Abstract
BackgroundEpoetin beta pegol (continuous erythropoietin receptor activator; C.E.R.A.) is currently widely used for the treatment of anemia associated with chronic kidney disease (CKD). Therapeutic control of anemia is assessed by monitoring haemoglobin (Hb) levels. However, certain qualitative aspects of erythrocytes are also impaired in CKD, including loss of deformability and shortened life-span. Therefore, monitoring Hb alone could potentially fail to reveal pathological changes in erythrocytes. Focusing on erythrocyte quality in CKD may lead to more effective anemia therapy with C.E.R.A.MethodsA CKD rat model was induced by uninephrectomy followed by anti-Thy1.1 antibody injection. From 5 weeks after the operation, C.E.R.A. (0.6 μg/kg) or vehicle was administered every 2 weeks. Erythrocyte deformability was quantified with ektacytometry and erythrocyte turnover was estimated by biotin labeling. Intracellular calcium level was assessed by Fluo-3/AM.ResultsErythrocyte deformability progressively declined in CKD rats. Furthermore, erythrocyte turnover in the circulation drastically accelerated in CKD rats. With administration of C.E.R.A. at a dose sufficient to adequately control Hb, deterioration of erythrocyte deformability and turnover in CKD rats were significantly improved. Intracellular calcium, which plays a pivotal role in the mediation of erythrocyte quality, was significantly increased in CKD and was normalized by C.E.R.A. treatment.ConclusionC.E.R.A. treatment exerted a favorable effect not only on anemia but also on the improvement of erythrocyte quality. C.E.R.A. administered for the treatment of CKD-associated anemia may confer therapeutic benefits on erythrocytes.
Highlights
IntroductionEpoetin beta pegol (continuous erythropoietin receptor activator; C.E.R.A.) is currently widely used for the treatment of anemia associated with chronic kidney disease (CKD)
Epoetin beta pegol is currently widely used for the treatment of anemia associated with chronic kidney disease (CKD)
Therapeutic effect of C.E.R.A. on anemia in CKD model rats Compared with Hb levels and red blood cell (RBC) numbers in the Sham group, Hb levels and RBC numbers decreased at 2 weeks after the UNX-Thy1 operation, recovered slightly until Week 5, and progressively decreased until the end of the experimental period (Hb, Fig. 1a; RBC, Fig. 1b)
Summary
Epoetin beta pegol (continuous erythropoietin receptor activator; C.E.R.A.) is currently widely used for the treatment of anemia associated with chronic kidney disease (CKD). Several erythropoiesis-stimulating agents (ESAs) play an indispensable role in clinical practice for the treatment of renal anemia. Among these is epoetin beta pegol (continuous erythropoietin receptor activator; C.E.R.A.), a modified EPO which has the longest half-life of all ESAs in the circulation of CKD patients [1]. A loss of deformability [2, 3] and a shortened life-span [4,5,6] can be observed in erythrocytes from CKD patients. The diameter of the peripheral arteries is 5 to 10 μm, whereas the diameter of a normal erythrocyte is approximately 8 μm [7]
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