Recombinant Human Erythropoietin (rhEPO) : Manfaat dalam Bidang Kedokteran Hewan

yanuartono yanuartono(1), Hary Purnamaningsih(2*), Alfarisa Nururrozi(3), Soedarmanto Indarjulianto(4), Slamet Raharjo(5)

(1) universitas gadjah Mada
(2) Departemen Ilmu Penyakit Dalam, Fakultas Kedokteran Hewan Universitas Gadjah Mada
(3) Departemen Ilmu Penyakit Dalam, Fakultas Kedokteran Hewan Universitas Gadjah Mada
(4) Departemen Ilmu Penyakit Dalam, Fakultas Kedokteran Hewan Universitas Gadjah Mada
(5) Departemen Ilmu Penyakit Dalam, Fakultas Kedokteran Hewan Universitas Gadjah Mada
(*) Corresponding Author


Recombinant human erythropoietin (rhEPO) is one of the biotechnology-based drugs that are needed by the human medicine and has also been used in the veterinary medicine. Currently RhEPO has been widely used in the world of human medicine for the treatment of anaemia caused by renal failure, cancer, chronic inflammation and AIDS. In veterinary medicine, although there is still not much data on its achievements, rhEPO has also been used for cases of chronic renal failure in dogs and cats. However, since rhEPO is not identical to feline EPO and canine EPO, some patients eventually produce antibodies against the drug. The antibodies not only prevent EPO therapy from being effective, but also may lead to severe and life-threatening anemia. This paper provides a review of the use of RhEPO, rfEPO and rcEPO in veterinary medicine, especially for the purpose of non-regenerative anemia therapy in cases of chronic renal failure in dogs and cats.



Recombinant human erythropoietin; anaemia; dog; cat; chronic renal failure


Andrews, D.A., Pyrah, I.T.G., Boren, B.M., Tannehill-Gregg, S.H., And Ruth M. Lightfoot-Dunn, R.M. (2014) High Hematocrit Resulting from Administration of Erythropoiesis-stimulating Agents Is Not Fully Predictive of Mortality or Toxicities in Preclinical Species. Toxicologic Pathology, 42: 510-523. DOI: 10.1177/0192623313486317

Barth, T., Oliveira, P.R., Felipe, B., D’avila, F.B. And Dalmora. S.L. (2008) Validation of the NormocythemicMice Bioassay for the Potency Evaluation of Recombinant Human Erythropoietin inmPharmaceutical Formulations. Journal Of Aoac International.91 (2): 85-291.

Beall, C.J., Phipps, A.J., Mathes, L.E., Stromberg, P., And Johnson, P.R. (2000) Transfer of the feline erythropoietin gene to cats using a recombinant adeno-associated virus vector. Gene Therapy 7 (6): 534–539. DOI: 10.1038/

Bernado, P., Rahardjo, And Rahajoe, P.S. (2016) Pengaruh recombinant human Erythropoietin terhadap jumlah osteoblas, osteoklas dan kadar hemoglobin pada penyembuhan fraktur tulang mandibula. Studi eksperimental pada fraktur mandibula tikus Sprague-Dawley. J Ked Gi. 7(2): 131-137

Bernaudin, M., Marti, H.H., Roussel, S., Divoux, D., Nouvelot, A., MacKenzie, E.T. And Petit, E. (1999) A potential role for erythropoietin in focal permanent cerebral ischemia in mice. J Cereb Blood Flow Metab. 19 (6):643–651. DOI:10.1097/00004647-199906000-00007

Boran, M., Dalva, I., Yazicioglu, A., Akbay, E. And Cetin, S. (1993). Correction of anaemia in haemodialysis patients with recombinant human erythropoietin. Int Urol Nephrol 25 (2): 197–203. PMID:8365853

Bron, D., Meuleman, N. And Mascaux, C. (2001) Biological basis of anemia. Semin Oncol 28(2 Suppl 8):1-6. PMID:11395845

