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. 1991 Jan;67(783):9–15. doi: 10.1136/pgmj.67.783.9

The use of erythropoietin in renal failure.

I C Macdougall 1, R D Hutton 1, G A Coles 1, J D Williams 1
PMCID: PMC2398938  PMID: 2057440

Abstract

The treatment of renal anaemia by recombinant human erythropoietin (EPO) is now well established. Several studies have examined the pharmacokinetics and efficacy of the drug given intravenously, intraperitoneally and subcutaneously and there is increasing evidence that the subcutaneous route has several advantages including the requirement for a lower dose. It is also important to stress the need for careful determination of baseline iron status of all patients before commencing EPO therapy. In the long term the extremely high iron stores of transfusion dependent patients will disappear. In the short term, however, the majority of the patients whose serum ferritin is less than 100 micrograms/l will require iron supplementation to allow an appropriate haemoglobin response. Alternatively, a fall in transferrin saturation to less than 20% is certainly an indication for iron supplementation and if oral iron therapy is not adequate then intravenous preparations may have to be considered. Although the anaemia of renal failure can be fully corrected by EPO, partial correction may be sufficient to reverse the problems of reduced exercise capacity, myocardial ischaemia and cardiomegaly which are frequently associated with end-stage renal disease. Partial correction will also result in a lesser rise in whole blood viscosity and, in turn, possibly reduce hypertension, thrombosis and increased peripheral resistance and thus lessen the side effects of EPO therapy.

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Selected References

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  1. Barnea N., Drory Y., Iaina A., Lapidot C., Reisin E., Eliahou H., Kellermann J. J. Exercise tolerance in patients on chronic hemodialysis. Isr J Med Sci. 1980 Jan;16(1):17–21. [PubMed] [Google Scholar]
  2. Boelaert J. R., Schurgers M. L., Matthys E. G., Belpaire F. M., Daneels R. F., De Cre M. J., Bogaert M. G. Comparative pharmacokinetics of recombinant erythropoietin administered by the intravenous, subcutaneous, and intraperitoneal routes in continuous ambulatory peritoneal dialysis (CAPD) patients. Perit Dial Int. 1989;9(2):95–98. [PubMed] [Google Scholar]
  3. Bommer J., Alexiou C., Müller-Bühl U., Eifert J., Ritz E. Recombinant human erythropoietin therapy in haemodialysis patients--dose determination and clinical experience. Nephrol Dial Transplant. 1987;2(4):238–242. [PubMed] [Google Scholar]
  4. Bommer J., Ritz E., Weinreich T., Bommer G., Ziegler T. Subcutaneous erythropoietin. Lancet. 1988 Aug 13;2(8607):406–406. doi: 10.1016/s0140-6736(88)92886-3. [DOI] [PubMed] [Google Scholar]
  5. Böcker A., Reimers E., Nonnast-Daniel B., Kühn K., Koch K. M., Scigalla P., Braumann K. M., Brunkhorst R., Böning D. Effect of erythropoietin treatment on O2 affinity and performance in patients with renal anemia. Contrib Nephrol. 1988;66:165–175. [PubMed] [Google Scholar]
