Foreword
While important advances in the management of anaemia associated with chronic kidney disease (CKD) have been made over the past 20 years, the need to optimize anaemia management continues. Erythropoiesis-stimulating agents (ESAs) have been the best tool in anaemia management since the first ESA, recombinant human erythropoietin (epoetin alfa), was introduced nearly two decades ago. The newer ESA, darbepoetin alfa, allows the move from standard twice- or thrice-weekly administration to extended dosing regimens such as the recently approved once-monthly schedule in suitable patients. This choice increases the opportunities to tailor anaemia treatment to the patients’ needs.ESAs are approved in Europe for treating CKD-associated anaemia in haemodialysis (HD) or peritoneal dialysis (PD) patients as well as in CKD patients not receiving dialysis and in patients with continued renal anaemia following kidney transplant [1]. In terms of anaemia, the last few years have shown us that the risk for adverse outcomes may be greater in patients whose haemoglobin (Hb) levels are not consistently maintained within the target ranges (Hb stability) [2].
The CKD population includes patients with several types and different degrees of comorbidities. Although many patients achieve Hb stability with standard ESA regimens, as discussed here by Bárány and Müller, a significant proportion of patients do not, due to a number of conditions related to either the patient or the treatment [3,4].
The European Best Practice Guidelines (EBPG) for the management of anaemia in patients with chronic kidney disease, published in 1999 and updated in 2004 [1], state that Hb targets for all patients should be above 11 g/dl, but that the upper limit should be adapted to each individual patient. It is recommended that patients with cardiovascular disease or diabetes should maintain Hb levels <12 g/dl, whereas for patients without comorbidities, normalization of Hb could be considered, as this goal may improve quality of life and possibly reduce the risk of adverse events.
Recent pharmacokinetic and pharmacodynamic studies, discussed here by Macdougall et al., indicate that the terminal half-life of darbepoetin alfa is longer than that of other currently available ESAs, and indeed, longer than was initially reported for darbepoetin alfa. The optimal pharmacokinetic and pharmacodynamic profiles of darbepoetin alfa, including its longer half-life, its low binding affinity, and its high erythropoietic potency, contribute to its clinical efficacy in treating CKD anaemia. A series of studies have confirmed its efficacy in patients using darbepoetin alfa for initial treatment of CKD anaemia and in patients previously receiving other ESAs.
The choice of extended ESA dosing of once every other week (Q2W) or once monthly (QM), in contrast to the once-, twice-, or thrice-weekly regimens of earlier years, offers better flexibility for healthcare professionals and convenience for patients in all clinical settings at all CKD stages [5]. Evidence reviewed in the present supplement shows that the dosing interval for ESAs can be extended to Q2W or QM while maintaining stable Hb levels. Extended dosing regimens are more time-efficient than standard regimens and will likely improve patient compliance and outcomes of therapy, but these potential gains must be balanced against the importance of adequate Hb control and the comparative cost of the pharmaceutical agent [6].
The article by Carrera et al. in this supplement gives recommendations for the use of extended dosing regimens with ESAs based on the ESA type and dose, the administration route, the anaemia treatment phase (initiation or maintenance) and the patient's dialysis status.
A number of algorithms and tools have been developed to assist healthcare professionals and patients in achieving Hb stability [7]. A computer program which has been in use continuously for 8 years in Leeds, UK, recommends changes in ESA doses and iron supplementation at defined threshold and ceiling values for Hb, serum ferritin and red cell hypochromia or transferrin saturation, as described in the article by Will et al. in this issue. Individual modifications are made as needed but these are rare and generally occasioned by conditions causing ESA treatment resistance.
The articles in this supplement summarize and review recent data and new concepts for improving anaemia management in patients at different CKD stages or on dialysis. The mechanisms of action and pharmacological profiles of ESAs are discussed in detail and in relation to the patients’ clinical characteristics. Achieving the best possible anaemia management remains paramount when treating CKD patients.
Guest Editor
References
- Locatelli F, Aljama P, Barany P, et al. Revised European Best Practice Guidelines for the management of anaemia in patients with chronic renal failure. Nephrol Dial Transplant (2004) 19(Suppl 2):ii1–ii47.
[Free Full Text] - Ofsthun N, Labrecque J, Lacson E, Keen M, Lazarus JM. The effects of higher hemoglobin levels on mortality and hospitalization in hemodialysis patients. Kidney Int (2003) 63:1908–1914.[CrossRef][Web of Science][Medline]
- Macdougall IC, Cooper AC. Hyporesponsiveness to erythropoietic therapy due to chronic inflammation. Eur J Clin Invest (2005) 35(Suppl 3):32–35.[Web of Science][Medline]
- Lacson E Jr, Ofsthun N, Lazarus JM. Effect of variability in anemia management on hemoglobin outcomes in ESRD. Am J Kidney Dis (2003) 41:111–124.[CrossRef][Web of Science][Medline]
- Lindberg J. Darbepoetin alfa: a new therapy for the management of anaemia associated with chronic kidney disease. Expert Opin Biol Ther (2002) 2:977–984.[CrossRef][Web of Science][Medline]
- Tolman C, Richardson D, Bartlett C, Will E. Structured conversion from thrice weekly to weekly erythropoietic regimens using a computerized decision-support system: a randomized clinical study. J Am Soc Nephrol (2005) 16:1463–1470.
[Abstract/Free Full Text] - Richardson D, Bartlett C, Will EJ. Intervention thresholds and ceilings can determine the haemoglobin outcome distribution in a haemodialysis population. Nephrol Dial Transplant (2000) 15:2007–2013.
[Abstract/Free Full Text]
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