American Journal of Kidney Diseases
Volume 55, Issue 3 , Pages 535-548 , March 2010

Systematic Review and Meta-analysis of Exercise Tolerance and Physical Functioning in Dialysis Patients Treated With Erythropoiesis-Stimulating Agents

  • Kirsten L. Johansen, MD

      Affiliations

    • University of California, San Francisco, CA
    • Corresponding Author InformationAddress correspondence to Kirsten L. Johansen, MD, University of California, San Francisco, San Francisco VA Medical Center, 4150 Clement St, San Francisco, CA 94121
  • ,
  • Fredric O. Finkelstein, MD

      Affiliations

    • Hospital of St. Raphael, Yale University, New Haven, CT
  • ,
  • Dennis A. Revicki, PhD

      Affiliations

    • United BioSource Corp, Bethesda, MD
  • ,
  • Matthew Gitlin, PharmD

      Affiliations

    • Amgen, Thousand Oaks, CA
  • ,
  • Christopher Evans, PhD

      Affiliations

    • Mapi Values, Boston, MA
  • ,
  • Tracy J. Mayne, PhD

      Affiliations

    • Amgen, Thousand Oaks, CA

Received 4 July 2009 ,Accepted 8 December 2009.

References 

  1. Lopes AA, Bragg-Gresham JL, Satayathum S, et al. Health-related quality of life and associated outcomes among hemodialysis patients of different ethnicities in the United States: the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis. 2003;41:605–615
  2. Hedayati SS, Bosworth HB, Briley LP, et al. Death or hospitalization of patients on chronic hemodialysis is associated with a physician-based diagnosis of depression. Kidney Int. 2008;74:930–936
  3. Suri RS, Garg AX, Chertow GM, et al. Frequent Hemodialysis Network (FHN) randomized trials: study design. Kidney Int. 2007;71:349–359
  4. Jaber BL, Finkelstein FO, Glickman JD, et al. Scope and design of the Following Rehabilitation, Economics and Everyday-Dialysis Outcome Measurements (FREEDOM) Study. Am J Kidney Dis. 2009;53:310–320
  5. Singh AK, Szczech L, Tang KL, et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med. 2006;355:2085–2098
  6. Drueke TB, Locatelli F, Clyne N, et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med. 2006;355:2071–2084
  7. Butland RJ, Pang J, Gross ER, Woodcock AA, Geddes DM. Two-, six-, and 12-minute walking tests in respiratory disease. Br Med J. 1982;284:1607–1608
  8. Guyatt GH, Pugsley SO, Sullivan MJ, et al. Effect of encouragement on walking test performance. Thorax. 1984;39:818–822
  9. Guyatt GH, Sullivan MJ, Thompson PJ, et al. The 6-minute walk: a new measure of exercise capacity in patients with chronic heart failure. CMAJ. 1985;132:919–923
  10. Demers C, McKelvie RS, Negassa A, Yusuf S. Reliability, validity, and responsiveness of the six-minute walk test in patients with heart failure. Am Heart J. 2001;142:698–703
  11. O'Keeffe ST, Lye M, Donnellan C, Carmichael DN. Reproducibility and responsiveness of quality of life assessment and six minute walk test in elderly heart failure patients. Heart. 1998;80:377–382
  12. Ingle L, Shelton RJ, Rigby AS, Nabb S, Clark AL, Cleland JG. The reproducibility and sensitivity of the 6-min walk test in elderly patients with chronic heart failure. Eur Heart J. 2005;26:1742–1751
  13. Nogueira PA, Leal AC, Pulz C, Nogueira ID, Filho JA. Clinical reliability of the 6 minute corridor walk test performed within a week of a myocardial infarction. Int Heart J. 2006;47:533–540
  14. Levendoglu F, Altintepe L, Okudan N, et al. A twelve week exercise program improves the psychological status, quality of life and work capacity in hemodialysis patients. J Nephrol. 2004;17:826–832
  15. Eng JJ, Dawson AS, Chu KS. Submaximal exercise in persons with stroke: test-retest reliability and concurrent validity with maximal oxygen consumption. Arch Phys Med Rehabil. 2004;85:113–118