  6. Casati S., Passerini P., Campise M. R., Graziani G., Cesana B., Perisic M., Ponticelli C. Benefits and risks of protracted treatment with human recombinant erythropoietin in patients having haemodialysis. Br Med J (Clin Res Ed) 1987 Oct 24;295(6605):1017–1020. doi: 10.1136/bmj.295.6605.1017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cavill I. Disorders of iron metabolism. Diagnostic methods. Clin Haematol. 1982 Jun;11(2):259–273. [PubMed] [Google Scholar]
  8. Cook J. D., Skikne B. S., Lynch S. R., Reusser M. E. Estimates of iron sufficiency in the US population. Blood. 1986 Sep;68(3):726–731. [PubMed] [Google Scholar]
  9. De Paepe M. B., Schelstraete K. H., Ringoir S. M., Lameire N. H. Influence of continuous ambulatory peritoneal dialysis on the anemia of endstage renal disease. Kidney Int. 1983 May;23(5):744–748. doi: 10.1038/ki.1983.88. [DOI] [PubMed] [Google Scholar]
  10. Degoulet P., Legrain M., Réach I., Aimé F., Devriés C., Rojas P., Jacobs C. Mortality risk factors in patients treated by chronic hemodialysis. Report of the Diaphane collaborative study. Nephron. 1982;31(2):103–110. doi: 10.1159/000182627. [DOI] [PubMed] [Google Scholar]
  11. Duke M., Abelmann W. H. The hemodynamic response to chronic anemia. Circulation. 1969 Apr;39(4):503–515. doi: 10.1161/01.cir.39.4.503. [DOI] [PubMed] [Google Scholar]
  12. Eschbach J. W., Adamson J. W. Recombinant human erythropoietin: implications for nephrology. Am J Kidney Dis. 1988 Mar;11(3):203–209. doi: 10.1016/s0272-6386(88)80150-1. [DOI] [PubMed] [Google Scholar]
  13. Eschbach J. W., Downing M. R., Egrie J. C., Browne J. K., Adamson J. W. USA multicenter clinical trial with recombinant human erythropoietin (Amgen). Results in hemodialysis patients. Contrib Nephrol. 1989;76:160–218. doi: 10.1159/000417892. [DOI] [PubMed] [Google Scholar]
  14. Eschbach J. W., Egrie J. C., Downing M. R., Browne J. K., Adamson J. W. 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 Jan 8;316(2):73–78. doi: 10.1056/NEJM198701083160203. [DOI] [PubMed] [Google Scholar]
  15. Eschbach J. W., Jr, Funk D., Adamson J., Kuhn I., Scribner B. H., Finch C. A. Erythropoiesis in patients with renal failure undergoing chronic dialysis. N Engl J Med. 1967 Mar 23;276(12):653–658. doi: 10.1056/NEJM196703232761202. [DOI] [PubMed] [Google Scholar]
  16. Eschbach J. W., Kelly M. R., Haley N. R., Abels R. I., Adamson J. W. Treatment of the anemia of progressive renal failure with recombinant human erythropoietin. N Engl J Med. 1989 Jul 20;321(3):158–163. doi: 10.1056/NEJM198907203210305. [DOI] [PubMed] [Google Scholar]
  17. Eschbach J. W. The anemia of chronic renal failure: pathophysiology and the effects of recombinant erythropoietin. Kidney Int. 1989 Jan;35(1):134–148. doi: 10.1038/ki.1989.18. [DOI] [PubMed] [Google Scholar]
  18. Frenken L. A., Coppens P. J., Tiggeler R. G., Koene R. A. Intraperitoneal erythropoietin. Lancet. 1988 Dec 24;2(8626-8627):1495–1495. doi: 10.1016/s0140-6736(88)90975-0. [DOI] [PubMed] [Google Scholar]
  19. GRAETTINGER J. S., PARSONS R. L., CAMPBELL J. A. A correlation of clinical and hemodynamic studies in patients with mild and severe anemia with and without congestive failure. Ann Intern Med. 1963 Apr;58:617–626. doi: 10.7326/0003-4819-58-4-617. [DOI] [PubMed] [Google Scholar]
  20. GUYTON A. C., RICHARDSON T. Q. Effect of hematocrit on venous return. Circ Res. 1961 Jan;9:157–164. doi: 10.1161/01.res.9.1.157. [DOI] [PubMed] [Google Scholar]
