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Red cell transfusion in chronic kidney disease in the United States in the current era of erythropoiesis stimulating agents

Journal of Nephrology volume 33, pages 267–275 (2020)Cite this article

Abstract

Anemia is a major complication of chronic kidney disease (CKD) that leads to many symptoms of this disease and worsens cardiovascular health. Treatment of this condition was revolutionized three decades ago by the commercial availability of recombinant human erythropoietin which held the promise of completely eliminating the need for red blood cell transfusion (RBCT). Despite specific therapy now available for anemia in CKD, clinical data accumulated in the last 2 decades suggests that there is a continued need for RBCT, which, we surmise, is due to underutilization of Erythropoietin Stimulating Agents (ESA) or clinical settings such as active bleed, bone marrow resistance such as myelofibrosis or infections where ESAs are ineffective. The purpose of this narrative review is to highlight the adverse effects and summarize the current patterns of RBCT use in all stages of CKD while elaborating on the clinical characteristics of patients that increases their risks of transfusion exposure. We discuss, briefly, salient features of the pathophysiology of anemia in CKD and its contemporary therapies while presenting our perspectives on how to optimize transfusion strategies without compromising patient safety.

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Fig. 1
Fig. 2

(Reproduced with permission from [35])

Fig. 3

Adapted from Cappell KA, Shreay S, Cao Z, Varker HV, Paoli CJ, Gitlin M. Red blood cell (RBC) transfusion rates among US chronic dialysis patients during changes to Medicare end-stage renal disease (ESRD) reimbursement systems and erythropoiesis stimulating agent (ESA) labels. BMC Nephrol. 2014; 15:116

Fig. 4

References

  1. Babitt JL, Lin H (2012) Mechanisms of anemia in CKD. J Am Soc Nephrol 23(10):1631–1634

    CAS  Article  Google Scholar 

  2. Eschbach JW (1989) The anemia of chronic renal failure: pathophysiology and the effects of recombinant erythropoietin. Kidney Int 35(1):134–148

    CAS  Article  Google Scholar 

  3. Erslev A (1953) Humoral regulation of red cell production. Blood 8:349–357

    CAS  Article  Google Scholar 

  4. Eschbach JW, Abdulhadi MH, Browne JK, Delano BG, Downing MR, Egrie JC (1990) Recombinant human erythropoietin in anemic patients with end-stage renal disease: results of a phase III multicenter clinical trial. Ann Int Med 111(12):992–1000

    Article  Google Scholar 

  5. Johansen KL, Finkelstein FO, Revicki DA, Evans C, Wan S, Gitlin M (2012) Systematic review of the impact of erythropoiesis-stimulating agents on fatigue in dialysis patients. Nephrol Dial Transpl 27(6):2418–2425

    CAS  Article  Google Scholar 

  6. McMurray J, Parfrey P, Adamson JW, Aljama P, Berns JS, Bohlius J (2012) Kidney disease: improving global outcomes (KDIGO) anemia work group. KDIGO clinical practice guideline for anemia in chronic kidney disease. Kidney Int Suppl 2(4):279

    Article  Google Scholar 

  7. Tanhehco YC, Berns JS (2012) Red blood cell transfusion risks in patients with end-stage renal disease. Semin Dial 25(5):539–544

    Article  Google Scholar 

  8. Pfeffer MA, Burdmann EA, Chen CY, Cooper ME, De Zeeuw D, Eckardt KU (2009) A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med 361(21):2019–2032

    Article  Google Scholar 

  9. Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M (2006) Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 355(20):2085–2098

    CAS  Article  Google Scholar 

  10. United States Renal Data System. 2018 USRDS annual data report: Epidemiology of kidney disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD. https://www.usrds.org/2018/view/v2_02.aspx. Accessed 17 Feb 2019

  11. Goel R, Chappidi MR, Patel EU, Ness PM, Cushing MM, Frank SM (2018) Trends in red blood cell, plasma, and platelet transfusions in the United States, 1993–2014. JAMA 319(8):825–827

    Article  Google Scholar 

  12. St Peter WL, Guo H, Kabadi S, Gilbertson DT, Peng Y, Pendergraft T (2018) Prevalence, treatment patterns, and healthcare resource utilization in Medicare and commercially insured non-dialysis-dependent chronic kidney disease patients with and without anemia in the United States. BMC Nephrol. 19(1):67. https://bmcnephrol.biomedcentral.com/track/pdf/10.1186/s12882-018-0861-1. Accessed 19 May 2019

