Reticulocyte dynamic and hemoglobin variability in hemodialysis patients treated with Darbepoetin alfa and C.E.R.A.: a randomized controlled trial

BMC Nephrology

Luca Gabutti¹  Michel Burnier²  Philippe Vuistiner³  Igor Salvadé¹  Adam Ogna¹  Giorgia Bianchi¹  Valentina Forni² 

[1] Division of Internal Medicine and Nephrology, Ospedale Regionale di Locarno, via all’Ospedale 1, 6600, Locarno, Switzerland;Division of Nephrology, Lausanne University Hospital, Bugnon 17, 1011, Lausanne, Switzerland;Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Route de la Corniche 10, 1010, Lausanne, Switzerland

关键词: Variability;    Reticulocytes;    Hemoglobin;    Erythropoietin stimulating agents;   

Others  :  1082882
DOI  :  10.1186/1471-2369-14-157

 received in 2012-08-16, accepted in 2013-07-18,  发布年份 2013

【 摘 要 】

Background

In a simulation based on a pharmacokinetic model we demonstrated that increasing the erythropoiesis stimulating agents (ESAs) half-life or shortening their administration interval decreases hemoglobin variability. The benefit of reducing the administration interval was however lessened by the variability induced by more frequent dosage adjustments. The purpose of this study was to analyze the reticulocyte and hemoglobin kinetics and variability under different ESAs and administration intervals in a collective of chronic hemodialysis patients.

Methods

The study was designed as an open-label, randomized, four-period cross-over investigation, including 30 patients under chronic hemodialysis at the regional hospital of Locarno (Switzerland) in February 2010 and lasting 2 years. Four subcutaneous treatment strategies (C.E.R.A. every 4 weeks Q4W and every 2 weeks Q2W, Darbepoetin alfa Q4W and Q2W) were compared with each other. The mean square successive difference of hemoglobin, reticulocyte count and ESAs dose was used to quantify variability. We distinguished a short- and a long-term variability based respectively on the weekly and monthly successive difference.

Results

No difference was found in the mean values of biological parameters (hemoglobin, reticulocytes, and ferritin) between the 4 strategies. ESAs type did not affect hemoglobin and reticulocyte variability, but C.E.R.A induced a more sustained reticulocytes response over time and increased the risk of hemoglobin overshooting (OR 2.7, p = 0.01). Shortening the administration interval lessened the amplitude of reticulocyte count fluctuations but resulted in more frequent ESAs dose adjustments and in amplified reticulocyte and hemoglobin variability. Q2W administration interval was however more favorable in terms of ESAs dose, allowing a 38% C.E.R.A. dose reduction, and no increase of Darbepoetin alfa.

Conclusions

The reticulocyte dynamic was a more sensitive marker of time instability of the hemoglobin response under ESAs therapy. The ESAs administration interval had a greater impact on hemoglobin variability than the ESAs type. The more protracted reticulocyte response induced by C.E.R.A. could explain both, the observed higher risk of overshoot and the significant increase in efficacy when shortening its administration interval.

Trial registration

ClinicalTrials.gov: NCT01666301

【 授权许可】

   
2013 Forni et al.; licensee BioMed Central Ltd.

【 图 表 】

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