Skip to main content

Advertisement

SpringerLink
Log in

Correction of Anemia with Erythropoietin in Chronic Kidney Disease (stage 3 or 4): Effects on Cardiac Performance

  • Published:
Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

Abstract

Background

It is not clear whether the correction of anemia with erythropoietin (rhuEpo) in patients with chronic kidney disease (CKD) has any benefit on cardiac function and geometry. Most studies are based on indices of systolic function and left ventricular mass (LVM) and the results are conflicting.

Patients and methods

We sought to investigate the effect of rhuEpo on LV systolic and diastolic performance using conventional and novel echocardiographic indices. Thirty one patients with CKD (stage 3 or 4) were included. Fifteen patients (group I) treated with rhuEpo targeting at Hb ≥13.0 g/dL, while the remaining (group II) were not treated. Clinical and laboratory parameters were recorded at baseline and 1 year later. Ejection fraction (EF) and LVM were carefully determined. Diastolic function was assessed by mitral inflow indices (E and A wave velocities, Edt deceleration time and E/A) and novel indices of mitral annulus motion using Tissue Doppler Imaging (Em, Am, and E/Em). An index of global cardiac function (Tei) was also calculated.

Results

At baseline, the 2 groups had comparable clinical and laboratory characteristics. After 1 year, a significant improvement in Hb levels (13.6 ± 1.2 vs 10.3 ± 1.2 g/dL, p < 0.05) as well as in systolic and diastolic function indexes was observed in group I compared to group II patients: EF (70.5 ± 7.6 vs 63.4 ± 9.3%, p < 0.05), LVM (116.5 ± 34.9 vs 155.6 ± 51.6 g/m2, p < 0.05), Edt (233.9 ± 98.6 vs 166.9 ± 45.1 ms, p < 0.05), Tei index (0.35 ± 0.12 vs 0.51 ± 0.17, p < 0.01) and E/Em (9.7 ± 2.4 vs 14.8 ± 5.2, p < 0.05), respectively. Blood pressure and heart rate did not show significant changes.

Conclusions

Correction of anemia with rhuEpo in patients with CKD seems to improve cardiac performance and geometry.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risk of death, cardiovascular events, and hospitalization. N Engl J Med 2004;351:1296–305.

    Article  PubMed  CAS  Google Scholar 

  2. Vanholder R, Massy Z, Argiles A, et al. Chronic kidney disease as cause of cardiovascular morbidity and mortality. Nephrol Dial Transplant 2005;20:1048–56.

    Article  PubMed  CAS  Google Scholar 

  3. Fort J. Chronic renal failure: a cardiovascular risk factor. Kidney Int 2005;68:S25–9.

    Article  Google Scholar 

  4. Parfrey PS, Foley RN, Harnett JD, Kent GM, Murray DC, Barre PE. Outcome and risk factors for left ventricular disorders in chronic uraemia. Nephrol Dial Transplant 1996;11:1277–85.

    PubMed  CAS  Google Scholar 

  5. Levin A, Singer J, Thompson CR, Ross H, Lewis M. Prevalent left ventricular hypertrophy in the predialysis population: identifying opportunities for intervention. Am J Kidney Dis 1996;27:347–54.

    PubMed  CAS  Google Scholar 

  6. Levin A, Thompson CR, Ethier J, Carlisle EJ, 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;34:125–34.

    PubMed  CAS  Google Scholar 

  7. Silberberg JS, Barre PE, Prichard SS, Sniderman AD. Impact of left ventricular hypertrophy on survival in end-stage renal disease. Kidney Int 1989;36:286–90.

    Article  PubMed  CAS  Google Scholar 

  8. Foley RN, Parfrey PS, Morgan J, Barre PE, Cambell P, Cartier P, et al. Effect of hemoglobin levels in hemodialysis patients with asymptomatic cardiomyopahty. Kidney Int 2000;58:1325–35.

    Article  PubMed  CAS  Google Scholar 

  9. Ma JZ, Ebben J, Xia H, Collins AJ. Hematocrit level and associated mortality in hemodialysis patients. J Am Soc Nephrol 1999;10:610–9.