Browne, J.K., Cohen, A.M., Egrie, J.C., Lai, P.H., Lin, F.K., Strickland, T., Watson, E. And Stebbing, N. (1986) Erythropoietin: gene cloning, protein structure, and biological properties. Cold Spring Harb Symp Quant Biol. 51(Pt1) :693–702. doi:10.1101/SQB.1986.051.01.082

Bugelski, P. J., Nesspor, T., Volk, A., O’Brien, J., Makropoulos, D., Shamberger, K., Fisher, P. W., James, I., Graden, D., And Capocasale, R. J. (2008) Pharmacodynamics of recombinant human erythropoietin in murine bone marrow. Pharm Res 25(2): 369–78. DOI:10.1007/s11095-007-9372-7

Chalhoub, S., Langston, C.E. And Eatroff, A. (2011) Anemia of renal disease. J Fel Med Surg. 13(9):629-640. doi: 10.1016/j.jfms.2011.07.016.

Chalhoub, S., Langston, C.E. and Farrelly, J. (2012) The Use of Darbepoetin to Stimulate Erythropoiesis in Anemia of Chronic Kidney Disease in Cats: 25 Cases. J Vet Intern Med 26 (2):363–369. doi: 10.1111/j.1939-1676.2011.00864.x

Chew, D.J., DiBartola, S.P., And Schenck, P. (2011) editors. Chronic renal failure. In Canine and Feline Nephrology and Urology. St. Louis, Missouri: Elsevier Saunders.; 145-96.

Choi, D., Kim, M. And Park, J. (1996) Erythropoietin: physico- and biochemical analysis. Journal of Chromatography. 687(1): 189-199.

Coleman, T. And Brines. M. (2004) Science review: Recombinant human erythropoietin in critical illness: a role beyond anemia? Critical Care 8 (5): 337-341 DOI 10.1186/cc2897)

Conley, A.J., Mohib, K., Jevnikar, A.M. And Brandle. J.E. 2009 Plant recombinant erythropoietin attenuates inflammatory kidney cell injury. Plant Biotechnology Journal 7(2): 183–199. doi: 10.1111/j.1467-7652.2008.00389.x

Cowgill, L D., James, K. M., Levy, J. K, Browne, J.K., Miller, A., Lobingier, R.T., And Egrie, J.C. (1998) Use of recombinant human erythropoietin for management of anemia in dogs and cats with renal failure. Journal of the American Veterinary Medical Association 212(4):521-528. PMID:9491159

Cowgill, L.D. (1991) Erythropoietin: Its use in the treatment of chronic renal failure in dogs and cats. Proc Annu Waltham/OSU Symp Treat Small Anim Dis.15:65–71.

Delorme, E., Lorenzini, T., Giffin, J., Martin, F., Jacobsen, F., Boone, T. And Elliott, S. (1992) Role of glycosylation on the secretion and biological activity of erythropoietin. Biochemistry. 31(41): 9871–9876. DOI: 10.1021/bi00156a003

Eder, H., Roblenbroich, B. And Failing, K. (1989) A dose-dependent effect of recombinant erythropoietin on the reticulocyte population of rats. Blut. 59(2): 184-187. PMID:2475191

Egrie, J. (1990) The cloning and production of recombinant human erythropoietin. Pharmacotherapy 10(Pt2):3S–8S. PMID:2345709

Egrie, J.C., Strickland, T.W., Lane, J., Aoki, K., Cohen, A.M., Smalling, R., Trail, G., Lin, F.K., Browne, J.K. And Hines, D.K. (1986) Characterization and biological effects of recombinant human erythropoietin. Immunobiology. 172(3-5):213-24. DOI:10.1016/S0171-2985(86)80101-2

Egrie, J. C. And Browne, J. K. (2001) Development and characterization of novel erythropoiesis stimulating protein (NESP). Br J Cancer. 84 (Suppl 1): 3–10. doi: 10.1054/bjoc.2001.1746

