Blood Reviews
Volume 24, Issue 1 , Pages 39-47 , January 2010

Anemia in renal disease: Diagnosis and management

  • Christina E. Lankhorst

      Affiliations

    • Division of Nephrology, University Hospitals Case Medical Center, 11100 Euclid Ave, Cleveland, OH 44106, United States
    • Tel.: +1 216 844 5525, mobile: +1 216 965 9058; fax: +1 216 844 5204.
  • ,
  • Jay B. Wish

      Affiliations

    • Case Western Reserve University, Division of Nephrology, University Hospitals Case Medical Center, 11100 Euclid Ave, Cleveland, OH 44106, United States
    • Corresponding Author InformationCorresponding author. Tel.: +1 216 844 3163, mobile: +1 216 849 3950; fax: +1 216 844 3328.

References 

  1. National Kidney Foundation. Chronic kidney disease. <www.kidney.org/kidneydisease/ckd/index.cfm>; 2009 [accessed 7.07.09].
  2. Weiner DE, Tighiouart H, Vlagopoulos PT, et al. Effects of anemia and left ventricular hypertrophy on cardiovascular disease in patients with chronic kidney disease. J Am Soc Nephrol. 2005;16:1803–1810
  3. World Health Organization. Database of anemia. Worldwide prevalence of anaemia 1993–2005. <www.who.int/vmnis>; 2009 [accessed 7.07.09].
  4. Hsu CY, McCulloch CE, Curhan GC. Epidemiology of anemia associated with chronic renal insufficiency among adults in the United States: results from the third national health and nutrition examination survey. J Am Soc Nephrol. 2002;13:504–510
  5. Astor BC, Muntner P, Levin A, Eustace JA, Coresh J. Association of kidney function with anemia: the third national health and nutrition examination survey (1988–1994). Arch Intern Med. 2002;162:1401–1408
  6. Fehally J, Floege J, Johnson R. Comprehensive clinical nephrology. Philadelphia: Mosby Elsevier; 2003;p. 853–60
  7. Eckardt KU. Erythropoietin: oxygen-dependent control of erythropoiesis and its failure in renal disease. Nephron. 1994;67:7–23
  8. Eschbach JW, Adamson JW, Cook JD. Disorders of red cell production in uremia. Arch Intern Med. 1970;126:812–815
  9. Koch KM, Patyna D, Shaldon S, Werner E. Anemia of the regular hemodialysis patient and its treatment. Nephron. 1974;12:405–419
  10. Geerlings W, Morris RW, Brunner FP, et al. Factors influencing anaemia in dialysis patients. A special survey by the EDTA-ERA registry. Nephrol Dial Transplant. 1993;8:585–589
  11. Katzarski KS, Charra B, Luik AJ, et al. Fluid state and blood pressure control in patients treated with long and short dialysis. Nephrol Dial Transplant. 1999;14:369–375
  12. Locatelli F, Del Vecchio L. Dialysis adequacy and response to erythropoietic agents: what is the evidence base?. Nephrol Dial Transplant. 2003;18(Suppl. 8):viii29–viii35
  13. National Kidney Foundation. KDOQI clinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease. <www.kidney.org/PROFESSIONALS/kdoqi/guidelines_anemia/guide2.htm#cpr11>; 2009 [accessed 7.07.09].
  14. Orino K, Lehman L, Tsuji Y, Ayaki H, Torti SV, Torti FM. Ferritin and the response to oxidative stress. Biochem J. 2001;357(1):241–247
  15. Parkkinen J, von Bonsdorff L, Peltonen S, Gronhagen-Riska C, Rosenlof K. Catalytically active iron and bacterial growth in serum of haemodialysis patients after i.v. iron-saccharate administration. Nephrol Dial Transplant. 2000;15:1827–1834
  16. Kovesdy CP. Iron and clinical outcomes in dialysis and non-dialysis dependent chronic kidney disease patients. Adv Chronic Kidney Dis. 2009;16(2):109–116
  17. Paradkar P, De Domenico I, Durchfort N, Zohn I, Kaplan J, McVey Ward D. Iron depletion limits intracellular growth in macrophages. Blood. 2008;12(3):866–874
