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Hematological Problems of Renal Failure

  • Joseph W. Eschbach

Abstract

Renal failure, whether acute or chronic, adversely affects a number of hematological parameters. Red cell production and destruction, granulocyte and lymphocyte function, platelet function and coagulation are affected to various degrees. These changes result in anemia, and an increased susceptibility to infection and hemorrhage. This chapter will deal primarily with the pathogenesis of the anemia of chronic renal failure, erythropoietin (Epo) metabolism, the treatment of this anemia with recombinant human Epo (epoetin), and the benefits of this therapy. Infection, immunological dysfunction and bleeding disorders are reviewed in Chapters 7B, 8 and 9.

Keywords

Chronic Renal Failure Dialysis Patient Serum Ferritin Hemodialysis Patient Recombinant Human Erythropoietin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Naets JP, Brauman H, Kraytman M: Etude de l’erythropoiese au cours de l’insuffisance renale aigue et chronique. Acta Haematol 24: 169, 1960Google Scholar
  2. 2.
    Emerson CP: The pathogenesis of anemia in acute glomerulonephritis. Estimations of blood production and blood destruction in a case receiving massive transfusions. Blood 3: 363, 1984Google Scholar
  3. 3.
    Eisenberg S: Blood volume in patients with acute glomerulonephritis as determined by radioactive chronium tagged red cells. Am J Med 27: 241, 1959PubMedGoogle Scholar
  4. 4.
    Eschbach JW, Adamson JW: Anemia of end-stage renal disease (ESRD). Editorial review. Kidney Int 28: 1, 1985PubMedGoogle Scholar
  5. 5.
    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 II: 1175, 1986Google Scholar
  6. 6.
    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 trail. N Engl J Med 316: 73, 1987PubMedCrossRefGoogle Scholar
  7. 7.
    Eschbach JW, Kelly JR, Haley NR, Abels RI, Adamson JW: Treatment of the anemia of progressive renal failure with recombinant human erythropoietin. N Engl J Med 321: 158, 1989PubMedCrossRefGoogle Scholar
  8. 8.
    Chaplin H, Mollison PL: Red cell life-span in nephritis and in hepatic cirrhosis. Clinical Science 12: 351, 1953PubMedGoogle Scholar
  9. 9.
    Stewart JW: Haemolytic anaemia in acute and chronic renal failure. Q J Med 36: 85, 1967Google Scholar
  10. 10.
    Eschbach JW: The anemia of chronic renal failure: pathophysiology and the effects of recombinant erythropoietin. Kidney Int 35: 134, 1989PubMedGoogle Scholar
  11. 11.
    Adamson JW, Egrie JC, Haley NR, Schneider GL, Sherrard DJ, Eschbach JW: Why do some hemodialysis patients need large doses of recombinant erythropoietin? Kidney Int 37: 235(A), 1990Google Scholar
  12. 12.
    Fisher JW: Mechanism of the anemia of chronic renal failure. Editorial review. Nephron 25: 106, 1980PubMedCrossRefGoogle Scholar
  13. 13.
    McDermott FT, Galbraigh AJ, Corlett RJ: Inhibition of cell proliferation in renal failure and its significance to the uraemic syndrome: a review. Scot Med J 20: 317, 1975PubMedGoogle Scholar
  14. 14.
    Wallner SF, Vautrin RM: Evidence that inhibition of erythropoiesis is important in the anemia of chronic renal failure. J Lab Clin Med 97: 170, 1981PubMedGoogle Scholar
  15. 15.
    Delwiche F, Segal GM, Eschbach JW, Adamson JW: Hematopoietic inhibitors in chronic renal failure: lack of in vitro specificity. Kidney Int 29: 641, 1986PubMedGoogle Scholar
  16. 16.
    Segal GM, Eschbach JW, Egrie JC, Stueve T, Adamson JW: The anemia of end-stage renal disease: Hematopoietic progenitor cell response. Kidney Int 33: 983, 1988PubMedGoogle Scholar
  17. 17.
    Mladenovic J, Eschbach JW, Garcia JF, Adamson JW: The anaemia of chronic renal failure in sheep: Studies in vitro. Br J Hematol 58: 491, 1984Google Scholar
  18. 18.
    Eschbach JW, Mladenovic J, Garcia JF, Wahl PW, Adamson JW: The anemia of chronic renal failure in sheep: the response to erythropoietin-rich plasma in vivo. J Clin Invest 74: 434, 1984PubMedGoogle Scholar
  19. 19.
    Eschbach JW, Haley NR, Egrie JC, Adamson JW: A comparison of the responses to recombinant human erythropoietin in normal and uremic subjects. Kidney Int 43: 407, 1992Google Scholar
  20. 20.
    Geerling W, Morris RW, Brunner FP, Brynger H, Enrich JHH, Fassbinder W, Rizzoni G, Seiwood NH, Tufveson G, Wing AJ: Factors influencing anaemia in dialysis patients. A special survey by the EDTA-ERA registry. Nephrol Dial Transplant 8: 585, 1993Google Scholar
  21. 21.
    Egrie JC, Strickland TW, Lane J, Aoki K, Cohen AM, Smalling R, Trail G, Lin FK, Browne JK, Hines DK. Characterization and biological effects of recombinant human erythropoietin. Immunobiology 172: 213, 1986PubMedGoogle Scholar
  22. 22.
    Carnot P, Deflandre C: Sur l’activité hématopoietique de serum au cours de la regénération du sang. C R Acad Sci (Paris) 143: 384, 1906Google Scholar
  23. 23.
    Erslev AJ: Humoral regulation of red cell production. Blood 8: 349, 1953PubMedGoogle Scholar
  24. 24.
    Jacobson LO, Goldwasser E, Fried W, Plazk L: Role of the kidney in erythropoiesis. Nature 179: 633, 1957PubMedGoogle Scholar
  25. 25.
    Adamson JW: The erythropoietin/hematocrit relationship in normal and polycythemic man: Implications of marrow regulation. Blood 32: 597, 1968PubMedGoogle Scholar
  26. 26.
    Erslev AJ: In vitro production of erythropoietin by kidneys perfused with a serum-free solution. Blood 44: 77, 1974PubMedGoogle Scholar
  27. 27.
    Miyake T, Kung CKH, Goldwasser E: Purification of human erythropoietin. J Biol Chem 252: 5558, 1977PubMedGoogle Scholar
  28. 28.
    Lin F-K, Suggs S, Lin C-H, Browne JK, Smalling R, Egrie JC, Chen KK, Fox GM, Martin F, Stabinsky Z, Badrawi SM, Lai P-H, Goldwasser E: Cloning and expression of the human erythropoietin gene. Proc Natl Acad Sci USA 82: 7580, 1985PubMedGoogle Scholar
  29. 29.