Elliott, S., Pham, E. And Macdougall, I.C. (2008) Erythropoietins: A common mechanism of action. Exp Hematol. 36(12):1573–84. doi: 10.1016/j.exphem.2008.08.003

Eschbach, J.W. (1989) The anemia of chronic renal failure: Pathophysiology and the effects of recombinant erythropoietin. Kidney Int. 35(1):134–148. DOI:

Eschbach, J.W., Egrie, J.C., Downing, M.R., Browne, J.K. And Adamson, J.W. (1987) Correction of the anaemia 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) :73–78. DOI: 10.1056/NEJM198701083160203

Fiocchi, E.H., Cowgill, L.D., Brown, D.C., Markovich, J.E., Tucker, S., Labato, M.A., And Callan, M.B. (2017) The Use of Darbepoetin to Stimulate Erythropoiesis in the Treatment of Anemia of Chronic Kidney Disease in Dogs. J Vet Intern Med. 31(2):476–485 DOI: 10.1111/jvim.14681

Fuadi, I. And Bisri, T. (2015) Efek Proteksi Otak Erythropoietin. JNI 4 (2): 149–56

Gao, G., Lebherz, C., Weiner, D.J., Grant, R., Calcedo, R., McCullough, B., Bagg, A., Zhang, Y. And Wilson, J.M. (2004) Erythropoietin gene therapy leads to autoimmune anemia in macaques. Blood. 103 (9): 3300-3302. doi:10.1182/blood-2003-11-3852

Garrido, P., Reis, F., Costa, E., Almeida, A., Parada, B.E., Teixeira-Lemos, E., Santos, P., Alves, R., Sereno, J., Pinto, R., Tavares, C.A., Figueiredo, A., Rocha-Pereira, P., Belo, L., Santos-Silva, A. And Teixeira, F. (2010) Effect of Recombinant Human Erythropoietin in a Rat Model of Moderate Chronic Renal Failure – Focus on Inflammation, Oxidative Stress and Function/Renoprotection. The Open Drug Discovery 22(2) : 25-32. DOI: 10.2174/1877381801002020025

Giger U. (1992) Erythropoietin and its clinical use. Compend Contin Educ Pract Vet 14 :25–34.

Giger, U. (1991) Serum erythropoietin concentrations in polycythemic and anemic dogs. Proc 9th ACVIM Forum:143–145.

Goodnough, L.T., Skikne, B. And Brugnara, C. (2000) Erythropoietin, iron, and erythropoiesis. Blood 96 (3): 823-833. PMID:10910892

Goto, M., Akai, K., Murakami, A., Hashimoto, C., Tsuda, E., Ueda, M., Kawanishi, G., Takahashi, N., Ishimoto, A., Chiba, H. And Sasaki, R. (1988) Production of recombinant human erythropoietin in mammalian cells: host-cell dependency of the biological activity of the cloned glycoprotein. Nature Biotechnology. 6(1): 67–71. DOI: 10.1038/nbt0188-67

Hamilton, S.R., Davidson, R.C., Sethuraman, N., Nett, J.H., Jiang, Y., Rios, S., Bobrowicz, P., Stadheim, T.A., Li, H., Choi, B.K., Hopkins, D., Wischnewski, H., Roser, J., Mitchell, T., Strawbridge, R.R., Hoopes, J., Wildt, S. And Gerngross, T.U. (2006) Humanization of yeast to produce complex terminally sialylated glycoproteins. Science, 313: 1441–1443. DOI:10.1126/science.1130256

Henry, P. (1994) Human recombinant erythropoietin used to treat a cat with anemia caused by chronic renal failure. Can Vet J. 35(6) :375. PMID: 8069840

Hoeksema, F. (2011) Selection markers and expression enhancing elements: Novel strategies to create mammalian production cell lines. Faculty of Science. University of Amsterdam. Thesis Dissertation. Available at: 482571