  18. Zaritsky J, Young B, Wang H, Westerman M, Olbina G, Nemeth E, et al. A potential novel biomarker for iron status in chronic kidney disease. Clin J Am Soc Nephrol. 2009;4(6):1051–1056
  19. Malyszko J. Hepcidin assays: ironing out some details. Clin J Am Soc Nephrol. 2009;4(6):1015–1016
  20. Ganz T, Olbina G, Girelli D, Nemeth W, Westerman M. Immunoassay for human serum hepcidin. Blood. 2008;112:4292–4297
  21. Mittman N, Sreedhara R, Mushnick R, Chattopadhyay J, Zelmanovic D, Vaseghi M, et al. Reticulocyte hemoglobin content predicts functional iron deficiency in hemodialysis patients receiving rHuEPO. Am J Kidney Dis. 1997;30:912–922
  22. Fishbane S, Shapiro W, Dutka P, Valenzuela OF, Faubert OF. A randomized trial of iron deficiency testing strategies in hemodialysis patients. Kidney Int. 2001;60:2406–2411
  23. Levin A, Thompson C, Ethier J, Carlisle E, Tobe S, Mendelssohn D, et al. Left ventricular mass index increase in early renal disease: impact of decline in hemoglobin. Am J Kidney Dis. 1999;34(1):125–134
  24. Silverberg DS, Wexler D, Blum M, Tchebiner JZ, Sheps D, Keren G, et al. The effect of correction of anaemia in diabetics and non-diabetics with severe resistant congestive heart failure and chronic renal failure by subcutaneous erythropoietin and intravenous iron. Nephrol Dial Transplant. 2003;18:141–146
  25. Painter P, Moore G, Carlson L, Paul S, Myll J, Phillips W, 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
  26. Valderrabano F, Jofre R, Lopez-Gomez JM. Quality of life in end-stage renal disease patients. Am J Kidney Dis. 2001;38:443–464
  27. Pisioni RL, Bragg-Gresham JL, Young EW, Akizawa T, Asano Y, Locatelli F, et al. Anemia management and outcomes from 12 countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis. 2004;44:94–111
  28. Popovsky MA, Ransil BJ. Long-term impact of recombinant human erythropoietin on transfusion support in patients with chronic renal failure. Immunohematology. 1996;12(1):1–3
  29. Aranesp (darbepoetin alfa) for injection [prescribing information]. Thousand Oaks, CA: Amgen Inc. <www.aranesp.com/professionalprescribing_information.jsp>; 2007 [accessed 8.07.09].
  30. Procrit (epoetin alfa) for injecton [prescribing information]. Thousand Oaks, CA: Amgen Inc. Distributed by Ortho Biotech Products, LP: Raritan, NJ. <www.procrit.com/ppi.pdf>; 2007 [accessed 8.07.09].
  31. Epogen (epoetin alfa) for injection [prescribing information]. Thousand Oaks, CA: Amgen Inc, 2007. <www.epogen.com/pdf/epogen_pi.pdf>; 2009 [accessed 8.07.09].
  32. Nissenson AR, Swan SK, Lindberg JS, et al. Randomized, controlled trial of darbepoetin alfa for the treatment of anemia in hemodialysis patients. Am J Kidney Dis. 2002;40(1):110–118
  33. Kaufman JS, Reda DJ, Fye CL, et al. Subcutaneous compared with intravenous epoetin in patients receiving hemodialysis. Department of veterans affairs cooperative study group on erythropoietin in hemodialysis patients. N Engl J Med. 1998;339:578–583
  34. Germain M, Ram CV, Bhaduri S, Tang KL, Klausner M, Curzi M. Extended epoetin alfa dosing in chronic kidney disease patients: a retrospective review. Nephrol Dial Transplant. 2005;20(10):2146–2152
  35. Provenzano R, Bhaduri S, Singh AK PROMPT Study Group. Extended epoetin alfa dosing as maintenance treatment for the anemia of chronic kidney disease: the PROMPT study. Clin Nephrol. 2005;64(2):113–123