    Jacobs K, Shoemaker C, Rudersdorf R, Neill SD, Kaufman RJ, Mufson A, Seehra J, Jones SS, Hewick R, Fritsch EF, Kawakita M, Shimizu T, Miyake T: Isolation and characterization of genomic and cDNA clones of human erythropoietin. Nature Lond 313: 806, 1985PubMedGoogle Scholar
  30. 30.
    Powell JS, Gerkner KL, Lebo RV, Adamson JW: Human erythropoietin gene: high level expresssion in stably transfected mammalian cells and chromosome localization. Proc Natl Acad Sci USA 83: 6465, 1986PubMedGoogle Scholar
  31. 31.
    Koury ST, Bondurant MC, Koury MJ: Localization of erythropoietin synthesizing cells in murine kidneys by in situ hybridization. Blood 71: 524, 1988PubMedGoogle Scholar
  32. 32.
    Lacombe C, DaSilva J-L, Bruneval P, Fournier J-G, Wendling F, Casadevall N, Camilleri J-P, Bariety J, Varet B, Tambourin P: Peritubular cells are the site of erythropoietin synthesis in the murine hypoxic kidney. J Clin Invest 81: 620, 1988PubMedGoogle Scholar
  33. 33.
    Bachmann S, LeHir M, Eckardt K-U: Co-localization of erythropoietin mRNA and ecto-5’-nucleotidase immunoreactivity in peritubular cells of rat renal cortex indicates that fibroblasts produce erythropoietin. J Histochem Cytochem 41: 335, 1993PubMedGoogle Scholar
  34. 34.
    Maxwell PH. Osmond MK, Pugh CW, Heryet A, Nicholls LG, Tan CC, Doe BG, Ferguson DJP, Johnson MH, Ratcliffe PJ: Identification of the renal erythropoietin-producing cells using transgenic mice. Kidney Int 44: 1149, 1993PubMedGoogle Scholar
  35. 35.
    Wang F, Fried W: Renal and extrarenal erythropoietin production in male and female rats of various ages. J Lab Clin Med 79: 181, 1972PubMedGoogle Scholar
  36. 36.
    Tan CC, Eckardt K-U, Firth JD, Ratcliffe PJ: Feedback modulation of renal and hepatic erythropoietin mRNA in response to graded anemia and hypoxia. Am J Physiol 263: F474, 1992PubMedGoogle Scholar
  37. 37.
    Koury ST, Bondurant MC, Koury MJ, Semenza GL: Localization of cells producing erythropoietin in murine liver by in situ hybridization. Blood 77: 2497, 1991PubMedGoogle Scholar
  38. 38.
    Meyrier A, Simon P, Boffa G, Brissot P: Uremia and the liver: the liver and erythropoiesis in chronic renal failure. Nephron 29: 3, 1981PubMedGoogle Scholar
  39. 39.
    Kolk-Vegter AJ, Bosch E, VanLeeuwen AM: Influence of serum hepatitis on haemoglobin level in patients on regular haemodialysis. Lancet I: 526, 1971Google Scholar
  40. 40.
    Brown S, Caro J, Erslev AJ, Murray TG: Spontaneous increase in erythropoietin and hematocrit value associated with transient liver enzyme abnormalities in an anephric patient undergoing hemodialysis. Am J Med 68: 280, 1980PubMedGoogle Scholar
  41. 41.
    Ratcliffe PJ: Molecular biology of erythropoietin. Kidney Int 44: 887, 1993PubMedGoogle Scholar
  42. 42.
    Schurek HJ, Jost U, Baumgartl H, Bertram H, Heckmann U: Evidence for a preglomerular oxygen diffusion shunt in rat renal cortex. Am J Physiol 259: F910, 1990PubMedGoogle Scholar
  43. 43.
    Echardt K-U, Kurtz A, Bauer C: Regulation of erythropoietin production is related to proximal tubular functin. Am J Physiol 256: F942, 1989Google Scholar
  44. 44.
    Tan CC, Ratcliffe PJ: Oxygen sensing and erythropoietin mRNA production in isolated perfused rat kidneys. in Pathophysiology and Pharmacology of Erythropoietin, edited by Pagel H, Weiss C, Jelkmann W, Berlin, Springer-Verlag, 1992, p 57Google Scholar
  45. 45.
    Goldberg MA, Dunning SP, Bunn HF: Regulation of the erythropoieitn gene: evidence that the oxygen sensor is a heme protein. Science 242: 1412, 1988PubMedGoogle Scholar
  46. 46.
    Goldberg MA, Imagawa S, Dunning PS, Bunn HF: Oxygen sensing and erythropoietin gene regulation. in Erythropoietin: From Molecular Structure to Clinical Application, edited by Baldamus CA, Scigalla P, Wieczorek L, Koch KM, Contrib Nephrol 76: 39, 1989Google Scholar
  47. 47.
    Caro J, Schuster S, Raminez S: Regulating mechanisms involved in the expression of the erythropoietin gene. in Erythropoietin: From Molecular Structure to Clinical Application, edited by Baldamus CA, Scigalla P, Wieczorek L, Koch KM, Contrib Nephrol 76: 7, 1989Google Scholar
  48. 48.
    Koury MJ, Koury ST, Bondurant MC, Graber SE: Correlation of the molecular and anatomical aspects of renal erythropoietin production. in Erythropoietin: From Molecular Structure to Clinical Application, edited by Baldamus CA, Scigalla P, Wieczorek L. Koch KM, Contrib Nephrol 76: 24, 1989Google Scholar
  49. 49.
    Erslev AJ, Caro J, Kansu E, Miller O, Cobbs E: Plasma erythropoietin in polycythemia. Am J Med 66: 243, 1979PubMedGoogle Scholar
  50. 50.
    Naets JP, Garcia JF, Tousaaint Ch, Buset M, Waks D: Radioimmunoassay of erythropoietin in chronic uraemia or anephric patients. Scand J Haematol 37: 390, 1986PubMedCrossRefGoogle Scholar
  51. 51.
    Wide L, Bengtsson C, Birgegard G: Circadian rhythm of erythropoietin in human serum. Br J Haematology 72: 85, 1989Google Scholar
  52. 52.
    Coles GA, Liberek T, Davies ME, Robinson M, Jones J, Thomas G, Davies M, Macdougall IC, Williams JD: Estimation of erythropoietin secretion rate in normal and uremic subjects. Am J Physiol 263: F939, 1992PubMedGoogle Scholar
  53. 53.
