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Vol. 31. Issue. 3.May 2011
Pages 0-378
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Good practice guidelines on the use of erythropoiesis-stimulating agents in 2011
Buenas prácticas clínicas para el empleo de los agentes estimulantes de la eritropoyesis en 2011
J.F.. Pérez-Oliva Díaza, Jorge F. Perez-Oliva Diazb
a Direcci��n de Atenci��n al Programa de Enfermedad Renal, Di��lisis y Trasplante Renal, Instituto Nacional de Nefrologia Dr. Abelardo Buch L��pez, La Habana, Cuba,
b Direccion Atencion al Programa Enfermedad Renal, Dialisis y Trasplante Renal, Instituto nacional de Nefrologia "Dr. Abelardo Buch L��pez", La Habana, La Habana, Cuba,
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To the Editor,

As coordinator of the Kidney, Dialysis and Transplant Programme in Cuba, I would be extremely grateful if you could publish this letter. I would like to highlight my opinions regarding the safe use of erythropoiesis-stimulating agents (ESA), and give my contributions on its optimal use, which is currently subject to debate.1

For me, introducing recombinant human erythropoietin (rhEPO) and ESA to clinical practice following replacement dialysis has been one of the most important advances in stage 5 chronic kidney disease (CKD) treatment. These techniques are the best example of how biotechnology has been successfully applied as a clinical treatment as it is used to correct severe anaemia linked with CKD, despite the adverse results highlighted by the most recent prospective and controlled studies.2 Furthermore, we must remember that to do so we have to use supraphysiological doses of erythropoietin, justified by its non-haematopoietic effects.3

The reason why these studies report a greater risk to negative events, mortality and cancer makes us reflect upon important questions that are yet to be completely resolved:

1.   Would the population with the greatest haemoglobin levels and worst results show other rhEPO effects and be likely to have to a homogeneous analysis?

2.   Is the maximum rhEPO dose to be employed for each haemoglobin level clear?

3.   Have we considered that rhEPO dose does not have to be increased to reach any haemoglobin level?

4.   Are patients with adverse effects and a higher ESA dosage those with an accepted ‘accelerated atherosclerosis’ and clinical or subclinical problems determining worse results in terms of mortality, previously hyporesponsive to the ESA (ferric state actually representing a deficit or decreased availability from the deposits, acute inflammation or chronic microinflammation, secondary hyperparathyroidism, among other factors)?

Recently, we are reaching a crucial moment and are currently analysing a prospective, phase IV, multicentre, open, non-controlled study, to assess the effectiveness of Cuban rhEPO. We are assessing haemoglobin levels and rhEPO doses employed over a period of 12 months, the type of response over time (variability), and adverse events. We included 617 patients from 15 nephrology departments throughout Cuba.4

This study highlights problems in controlling haemoglobin levels and rhEPO doses similar to those detected in other international studies.5

I have summarised my opinion based on the current evidence, as a strategy for guaranteeing efficient ESA use with minimum risks and in line with good clinical practice:

1.   Avoid blood transfusions.

2.   Start rhEPO treatment in renal anaemia patients with haemoglobin of 10g/dl.

3.   Keep haemoglobin levels between 11.5g/dl and 13g/dl.

4.   Never try and reach the latter by increasing rhEPO doses.

5.   Question rhEPO doses over 8000U/week.

6.   Use the best intravenous iron products available, depending on the elements of iron metabolism for each patient.

7.   Increase the clinical method, scientific and rigorous search of the factors concerning a lack of response that are associated with ESA, undertake energetic and effective actions on this, and on those well identified mortality factors for patients with stage 5 CKD.

In summary, we must be careful in our prescription and assess the risk-benefit for each haemoglobin level, in accordance with each patient’s characteristics and needs. We must consider that an inadequate EPO response or using it at a high dosage is a risk marker for mortality.

We must not forget that stage 5 CKD patients are becoming increasingly more heterogeneous with regards epidemiological and clinical aspects and related comorbidities.

De Bakris G, Singh A. Managing anemia in��CKD-new insights on a challenging problem. Medscape Nephrology,��December��2010.
Solomon SD, Uno H, Lewis EF, Eckardt KU, Lin J, Burdmann EA, et al.,��Trial to Reduce Cardiovascular Events with Arasnep Therapy (TREAT) Investigators. Erytrhopoietic response and outcomes in kidney disease and type 2 diabetes. N Engl J Med 2010;362(12):1146-55.
Ortega LM, Contreras G. El impacto cl��nico de los efectos fisiol��gicos��de la eritropoyetina (EPO) y de los agentes estimulantes de la eritropoyetina en la incidencia de malignidad, trombosis e hipertensi��n: m��s all�� de la anemia. Nefrologia 2009;29(4):288-94. [Pubmed]
Hasegawa T, Bragg-Gresham JL, Pisoni RL, Robinson BM, Fukuhara S, Akiba T, et al.��Changes in anemia management and hemoglobin levels following revisi��n of a bundling policy to incorp��rate recombinant human erythroppoietin. Kidney Int. Published online 20 October 2010.
P��rez-Oliva DJF. Effectiveness and Safety of ior EPOCIM in patients with Chronic Renal Failure on dialysis methods. Registro P��blico Cubano de Ensayos Cl��nicos. Reference Number: 24-076-07-B. Secondary Identifying Numbers: IIC RD-091. Centro Nacional Coordinador de Ensayos Cl��nicos.
Nefrología (English Edition)

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