  13. Gill KS, Muntner P, Lafayette RA, Petersen J, Fink JC, Gilbertson DT (2013) Red blood cell transfusion uses in patients with chronic kidney disease. Nephrol Dial Transpl 28(6):1504–1515

    CAS  Article  Google Scholar 

  14. Vaziri ND, Zhou XJ (2008) Potential mechanisms of adverse outcomes in trials of anemia correction with erythropoietin in chronic kidney disease. Nephrol Dial Transpl 24(4):1082–1088

    Article  Google Scholar 

  15. Hsu CY, McCulloch CE, Curhan GC (2002) 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 13(2):504–510

    Article  Google Scholar 

  16. Moreno F, Aracil FJ, Pérez R, Valderrábano F (1996) 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 27(4):548–556

    CAS  Article  Google Scholar 

  17. Levin A, Singer J, Thompson CR, Ross H, Lewis M (1996) Prevalent left ventricular hypertrophy in the predialysis population: identifying opportunities for intervention. Am J Kidney Dis 27(3):347–354

    CAS  Article  Google Scholar 

  18. Parfrey PS, Lauve M, Latremouille-Viau D, Lefebvre P (2009) Erythropoietin therapy and left ventricular mass index in CKD and ESRD patients: a meta-analysis. Clin J Am Soc Nephrol 4(4):755–762

    CAS  Article  Google Scholar 

  19. Palmer SC, Navaneethan SD, Craig JC, Johnson DW, Tonelli M, Garg AX (2010) Meta-analysis: erythropoiesis-stimulating agents in patients with chronic kidney disease. Ann Intern Med 153:23–33

    Article  Google Scholar 

  20. Johnson DW (2016) Erythropoietin corrects anemia and reduces the risk of blood transfusion in people with chronic kidney disease, but has uncertain effects on other patient-level outcomes. BMJ Evid-Based Med 21:178

    Article  Google Scholar 

  21. Palmer SC, Saglimbene V, Craig JC, Navaneethan SD, Strippoli GFM (2014) Darbepoetin for the anemia of chronic kidney disease. Cochrane Database Syst Rev (3):CD009297. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD009297.pub2/epdf/full. Accessed 19 May 2019

  22. National Collaborating Centre for Chronic Conditions, Royal College of Physicians (2015). Guideline on anaemia management in chronic kidney disease. National Institute for Clinical Excellence. Available on http://www.nice.org.uk/guidance/NG8/evidence. Accessed 26 Aug 2019

  23. Locatelli F, Bárány P, Covic A et al (2013) Kidney disease: improving global outcomes guidelines on anaemia management in chronic kidney disease: a European renal best practice position statement. Nephrol Dial Transpl 28(6):1346–1359

    CAS  Article  Google Scholar 

  24. Besarab A, Bolton WK, Browne JK, Egrie JC, Nissenson AR, Okamoto DM (1998) 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 339(9):584–590

    CAS  Article  Google Scholar 

  25. Chaknos CM, Berns JS (2013) Erythropoiesis-stimulating agents on trial: are higher dosages causing harm? Am J Kidney Dis 61(1):6–8

    Article  Google Scholar 

  26. Carson JL, Triulzi DJ, Ness PM (2017) Indications for and adverse effects of red-cell transfusion. N Engl J Med 377(13):1261–1272

    Article  Google Scholar 

  27. Zou S, Dorsey KA, Notari EP, Foster GA, Krysztof DE, Musavi F (2010) Prevalence, incidence, and residual risk of human immunodeficiency virus and hepatitis C virus infections among United States blood donors since the introduction of nucleic acid testing. Transfusion 50(7):1495–1504

    Article  Google Scholar 

  28. Blajchman MA, Goldman M, Freedman JJ, Sher GD (2001) Proceedings of a consensus conference: prevention of post-transfusion CMV in the era of universal leukoreduction. Transfus Med Rev 15:1–20

    CAS  Article  Google Scholar 

  29. Fang DC, McCullough J (2016) Transfusion transmitted Babesia microti. Transfus Med Rev 30:132–138

    Article  Google Scholar 

  30. Scornik JC, Bromberg JS, Norman DJ, Bhanderi M, Gitlin M, Petersen J (2013) An update on the impact of pre-transplant transfusions and allosensitization on time to renal transplant and on allograft survival. BMC Nephrol 14:217. https://bmcnephrol.biomedcentral.com/track/pdf/10.1186/1471-2369-14-217. Accessed 19 May 2019

