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Renal Anemia pp 99–106Cite as

Do ACE inhibitors limit response to EPO and should EPO be continued in patients with sepsis or fever?

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Abstract

Angiotensin-converting-enzyme inhibitors (ACEI) are a class of antihypertensive drugs that block the formation of angiotensin II, thereby abrogating the vasoconstrictive and trophic properties of this compound. They have been shown to decrease cardiovascular mortality [1] and decline in progression of both diabetic and non-diabetic renal disease [2, 3]. The cardiovascular benefit of ACEI may be extended to patients with end stage renal disease on dialysis given the high prevalence of diabetes, hypertension and other risk factors [4, 5]. Among other side effects such as cough and hyperkalemia, one observation of interest is the development or worsening of anemia and increased requirement for erythropoietin (EPO) when ACEI are used in dialysis or transplant patients. It has been suggested that ACEI may induce anemia in dialysis patients by reducing the production of residual endogenous EPO, by raising serum levels of an inhibitor of erythropoiesis or directly inhibiting bone marrow erythropoiesis. Clinical studies, mostly retrospective data addressing this question have been anecdotal. While some studies suggest that anemia can be induced by ACEI in dialysis patients, others do not support this notion. The controversy regarding the use of EPO in dialysis patients with fever or sepsis will also be discussed.

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References

  1. Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000;342:145–53.

    Article  PubMed  CAS  Google Scholar 

  2. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med. 1993;329:1456–62.

    Article  PubMed  CAS  Google Scholar 

  3. Ruggenenti P, Perna A, Gherardi G, Garini G, Zoccali C, Salvadori M, Scolari F, Schena FP, Remuzzi G. Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria. Lancet. 1999;354:359–64.

    Article  PubMed  CAS  Google Scholar 

  4. Collins AJ, Li S, Ma JZ, Herzog C. Cardiovascular disease in end-stage renal disease patients. Am J Kidney Dis. 2001;38:S26–9.

    Article  PubMed  CAS  Google Scholar 

  5. U.S. Renal Data System: USRDS 2000 Annual Data Report, The National Institute of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, June 2000.

    Google Scholar 

  6. Kurtz A, Eckardt KU, Neumann R, Kaissling B, LeHir M, Bauer C. Site of erythropoietin formation. Contr Nephrol. 1989;76:14–23.

    CAS  Google Scholar 

  7. Koury ST, Bondurant MC, Koury MJ. Localization of erythropoietin sensitizing cells in murine kidney by in situ hybridization. Blood. 1988;71:524–7.

    PubMed  CAS  Google Scholar 

  8. Lacombe C, Da Silva JL, Bruneval P, Fournier JG, Wendling F, Casadevall N, Camilleri JP, Bariety J, Varet B, Tambourin P. Peritubular cells are the site of erythropoietin synthesis in the murine hypoxic kidney. J Clin Invest. 1988;81: 620–3.

    Article  PubMed  CAS  Google Scholar 

  9. Scholz H, Schurek HJ, Eckardt KU, Bauer C. Role of erythropoietin in adaptation to hypoxia. Experientia. 1990;46:1197–201.

    Article  PubMed  CAS  Google Scholar 

  10. Osswald H, Gleiter C, Muhlbauer B. Therapeutic use of theophylline to antagonize renal effects of adenosine. Clin Nephrol. 1995;43(supplement 1):S33–7.

    PubMed  Google Scholar 

  11. Grekas D, Dioudis C, Valkouma D, Papoulidou F, Tourkantonis A. Theophylline modulates erythrocytosis after renal transplantation. Nephron. 1995;70:25–7.

    Article  PubMed  CAS  Google Scholar 

  12. Vlahakos DV, Balodimos C, Papachristopoulos V, Vassilakos P, Hinari E, Vlachojannis JG. Renin angiotensin system stimulates erythropoietin secretion in chronic hemodialysis patients. Clin Nephrol. 1995;43:53–59.

    PubMed  CAS  Google Scholar 

  13. Freyssinier JM, Lecoq-Lafon C, Amsellem S, Picard F, Ducrocq R, Mayeux P, Lacombe C, Fichelson S. Purification, amplification and characterization of a population of human erythroid progenitors. Br J Haematol. 1999;106:912–22.