    Jensen JD, Madsen JK, Jensen LW, Pedersen EB: Reduced production, absorption, and elimination of erythropoietin in uremia compared with healthy volunteers. J Am Soc Nephrol 5: 177, 1994PubMedGoogle Scholar
  54. 54.
    Wasley LC, Timony G, Murtha P, Stoudemire J, Dorner AJ, Caro J, Krieger M, Kaufman RJ: The importance of N and O-linked oligosaccharides for the biosynthesis and in vitro and in vivo biologic activities of erythropoietin. Blood 77: 2624, 1991PubMedGoogle Scholar
  55. 55.
    Salmonson T, Danielson BG, Wikstrom B: The pharmacokinetics of recombinant human erythropoietin after intravenous and subcutaneous administration to healthy subjects. Br J Clin Pharmac 29: 709, 1990Google Scholar
  56. 56.
    Brockmoller J, Kochling J, Weber W, Looby M, Roots I, Neumayer H-H: The pharmacokinetics and pharmacodynamics of recombinant human erythropoietin in haemodialysis patients. Br J Clin Pharmac 34: 499, 1992Google Scholar
  57. 57.
    McMahon FG, Vargas R, Ryan M, Jain AK, Abels RI, Perry B, Smith IL: Pharmacokinetics and effects of recombinant human erythropoietin after intravenous and subcutaneous injections in healthy volunteers. Blood 76: 1718, 1990PubMedGoogle Scholar
  58. 58.
    Piroso E, Erslev AJ, Flaharty KK, Caro J: Erythropoietin life span in rats with hypoplastic and hyperpllastic bone marrows. Am J Hematology 36: 105, 1991Google Scholar
  59. 59.
    Dessypris EN, Graber SE, Krantz SB, Stone WJ: Effects of recombinant erythropoietin on the concentration and cycling status of human marrow hematopoietic progenitor cells in vivo. Blood 72: 2060, 1988PubMedGoogle Scholar
  60. 60.
    Sawada K, Krantz SB, Sawada ST, Civin CI: Quantitation of specific binding of erythropoietin to human erythroid colony-forming cells. J Cell Physiol 137: 337, 1988PubMedGoogle Scholar
  61. 61.
    D’Andrea AD, Zon LI: Erythropoietin receptor. Subunit structure and activation. J Clin Invest 86: 681, 1990PubMedGoogle Scholar
  62. 62.
    Mayeux P, Lacombe C, Casadevall N, Chretien S, Dusanter I, Gisselbrecht S: Structure of the murine erythropoietin receptor complex. Characterization of the erythropoietin cross-linked proteins. J Biol Chem 266: 23380 1991PubMedGoogle Scholar
  63. 63.
    Koury MJ, Bondurant MC: Erythropoietin retards DNA breakdown and prevents programmed death in erythroid progenitor cells. Science 248: 378, 1990PubMedGoogle Scholar
  64. 64.
    Finch CA, Deubelbeiss K, Cook JD, Eschbach JW, Harker LA, Funk DD, Marsaglia G, Hillman RS, Slichter S, Adamson JW, Ganzoni A, Gilbert ER. Ferrokinetics in man. Medicine 49: 17, 1970PubMedGoogle Scholar
  65. 65.
    Eschbach JW, Abdulhadi MH, Browne JK, Delano BG, Downing MR, Egie JC, Evans RW, Friedman EA, Graber SE, Haley NR, Korbet S, Krantz SB, Lundin AP, Nissenson AR, Odgen DA, Paganini EP, Rader B, Rutsky EA, Stivelman J, Stone WJ, Teschan P, Van Stone JC, Van Wyck DB, Zuckerman K, Adamson JW: Recombinant human erythropoietin in anemic patients with endstage renal disease. Ann Intern Med 111: 992, 1989PubMedGoogle Scholar
  66. 66.
    Bommer J, Kugel M, Schoeppe W, Brunkhorst R, Samtleben W, Bramsiepe P, Scigalla P: Dose-related effects of recombinant human erythropoietin on erythropoiesis. Results of a multicenter trial in patients with end-stage renal disease. Contrib Nephrol 66: 85, 1988PubMedGoogle Scholar
  67. 67.
    Urabe A, Takaku F, Mizoguchi H, Kubo K, Ota K, Shimizu N, Tanaka K, Mimura N, Nihei H, Koshikawa S, Akizawa T, Akiyama N, Otsubo O, Kawaguchi Y, Maeda T: Effect of recombinant human erythropoietin on the anemia of chronic renal failure. Intern J Cell Cloning 6: 179, 1988Google Scholar
  68. 68.
    Canadian Erythropoietin Study Group: Association between recombinant human erythropoietin and quality of life and exercise capacity of patients receiving haemodialysis. Br Med J 300: 573, 1990Google Scholar
  69. 69.
    Sundal E, Kaeser U: Correction of anaemia of chronic renal failure with recombinant human erythropoietin: safety and efficacy of one year’s treatment in a European multicentre study of 150 haemodialysis-dependent patients. Nephrol Dial Transplant 4: 979, 1989PubMedGoogle Scholar
  70. 70.
    Bennett WM: A multicenter clinical trial of epoetin beta for anemia of end-stage renal disease. J Am Soc Nephrol 1: 990, 1991PubMedGoogle Scholar
  71. 71.
    Ateshkadi A, Johnson CA, Oxton LL, Hammond TG, Bohenek WS, Zimmerman SW: Pharmacokinetics of intraperitoneal, intravenous, and subcutaneous recombinant human erythropoietin in patients on continuous ambulatory peritoneal dialysis. Am J Kidney Dis 21: 635, 1993PubMedGoogle Scholar
  72. 72.
    Besarab A, Flaharty K2K, Erslev AJ, McCrea JB, Vlasses PH, Medina F, Caro J, Morris E: Clinical pharmacology and economics of recombinant human erythropoietin in end-stage renal disease: the case for subcutaneous administration. J Am Soc Nephrol 2: 1405, 1992PubMedGoogle Scholar
  73. 73.
    Boelaert JR, Schurgers ML, Mattysy EG, Belpaire FM, Daneel RF, De Cre MJ, Bogaert MG: Comparative pharmacokinetics of recombinant erythropoietin administered by the intravenous, subcutaneous, and intraperitoneal routes in countinuous ambulatory peritoneal dialysis (CAPD) patients. Perit Dial Int 9: 95, 1989PubMedGoogle Scholar
  74. 74.
