Erythropoiesis Stimulating Agents (ESAs) in the Treatment of Cardio-Renal Syndrome Anaemia


Coexistence of chronic kidney disease (CKD) and chronic heart failure (CHF) define a recently recognized clinical entity known as cardio-renal syndrome. Sufficient evidence suggests that the two pathological conditions share common pathogenic etiology which is not yet fully defined. Superimposed anaemia is a common finding among patients suffering from cardio-renal syndrome. The combination of CKD, CHF and anaemia increase the probability of death by 6 times compared to normal individuals. Early attempts to restore anaemia either by iron supplementation, erythropoiesis stimulating agents (ESAs) or combination of the two have reported to improve quality of life, morbidity and mortality especially among patients treated by cardiologists. Recent publications of well controlled epidemiological studies failed to prove convincing beneficial effect of the above mentioned therapy moreover skepticism has raised concerning the safety of restoring anaemia among patients with cardio-renal syndrome as well as used medications. There are still unresolved problems concerning the definition of anaemia, by means of hemoglobin level among these patients, the target hemoglobin level and the therapeutic regimen of ESAs administration and iron supplementation. We need much more evidence in order to define an effective and safe treatment strategy correcting anaemia among patients with cardio-renal syndrome.

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I. Koulouridis and E. Koulouridis, "Erythropoiesis Stimulating Agents (ESAs) in the Treatment of Cardio-Renal Syndrome Anaemia," Open Journal of Nephrology, Vol. 2 No. 3, 2012, pp. 23-28. doi: 10.4236/ojneph.2012.23004.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] C. Longhini, C. Molino and F. Fabbian Cardiorenal, “Syndrome: Still Not a Defined Entity,” Clinical and Experimental Nephrology, Vol. 14, No. 1, 2010, pp. 12-21. Hdoi:10.1007/s10157-009-0257-4
[2] C. Ronco, P. McCollough, S. D. Anker, I. Anand, N. Aspromonte, S. M.Bagshaw, et al., “For the Acute Dialysis Quality Initiative (ADQI) Consensus Group. Cardio-Renal Syndromes: Report from the Consensus Conference of the Acute Dialysis Quality Initiative,” European Heart Journal, Vol. 31, No. 6, 2010, pp. 703-711. Hdoi:10.1093/eurheartj/ehp507
[3] H. M. Krumholtz, Y. T. Chen, V. Vaccarino, Y. Wang, M. J. Radford, W. D. Bradford, et al., “Correlates and Impact on Outcomes of Worsening Renal Function in Patients ≥ 65 Years of Age with Heart Failure,” American Journal of Cardiology, Vol. 85, No. 9, 2000, pp. 1110-1113. Hdoi:10.1016/S0002-9149(00)00705-0
[4] D. E. Forman, J. Butler, Y. Wang, W. T. Abraham, C. M. O’Conor, S. S. Gottlieb, et al., “Incidence, Predictors at Admission, and Impact of Worsening Renal Function among Patients Hospitalized with Heart Failure,” Journal of the American College of Cardiology, Vol. 43, No. 1, 2004, pp. 61-67. Hdoi:10.1016/j.jacc.2003.07.031
[5] R. N. Foley, A. M. Murray, S. Li, C. A. Herzog, A. M. McBean, P. W. Eggers and A. J. Collins, “Chronic Kidney Disease and the Risk for Cardiovascular Disease, Renal Replacement, and Death in the United States Medicare Population, 1998 to 1999,” Journal of American Society of Nephrology, Vol. 16, No. 2, 2005, pp. 498-495. Hdoi:10.1681/ASN.2004030203
[6] G. C. Fonarow, K. F. Adams, W. T. Abraham, C. W. Yancy and W. J. Boscardin, “For the ADHERE Scientific Advisory Committee, Study Group, and Investigators. Risk Stratification for In-Hospital Mortality in Acutely Decompensated Heart Failure: Classification and Regression Tree Analysis,” The Journal of the American Medical Association, Vol. 293, No. 5, 2005, pp. 572-580.
[7] G. L. Smith, J. H. Lichtman, M. B. Bracken, M. G. Shlipak, C. O. Phillips, P. DiCapua, et al., “Renal Impairment and Outcome in Heart Failure. Systematic Review and Meta-Analysis,” Journal of the American College of Cardiology, Vol. 47, No. 10, 2006, pp. 1987-1996. Hdoi:10.1016/j.jacc.2005.11.084
[8] A. Kazory and E. A. Ross, “Anemia: The Point of Convergence or Divergence for Kidney Disease and Heart Failure,” Journal of the American College of Cardiology, Vol. 53, No. 8, 2009, pp. 639-647. Hdoi:10.1016/j.jacc.2008.10.046
[9] W. McClellan, S. L. Aronoff, W. K. Bolton, S. Hood, D. L. Lorber, K. L. Tang, et al., “The Prevalence of Anemia in Patients with Chronic Kidney Disease,” Current Medical Research and Opinion, Vol. 20, No. 9, 2004, pp. 1501-1510. Hdoi:10.1185/030079904X2763