    PubMed  CAS  Google Scholar 

  10. Block GA, Hulbert-Shearon TE, Levin NW, Port FK. Association of serum phosphorus and calcium X phosphate product with mortality risk in chronic hemodialysis patients: a national study. Am J Kidney Dis 1988;31:607–7.

    Google Scholar 

  11. Foley RN, Parfrey PS, Harnett JD, Kent GM, Martin CJ, Murray DC, Barre PE. Clinical and echocardiographic disease in patients starting end-stage renal disease therapy. Kidney Int 1995;47:186–92.

    Article  PubMed  CAS  Google Scholar 

  12. Foley RN, Parfrey PS, Kent GM, Harnett JD, Murray DC, Barre PE. Serial change in echocardiographic parameters and cardiac failure in end-stage renal disease. J Am Soc Nephrol 2000;11:912–6.

    PubMed  CAS  Google Scholar 

  13. Portoles J, Torralbo A, Martin P, Rodrigo J, Herrero JA, Barrientos A. Cardiovascular effects or recombinant human erythropoietin in predialysis patients. Am J Kidney Dis 1997;29:541–8.

    PubMed  CAS  Google Scholar 

  14. Hayashi T, Suzuki A, Shoji T, Togawa M, Okada N, Tsubakihara Y, Imai E, Hori M. Cardiovascular effect of normalizing the hematocrit level during erythropoietin therapy in predialsyis patients with chronic renal failure. Am J Kidney Dis 2000;35:250–6.

    PubMed  CAS  Google Scholar 

  15. Roger SD, McMahon LP, Clarkson A, Disney A, Harris D, Hawley C, et al. Effects of early and late intervention with epoetin alpha on left ventricular mass among patients with chronic kidney disease (stage 3 or 4): results of a randomized clinical trial. J Am Soc Nephrol 2004;15:148–56.

    Article  PubMed  CAS  Google Scholar 

  16. Ayus JC, Go AS, Valderrabano F, Verde E, Garcia de Vinuesa S, Achinger SG, Lorenzo V, Arieff AI, Luno J. Effects of erythropoietin on left ventricular hypertrophy in adults with severe chronic renal failure and hemoglobin <10 g/dL. Kidney Int 2005;68:788–95.

    Article  PubMed  CAS  Google Scholar 

  17. Eckart KU, Mcdougall I, Locatelli F, Tsakiris D, Clyne N, Drueke T. Effects of epoetin beta on left ventricular mass in patients with chronic kidney disease: echocardiographic results of the CREATE study. J Am Soc Nephrol 2005;16:37A.

    Google Scholar 

  18. Levin A, Djurdjev O, Thompson C, Barrett B, Ethier J, et al. Canadian randomized trial of haemoglobin maintenance to prevent or delay left ventricular mass growth in patients with CKD. Am J Kidney Dis 2005;46:799–11.

    Article  PubMed  CAS  Google Scholar 

  19. Drueke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D, et al. Normalization of haemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 2006;355:2071–84.

    Article  PubMed  CAS  Google Scholar 

  20. 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;66:753–60.

    Article  PubMed  Google Scholar 

  21. Cockroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16:31–41.

    Google Scholar 

  22. Eckardt KU, Casadevall N. Pure red-cell aplasia due to anti-erythropoietin antibodies. Nephrol Dial Transplant 2003;18:865–9.

    Article  PubMed  Google Scholar 

  23. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499–502.

    PubMed  CAS  Google Scholar 

  24. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005;18:1440–63.

    Article  PubMed  Google Scholar 

  25. Devereux R, Reichek N. Echocardiographic determimation of left ventricular mass in man. Circulation 1997;55:1325–50.

    Google Scholar 

  26. Tei C, Ling LH, Hodge DO, Bailey KR, Oh JK, Rodeheffer RJ, et al. New index of combined systolic and diastolic myocardial performance: a simple and reproducible measure of cardiac function—a study in normals and dilated cardiomyopathy. J Cardiol 1995;26:357–66.