    Kampf D, Kahl A, Passlick J, Pustelnik A, Echardt K-V, Ehmer B, Jacobs C, Baumelous A, Gransbensee B, Gahl HM: Single-dose kinetics of recombinant human erythropoietin after intravenous, subcutaneous and intraperitoneal adminsitration. Contrib Nephrol 76: 106, 1989PubMedGoogle Scholar
  75. 75.
    Granolleras C, Branger B, Beau MC, Deschodt G, Alsabadani B, Shaldon S: Experience with daily self-administered subcutaneous erythropoietin. Contrib Nephrol 76: 143, 1989PubMedGoogle Scholar
  76. 76.
    Eschbach JW, Haley NR, McCabe D, Egrie JC: Epoetin dosing: what route and frequency is best? J Am Soc Nephrol 2: 376(A), 1991Google Scholar
  77. 77.
    Eschbach JW, Haley NR, Adamson JW: The use of recombinant erythropoietin in the treatment of the anemia of chronic renal failure. in Molecular and Cellular Controls of Hematopoiesis, edited by Orlic D, New York Acad Sci, 554, 1989, p 225Google Scholar
  78. 78.
    Eschbach JW, Cook JD, Scribner BH, Finch CA: Iron balance in hemodialysis patients. Ann Intern Med 87: 710, 1977PubMedGoogle Scholar
  79. 79.
    Bainton DF, Finch CA: The diagnosis of iron deficiency anemia. Am J Med 37: 62, 1964PubMedGoogle Scholar
  80. 80.
    Adamson JW, Eschbach JW: The management of the anaemia of chronic renal failure with recombinant erythropoietin. Quart J Med 73: 1093, 1989PubMedGoogle Scholar
  81. 81.
    Means RT Jr, Olsen NJ, Krantz SB, Dessypris EN, Graber SE, Stone WJ, O’Neil VL, Pincus T: Treatment of the anemia of rheumatoid arthritis with recombinant human erythropoietin: clinical and in vitro studies. Arth & Rheum 32: 638, 1989Google Scholar
  82. 82.
    Gudbjornsson B, Hallgran R, Wide L, Birgegard G: Response of anaemia in rheumatoid arthritis to treatment with subcutaneous recombinant human erythropoietin. Ann Rheum Dis 51: 747, 1992PubMedGoogle Scholar
  83. 83.
    Horina JH, Petritsch W, Schmid CR, Reicht G, Wenzl H, Silly H, Krejs GJ: Treatment of anemia in inflammatory bowel disease with recombinant human erythropoietin: results in three patients. Gastroent 104: 1828, 1993Google Scholar
  84. 84.
    Sudhaker RD, Shih M-S, Mohini R: Effect of serum parathyroid hormone and bone marrow fibrosis on the response to erythropoietin in uremia. N Engl J Med 328: 171, 1993Google Scholar
  85. 85.
    Casati S, Passerini P, Campise MR, 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 295: 1017, 1987CrossRefGoogle Scholar
  86. 86.
    Alfurayh O, Sobh M, Barri Y, Qunibi W, Taher S: Aluminum overload and response to recombinant human erythropoietin in patients under chronic haemodialysis. Nephrol Dial Transplant 7: 939, 1992PubMedGoogle Scholar
  87. 87.
    Cheng IKP, Lu H-B, Wei DCC, Cheng S-W, Chan C-Y, Lee FCP: Influence of thalassemia on the response to recombinant human erythropoietin in dialysis patients. Am J Nephrol 13: 142, 1993PubMedGoogle Scholar
  88. 88.
    Urena P, Echardt K-U, Sarfati E, Zingraff J, Zins B, Roullet JB, Roland E, Drueke T, Kurtz A: Serum erythropoietin and erythropoiesis in primary and secondary hyperparathroidism: effect of parathyroidectomy. Nephron 59: 384, 1991PubMedGoogle Scholar
  89. 89.
    Eschbach JW: (Panel discussion.) Contrib Nephrol 76: 216, 1989Google Scholar
  90. 90.
    Lazarus JM: Update on adverse reactions to erythropoietin therapy. ASA1O J 40: 70, 1994Google Scholar
  91. 91.
    Edmunds ME, Walls J: Pathogenesis of seizures during recombinant human erythropoietin therapy. Sem Dial 4: 163, 1991Google Scholar
  92. 92.
    Amgen Inc: Epogen (epoetin alfa) prescribing information. 29 June 1994Google Scholar
  93. 93.
    Samtleben W, Baldamus CA, Bommer J, Fassbinder W, Nonnast-Daniel B, Gurland HJ: Blood pressure changes during treatment with human erythropoietin. Contrib Nephrol 66: 114, 1988PubMedGoogle Scholar
  94. 94.
    Besarab A, Gaughan W, Medina F: Effect of erythropoietin on blood pressure in anemic hemodialysis patients. Kidney Int 35: 240(A), 1989Google Scholar
  95. 95.
    Schaefer R, Buemer B, Zech M, Denninger G, Borneff C, Heidland A: Treatment of the anemia of hemodialysis patients with recombinant human erythropoietin. Int J Artif Organs 11:249, 1988PubMedGoogle Scholar
  96. 96.
    Dreis H, Zins B, Naret C, Casadevall N, Goureau Y, Peterlongo F, Varet B, Najean Y, Jacquot C, Drueke T: Recombinant erythropoietin: personal experience with a new treatment fo the anemia of chronic renal failure. Transpl Proc 21: 55, 1989Google Scholar
  97. 97.
    Nielsen OJ, Thaysen JH: Response to erythropoietin in anaemic haemodialysis patients. J Int Med 226: 89, 1989Google Scholar
  98. 98.
    Sundal E, Businger J, Kappeler A: Treatment of transfusion-dependent anaemia of chronic renal failure with recombinant human erythropoietin. Nephrol Dial Transplant 6: 955, 1991PubMedGoogle Scholar
  99. 99.
    Suzuki M, Hirasawa Y, Hirashima K, Arakawa M, Odaka M, Ogura Y, Yoshikawa Y, Sanaka T, Shinoda A, Morii H: Dose-finding, double-blind, clinical trial of recombinant human erythropoietin (Chugai) in Japanese patients with end-stage renal disease. Contrib Nephrol 76: 179, 1989PubMedGoogle Scholar
  100. 100.
    Duff MD, Golper TA, Sloan RS, Brier ME, Aronoff GR: Low-dose recombinant human erythropoietin therapy in chronic hemodialysis patients. Am J Kidney Dis 18: 60, 1991PubMedGoogle Scholar
  101. 101.
    Abraham PA, Macres MG: Blood pressure in hemodialysis patients during amelioration of anemia with erythropoietin. J Am Soc Nephrol 2: 927, 1991PubMedGoogle Scholar
  102. 102.