  36. Jadoul M, Vanrenterghem Y, Foret M, Walker R, Gray SJ. Darbepoetin alfa administered once monthly maintains haemoglobin levels in stable dialysis patients. Nephrol Dial Transplant. 2004;19(4):898–903
  37. Ling B, Walczyk M, Agarwal A, Carroll W, Liu W, Brenner R. Darbepoetin alfa administered once monthly maintains hemoglobin concentrations in patients with chronic kidney disease. Clin Nephrol. 2005;63(5):327–334
  38. Macdougall IC, Eckardt KU. Novel strategies for stimulating erythropoiesis and potential new treatments for anaemia. Lancet. 2006;368:947–953
  39. Macdougall IC, Padhi D, Jang G. Pharmacology of darbepoetin alfa. Nephrol Dial Transplant. 2007;22(Suppl. 4):iv2–iv9
  40. Bunn HF. New agents that stimulate erythropoiesis. Blood. 2007;109:868–873
  41. Kimel M, Leidy NK, Mannix S, Dixon J. Does epoetin alfa improve health-related quality of life in chronically ill patients with anemia? Summary of trials of cancer, HIV/AIDS, and chronic kidney disease. Value Health. 2008;11(1):57–75
  42. Regidor DL, Kopple JD, Kovesdy CP, et al. Associations between changes in hemoglobin and administered erythropoiesis-stimulating agent and survival in hemodialysis patients. J Am Soc Nephrol. 2006;17(4):1181–1191
  43. Besarab A, Bolton WK, Browne JK, et al. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med. 1998;339(9):584–590
  44. Roth D, Smith RD, Schulman G, et al. Effects of recombinant human erythropoietin on renal function in chronic renal failure predialysis patients. Am J Kidney Dis. 1994;24(5):777–784
  45. Gouva C, Nikolopoulos P, Ioannidis JP, Siamopoulos KC. Treating anemia early in renal failure patients slows the decline of renal function: a randomized controlled trial. Kidney Int. 2004;66(2):753–760
  46. Drueke TB, Locatelli F, Clyne N, et al. CREATE Investigators. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med. 2006;355(20):2071–2084
  47. Frank H, Heusser K, Hoffken B, Huber P, Schmieder RE, Schobel HP. Effect of erythropoietin on cardiovascular prognosis parameters in hemodialysis patients. Kidney Int. 2004;66(2):832–840
  48. Ayus JC, Go AS, Valderrabano F, et al. Spanish group for the study of the anemia and left ventricular hypertrophy in pre-dialysis patients. Effects of erythropoietin on left ventricular hypertrophy in adults with severe chronic renal failure and hemoglobin <10 g/dL. Kidney Int. 2005;68(2):788–795
  49. Wish J, Schulman K, Law A, Nassar G. Healthcare expenditure and resource utilization in patients with anaemia and chronic kidney disease: a retrospective claims database analysis. Kidney Blood Press Res. 2009;32(2):110–118
  50. Maddux FW, Shetty S, del Aguila MA, Nelson MA, Murray BM. Effect of erythropoiesis-stimulating agents on healthcare utilization, costs, and outcomes in chronic kidney disease. Ann Pharmacother. 2007;41(11):1761–1769
  51. London R, Solis A, Goldberg GA, Wade S, Ryu S. Health care resource utilization and the impact of anemia management in patients with chronic kidney disease. Am J Kidney Dis. 2002;40(3):539–548
  52. Papatheofanis F, Bookhart BK, Muser E, Piech CT. An examination of productivity and resource utilization associated with epoetin alfa treatment in employees with predialysis chronic kidney disease. J Occup Environ Med. 2008;50(5):584–589
  53. Moyneur E, Bookhart BK, Mody SH, Fournier AA, Mallett D, Duh MS. The economic impact of pre-dialysis epoetin alpha on health care and work loss costs in chronic kidney disease: an employer’s perspective. Dis Manag. 2008;11(1):49–58
  54. 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(2):353–361