  16. Karnofsky D, Burchenal JH. The clinical evaluation of chemotherapeutic agents in cancer. In: MacLeod CM, ed. Evaluating Chemotherapeutic Agents. New York, NY: Columbia University; 1049:191-205.
  17. Gutman RA, Stead WW, Robinson RR. Physical activity and employment status of patients on maintenance dialysis. N Engl J Med. 1981;304:309–313
  18. Evans RW, Rader B, Manninen DL. The quality of life of hemodialysis recipients treated with recombinant human erythropoietin (Cooperative Multicenter EPO Clinical Trial Group). JAMA. 1990;263:825–830
  19. McClellan WM, Anson C, Birkeli K, Tuttle E. Functional status and quality of life: predictors of early mortality among patients entering treatment for end stage renal disease. J Clin Epidemiol. 1991;44:83–89
  20. Ifudu O, Paul HR, Homel P, Friedman EA. Predictive value of functional status for mortality in patients on maintenance hemodialysis. Am J Nephrol. 1998;18(2):109–116
  21. Moreno F, Sanz-Guajardo D, Lopez-Gomez JM, Jofre R, Valderrabano F. Increasing the hematocrit has a beneficial effect on quality of life and is safe in selected hemodialysis patients (Spanish Cooperative Renal Patients Quality of Life Study Group of the Spanish Society of Nephrology). J Am Soc Nephrol. 2000;11:335–342
  22. Arogundade FA, Zayed B, Daba M, Barsoum RS. Correlation between Karnofsky Performance Status scale and Short-Form Health Survey in patients on maintenance hemodialysis. J Natl Med Assoc. 2004;96:1661–1667
  23. Bergner M, Bobbitt RA, Kressel S, Pollard WE, Gilson BS, Morris JR. The Sickness Impact Profile: conceptual formulation and methodology for the development of a health status measure. Int J Health Serv. 1976;6:393–415
  24. Bergner M, Bobbitt RA, Carter WB, Gilson BS. The Sickness Impact Profile: development and final revision of a health status measure. Med Care. 1981;19:787–805
  25. de Bruin AF, de Witte LP, Stevens F, Diederiks JP. Sickness Impact Profile: the state of the art of a generic functional status measure. Soc Sci Med. 192;35(8):1003-1014.
  26. Laupacis A, Wong C, Churchill D. The use of generic and specific quality-of-life measures in hemodialysis patients treated with erythropoietin (The Canadian Erythropoietin Study Group). Control Clin Trials. 1991;12:168S–179S
  27. Essink-Bot ML, Krabbe PF, van Agt HM, Bonsel GJ. NHP or SIP—a comparative study in renal insufficiency associated anemia. Qual Life Res. 1996;5:91–100
  28. Ware JE, Snow KK, Kosinsky M, Gandek B. SF-36 Health Survey: Manual and Interpretation Guide.. Boston, MA: The Health Institute, New England Medical Center; 1993;
  29. Meyer KB, Espindle DM, DeGiacomo JM, Jenuleson CS, Kurtin PS, Davies AR. Monitoring dialysis patients' health status. Am J Kidney Dis. 1994;24:267–279
  30. Delano BG. Improvements in quality of life following treatment with r-HuEPO in anemic hemodialysis patients. Am J Kidney Dis. 1989;14:14–18
  31. Harris DC, Chapman JR, Stewart JH, Lawrence S, Roger SD. Low dose erythropoietin in maintenance haemodialysis: improvement in quality of life and reduction in true cost of haemodialysis. Aust N Z J Med. 1991;21:693–700
  32. McMahon LP, Johns JA, McKenzie A, Austin M, Fowler R, Dawborn JK. Haemodynamic changes and physical performance at comparative levels of haemoglobin after long-term treatment with recombinant erythropoietin. Nephrol Dial Transplant. 1992;7:1199–1206
  33. Canadian Erythropoietin Study Group. Association between recombinant human erythropoietin and quality of life and exercise capacity of patients receiving hemodialysis. BMJ. 1990;200:573–578