    Radermacher J, Koch KM: Erythropoietin and hypertension. in Erythropoietin: Molecular Physiology and Clinical Applications, edited by Bauer C, Koch KM, Scigalla P, Wieczorek L, New York, Marcel Dekker, 1993, p 129Google Scholar
  103. 103.
    Baskin S, Lasker N: Erythropoietin-associated hypertension. N Engl J Med 323: 999, 1990PubMedCrossRefGoogle Scholar
  104. 104.
    Heidenrich S, Rahn K, Zidek W: Direct vasopressor effect of recombinant human erythropoietin on renal resistance vessel. Kidney Int 39: 259, 1991Google Scholar
  105. 105.
    Anagnostou A, Lee ES, Kessimian N, Levinson R, Steiner M. Erythropoietin has a mitogenic and positive chemotactic effect on endothelial cells. Proc Natl Acad Sci 87: 5978, 1990PubMedGoogle Scholar
  106. 106.
    Carlini RG, Dusso AS, Obialo CI, Alvarez UM, Rothstein M: Recombinant human erythropoietin (rHuEPO) increases endothelin-1 release by endothelial cells. Kidney Int 43: 1010, 1993PubMedGoogle Scholar
  107. 107.
    Bund SJ, Heagerty A, Edmunds M, Walls J: Erythropoietin does not induce vasoconstriction directly in human subcutaneous resistance arterioles. Nephron 54: 173, 1989Google Scholar
  108. 108.
    Pagel H, Jelkmann W, Weiss Ch: Erythropoietin and blood pressure. Horm Metabol Res 21: 224, 1989Google Scholar
  109. 109.
    Carlini R, Obialo CI, Rothstein M: Intravenous erythropoietin (rHuEPO) administration increases plasma endothelin and blood pressure in hemodialysis patients. Am J Hypertension 6: 103, 1993Google Scholar
  110. 110.
    Churchill DN, Taylor DW, Cook RJ, LaPlante P, Barre P, Cartier P, Fay WP, Goldstein MB, Jindal K, Mandin H, Mckenzie JK, Muirhead N, Parfrey PS, Posen GA, Slaughter D, Ulan RA, Werb R: Canadian hemodialysis morbidity study. Am J Kidney Dis 19: 214, 1992PubMedGoogle Scholar
  111. 111.
    Muirhead N, Laupacis A, Wong C: Erythropoietin for anaemia in haemodialysis patients: results of a maintenance study (The Canadian Erythropoietin Study Group). Nephrol Dial Transplant 7: 811, 1992PubMedGoogle Scholar
  112. 112.
    Muirhead N: Erythropoietin is a cause of access thrombosis. Sem Dial 6: 184, 1993Google Scholar
  113. 113.
    Eschbach JW: Erythropoietin is not a cause of access thrombosis. Sem Dial 6: 180, 1993Google Scholar
  114. 114.
    Besarab A, Medina F, Musial E, Picarello N, Michael H: Recombinant human erythropoietin does not increase clotting in vascular accesses. ASAIO Trans 36: M749, 1990PubMedGoogle Scholar
  115. 115.
    Standage BA, Schuman EW, Ackerman D, Gross GF, Ragsdale JW: Does the use of erythropoietin in hemodialysis patients increase dialysis graft thrombosis rates? Am J Surg 165:650, 1993PubMedGoogle Scholar
  116. 116.
    Kopple JD, Swendseid M: Evidence that histidine is an essential amino acid in normal and chronically uremic man. J Clin Invest 55: 881, 1975PubMedGoogle Scholar
  117. 117.
    Reeves RD, Barbour GL, Robertson CS, Crumb CK: Failure of histidine supplementation to improve anemia in chronic dialysis patients. Am J Clin Nutr 30: 579, 1977PubMedGoogle Scholar
  118. 118.
    Neuhauser M, Ulm A, Leber HW, Schutterle G: Influence of essential amino adids and keto acids on protein metabolism and the anaemia of patients on chronic intermittent haemodialysis. Proc Eur Dial Transplant Assoc 14:557, 1978Google Scholar
  119. 119.
    Trovato GM, Ginardi V, Marco VD, Dell’aira AE, Corsi M: Long-term L-carnitine treatment of chronic anaemia of patients with end-stage renal failure. Curr Ther Res 31: 1042, 1982Google Scholar
  120. 120.
    Kooistra MP, Struyvenberg A, Van Es A: The response to recombinant human erythropoietin in patients with the anemia of end-stage renal disease is correlated with serum carnitine levels. Nephron 57: 127, 1991PubMedGoogle Scholar
  121. 121.
    Ballal SH, Domoto DT, Polack DC, Marciulonis P, Martin KJ: Androgens potentiate the effect of erythropoietin in the treatment of anemia of end stage renal disease. Am J Kidney Dis 17: 29, 1991PubMedGoogle Scholar
  122. 122.
    Berns JS, Rudnick MR, Cohen RM: A controlled trial of recombinant human erythropoietin and nandrolone decanoate in the treatment of anemia in patients on chronic hemodialysis. Clin Nephrol 37: 264, 1992PubMedGoogle Scholar
  123. 123.
    Eschbach JW, Adamson JW, Cook JD: Disorders of red blood cell production in uremia. Arch Int Med 126: 812, 1970Google Scholar
  124. 124.
    Santiago GC, Rao TKS, Laird NM: Effect of dialysis therapy on the hematopoietic system: The National Cooperative Dialysis Study. Kidney Int 23(Suppl 13): 95S, 1983Google Scholar
  125. 125.
    Teschan PE, Ginn HE, Bourne JR, Ward JR, Sdhaffer JD: A prospective study of renal dialysis. Trans Am Soc Artif Intern Organs J 3: 108, 1983Google Scholar
  126. 126.
    Goldberg AP, Geltman EM, Hagberg JM, Gavin JR, Detmez JA, Carney RM, Naumowicz A, Oldfield MH, Harter HR: Therapeutic benefits of exercise training for hemodialysis patients. Kidney Int 24(Suppl 16): 303S, 1983Google Scholar
  127. 127.
    Said R, Quintanilla A, Levin N, Ivanovich P: Acute hemolysis due to profound hypo-osmolality. A complication of hemodialysis. J Dial 1: 447, 1977PubMedGoogle Scholar
  128. 128.
    Pun KK, Yeung CK, Chan TK: Acute intravascular hemolysis due to accidental formalin intoxication during hemodialysis. Clin Nephrol 21: 188, 1984PubMedGoogle Scholar
  129. 129.