    Article  PubMed  CAS  Google Scholar 

  14. Hess E, Sperschneider H, Stein G. Do ACE inhibitors influence the dose of human recombinant erythropoietin in dialysis patients? Nephrol Dial Transplantation. 1996;11:749–51.

    Article  CAS  Google Scholar 

  15. Vlahakos DV, Canzanello VJ, Madaio MP, Madias NE. Enalapril-associated anemia in renal transplant recipients treated for hypertension. Am J Kidney Dis. 1991; 17:199–205.

    PubMed  CAS  Google Scholar 

  16. Perazella M, McPherdran P, Kliger A, Lorber M, Levy E, Bia MJ. Enalapril treatment of Posttransplant Erythrocytosis. Am J Kidney Dis. 1995;26:495–500.

    Article  PubMed  CAS  Google Scholar 

  17. Suh BY, Suh JD, Kwun KB. Effect of caporal in the treatment of erythrocytosis after renal transplantation. Transpl Proc. 1996;28:1557–8.

    CAS  Google Scholar 

  18. Kupin W, Venkat KK, Goggins M et al. Benefit of angiotensin II receptor blockade in the treatment of posttransplant polycytemia in renal transplant recipients. Transpl Proc. 1997;29:207–8.

    Article  CAS  Google Scholar 

  19. Mrug M, Stopka T, Julian BA, Prchal JF, Prchal JT. Angiotensin II stimulates proliferation of normal early erythroid progenitors. J Clin Invest. 1997;100: 2310–4.

    Article  PubMed  CAS  Google Scholar 

  20. Rodgers KE, Xiong S, Steer R, diZerega GS. Effect of angiotensin II on hematopoietic progenitor cell proliferation. Stem Cells, 2000;18:287–94.

    Article  PubMed  CAS  Google Scholar 

  21. Lenfant M, Wdzieczak-Bakala J, Guittet E, Prome JC, Sotty D and Frindel E. Inhibitor of hematopoietic pluripotent stem cell proliferation: purification and determination of its structure. Proc Natl Acad Sci USA. 1989;86: 779–82.

    Article  PubMed  CAS  Google Scholar 

  22. Bonnet D, Lemoine FM, Ponvert-Delucq S, Baillou C, Najman A, Guignon M. Direct and reversible inhibitory effect of the tetrapeptide acetyl-N-ser-asp-lys-pro (serapenide) on the growth of human CD34+ subpopulations in response to growth factors. Blood. 1993;82:3307–14.

    PubMed  CAS  Google Scholar 

  23. Rieger K-J, Saez-Servent N, Papet M-P, Wdzieczak-Bakala J, Morgat J-L, Thierry J, Voelter W, Lenfant M. Involvement of human plasma angiotensin I-converting enzyme in the degradation of the haemoregulatory peptide N-acetyl seryl aspartyl lysyl proline. Biochem J. 1993; 296:1–6.

    Google Scholar 

  24. Le Meur Y, Lorgeot V, Comte L, Szelag JC, Aldigier JC, Leroux-Robert C, Praloran V. Plasma levels and metabolism of AcSDKP in patients with chronic renal failure: relationship with erythropoietin requirements. Am J Kidney Dis. 2001; 38:510–17.

    Article  PubMed  Google Scholar 

  25. Azizi M, Rousseau A, Ezan E, Guyene T, Michelet S, Grognet J, Lenfant M, Corvol P, Ménard J. Acute angiotensin-converting enzyme inhibition increases the plasma level of the natural stem cell regulator N-acetyl-seryl-aspartyl-lysyl-proline. J Clin Invest. 1996;97:839–44.

    Article  PubMed  CAS  Google Scholar 

  26. Morrone LF, Di Paolo S, Logoluso F, Schena A, Stallone G, Giorgino F, Schena FP. Interference of angiotensin-converting enzyme inhibitors on erythropoiesis in kidney transplant recipients: role of growth factors and cytokines. Transplantation. 1997;64:913–8.