  55. 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(7):2180–2189
  56. Singh AK, Szczech L, Tang KL, et al. CHOIR investigators. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med. 2006;355(20):2085–2098
  57. Sczcech LA, Burnhart HXS, Inrig JK, Reddan DN, Sapp S, Califf RM, et al. Secondary analysis of the CHOIR trial epoetin-α dose and achieved hemoglobin outcomes. Kidney Int. 2008;74:791–798
  58. Besarab A, Frinak S, Yee J. What is so bad about a hemoglobin of 12–13 g/dL for chronic kidney disease patients anyway?. Adv Chronic Kidney Dis. 2009;16(2):131–142
  59. Miyashita K, Tojo A, Kimura K, et al. Blood pressure response to erythropoietin injection in hemodialysis and predialysis patients. Hypertens Res. 2004;27(2):79–84
  60. Kalantar-Zadeh K, Regidor DL, McAllister CJ, Michael B, Warnock DG. Time-dependent associations between iron and mortality in hemodialysis patients. J Am Soc Nephrol. 2005;16(10):3070–3080
  61. Fletes R, Lazarus JM, Gage J, Chertow GJ. Suspected iron dextran-related adverse drug advents in hemodialysis patients. Am J Kidney Dis. 2001;37:743–749
  62. Spinowitz BS, Kausz AT, Baptista J, Noble SD, Sothinathan R, Bernardo MV, et al. Ferumoxytol for treating iron deficiency anemia in CKD. J Am Soc Nephrol. 2008;19:1599–1605
  63. Horl WH. Adjunctive therapy in anaemia management. Nephrol Dial Transplant. 2002;17(Suppl. 5):56–59
  64. Brewster UC. Intravenous iron therapy in end-stage renal disease. Semin Dial. 2006;19(4):285–290
  65. Hoen B, Paul-Dauphin A, Kessler M. Intravenous iron administration does not significantly increase the risk of bacteremia in chronic hemodialysis patients. Clin Nephrol. 2002;57(6):457–461
  66. Admas PC, Deugnier Y, Moirand R, Brissot P. The relationship between iron overload, clinical symptoms, and age in 410 patients with genetic hemochromatosis. Hepatology. 1997;25:162–166
  67. Adamson J. Hyporesponsiveness to erythropoiesis stimulating agents in chronic kidney disease: the many faces of inflammation. Adv Chronic Kidney Dis. 2009;16(2):76–82
  68. Kamgar M, Zaldivar F, Vaziri ND, Pahl MV. Antioxidant therapy does not ameliorate oxidative stress and inflammation in patients with end-stage renal disease. J Natl Med Assoc. 2009;101(4):336–344
  69. Sirover WD, Siddiqui AA, Benz RL. Beneficial hematologic effects of daily oral ascorbic acid therapy in ESRD patients with anemia and abnormal iron homeostasis: a preliminary study. Renal Failure. 2008;30(9):884–889
  70. Keven K, et al. Randomized, crossover study of the effect of vitamin C on EPO response in hemodialysis patients. Am J Kidney Dis. 2003;41(6):1233–1239
  71. Attallah N, Osman-Malik Y, Frinak S, Besarab A. Effect of intravenous ascorbic acid in hemodialysis patients with EPO-hyporesponsive anemia and hyperferritinemia. Am J Kidney Dis. 2006;47(4):644–654
  72. Tarng DC, Huang TP, Wei YH. Erythropoietin and iron: the role of ascorbic acid. Nephrol Dial Transplant. 2001;16(Suppl. 5):35–39
  73. Giancaspro V, et al. Intravenous ascorbic acid in hemodialysis patients with functional iron deficiency: a clinical trial. J Nephrol. 2000;13(6):444–449
  74. Kletzmayr J, Mayer G, Legenstein G, et al. Anemia and carnitine supplementation in hemodialyzed patients. Kidney Int. 1999;55(Suppl. 69):93–106
  75. Labonia WD. l-Carnitine effects on anemia in hemodialyzed patients treated with erythropoietin. Am J Kidney Dis. 1995;26:757–764

PII: S0268-960X(09)00054-X

doi: 10.1016/j.blre.2009.09.001

Blood Reviews
Volume 24, Issue 1 , Pages 39-47 , January 2010