    Manzler AD, Schreiner AW: Copper-induced acute hemolytic anemia. A new complication of hemodialysis. Am Intern Med 73: 409, 1970Google Scholar
  130. 130.
    Higgins MR, Gace M, Ulan RA: Anemia in hemodialysis patients. Arch Intern Med 137: 172, 1977PubMedGoogle Scholar
  131. 131.
    Weinberg SG, Lubin A, Wiener SN, Deoras MP, Ghose MK, Kopelman RC: Myelofibrosis and renal osteodystrophy. Am J Med 63: 755, 1977PubMedGoogle Scholar
  132. 132.
    Schwartz AB, Kahn SB, Kelch B, Kim KE, Pequignot E: RBC improved survival due to recombinant human erythropoietin explains effectiveness of less frequent, low dose subcutaneous therapy. Clin Nephrol 38: 283, 1992PubMedGoogle Scholar
  133. 133.
    Hughes RT, Cotes PM, Pippard MJ, Stevens JM, Oliver DO, Winearls CG, Royston JP: Subcutaneous adminstration of recombinant human erythropoietin to subjects on continuous ambulatory peritoneal dialysis: an erythrokinetic assessment. Br J Haematol 75: 268, 1990PubMedGoogle Scholar
  134. 134.
    Eschbach JW, Glenny R, Robertson T, Guthrie M, Rader B, Evans R, Chandler W, Davidson R, Easterling T, Denney J, Schneider G: Normalizing the hematocrit in hemodialysis patients with Epo improves quality of life and is safe, J Am Soc Nephrol 4: 425(A), 1993Google Scholar
  135. 135.
    Schilling RF: Anemia of chronic disease: a misnomer. Ann Intern Med 115: 572, 1991PubMedGoogle Scholar
  136. 136.
    Mayer G, Thum J, Cada E, Stummvoll HK, Graf H: Working capacity is increased following recombinant human erythropoietin treatment. Kidney Int 34: 525, 1988PubMedGoogle Scholar
  137. 137.
    Robertson HT, Haley NR, Gurthrie M, Cardenas D, Eschbach JW, Adamson JW: recombinant erythropoietin improves exercise capacity in anemic hemodialysis patients. Am J Kidney Dis 15: 325, 1990PubMedGoogle Scholar
  138. 138.
    Barany P, Freyschuss U, Pettersson E, Bergstrom J: Treatment of anaemia in haemodialysis patients with erythropoietin: long-term effects on exercsie capacity. Clin Sci 84:441, 1993PubMedGoogle Scholar
  139. 139.
    Davenport A: The effect of treatment with recombinant human erythropoietin on skeletal muscle function in patients with end-stage renal failure treated with regular hospital hemodialysis. Am J Kidney Dis 22: 685, 1993PubMedGoogle Scholar
  140. 140.
    Guthrie M, Cardenas D, Eschbach JW, Haley NR, Robertson HT, Evans RW: Effects of erythropoietin on strength and functional status of patients on hemodialysis. Clin Nephrol 39: 97, 1993PubMedGoogle Scholar
  141. 141.
    Painter P, Moore GE: The impact of recombinant human erythropoietin on exercise capacity in hemodialysis patients. Adv in Renal Repl Ther 1: 55, 1994Google Scholar
  142. 142.
    Moore GE, Parsons DB, Stray-Gundersen J, Painter PL, Brinker KR, Mitchell JH: Uremic myopathy limits aerobic capacity in hemodialysis patients. Am J Kidney Dis 22: 277, 1993PubMedGoogle Scholar
  143. 143.
    Frenneaux M: Personal communication, 1994Google Scholar
  144. 144.
    London GM, Fabiani F, Marchais SJ, De Vemejoul M-Ch, Guerin AP, Safar ME, Metivier F, Llach F: Uremic cardiomyopathy: an inadequate left ventricular hyperthropy. Kidney Int 31: 973, 1987PubMedGoogle Scholar
  145. 145.
    Silberberg J, Racine N, Barre P, Sniderman AD: Regression of left ventricular hypertrophy in dialysis patients following correction of anemia with recombinant human erythropoietin. Can J Cardiol 6: 1, 1990PubMedGoogle Scholar
  146. 146.
    Low I, Grutzmacher P, Bergmann M, Schoeppe W: Echocardiographic findings in patients on maintenance hemodialysis substituted with recombinant human erythropoietin. Clin Nephrol 31: 26, 1989PubMedGoogle Scholar
  147. 147.
    Pascual J, Teruel JL, Moya JL, Liano F, Jimenez-Mena M, Ortunao J: Regression of left ventricular hypertrophy after partial correction of anemia with erythropoietin in patients on hemodialysis: a prospective study. Clin Nephrol 35: 280, 1991PubMedGoogle Scholar
  148. 148.
    Fellner SK, Lang RM, Neumann A, Lorcarz C, Borow KM: Cardiovascular consequences of correctin of the anemia of renal failure with erythropoietin. Kidney Int 44: 1309, 1993PubMedGoogle Scholar
  149. 149.
    London GM, Zins B, Pannier B, Naret C, Berthelot J-M, Jacquot C, Safar M, Drueke TB: Vascular changes in hemodialysis patients in response to recombinant human erythropoietin. Kidney Int 36: 878, 1989PubMedGoogle Scholar
  150. 150.
    Wizemann V, Schafer R, Kramer W: Follow-up of cardiac changes induced by anemia compensation in normotensive hemodialysis patients with left-ventricular hypertrophy. Nephron 62: 202, 1993CrossRefGoogle Scholar
  151. 151.
    Morris KP, Skinner JR, Hunter S, Coulthard MG: Short term correction of anaemia with recombinant human erythropoietin and reduction of cardiac output in end stage renal failure. Arch Dis Child 68: 644, 1993PubMedGoogle Scholar
  152. 152.
    Macdougall IC, Lewis NP, Saunders MJ, Cochlin DL, Davies ME, Hutton RD, Fox KAA, Coles GA, Williams JD: Long-term cardiorespiratory effects of amelioration of renal anaemia by erythropoietin. Lancet 335: 489, 1990PubMedGoogle Scholar
  153. 153.
    Wizemann V, Kaufmann J, Kramer W: Effect of erythropoietin on ischemia tolerance in anemic hemodialysis patients with confirmed coronary artery disease. Nephron 62: 161, 1992PubMedGoogle Scholar
  154. 154.
    Steinman TI: Angina during hemodialysis: II. Sem Dial 6: 386, 1993Google Scholar
  155. 155.
