (1987) Human recombinant erythropoietin promotes differentiation of murine megakaryocytes in vitro. J Clin Investig 79(1):286–289CrossRefPubMedGoogle Scholar
  82. 82.
    Azad M, Goudarzi M, Sahmani M, Dehghanifard A, Mobarra N, Vatanmakanian M et al (2015) Correlation between methylation and expression level of P15 and P16 genes during differentiation of cord blood stem cells into erythroid lineage mediated by erythropoietin. Nov Biomed 1:6–12Google Scholar
  83. 83.
    Gershon SK, Luksenburg H, Cote TR, Braun MM (2002) Pure red-cell aplasia and recombinant erythropoietin. N Engl J Med. 346(20):1584–1586CrossRefPubMedGoogle Scholar
  84. 84.
    Casadevall N (2002) Antibodies against rHuEPO: native and recombinant. Nephrol Dial Transplant 17(suppl_5):42–47CrossRefPubMedGoogle Scholar
  85. 85.
    Iki S, Yagisawa M, Ohbayashi Y, Sato H, Urabe A (1991) Adverse effect of erythropoietin in myeloproliferative disorders. Lancet 337(8734):187–188CrossRefPubMedGoogle Scholar
  86. 86.
    Bauer E, Danhauser-Riedl S, De Riese W, Raab HR, Sandner S, Meyer HJ et al (1992) Effects of recombinant human erythropoietin on clonogenic growth of primary human tumour specimens in vitro. Eur J Cancer 28A(10):1769CrossRefPubMedGoogle Scholar
  87. 87.
    Poniewierska-Baran A, Rajewska-Majchrzak J, Ratajczak MZ (2017) Erythropoietin enhances migration of human neuroblastoma cells: in vitro studies and potential therapeutic implications. J Cancer Stem Cell Res 5:e1003PubMedPubMedCentralGoogle Scholar
  88. 88.
    Carlini RG, Dusso AS, Obialo CI, Alvarez UM, Rothstein M (1993) Recombinant human erythropoietin (rHuEPO) increases endothelin-1 release by endothelial cells. Kidney Int 43(5):1010–1014CrossRefPubMedGoogle Scholar
  89. 89.
    Ng TMG, Littlewood T, Macdougall I (2003) Recombinant erythropoietin in clinical practice. Postgrad Med J 79(933):367–376CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    MPR (2018) EPOGEN Dosage & Rx Info. [Cited 15 march 2019].
  91. 91.
    Medscape (2018) darbepoetin alfa (Rx). [Cited 24 march 2019].
  92. 92.
    DrugBank (2015) Peginesatide. [Cited 17 April 2019].
  93. 93.
    Medscape (2018) peginesatide (Discontinued). [Cited 7 march 2019].
  94. 94. (2018) Mircera Dosage. [Cited 7 march 2019].
  95. 95.
    European Medicines Agency (EMA) (2018) NeoRecormon. [Cited 10 April 2019].
  96. 96.
    Medicine UK (2015) NeoRecormon (Package leaflet: Information for the user). [Cited 18 April 2019].
  97. 97.
    Azmandian J, Abbasi MR, Pourfarziani V, Nasiri AA, Ossareh S, Ezzatzadegan Jahromi S et al (2018) Comparing therapeutic efficacy and safety of epoetin beta and epoetin alfa in the treatment of anemia in end-stage renal disease hemodialysis patients. Am J Nephrol 48(4):251–259CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Wilhelm-Leen ER, Winkelmayer WC (2015) Mortality risk of darbepoetin alfa versus epoetin alfa in patients with CKD: systematic review and meta-analysis. Am J Kidney Dis 66(1):69–74CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Hermanson T, Bennett CL, Macdougall IC (2016) Peginesatide for the treatment of anemia due to chronic kidney disease—an unfulfilled promise. Expert Opin Drug Saf 15(10):1421–1426CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Tsuruya K, Uemura Y, Hirakata H, Kitazono T, Tsubakihara Y, Suzuki M et al (2017) Association between responsiveness to methoxy polyethylene glycol-epoetin beta and renal survival in patients with non-dialysis-dependent chronic kidney disease: A pooled analysis of individual patient-level data from clinical trials. Nephrology (Carlton) 22(10):769–775CrossRefGoogle Scholar
  101. 101.
    Kawai T, Kusano Y, Yamada K, Ueda C, Kawai A, Masaki T (2018) Long-term maintenance of hemoglobin levels in hemodialysis patients treated with bi-weekly epoetin beta pegol switched from darbepoetin alfa: a single-center, 12-month observational study in Japan. J Artif Organs 22:146–153CrossRefPubMedGoogle Scholar

Copyright information

© Indian Society of Hematology and Blood Transfusion 2019

Authors and Affiliations

  • Zahra Moradi
    • 1
  • Amirhosein Maali
    • 2
    • 3
  • Javad Sadeghi Shad
    • 2
    • 4
  • Alireza Farasat
    • 5
  • Reza Kouchaki
    • 6
  • Mona Moghadami
    • 2
    • 3
  • Mohamad Hosein Ahmadi
    • 6
  • Mehdi Azad
    • 6
    Email author
  1. 1.Student Research CommitteeIran University of Medical SciencesTehranIran
  2. 2.Student Research CommitteeBabol University of Medical SciencesBabolIran
  3. 3.Department of Medical Biotechnology, Faculty of MedicineBabol University of Medical SciencesBabolIran
  4. 4.Department of Clinical Biochemistry, Faculty of MedicineBabol University of Medical SciencesBabolIran
  5. 5.Cellular and Molecular Research CenterQazvin University of Medical SciencesQazvinIran
  6. 6.Faculty of Allied MedicineQazvin University of Medical SciencesQazvinIran

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