  34. Parfrey PS, Foley RN, Wittreich BH, Sullivan DJ, Zagari MJ, Frei D. Double-blind comparison of full and partial anemia correction in incident hemodialysis patients without symptomatic heart disease. J Am Soc Nephrol. 2005;16:2180–2189
  35. Barany P, Pettersson E, Konarski-Svensson JK. Long-term effects on quality of life in haemodialysis patients of correction of anaemia with erythropoietin. Nephrol Dial Transplant. 1993;8:426–432
  36. Mayer G, Thum J, Cada EM, Stummvoll HK, Graf H. Working capacity is increased following recombinant human erythropoietin treatment. Kidney Int. 1988;34:525–528
  37. Metra M, Cannella G, La Canna G, et al. Improvement in exercise capacity after correction of anemia in patients with end-stage renal failure. Am J Cardiol. 1991;68:1060–1066
  38. Topuzovic N. Worsening of left ventricular diastolic function during long-term correction of anemia with erythropoietin in chronic hemodialysis patients--an assessment by radionuclide ventriculography at rest and exercise. Int J Card Imaging. 1999;15:233–239
  39. Tsutsui M, Suzuki M, Hirasawa Y. Renewed cardiovascular dynamics induced by recombinant erythropoietin administration. Nephrol Dial Transplant. 1989;4(suppl 3):S146–S150
  40. Macdougall IC, Davies ME, Hutton RD, et al. The treatment of renal anaemia in CAPD patients with recombinant human erythropoietin. Nephrol Dial Transplant. 1990;5:950–955
  41. Rosenlof K, Gronhagen-Riska C, Sovijarvi A, et al. Beneficial effects of erythropoietin on haematological parameters, aerobic capacity, and body fluid composition in patients on haemodialysis. J Intern Med. 1989;226:311–317
  42. Braumann KM, Nonnast-Daniel B, Boning D, Bocker A, Frei U. Improved physical performance after treatment of renal anemia with recombinant human erythropoietin. Nephron. 1991;58(2):129–134
  43. Juric M, Rupcic V, Topuzovic N, et al. Haemodynamic changes and exercise tolerance in dialysis patients treated with erythropoietin. Nephrol Dial Transplant. 1995;10(8):1398–1404
  44. Macdougall IC, Lewis NP, Saunders MJ, et al. Long-term cardiorespiratory effects of amelioration of renal anaemia by erythropoietin. Lancet. 1990;335:489–493
  45. McMahon LP, Mason K, Skinner SL, Burge CM, Grigg LE, Becker GJ. Effects of haemoglobin normalization on quality of life and cardiovascular parameters in end-stage renal failure. Nephrol Dial Transplant. 2000;15:1425–1430
  46. Robertson HT, Haley NR, Guthrie M, Cardenas D, Eschbach JW, Adamson JW. Recombinant erythropoietin improves exercise capacity in anemic hemodialysis patients. Am J Kidney Dis. 1990;15:325–332
  47. Davenport A, Will EJ, Khanna SK, Davison AM. Blood lactate is reduced following successful treatment of anaemia in haemodialysis patients with recombinant human erythropoietin both at rest and after maximal exertion. Am J Nephrol. 1992;12:357–362
  48. Lundin AP, Akerman MJ, Chesler RM, et al. Exercise in hemodialysis patients after treatment with recombinant human erythropoietin. Nephron. 1991;58:315–319
  49. Painter P, Moore G, Carlson L, et al. Effects of exercise training plus normalization of hematocrit on exercise capacity and health-related quality of life. Am J Kidney Dis. 2002;39:257–265
  50. Wizemann V, Kaufmann J, Kramer W. Effect of erythropoietin on ischemia tolerance in anemic hemodialysis patients with confirmed coronary artery disease. Nephron. 1992;62(2):161–165
  51. Hase H, Imamura Y, Nakamura R, Inishi Y, Machii K, Yamaguchi T. Effects of rHuEPO therapy on exercise capacity in hemodialysis patients with coronary artery disease. Jpn Circ J. 1993;57:131–137
  52. Akiba T, Matsui N, Shinohara S, Fujiwara H, Nomura T, Marumo F. Effects of recombinant human erythropoietin and exercise training on exercise capacity in hemodialysis patients. Artif Organs. 1995;19:1262–1268