    Horina JH, Fazekas F, Niederkom K, Payer F, Valetitsch H, Winkler HM, Homer S, Freidl W, Pogglitsch H, Krejs GJ: Cerebral hemodynamic changes following treatment with erythropoietin. Nephron 58: 407, 1991PubMedGoogle Scholar
  156. 156.
    Temple RM, Langan SJ, Deary IJ, Winney RJ: Recombinant erythropoietin improves cognitive function in chronic haemodialysis patients. Nephrol Dial Transplant 7: 240, 1992PubMedGoogle Scholar
  157. 157.
    Grimm G, Stockenhuber F, Schneeweiss B, Madl C, Zeitlhofer J, Schneider B: Improvement of brain function in hemodialysis patients treated with erythropoietin. Kidney Int 38: 480, 1990PubMedGoogle Scholar
  158. 158.
    Marsh JT, Brown WS, Wolcott D, Carr CR, Harper R, Schweitzer SV, Nissenson AR: rHuEPO treatment improves brain and cognitive function of anemic dialysis patients. Kidney Int 39: 155, 1991PubMedGoogle Scholar
  159. 159.
    Sagales T, Gimeno V, Planella MJ, Raguer N, Bartolome J: Effects of rHuEPO on Q-EEG and event-related potentials in chronic renal failure. Kidney Int 44: 1109, 1993PubMedGoogle Scholar
  160. 160.
    Johnson WJ, McCarthy JT, Yanagihara T, Osmundson PJ, Ilstrup DM, Jenson BM, Bowie EJW: Effects of recombinant human erythropoietin on cerebral and cutaneous blood flow and on blood coagulability. Kidney Int 38: 919, 1990PubMedGoogle Scholar
  161. 161.
    Hirakata H, Yao H, Osato S, Ibayashi S, Onoyama K, Otsuka M, Ichiya Y, Kuwabara Y, Masuda Y, Fujishima M: CBF and oxygen metabolism in hemodialysis patients: effects of anemia correction with recombinant human EPO. Am J Physiol 262 (Renal Fluid Electrolyte Physiol 31): F737, 1992PubMedGoogle Scholar
  162. 162.
    Eschbach JW, Adamson JW: Recombinant human erythropoietin: implications for nephrology. Am J Kidney Dis 11: 203, 1988PubMedGoogle Scholar
  163. 163.
    Delano BG: Improvements in quality of life following treatment with rHuEpo in anemic hemodialysis patients. Kidney Int 14: 14, 1989Google Scholar
  164. 164.
    Bommer J, Kugel M, Schwobel B, Ritz E, Barth HP, Seelig R: Improved sexual function during erythropoietin therapy. Nephrol Dial Transplant 5: 204, 1990PubMedGoogle Scholar
  165. 165.
    Steffensen G, Au Aunsholt N: Does erythropoietin cause hormonal changes in haemodialysis patients? Nephrol Dial Transplant 8: 1215, 1993PubMedGoogle Scholar
  166. 166.
    Schaefer RM, Kokot F, Wernze H, Geiger H, Heidland A: Improved sexual function in hemodialysis patients on recombinant erythropoietin: a possible role for prolactin. Clin Nephrol 31: 1, 1989PubMedGoogle Scholar
  167. 167.
    Imagawa A, Kawanishi Y, Numata A: Is erythropoietin effective for impotence in dialysis patients? Nephron 54: 95, 1990PubMedGoogle Scholar
  168. 168.
    Sobh MA, Abd el Hamid I, Atta MG, Refaie AF: Effect of erythropoietin on sexual potency in chronic haemodialysis patients. Scand J Urol Nephrol 26: 181, 1992PubMedGoogle Scholar
  169. 169.
    Haley NR, Matsumoto AM, Eschbach JW, Adamson JW: Low testosterone levels increase in male hemodialysis patients treated with recombinant human erythropoietin. Kidney Int 35: 193(A), 1989Google Scholar
  170. 170.
    Kokot F, Wiecek A, Grzeszczak W, Klepacka J, Klin M, Lao M: Influence of erythropoietin treatment on endocrine abnormalities in haemodialyzed patients. Contrib Nephrol 76: 257, 1989PubMedGoogle Scholar
  171. 171.
    Ramirez G, Bittle PA, Sanders H, Bereu BB: Hypothalamo-hypophyseal thryoid and gonadal function before and after erythropoietin therapy in dialysis patients. J Clin End & Metab 74: 517, 1992Google Scholar
  172. 172.
    Bernini GP, Mariotti F, Brogi G, Cerri F, Santoni M, Ciardella F, Franchi F: Effects of erythropoietin adminstration on prolactin secretion in normal subjects. Nephron 65: 522, 1993PubMedGoogle Scholar
  173. 173.
    Schaefer RM, Kokot F, Heidland A: Impact of recombinant erythropoietin on sexual function in hemodialysis patients. Contrib Nephrol 76: 273, 1989PubMedGoogle Scholar
  174. 174.
    Hou SH: Frequency and outcome of pregnancy in women on dialysis. Am J Kidney Dis 23: 60, 1994PubMedGoogle Scholar
  175. 175.
    Sennesael JJ, Van der Niepen P, Verbeelen DL: Treatment with recombinant human erythropoietin increases antibody titers after hepatitis B vaccination in dialysis patients. Kidney Int 40: 121, 1991PubMedGoogle Scholar
  176. 176.
    Pfaffl W, Gross H-J, Neumeier D, Nattermann U, Samtleben W, Gurland HJ: Lymphocyte subsets and delayed cutaneous hypersensitivity in hemodialysis patients receiving recombinant human erythropoietin. Contrib Nephrol 66: 195, 1988PubMedGoogle Scholar
  177. 177.
    Ueki Y, Nagata M, Miyake S, Tominaga Y: Lymphocyte subsets in hemodialysis patients treated with recombinant human erythropoietin. J Clin Immunol 13: 279, 1993PubMedGoogle Scholar
  178. 178.
    Gafter U, Kalechman Y, Orlin JB, Levi J, Sredni B: Anemia of uremia is associated with reduced in vitro cytokine secretion: immunopotentiating activity of red blood cells. Kidney Int 45: 224, 1994PubMedGoogle Scholar
  179. 179.
    Hebert LA, Birmingham DJ, Dillon JJ, Cosio FG, Shen X-P: Erythropoietin therapy in humans increases erythrocyte expression of complement receptor type 1 (CD35). J Am Soc Nephrol 4: 1786, 1994PubMedGoogle Scholar
  180. 180.