    Article  PubMed  CAS  Google Scholar 

  27. Constantinescu CS, Goodman DB, Ventura ES. Captopril and lisinopril suppress production of interleukin-12 by human peripheral blood mononuclear cells. Immunol Lett. 1998;62:25–31.

    Article  PubMed  CAS  Google Scholar 

  28. Walter J. Does Captopril decrease the effect of human recombinant erythropoietin in hemodialysis patients? Nephrol Dial Transplantation. 1993;8:1428.

    CAS  Google Scholar 

  29. Erturk S, Ates K, Duman N, Karatan O, Erbay B, Ertug E. Unresponsiveness to recombinant human erythropoietin in haemodialysis patients: possible implications of angiotensin converting enzyme inhibitors. Nephrol Dial Transplantation. 1996;11:396–97.

    Article  CAS  Google Scholar 

  30. Matsumura M, Nomura H, Koni I, Mabuchi H. Angiotensin-Converting enzyme inhibitors are associated with the need for increased recombinant human erythropoietin maintenance doses in hemodialysis patients. Nephron. 1997;77: 164–8.

    Article  PubMed  CAS  Google Scholar 

  31. Albitar S, Genin R, Fen-Chong M, Serveaux M-O, Bourgeon B. High dose enalapril impairs the response to erythropoietin treatment in haemodialysis patients. Nephrol Dial Transplantation. 1998;13:1206–10.

    Article  CAS  Google Scholar 

  32. Hess E, Sperschneider H, Stein G. Do ACE inhibitors influence the dose of human recombinant erythropoietin in dialysis patients? Nephrol Dial Transplantation. 1996;11:749–51.

    Article  CAS  Google Scholar 

  33. Erturk S, Nergizoglu G, Ates K, Duman N, Erbay B, Karatan O, Ertug AE. The impact of weaning of ACE inhibitors on erythropoietin responsiveness and left ventricular hypertrophy in haemodialysis patients. Nephrol Dial Transplantation. 1999;14:1912–16.

    Article  CAS  Google Scholar 

  34. Onoyama K, Sanai T, Motomura K, Fujishima M. Worsening of anemia by angiotensin converting enzyme inhibitors and its prevention by antiestrogenic steroid in chronic hemodialysis patients. J Cardiovasc Pharmacol. 1989;13:S27–30.

    Article  PubMed  Google Scholar 

  35. Dhondt AW, Vanholder RC, Ringoir SM. Angiotensin-Converting enzyme inhibitors and higher erythropoietin requirement in chronic haemodialysis patients. Nephrol Dial Transplantation. 1995;10:2107–9.

    CAS  Google Scholar 

  36. Mora C, Navarro JF. Negative effect of angiotensin-converting enzyme inhibitors on erythropoietin response in CAPD patients. Am J Nephrol. 2000;20:248.

    Article  PubMed  CAS  Google Scholar 

  37. Navarro JF, Macia ML, Mora-Fernandez C, Gallego E, Chahin J, Mendez ML, del Castillo N, Rivero A, Garcia J. Effects of angiotensin-converting enzyme inhibitors on anemia and erythropoietin requirements in peritoneal dialysis patients. Adv Peritoneal Dial. 1997;13:257–9.

    CAS  Google Scholar 

  38. Conlon PJ, Albers F, Butterly D, Schwab SJ. ACE inhibitors do not affect erythropoietin efficacy in haemodialysis patients. Nephrol Dial Transplantation. 1994;9:1358.

    CAS  Google Scholar 

  39. Sanchez JA. ACE inhibitors do not decrease r-HuEPO response in patients with end-stage renal failure. Nephrol Dial Transplantation. 1995;10:1476–7.

    CAS  Google Scholar 

  40. Cruz DN, Perazella MA, Abu-Alfa AK, Mahnensmith RL. Angiotensin-converting enzyme inhibitor therapy in chronic hemodialysis patients: any evidence of erythropoietin resistance? Am J Kidney Dis. 1996;28:535–40.