  31. Opelz G, Graver B, Mickey MR, Terasaki P (1981) Lymphocytotoxic antibody responses to transfusions in potential kidney transplant recipients. Transplantation 32(3):177–183

    CAS  Article  Google Scholar 

  32. Naci H, de Lissovoy G, Hollenbeak C, Custer B, Hofmann A, McClellan W et al (2012) Historical clinical and economic consequences of anemia management in patients with end-stage renal disease on dialysis using erythropoietin stimulating agents versus routine blood transfusions: a retrospective cost-effectiveness analysis. J Med Econ 15(2):293–304

    Article  Google Scholar 

  33. Glenngård AH, Persson U, Schön S (2008) Cost-effectiveness analysis of treatment with epoetin-α for patients with anemia due to renal failure: the case of Sweden. Scand J Urol Nephrol 42(1):66–73

    Article  Google Scholar 

  34. Maoujoud O, Ahid S, Cherrah Y (2016) The cost-utility of treating anemia with continuous erythropoietin receptor activator or Epoetin versus routine blood transfusions among chronic hemodialysis patients. Int J Nephrol Renovasc Dis 9:35–43

    CAS  Article  Google Scholar 

  35. Hauber B, Caloyeras J, Posner J, Brommage D, Tzivelekis S, Pollock A (2017) Hemodialysis patients’ preferences for the management of anemia. BMC Nephrol. 18(1):254. https://bmcnephrol.biomedcentral.com/track/pdf/10.1186/s12882-017-0664-9. Accessed 19 May 2019

  36. Collins AJ, Foley RN, Herzog C, Chavers B, Gilbertson D, Ishani A (2011) US Renal Data System 2010 annual data report. Am J Kidney Dis 57(1 suppl 1):e1–e526

    Google Scholar 

  37. Collins AJ, Foley RN, Herzog C, Chavers B, Gilbertson D, Herzog C (2013) US Renal Data System 2012 annual data report. Am J Kidney Dis 61(1 suppl 1):e1–e476

    Google Scholar 

  38. Department of Health and Human Services, Centers for Medicare & Medicaid Services(2010) 42 CFR Parts 410, 413, and 414; medicare program; end-stage renal disease prospective payment system; final rule and proposed rule. http://www.access.gpo.gov 75[155]. Accessed 19 Mar 2019

  39. FDA(2011). FDA drug safety communication: modified dosing recommendations to improve the safe use of erythropoiesis-stimulating agents in chronic kidney disease. http://www.fda.gov/Drugs/DrugSafety/ucm259639.htm. Accessed 29 Apr 2019

  40. Centers for Medicare and Medicaid Services. https://www.cms.gov/Medicare/Quality-Initiatives-Patient-Assessment-Instruments/ESRDQIP/Downloads/PY_2013_Program_Details.pdf. Accessed 29 Apr 2019

  41. http://www.gao.gov/products/GAO-13-190R. Accessed 18 Mar 2019

  42. Collins AJ, Monda KL, Molony JT, Li S, Gilbertson DT, Bradbury BD (2014) Effect of facility-level hemoglobin concentration on dialysis patient risk of transfusion. Am J Kidney Dis 63(6):997–1006

    CAS  Article  Google Scholar 

  43. Cappell KA, Shreay S, Cao Z, Varker HV, Paoli CJ, Gitlin M (2014) Red blood cell (RBC) transfusion rates among US chronic dialysis patients during changes to Medicare end-stage renal disease (ESRD) reimbursement systems and erythropoiesis stimulating agent (ESA) labels. BMC Nephrol 15:116. https://doi.org/10.1186/1471-2369-15-116

    Article  PubMed  PubMed Central  Google Scholar 

  44. Park H, Liu X, Henry L, Harman J, Ross EA (2018) Trends in anemia care in non-dialysis-dependent chronic kidney disease (CKD) patients in the United States (2006–2015). BMC Nephrol. 19(1):318. https://bmcnephrol.biomedcentral.com/track/pdf/10.1186/s12882-018-1119-7. Accessed 19 May 2019

  45. Fuller DS, Bieber BA, Pisoni RL, Li Y, Hal Morgenstern, Akizawa T (2016) International comparisons to assess effects of payment and regulatory changes in the United States on Anemia Practice in patients on hemodialysis: the dialysis outcomes and practice patterns study. J Am Soc Nephrol 27(7):2205–2215