    Hebert LA, Birmingham DJ, Shen X-P, Brandt JT, Sedmak DD, Dillon JJ: Effect of recombinant erythropoietin therapy on autoimmunity in systemic lupus erythrematosus. Am J Kidney Dis 24: 25, 1994PubMedGoogle Scholar
  181. 181.
    Marchi SD, Cecchin E, Villalta D, Sepiacci G, Santini G, Bartoli E: Relief of pruritis and decreases in plasma histamine concentrations during erythropoietin therapy in patients with uremia. N Engl J Med 326: 969, 1992PubMedCrossRefGoogle Scholar
  182. 182.
    Pollock CA, Wyndham R, Collett PV, Elder G, Field M, Kalowski S, Lawrence JR, Waugh DA, George CRP: Effects of erythropoietin therapy on the lipid profile in end-stage renal failure. Kidney Int 45: 897, 1994PubMedGoogle Scholar
  183. 183.
    Eschbach JW: Erythropoietin: the promise and the facts. Kidney Int 45(Suppl 44): 70S, 1994Google Scholar
  184. 184.
    United States Renal Data System: USRDS 1994 Annual Data Report. The National Institute of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, June 1994Google Scholar
  185. 185.
    Grimm PC, Sinai-Trieman L, Sekiya NM, Robertson LS, Robinson BJ, Fine RN, Ettenger RB: Effects of recombinant human erythropoietin on HLA sensitization and cell mediated immunity. Kidney Int 38: 12, 1990PubMedGoogle Scholar
  186. 186.
    Kaupke CJ, Butler GC, Vaziri ND: Effect of recombinant human erythropoietin on platelet production in dialysis patients. J Am Soc Nephrol 3: 1672, 1993PubMedGoogle Scholar
  187. 187.
    Horina JH, Schmid CR, Roob JM, Winkler HM, Samitz MA, Hammer HF, Pogglitsch H, Krejs GJ: Bone marrow changes following treatment of renal anemia with erythropoietin. Kidney Int 40: 917, 1991PubMedGoogle Scholar
  188. 188.
    Ishibashi T, Koziol JA, Burstein SA: Human recombinant erythropoietin promotes differentiation of murine megakaryocytes in vitro. J Clin Invest 79: 286, 1987PubMedGoogle Scholar
  189. 189.
    Dessypris EN, Gleaton JH, Armstrong OL: Effect of human recombinant erythropoietin on human marrow megakaryocyte colony formation in vitro. BrJ Haematol 65: 265, 1987Google Scholar
  190. 190.
    Livio M, Marchesi D, Remuzzi G, Gotti E, Medda G, De Gaetano G: Uraemic bleeding: role of anaemia and beneficial effect of red cell transfusions. Lancet II: 1013, 1982Google Scholar
  191. 191.
    Fernandez F, Goudable C, Sie P, Ton-That H, Durand D, Suc JM, Boneu B: Low haematocrit and prolonged bleeding time in uraemic patients: effect of red cell transfusions. Br J Haematol 59: 139, 1985PubMedGoogle Scholar
  192. 192.
    Moia M, Mannucci PM, Vizzotto L, Casati S, Cattaneo M, Ponticelli C: Improvement in the haemostatic defect of uraemia after treatment with recombinant human erythropoietin. Lancet II: 1227, 1987Google Scholar
  193. 193.
    Vigano G, Benigni A, Mendogni D, Mingardi G, Mecca G, Remuzzi G: Recombinant human erythropoietin to correct uremic bleeding. Am J Kidney Dis 18: 44, 1991PubMedGoogle Scholar
  194. 194.
    Cases A, Escolar G, Reverter J2C, Ordinas Aj, Lopez-Pedret J, Revert L, Castillo R: Recombinant human erythropoietin treatment improves platelet function in uremic patients. Kidney Int 42: 668, 1992PubMedGoogle Scholar
  195. 195.
    Evans RW, Rader B, Manninen DL: The quality of life of hemodialysis recipients treated with recombinant human erythropoietin. JAMA 262: 825, 1990Google Scholar
  196. 196.
    Auer J, Oliver DO, Winearls CG: The quality of life of dialysis patients treated with recombinant human erythropoietin. Scand J Urol Nephrol 131(Suppl): 55, 1990Google Scholar
  197. 197.
    Keown PA: Quality of life in end-stage renal disease patients during recombinant human erythropoietin therapy. Contrib Nephrol 88: 81, 1991PubMedGoogle Scholar
  198. 198.
    Barany P, Pettersson E, Bergstrom J: Erythropoietin treatment improves quality of life in hemodialysis patients. Scand J Urol Nephrol 131: 55, 1990Google Scholar
  199. 199.
    Disney APS (ed): Fifteenth Report of the Australia and New Zealand Dialysis and Transplant Registry (Anzdata), Sponsored by the Australian Kidney Foundation, October 1992Google Scholar
  200. 200.
    Levin NW, Lazarus JM, Nissenson AR: National cooperative rHu erythropoietin study in patients with chronic renal failure — an interim report. Am J Kidney Dis 22(Suppl 1): 3, 1993PubMedGoogle Scholar
  201. 201.
    Ifudu O, Paul H, Mayers JD, Cohen LS, Brezsnyak WF, Herman AI, Avram MM, Friedman EA: Pervasive failed rehabilitation in center-based maintenance hemodialysis patients. Am J Kidney Dis 23: 394, 1994PubMedGoogle Scholar
  202. 202.
    Shinaberger JH, Miller JH, Gardner PW: Disadvantages and risks of normal hematocrit hemodialysis. Kidneys Int 35: 264(A), 1989Google Scholar
  203. 203.
    George C, Lundin AP, Delano BG, Brown C, Friedman EA: Absence of anemia in maintenance hemodialysis patients. Int J Artif Org 4: 277, 1981Google Scholar
  204. 204.
    Sheingold S, Churchill D, Muirhead N, Laupacis A, Labelle R, Goeree R: The impact of recombinant human erythropoietin on medical care costs for hemodialysis patients in Canada. Soc Sci Med 34: 983, 1992PubMedGoogle Scholar
  205. 205.
    Eschbach JW, Aquiling T, Haley NR, Fan MH, Blagg CR: The long term effects recombinant human erythropoietin on the cardiovascular system. Clin Nephrol 38(Suppl 1): 98S, 1992Google Scholar
  206. 206.
    Ritz E, Zeier M, Schneider P, Jones E: Cardiovascular mortality of patients with polycystic kidney disease on dialysis: is there a lesson to learn? Nephron 66: 125, 1994PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1996

Authors and Affiliations

  • Joseph W. Eschbach
    • 1
  1. 1.Department of MedicineUniversity of WashingtonSeattleUSA

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