    Article  PubMed  CAS  Google Scholar 

  41. Charytan C, Goldfarb-Rumyantzev A, Wang YF, Schwenk MH, Spinowitz BS. Effect of angiotensin-converting enzyme inhibitors on response to erythropoietin therapy in chronic dialysis patients. Am J Nephrol. 1998;18:498–503.

    Article  PubMed  CAS  Google Scholar 

  42. Schwenk MH, Jumani AQ, Rosenberg CR, Kulogowski JE, Charytan C, Spinowitz BS. Potential angiotensin-converting enzyme inhibitor-epoetin alfa interaction in patients receiving chronic hemodialysis. Pharmacotherapy. 1998;18:627–30.

    PubMed  CAS  Google Scholar 

  43. Kato A, Takita T, Furuhashi M, Takahashi T, Maruyama Y, Hishida A. No effect of losartan on response to erythropoietin therapy in patients undergoing hemodialysis. Nephron. 2000;86:538–9.

    Article  PubMed  CAS  Google Scholar 

  44. Chew CG, Weise MD, Disney APS. The effect of angiotensin II receptor antagonist on the exogenous erythropoietin requirement of haemodialysis patients. Nephrol Dial Transplantation. 1999;14:2047–9.

    Article  CAS  Google Scholar 

  45. Macdougall IC. Poor response to erythropoietin: practical guidelines on investigation and management. Nephrol Dial Transplantation. 1995;10: 607–14.

    Article  CAS  Google Scholar 

  46. Macdougall IC. The role of ACE inhibitors and angiotensin II receptor blockers in the response to epoetin Nephrol Dial Transplantation. 1999;14:1836–41.

    Article  CAS  Google Scholar 

  47. Rusten LS, Jacobsen SE. Tumor necrosis factor (TNF)-alpha directly inhibits human erythropoiesis in vitro: role of p55 and p75 TNF receptors. Blood. 1995; 85:989–96.

    PubMed  CAS  Google Scholar 

  48. Schooley JC, Kullgren B, Allison AC. Inhibition by interleukin-1 of the action of erythropoietin on erythroid precursors and its possible role in the pathogenesis of hypoplastic anaemias. Br J Haematol. 1987;67:11–17.

    Article  PubMed  CAS  Google Scholar 

  49. Allen DA, Breen C, Yaqoob MM, Macdougall IC. Inhibition of CFU-E colony formation in uremic patients with inflammatory disease: role of IFN-gamma and TNF-alpha. J Investig Med. 1999;47:204–11.

    PubMed  CAS  Google Scholar 

  50. Rogiers P, Zhang H, Leeman M, Nagler J, Neels H, Melot C, Vincent JL. Erythropoietin response is blunted in critically ill patients. Intensive Care Med. 1997;23:159–62.

    Article  PubMed  CAS  Google Scholar 

  51. Abel J, Spannbrucker N, Fandrey J, Jelkmann W. Serum erythropoietin levels in patients with sepsis and septic shock. Eur J Haematol. 1996;57:359–63.

    Article  PubMed  CAS  Google Scholar 

  52. Karle H. The pathogenesis of the anaemia of chronic disorders and the role of fever in erythrokinetics. Scand J Haematol. 1974;13:81–6.

    Article  PubMed  CAS  Google Scholar 

  53. Besarab A. Physiological and pharmacodynamic considerations for route of EPO administration. Semin Nephrol. 2000;20:364–74.

    PubMed  CAS  Google Scholar 

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Authors
  1. Moro O. Salifu
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Editors and Affiliations

  1. Inpatient Dialysis Services, SUNY Downstate Medical Center, Brooklyn, New York, USA

    Onyekachi Ifudu (Associate Professor of Medicine, Director) (Associate Professor of Medicine, Director)

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Salifu, M.O. (2002). Do ACE inhibitors limit response to EPO and should EPO be continued in patients with sepsis or fever?. In: Ifudu, O. (eds) Renal Anemia. Springer, Dordrecht. https://doi.org/10.1007/978-94-015-9998-6_10

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  • DOI: https://doi.org/10.1007/978-94-015-9998-6_10

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-90-481-6045-7

  • Online ISBN: 978-94-015-9998-6

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