    PubMed  CAS  Google Scholar 

  27. Natsume T. Therapeutic advances in the treatment of LVH. Eur Heart J 1993;14:D33–7.

    Google Scholar 

  28. London GM, Marchais SJ, Guerin AP, Metivier F, Bruno P. Cardiac hypertrophy and arterial alterations in ESRD: hemodynamic factors. Kidney Int 1993;43:S42–9.

    Google Scholar 

  29. Foley RN, Parfrey PS, Harnett JD, Kent GM, Murray DC, Barre PE. The impact of anemia on cardionyopahty, morbidity, and mortality in end-stage renal disease. Am J Kidney Dis 2003;41:520–1.

    Google Scholar 

  30. Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, Reddan D. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 2006;355:2085–98.

    Article  PubMed  CAS  Google Scholar 

  31. Remuzzi G, Ingelfinger JR. Correction of anemia—payoffs and problems. N Engl J Med 2006;355:2144–6.

    Article  PubMed  CAS  Google Scholar 

  32. Van Veldhuisen DJ, McMurray JJV. Are erythropoietin stimulating proteins safe and efficacious in heart failure? Why we need an adequately powered randomised outcome trial. Eur J Heart Fail 2007;9:110–2.

    Article  PubMed  CAS  Google Scholar 

  33. Maiese K, Li F, Chong ZZ. New avenues of exploration for erythropoietin. JAMA 2005;293:90–5.

    Article  PubMed  CAS  Google Scholar 

  34. Bogoyevitch MA. An update on the cardiac effects of erythropoietin cardioprotection by erythropoietin and the lessons learnt from studies in neuroprotection. Cardiovasc Res 2004;63:208–16.

    Article  PubMed  CAS  Google Scholar 

  35. Henry DH, Bowers P, Romano MT, Provenzano R. Epoetin alfa. Clinical evolution of a pleiotropic cytokine. Arch Intern Med 2004;164:262–76.

    Article  PubMed  CAS  Google Scholar 

  36. Ogilvie M, Yu X, Nicolas-Metral V, Pulido SM, Liu C, Ruegg UT, Noguchi CT. Erythropoietin stimulates proliferation and interferes with differentiation of myoblasts. J Biol Chem 2000;275:39754–61.

    Article  PubMed  CAS  Google Scholar 

  37. Tramontano AF, Muniyappa R, Black AD, Blendea MC, Cohen I, Deng L, Sowers JR, Cutaia MV, El-Sherif N. Erythropoietin protects cardiac myocytes from hypoxia-induced apoptosis through an AKT dependent pathway. Biochem Biophys Res Commun 2003;112:990–4.

    Article  CAS  Google Scholar 

  38. Cai Z, Manalo DJ, Wei G, Rodriguez ER, Fox-Talbot K, Lu H, Zweier JL, Semenza GL. Hearts from rodents exposed to intermittent hypoxia or erythropoietin are protected against ischemia–reperfusion injury. Circulation 2003;108:79–85.

    Article  PubMed  CAS  Google Scholar 

  39. Moon C, Krawczyk M, Paik D, Coleman T, Brines M, Juhaszova M, Sollott S, Lakatta EG, Talan MI. Eryhtropoietin reduces myocardial infarction and left ventricular functional decline after coronary artery ligation in rats. Proc Natl Acad Sci U S A 2003;100:11612–7.

    Article  PubMed  CAS  Google Scholar 

  40. Madeddu P, Emanueli C. Switching on reparative angiogenesis: essential role of the vascular erythropoietin receptor. Circ Res 2007;100:599–601.

    Article  PubMed  CAS  Google Scholar 

  41. Westenbrink BD, Lipsic E, van der Meer P, van der Harst P, Oeseburg H, Du Marchie Sarvaas GJ, et al. Erythropoietin improves cardiac function through endothelial progenitor cell and vascular endothelial growth factor mediated neovascularization. Eur Heart J 2007;28:2018–7.