    CAS  Article  Google Scholar 

  46. Sibbel SP, Koro CE, Brunelli SM, Cobitz AR (2015) Characterization of chronic and acute ESA hyporesponse: a retrospective cohort study of hemodialysis patients. BMC Nephrol. 16:144. https://bmcnephrol.biomedcentral.com/track/pdf/10.1186/s12882-015-0138-x. Accessed 19 May 2019

  47. Bello AK, Ribic CM, Cournoyer SH, Kiaii M, LeBlanc M, Poulin-Costello M (2018) Transfusion Management of Incident Dialysis Patients in Canada: A Prospective Observational Study. Can J Kidney Health Dis. 5:2054358118778564. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5992794/pdf/10.1177_2054358118778564.pdf. Accessed 19 May 2019

  48. Fox KM, Yee J, Cong Z, Brooks JM, Petersen J, Lamerato L (2012) Transfusion burden in non-dialysis chronic kidney disease patients with persistent anemia treated in routine clinical practice: a retrospective observational study. BMC Nephrol. 13:5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3283448/pdf/1471-2369-13-5.pdf. Accessed 19 May 2019

  49. Lawler EV, Bradbury BD, Fonda JR, Gaziano JM, Gagnon DR (2010) Transfusion burden among patients with chronic kidney disease and anemia. Clin J Am Soc Nephrol 25(4):667–672

    Article  Google Scholar 

  50. Whitman CB, Shreay S, Gitlin M, Van Oijen MG, Spiegel BM (2013) Clinical factors and the decision to transfuse chronic dialysis patients. Clin J Am Soc Nephrol 8(11):1942–1951

    Article  Google Scholar 

  51. Foley RN, Curtis BM, Parfrey PS (2008) Hemoglobin targets and blood transfusions in hemodialysis patients without symptomatic cardiac disease receiving erythropoietin therapy. Clin J Am Soc Nephrol 3(6):1669–1675. https://doi.org/10.2215/CJN.02100508

    Article  PubMed  PubMed Central  Google Scholar 

  52. Carson JL, Stanworth SJ, Roubinian N, Fergusson DA, Triulzi D, Doree C (2016) Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion. Cochrane Database of Syst Rev. Issue 10. Art. No.: CD002042. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD002042.pub4/epdf/full. Accessed 19 May 2019

  53. Carson JL, Terrin ML, Noveck H, Sanders DW, Chaitman BR, Rhoads GG (2011) Liberal or restrictive transfusion in high-risk patients after hip surgery. N Engl J Med 365(26):2453–2462

    CAS  Article  Google Scholar 

  54. Atkins D, Eccles M, Flottorp S, Guyatt GH, Henry D, Hill S (2004) Systems for grading the quality of evidence and the strength of recommendations I: critical appraisal of existing approaches The GRADE Working Group. BMC health services research. 4(1):38. https://bmchealthservres.biomedcentral.com/track/pdf/10.1186/1472-6963-4-38. Accessed 19 May 2019

  55. Carson JL, Guyatt G, Heddle NM et al (2016) Clinical practice guidelines from the AABB: red blood cell transfusion thresholds and storage. JAMA 316:2025–2035

    Article  Google Scholar 

  56. Vora AN, Stanislawski M, Grunwald GK, Plomondon ME, Rumsfeld JS, Maddox TM (2017) Association Between Chronic Kidney Disease and Rates of Transfusion and Progression to End-Stage Renal Disease in Patients Undergoing Transradial Versus Transfemoral Cardiac Catheterization-An Analysis from the Veterans Affairs Clinical Assessment Reporting and Tracking (CART) Program. J Am Heart Assoc. 6(4):e004819. https://www.ahajournals.org/doi/pdf/10.1161/JAHA.116.004819. Accessed 19 May 2019

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Acknowledgements

We wish to sincerely thank Drs Elizabeth Adams-Eilers and Dr Robert P. Eilers for their valuable comments and suggestions in preparing this manuscript.

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  1. Division of Nephrology, Department of Medicine, Georgetown University/Washington Hospital Center, 110 Irving Street, Suite 2A 50, Washington, DC, NW, 20010, USA

    Nicole Brenner, Muhammad Ahsan & Anirban Ganguli

  2. University of South Carolina, Columbia, SC, USA

    Anuhya Kommalapati

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Brenner, N., Kommalapati, A., Ahsan, M. et al. Red cell transfusion in chronic kidney disease in the United States in the current era of erythropoiesis stimulating agents. J Nephrol 33, 267–275 (2020). https://doi.org/10.1007/s40620-019-00680-5

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Keywords

  • Red cell transfusion
  • Chronic kidney disease
  • Anemia