Huang, L.S. (1984) Cloning and expression of human erythropoietin cDNA in Escherichia coli. Proc. Natl. Acad. Sci. USA, 81(9): 2708-2712. PMID: 6371819

Ifeanyi, O.E. And Uzoma, O.G. (2016) Erythropoietin and Kidney Diseases: A Review. J. Biol. Chem. Research. 33 (2): 760-792

Ifudu, N., Matthew, J.J., Mayers, J.D., Macey, L.J., Brezsnyak, W., Reydel, C., McClendon, E., Surgrue, T., Sreepada Rao, T.K. And Friedman, E.A. (1997) Severity of AIDS and the response to EPO in uremia. American Journal of Kidney Diseases 30 (1): 28-35. DOI:

Imai, N., Kawamura, A., Higuci, M., Oh-Eda, M., Orita, T., Kawagchi, T., And Ochi, N. (1990) Physicochemical and Biological Comparison of Recombinant Human Erythropoietin with Human Urinary Erythropoietin1. Journal of Biochemistry 107(3) : 352-359 DOI::10.1093/oxfordjournals.jbchem.a123050

Inoue, N., Takeuchi, M., Ohashi, H. And Suzuki, T. (1995) The production of recombinant human erythropoietin. Biotechnol Annu Rev. 1995 (1):297-313.

Jacobs, K., Shoemaker, C., Rudersdorf, R., Neill, S.D., Kaufmann, R.J., Mufson, A., Seehra, J., Jones, S.S., Hewick, R., And Fritsch, E.F. (1985) Isolation and characterization of genomic and cDNA clones of human erythropoietin. Nature. 313(6005): 806-810. PMID:3838366

Jelkmann, W. (1992) Erythropoietin: structure, control of production and function. Physiol Rev. 72(2):449–89. DOI: 10.1152/physrev.1992.72.2.449

Jelkmann, W. (2000) Use of recombinant human erythropoietin as an anti-anemic and performance enhancing drug. Curr Pharmaceut Biotechnol. 1(1):11–31. DOI:

Jelkmann, W. (2008) Developments in the therapeutic use of erythropoiesis stimulating agents. British Journal of Haematology. 141(3): 287–297 doi:10.1111/j.1365-2141.2007.06948.x

Jelkmann, W. (2013) Physiology and Pharmacology of Erythropoietin. Transfus Med Hemother. 40(5):302–309 DOI: 10.1159/000356193

Kim, Y.K., Shin, H.S., Tomiya, N., Lee, Y.C., Betenbaugh, M.J. And Cha, H.J. (2005) Production and N-glycan analysis of secreted human erythropoietin glycoprotein in stably transfected Drosophila S2 cells. Biotechnol. Bioeng. 92(4): 452–461. DOI: 10.1002/bit.20605

King, L.G., Giger, U., Diserens, D., And Nagode, L.A. (1992) Anemia of chronic renal failure in dogs. J Vet Intern Med. 6 (5): 264–270. PMID: 1432900

Koury, S.T., Koury, M.J., Bondurant, M.C., Caro, J. And Graber, S.E. (1989) Quantitation of erythropoietin-producing cells in kidneys of mice by in situ hybridization: Correlation with hematocrit, renal erythropoietin mRNA, and serum erythropoietin concentration. Blood 74(2): 645-51. PMID: 2752138

Koury, S.T., Bondurant, M.C., And Koury, M.J. (1988) Localization of erythropoietin synthesizing cells in murine kidneys by in situ hybridization.Blood. 71:524–527. PMID:3337914

Kumar, J., Reccia, I., Kusano, T. And Agrawal, S. (2017) A Systematic Review on the Erythropoietin Receptors Expression in Various Cancers and Importance of Recombinant Erythropoietin in Chemotherapy Induced Anaemia. Hematol Transfus Int J. 4(1):1-6. DOI: 10.15406/htij.2017.04.00072