    Article  PubMed  CAS  Google Scholar 

  42. Sohn DW, Chai IH, Lee DJ, Kim HC, Kim HS, Oh BH, et al. Assessment of mitral annulus velocity by Doppler tissue imaging in the evaluation of left ventricular diastolic function. J Am Coll Cardiol 1997;30:474–80.

    Article  PubMed  CAS  Google Scholar 

  43. Ommen SR, Nishimura RA, Appleton CP, Miller FA, Oh JK, Redfield MM, Tajik AJ. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: a comparative simultaneous Doppler-chatheterization study. Circulation 2000;102:1788–94.

    PubMed  CAS  Google Scholar 

  44. Dujardin KS, Tei C, Yeo T, Hodge DO, Rossi A, Seward JB. Prognostic value of a Doppler index combining systolic and diastolic performance in idiopathic-dilated cardiomyopahty. Am J Cardiol 1998;82:1071–6.

    Article  PubMed  CAS  Google Scholar 

  45. Acil T, Wichter T, Stypmann J, Janssen F, Paul M, Grude M, Scheld HH, Breithardt G, Bruch C. Prognostic value of tissue Doppler imaging in patients with chronic congestive heart failure. Int J Cardiol 2005;103:175–81.

    Article  PubMed  Google Scholar 

  46. Benz RL, Pressman MR, Hovick ET, Peterson DD. A preliminary study of the effects of correction of anemia with recombinant human erythropoietin therapy on sleep, sleep disorders, and daytime sleepiness in hemodialysis patients (the SLEEPO study). Am J Kidney Dis 1999;34:1089–95.

    PubMed  CAS  Google Scholar 

  47. McMahon LP, McKenna MJ, Sangkabutra T, Mason K, Sostaric S, Skinner SL, Burge C, Murphy B, Crankshaw D. Physical performance and associated electrolyte changes after haemoglobin normalization: a comparative study in haemodialysis patients. Nephrol Dial Transplant 1999;14:1182–7.

    Article  PubMed  CAS  Google Scholar 

  48. 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;15:1425–30.

    Article  PubMed  CAS  Google Scholar 

  49. Kuriyama S, Tomonari H, Yoshida H, Hashimoto T, Kawaguchi Y, Sakai O. Reversal of anemia by erythropoietin therapy retards the progression of chronic renal failure, especially in nondiabetic patients. Nephron 1997;77:176–85.

    Article  PubMed  CAS  Google Scholar 

  50. Siamopoulos KC, Gouva C, Katopodis KP, Tzallas C, Nikolopoulos P, Papavasiliou EC, Tselepis AD. Long-term treatment with EPO increases serum levels of high-density lipoprotein in patients with CKD. Am J Kidney Dis 2006;48:242–9.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

The authors wish to thank Mrs. Aleka Papageorgiou for the skilled secretarial assistance.

Author information

Authors and Affiliations

  1. Department of Cardiology, Medical School, University of Ioannina, 45110, Ioannina, Greece

    Konstantinos D. Pappas, Panagiotis G. Korantzopoulos, Lampros K. Michalis & John A. Goudevenos

  2. Department of Nephrology, Medical School, University of Ioannina, 45110, Ioannina, Greece

    Chariklia D. Gouva, Konstantinos P. Katopodis, Petros M. Nikolopoulos & Kostas C. Siamopoulos

  3. Department of Internal Medicine, Medical School, University of Ioannina, 45110, Ioannina, Greece

    Kostas C. Siamopoulos

Authors
  1. Konstantinos D. Pappas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chariklia D. Gouva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Konstantinos P. Katopodis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Petros M. Nikolopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Panagiotis G. Korantzopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lampros K. Michalis
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. John A. Goudevenos
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kostas C. Siamopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kostas C. Siamopoulos.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pappas, K.D., Gouva, C.D., Katopodis, K.P. et al. Correction of Anemia with Erythropoietin in Chronic Kidney Disease (stage 3 or 4): Effects on Cardiac Performance. Cardiovasc Drugs Ther 22, 37–44 (2008). https://doi.org/10.1007/s10557-007-6075-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10557-007-6075-6

Key words

Search

Navigation