  21. Goldberg A. P., Hagberg J., Delmez J. A., Carney R. M., McKevitt P. M., Ehsani A. A., Harter H. R. The metabolic and psychological effects of exercise training in hemodialysis patients. Am J Clin Nutr. 1980 Jul;33(7):1620–1628. doi: 10.1093/ajcn/33.7.1620. [DOI] [PubMed] [Google Scholar]
  22. Granolleras C., Branger B., Beau M. C., Deschodt G., Alsabadani B., Shaldon S. Experience with daily self-administered subcutaneous erythropoietin. Contrib Nephrol. 1989;76:143–148. doi: 10.1159/000417890. [DOI] [PubMed] [Google Scholar]
  23. Himelman R. B., Landzberg J. S., Simonson J. S., Amend W., Bouchard A., Merz R., Schiller N. B. Cardiac consequences of renal transplantation: changes in left ventricular morphology and function. J Am Coll Cardiol. 1988 Oct;12(4):915–923. doi: 10.1016/0735-1097(88)90454-8. [DOI] [PubMed] [Google Scholar]
  24. Hüting J., Kramer W., Schütterle G., Wizemann V. Analysis of left-ventricular changes associated with chronic hemodialysis. A noninvasive follow-up study. Nephron. 1988;49(4):284–290. doi: 10.1159/000185077. [DOI] [PubMed] [Google Scholar]
  25. Levin N. Management of blood pressure changes during recombinant human erythropoietin therapy. Semin Nephrol. 1989 Mar;9(1 Suppl 2):16–20. [PubMed] [Google Scholar]
  26. Lim V. S., DeGowin R. L., Zavala D., Kirchner P. T., Abels R., Perry P., Fangman J. Recombinant human erythropoietin treatment in pre-dialysis patients. A double-blind placebo-controlled trial. Ann Intern Med. 1989 Jan 15;110(2):108–114. doi: 10.7326/0003-4819-110-2-108. [DOI] [PubMed] [Google Scholar]
  27. Lindner A., Charra B., Sherrard D. J., Scribner B. H. Accelerated atherosclerosis in prolonged maintenance hemodialysis. N Engl J Med. 1974 Mar 28;290(13):697–701. doi: 10.1056/NEJM197403282901301. [DOI] [PubMed] [Google Scholar]
  28. London G. M., Fabiani F., Marchais S. J., de Vernejoul M. C., Guerin A. P., Safar M. E., Metivier F., Llach F. Uremic cardiomyopathy: an inadequate left ventricular hypertrophy. Kidney Int. 1987 Apr;31(4):973–980. doi: 10.1038/ki.1987.94. [DOI] [PubMed] [Google Scholar]
  29. Lowrie E. G., Lazarus J. M., Hampers C. L., Merrill J. P. Editoral: Cardiovascular disease in dialysis patients. N Engl J Med. 1974 Mar 28;290(13):737–738. doi: 10.1056/NEJM197403282901311. [DOI] [PubMed] [Google Scholar]
  30. MacDougall I. C., Roberts D. E., Coles G. A., Williams J. D. Intraperitoneal erythropoietin. Lancet. 1989 Jun 17;1(8651):1389–1389. doi: 10.1016/s0140-6736(89)92833-x. [DOI] [PubMed] [Google Scholar]
  31. Macdougall I. C., Cavill I., Davies M. E., Hutton R. D., Coles G. A., Williams J. D. Subcutaneous recombinant erythropoietin in the treatment of renal anaemia in CAPD patients. Contrib Nephrol. 1989;76:219–226. doi: 10.1159/000417898. [DOI] [PubMed] [Google Scholar]
  32. Macdougall I. C., Hutton R. D., Cavill I., Coles G. A., Williams J. D. Poor response to treatment of renal anaemia with erythropoietin corrected by iron given intravenously. BMJ. 1989 Jul 15;299(6692):157–158. doi: 10.1136/bmj.299.6692.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Macdougall I. C., Lewis N. P., Saunders M. J., Cochlin D. L., Davies M. E., Hutton R. D., Fox K. A., Coles G. A., Williams J. D. Long-term cardiorespiratory effects of amelioration of renal anaemia by erythropoietin. Lancet. 1990 Mar 3;335(8688):489–493. doi: 10.1016/0140-6736(90)90733-l. [DOI] [PubMed] [Google Scholar]