Langston, C., Cook, A.. Eatroff, A., Mitelberg, E. And Chalhoub S. (2017). Blood Transfusions in Dogs and Cats Receiving Hemodialysis: 230 Cases (June 1997–September 2012). J Vet Intern Med. 31(2):402–409. DOI:10.1111/jvim.14658

Langston, C.E., Reine, N.J., And Kittrell, D. (2003) The use of erythropoietin. Vet Clin North Am Small Anim Pract. 33(6):1245-1260. PMID:14664197

Law, M.L., Cai, G.Y., Lin, F.K., Wei, Q., Huang, S.Z., Hartz, J.H., Morse, H., Lin, C. H., Jones, C. And Kao, F. T. (1986) Chromosomal assignment of the human erythropoietin gene and its DNA polymorphism. Proc Natl Acad Sci U S A. 83 (18):6920–6924. DOI: 10.1073/pnas.83.18.6920

Loughnan, A., Galil Rahman Ali, G.R. And Abeygunasekara, S.C. (2011) Comparison of the Therapeutic Efficacy of Epoetin Beta and Epoetin Alfa in Maintenance Phase Hemodialysis Patients, Renal Failure. 33 (3):373-375, DOI: 10.3109/0886022X.2011.559675

MacLeod, J.N. (2001) Clinical Trials of Recombinant Feline EPO Underway.

MacLeod, J.N., Tetreault, J.W., Lorschy, K.A., And Gu, D.N. (1998) Expression and bioactivity of recombinant canine erythropoietin. Am J Vet Res 59 (9):1144–1148. PMID: 9736393

Mikiciuk, M.G., Polzin, D.J., And Osborne, C.A. (1990) The use of erythropoietin in chronic renal failure. Adv Small Animal Med Surg. 3:1–3.

Miyazaki, Y., Kuryama, K., Higuchi, H., Sohda, H., Imai, N., Saito, M., Kondo, T. And Tomonaga, M, (1997) Establishment and characterization of a new erythropoietin-dependent acute myeloid leukaemia cell line, AS-E2. Leukemia, 11(11): 1941-1949. DOI: 10.1038/sj.leu.2400838

Oishi, A., Hamada, S., Sakamoto,H., And Shimizu, R. (1995) Preventive effects of recombinant human erythropoietin administration on anemia associated with repeated hemodialysis in nephrectomized dogs. J Vet Med Sci 57(5): 989–90. DOI: 10.1292/jvms.57.989

Peeters, H.R.M., Jongen-Lavrencic, M., Bakker, C.H., Vreugdenhil, G., Breedveld, F.C. And Swaak, A. J. G. (1999) Recombinant human erythropoietin improves health-related quality of lifein patients with rheumatoid arthritis and anaemia of chronic disease; utility measures correlate strongly with disease activity measures. Rheumatol Int. 18(5-6): 201–20.

Qiu, H., Belanger, A., Yoon, H.P. And Bunn, H.F. (1998) Homodimerization restores biological activity to an inactive erythropoietin mutant. Journal of Biological Chemistry. 273(18): 11173-11176. doi: 10.1074/jbc.273.18.11173

Ramakrishnan, R., Cheung, W.K., Farrell, F., Joffee, L., And Jusko, W.J. (2003) Pharmacokinetic and Pharmacodynamic Modeling of Recombinant Human Erythropoietin after Intravenous and Subcutaneous Dose Administration in Cynomolgus Monkeys. THE Journal Of Pharmacology And Experimental Therapeutics. 306 (1): 324-331.DOI: 10.1124/jpet.102.047191.

Randolph ,J.F., Stokol, T., Scarlett, J.M. And MacLeod ,J.N. (1999) Comparison of biological activity and safety of recombinant canine erythropoietin with that of recombinant human erythropoietin in clinically normal dogs. Am J Vet Res. 60(5):636–642. PMID:10328437

Randolph, J.F., Scarlett, J., Stokol, T. And MacLeod., J.N. (2004) Clinical Efficacy and Safety of Recombinant Canine Erythropoietin in Dogs with Anemia of Chronic Renal Failure and Dogs with Recombinant Human Erythropoietin‐Induced Red Cell Aplasia. J Vet Intern Med. 18(1):81–91.