[10] A. Sandhu, S. Soman, M. Hudson and A. Besarab, “Managing Anemia in Patients with Chronic Heart Failure; What Do We Know?” Vascular Health and Risk Management, Vol. 15, No. 6, 2010, pp. 237-252.
[11] D. V. Vlahakos, K. P. Marathias and N. E. Madias, “The Role of the Renin-Angiotensin System in the Regulation of Erythropoiesis,” American Journal of Kidney Diseases, Vol. 56, No. 3, 2010, pp. 558-565. Hdoi:10.1053/j.ajkd.2009.12.042
[12] P. van der Meer, D. J. Lok, J. L. Januzzi, P. W. de la Porte, E. Lipsic, J. Van Wijngaarden, et al., “Adequacy of Endogenous Erythropoietin Levels and Mortality in Anaemic Heart Failure Patients,” European Heart Journal, Vol. 29, No. 12, 2008, pp. 1510-1515. Hdoi:10.1093/eurheartj/ehn205
[13] J. W. Eschbach and J. W. Adamson, “Anemia of End-Stage Renal Disease (ESRD),” Kidney International, Vol. 28, No. 1, 1985, pp. 1-5. Hdoi:10.1038/ki.1985.109
[14] A. K. Abu-Alfa, “CKD Series: Evaluation and Treatment of Anemia in Chronic Kidney Disease,” Hospital Physician, Vol. 39, No. 7, 2003, pp. 31-38, 46.
[15] G. Remuzzi and J. R. Ingelfinger, “Correction of Anemia-Payoffs and Problems,” The New England Journal of Medicine, Vol. 355, No. 20, 2006, pp. 2144-2146. Hdoi:10.1056/NEJMe068233
[16] T. B. Drueke, F. Locatelli, N. Clyne, K. U. Eckardt, I. C. MacDougall, D. Tsakiris, et al., (for the CREATE investigators), “Normalization of hemoglobin level in patients with chronic kidney disease and anemia,” The New England Journal of Medicine, Vol. 355, No. 20, 2006, pp. 2071-2084. Hdoi:10.1056/NEJMoa062276
[17] A. K. Singh, L. Szczech, K. L. Tang, H. Barnhart, S. Sapp, M. Wolfson, et al., (for the CHOIR Investigators), “Correction of Anemia with Epoetin Alfa in Chronic Kidney Disease,” The New England Journal of Medicine, Vol. 355, No. 20, 2006, pp. 2085-2098. Hdoi:10.1056/NEJMoa065485
[18] J. K. Ghali, I. S. Anand, W. T. Abraham, G. C. Fonarow, B. Greenberg, H. Krum, et al., (for the STAMINA-HeFT Group), “Randomized Double-Blind Trial of Darbepoetin Alfa in Patients with Symptomatic Heart Failure and Anemia,” Circulation, Vol. 117, No. 4, 2008, pp. 526-535. Hdoi:10.1161/CIRCULATIONAHA.107.698514
[19] M. A. Pfeffer, E. A. Burdmann, C. Y. Chen, M. E. Cooper, D. de Zeeuw, K. U. Eckardt, et al., (for the TREAT Investigators), “A Trial of Darbepoetin Alfa in Type 2 Diabetes and Chronic Kidney Disease,” The New England Journal of Medicine, Vol. 361, No. 21, 2009, pp. 2019-2032. Hdoi:10.1056/NEJMoa0907845
[20] S. D. Solomon, H. Uno, E. F. Lewis, K. U. Eckardt, J. Lin, E. A. Burdmann, et al., (for the TREAT Investigators), “Erythropoietic Response and Outcomes in Kidney Disease and Type 2 Diabetes,” The New England Journal of Medicine, Vol. 363, No. 12, 2010, pp. 1146-1155. Hdoi:10.1056/NEJMoa1005109
[21] Y. Zhang, M. Thamer, J. S. Kaufman, D. J. Cotter and M. A. Herman, “High Doses of Epoetin Do Not Lower Mortality and Cardiovascular Risk among Elderly Hemodialysis Patients with Diabetes,” Kidney International, Vol. 80, No. 6, 2011, pp. 663-669. Hdoi:10.1038/ki.2011.188
[22] I. Koulouridis, M. Alfayez, T. Trikalinos, E. M. Balk and B. L. Jaber, “Dose of Erythropoiesis-Stimulating Agents (ESAs) and Adverse Outcomes in Chronic Kidney Disease (CKD): A Meta-Regression,” Poster Presentation, American Society of Nephrology Kidney Week 2011, 8-13 November 2011, Philadelphia.
[23] National Kidney Foundation KDOQI, “Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease,” American Journal of Kidney Diseases, Vol. 47, Suppl. 3, 2006, pp. S11-S15. Hdoi:10.1053/j.ajkd.2006.03.010
[24] J. J. V. McMurray, I. S. Anand, R. Diaz, A. P. Maggioni, C. O’Connor, M. A. Pfeffer, et al., (on Behalf of the RED-HF Committees and Investigators), “Design of the Reduction of Events with Darbepoetin Alfa in Heart Failure (RED-HF): A Phase III, Anaemia Correction, Morbidity-Mortality Trial,” European Journal of Heart Failure, Vol. 11, No. 8, 2009, pp. 795-801. Hdoi:10.1093/eurjhf/hfp098
[25] K. Van der Putten, K. E. Jie, M. E. Emans, J. A. Joles, M. J.Cramer , B. K. Velthuis, et al., “Erythropoietin Treatment in Patients with Combined Heart and Renal Failure: Objectives and Design of the EPOCARES Study,” Journal of Nephrology, Vol. 23, No. 4, 2010, pp. 363-368.

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