  34. Macdougall I. C., Roberts D. E., Neubert P., Dharmasena A. D., Coles G. A., Williams J. D. Pharmacokinetics of recombinant human erythropoietin in patients on continuous ambulatory peritoneal dialysis. Lancet. 1989 Feb 25;1(8635):425–427. doi: 10.1016/s0140-6736(89)90014-7. [DOI] [PubMed] [Google Scholar]
  35. Mayer G., Thum J., Cada E. M., Stummvoll H. K., Graf H. Working capacity is increased following recombinant human erythropoietin treatment. Kidney Int. 1988 Oct;34(4):525–528. doi: 10.1038/ki.1988.213. [DOI] [PubMed] [Google Scholar]
  36. Mayer G., Thum J., Graf H. Anaemia and reduced exercise capacity in patients on chronic haemodialysis. Clin Sci (Lond) 1989 Mar;76(3):265–268. doi: 10.1042/cs0760265. [DOI] [PubMed] [Google Scholar]
  37. McGonigle R. J., Husserl F., Wallin J. D., Fisher J. W. Hemodialysis and continuous ambulatory peritoneal dialysis effects on erythropoiesis in renal failure. Kidney Int. 1984 Feb;25(2):430–436. doi: 10.1038/ki.1984.35. [DOI] [PubMed] [Google Scholar]
  38. Meytes D., Bogin E., Ma A., Dukes P. P., Massry S. G. Effect of parathyroid hormone on erythropoiesis. J Clin Invest. 1981 May;67(5):1263–1269. doi: 10.1172/JCI110154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Moia M., Mannucci P. M., Vizzotto L., Casati S., Cattaneo M., Ponticelli C. Improvement in the haemostatic defect of uraemia after treatment with recombinant human erythropoietin. Lancet. 1987 Nov 28;2(8570):1227–1229. doi: 10.1016/s0140-6736(87)91849-6. [DOI] [PubMed] [Google Scholar]
  40. Neff M. S., Kim K. E., Persoff M., Onesti G., Swartz C. Hemodynamics of uremic anemia. Circulation. 1971 Jun;43(6):876–883. doi: 10.1161/01.cir.43.6.876. [DOI] [PubMed] [Google Scholar]
  41. Nonnast-Daniel B., Creutzig A., Kühn K., Bahlmann J., Reimers E., Brunkhorst R., Caspary L., Koch K. M. Effect of treatment with recombinant human erythropoietin on peripheral hemodynamics and oxygenation. Contrib Nephrol. 1988;66:185–194. doi: 10.1159/000416017. [DOI] [PubMed] [Google Scholar]
  42. Painter P., Messer-Rehak D., Hanson P., Zimmerman S. W., Glass N. R. Exercise capacity in hemodialysis, CAPD, and renal transplant patients. Nephron. 1986;42(1):47–51. doi: 10.1159/000183632. [DOI] [PubMed] [Google Scholar]
  43. Raine A. E. Hypertension, blood viscosity, and cardiovascular morbidity in renal failure: implications of erythropoietin therapy. Lancet. 1988 Jan 16;1(8577):97–100. doi: 10.1016/s0140-6736(88)90293-0. [DOI] [PubMed] [Google Scholar]
  44. Rostand S. G., Gretes J. C., Kirk K. A., Rutsky E. A., Andreoli T. E. Ischemic heart disease in patients with uremia undergoing maintenance hemodialysis. Kidney Int. 1979 Nov;16(5):600–611. doi: 10.1038/ki.1979.170. [DOI] [PubMed] [Google Scholar]
  45. Schaefer R. M., Hörl W. H., Massry S. G. Treatment of renal anemia with recombinant human erythropoietin. Am J Nephrol. 1989;9(5):353–362. doi: 10.1159/000167996. [DOI] [PubMed] [Google Scholar]
  46. Schaefer R. M., Leschke M., Strauer B. E., Heidland A. Blood rheology and hypertension in hemodialysis patients treated with erythropoietin. Am J Nephrol. 1988;8(6):449–453. doi: 10.1159/000167652. [DOI] [PubMed] [Google Scholar]
  47. Schwenk M. H., Halstenson C. E. Recombinant human erythropoietin. DICP. 1989 Jul-Aug;23(7-8):528–536. doi: 10.1177/1060028089023007-801. [DOI] [PubMed] [Google Scholar]