  53. Barany P, Wibom R, Hultman E, Bergstrom J. ATP production in isolated muscle mitochondria from haemodialysis patients: effects of correction of anaemia with erythropoietin. Clin Sci (Lond). 1991;81:645–653
  54. Bocker A, Reimers E, Nonnast-Daniel B, et al. Effect of erythropoietin treatment on O2 affinity and performance in patients with renal anemia. Contrib Nephrol. 1988;66:165–175
  55. Grunze M, Kohlmann M, Mulligan M, Gruner I, Koeppel M, Bommer J. Mechanisms of improved physical performance of chronic hemodialysis patients after erythropoietin treatment. Am J Nephrol. 1990;10(suppl 2):S15–S18
  56. Lewis NMacdougall IC, Willis N, Coles G, Williams J, Henderson A. Effects of the correction of renal anaemia by erythropoietin on physiological changes during exercise. Eur J Clin Invest. 1993;23:423–427
  57. Marrades RM, Roca J, Campistol JM, et al. Effects of erythropoietin on muscle O2 transport during exercise in patients with chronic renal failure. J Clin Invest. 1996;97:2092–2100
  58. Johansen KL. Physical functioning and exercise capacity in patients on dialysis. Adv Ren Replace Ther. 1999;6:141–148
  59. Muirhead N, Churchill DN, Goldstein M, et al. Comparison of subcutaneous and intravenous recombinant human erythropoietin for anemia in hemodialysis patients with significant comorbid disease. Am J Nephrol. 1992;12:303–310
  60. Foley RN, Parfrey PS, Morgan J, et al. Effect of hemoglobin levels in hemodialysis patients with asymptomatic cardiomyopathy. Kidney Int. 2000;58:1325–1335
  61. Furuland H, Linde T, Ahlmen J, Christensson A, Strombom U, Danielson BG. A randomized controlled trial of haemoglobin normalization with epoetin alfa in pre-dialysis and dialysis patients. Nephrol Dial Transplant. 2003;18:353–361
  62. Levin NW, Lazarus JM, Nissenson AR. Maximizing patient benefits with epoetin alfa therapy: the National Cooperative rHu Erythropietin Study in patients with chronic renal failure—an interim report. Am J Kidney Dis. 1993;22(suppl 1):S3–S12
  63. Moreno F, Aracil FJ, Perez R, Valderrabano F. Controlled study on the improvement of quality of life in elderly hemodialysis patients after correcting end-stage renal disease-related anemia with erythropoietin. Am J Kidney Dis. 1996;27:548–556
  64. Fukuhara S, Akizawa T, Morita S, Koshikawa S. Quality of life improvements in dialysis patients receiving darbepoetin alfa. Ther Apher Dial. 2008;12:72–77
  65. Beusterien KM, Nissenson AR, Port FK, Kelly M, Steinwald B, Ware JE. The effects of recombinant human erythropoietin on functional health and well-being in chronic dialysis patients. J Am Soc Nephrol. 1996;7:763–773
  66. Adamson JW, Eschbach JW. Management of the anaemia of chronic renal failure with recombinant erythropoietin. Q J Med. 1989;73:1093–1101
  67. Weisbord SD, Fried LF, Mor MK, et al. Renal provider recognition of symptoms in patients on maintenance hemodialysis. Clin J Am Soc Nephrol. 2007;2:960–967
  68. Leaf DE, Goldfarb DS. Interpretation and review of health-related quality of life data in CKD patients receiving treatment for anemia. Kidney Int. 2009;75:15–24
  69. Finkelstein FO, Story K, Firanek C, et al. Health-related quality of life and hemoglobin levels in chronic kidney disease patients. Clin J Am Soc Nephrol. 2009;4:33–38
  70. US Renal Data System. 2008 USRDS Annual Data Report: Atlas of Chronic Kidney Disease and End-stage Renal Disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2008;

 Originally published online as doi:10.1053/j.ajkd.2009.12.018 on February 4, 2010.

PII: S0272-6386(09)01596-0

doi: 10.1053/j.ajkd.2009.12.018

American Journal of Kidney Diseases
Volume 55, Issue 3 , Pages 535-548 , March 2010