Rodrigue, M.E., Brochu, I., orléans-Juste, P.D., Larivièrea, R., And Lebel, M. (2008) Effect of Erythropoietin on Blood Pressure and on the Vascular Endothelial ET-1/ETB Receptor System. Am J Hypertens. 21(6):639-643. doi:10.1038/ajh.2008.37

Sadamoto, Y., Igase, K., Sakanaka, M., Sato, K., Otsuka, H., Sakaki, S., Masuda, S. And Sasaki, R. (1998) Erythropoietin prevents place navigation disability and cortical infarction in rats with permanent occlusion of the middle cerebral artery. Biochem Biophys Res Commun 253(1):26–32. DOI: 10.1006/bbrc.1998.9748

Sanderson, S. (2005) Use of Erythropoietin and Calcitriol for Chronic Renal Failure in Dogs and Cats. 30th World Congress of The World Small Animal Veterinary association. May 11-14, 2005. Mexico City, Mexico

Sandhi, A. (2015) The Effect Of Erythropoietin Administration In Experimental Burns Wound Healing: An Animal Study. Thesis. Faculty Of Medicine University Of Indonesia Plastic Reconstructive And Aesthetic Surgery Study Program.

Shi., X., Yang., J., Zhu, H.,Ye, L., Feng, M., Li, J., Huang, H., Tao, Q., Ye, D., Sun, L.H.K., Sun, B.N.C., Sun, C.R.Y., Han, G., Liu, Y., Yao, M., Zhou, P. And Ju, D. (2013) Pharmacokinetics and Pharmacodynamics of Recombinant Human EPO-Fc Fusion Protein In Vivo. PloS ONE 8(8): e72673. doi:10.1371/journal.pone.0072673

Skibeli, V., Nissen-Lie, G. And Torjesen, P. (2001) Sugar Profiling Proves that Human Serum Erythropoietin Differs From Recombinant Human Erythropoietin. Blood. 98 (13): 3626-3632. DOI: 10.1182/blood.V98.13.3626

Storring, P.L., Tiplady, R.J., Gaines Das, R.E., Stenning, B.E., Lamikanra, A., Rafferty, B. And Lee, J. (1998) Epoetin alfa and beta differ in their erythropoietin isoform compositions and biological properties. Br J Haematol 100 (1): 79–89. DOI: 10.1046/j.1365-2141.1998.00521.x

Surabattula, R., Sambasiva, K. R. S. And Polavarapu, R. 2011. An optimized process for expression, scale-up and purification of recombinant erythropoietin produced in Chinese hamster ovary cell culture. Research in Biotechnology. 2(3): 58-74

Tamadon, M.R. And Beladi-Mousavi, S.S. (2013) Erythropoietin; a review on current knowledge and new concepts. J Renal Inj Prev. 2(4): 119-121. DOI: 10.12861/jrip.2013.38

Toledo, J.R., Sanchez, O., Segui, R.M., Garcia, G., Montanez, M., Zamora, P.A., Rodriguez, M.P. And Cremata, J.A. (2006) High expression level of recombinant human erythropoietin in the milk of non-transgenic goats. J. Biotechnol. 123(2): 225–235. DOI: 10.1016/j.jbiotec.2005.10.019

Wen, D., Boissel, J.P., Tracy, T.E., Gruninger, R.H., Mulcahy, L.S., Czelusniak, J., Goodman, M., And Bunn, H.F. (1993) Erythropoietin Structure-Function Relationships: High Degree Of Sequence Homology Among Mammals. Blood. 82 (5):1507-1516. PMID: 8364201

Yin, H. And Blanchard, K.L. (2000) DNA methylation represses the expression of the human erythropoietin gene by two different mechanisms. Blood. 95(4): 111-119. PMID: 10607693


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