  48. Silberberg J. S., Barre P. E., Prichard S. S., Sniderman A. D. Impact of left ventricular hypertrophy on survival in end-stage renal disease. Kidney Int. 1989 Aug;36(2):286–290. doi: 10.1038/ki.1989.192. [DOI] [PubMed] [Google Scholar]
  49. Sinai-Trieman L., Salusky I. B., Fine R. N. Use of subcutaneous recombinant human erythropoietin in children undergoing continuous cycling peritoneal dialysis. J Pediatr. 1989 Apr;114(4 Pt 1):550–554. doi: 10.1016/s0022-3476(89)80692-4. [DOI] [PubMed] [Google Scholar]
  50. Spivak J. L. Erythropoietin: a brief review. Nephron. 1989;52(4):289–294. doi: 10.1159/000185665. [DOI] [PubMed] [Google Scholar]
  51. Stevens J. M., Strong C. A., Oliver D. O., Winearls C. G., Cotes P. M. Subcutaneous erythropoietin and peritoneal dialysis. Lancet. 1989 Jun 17;1(8651):1388–1389. doi: 10.1016/s0140-6736(89)92832-8. [DOI] [PubMed] [Google Scholar]
  52. Stone W. J., Graber S. E., Krantz S. B., Dessypris E. N., O'Neil V. L., Olsen N. J., Pincus T. P. Treatment of the anemia of predialysis patients with recombinant human erythropoietin: a randomized, placebo-controlled trial. Am J Med Sci. 1988 Sep;296(3):171–179. doi: 10.1097/00000441-198809000-00005. [DOI] [PubMed] [Google Scholar]
  53. Strickland I. D., Chaput de Saintonge D. M., Boulton F. E., Brain A. J., Goodwin F. J., Marsh F. P., Zychova Z. A trial of oral iron in dialysis patients. Clin Nephrol. 1974 Jan-Feb;2(1):13–17. [PubMed] [Google Scholar]
  54. Strickland I. D., Chaput de Saintonge D. M., Boulton F. E., Francis B., Roubikova J., Waters J. I. The therapeutic equivalence of oral and intravenous iron in renal dialysis patients. Clin Nephrol. 1977 Feb;7(2):55–57. [PubMed] [Google Scholar]
  55. Van Wyck D. B., Stivelman J. C., Ruiz J., Kirlin L. F., Katz M. A., Ogden D. A. Iron status in patients receiving erythropoietin for dialysis-associated anemia. Kidney Int. 1989 Feb;35(2):712–716. doi: 10.1038/ki.1989.43. [DOI] [PubMed] [Google Scholar]
  56. Verbeelen D., Bossuyt A., Smitz J., Herman A., Dratwa M., Jonckheer M. H. Hemodynamics of patients with renal failure treated with recombinant human erythropoietin. Clin Nephrol. 1989 Jan;31(1):6–11. [PubMed] [Google Scholar]
  57. Watson A. J. Adverse effects of therapy for the correction of anemia in hemodialysis patients. Semin Nephrol. 1989 Mar;9(1 Suppl 1):30–34. [PubMed] [Google Scholar]
  58. Winearls C. G. Erythropoietin. Nephrol Dial Transplant. 1989;4(5):323–326. doi: 10.1093/oxfordjournals.ndt.a091884. [DOI] [PubMed] [Google Scholar]
  59. Winearls C. G., Oliver D. O., Pippard M. J., Reid C., Downing M. R., Cotes P. M. Effect of human erythropoietin derived from recombinant DNA on the anaemia of patients maintained by chronic haemodialysis. Lancet. 1986 Nov 22;2(8517):1175–1178. doi: 10.1016/s0140-6736(86)92192-6. [DOI] [PubMed] [Google Scholar]
  60. Zehnder C. Erythropoietin treatment: influence of haemoglobin concentration on dialyser creatinine clearance in haemodialysed patients. Nephron. 1989;51(3):424–425. doi: 10.1159/000185339. [DOI] [PubMed] [Google Scholar]
  61. van Geet C., Hauglustaine D., Verresen L., Vanrusselt M., Vermylen J. Haemostatic effects of recombinant human erythropoietin in chronic haemodialysis patients. Thromb Haemost. 1989 Feb 28;61(1):117–121. [PubMed] [Google Scholar]

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