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Red blood cell life span and ‘erythropoietin resistance’

2012; Elsevier BV; Volume: 81; Issue: 12 Linguagem: Inglês

10.1038/ki.2012.54

1523-1755

Yanna Dou, Anja Kruse, Peter Kotanko, Herman Rosen, Nathan W. Levin, Stephan Thijssen,

Hemoglobinopathies and Related Disorders

To the Editor: We read with interest Bamgbola's review on erythropoietin (EPO) resistance in a recent issue of the Journal.1.Bamgbola O.F. Pattern of resistance to erythropoietin-stimulating agents in chronic kidney disease.Kidney Int. 2011; 80: 464-474Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar Although the author presents a wide range of mechanisms and conditions associated with EPO resistance (including 'accelerated turnover rate of red cells'), the integral role of red blood cell (RBC) life span deserved more explicit elaboration, in our opinion. The response to EPO, meaning the hemoglobin (Hgb) concentration achieved with a certain EPO regimen, is really a continuum rather than a binary outcome, and RBC life span (RBCLS) is a basic component of the process.2.Uehlinger D.E. Gotch F.A. Sheiner L.B. A pharmacodynamic model of erythropoietin therapy for uremic anemia.Clin Pharmacol Ther. 1992; 51: 76-89Crossref PubMed Scopus (121) Google Scholar,3.Kruse A. Uehlinger D.E. Gotch F. et al.Red blood cell lifespan, erythropoiesis and hemoglobin control.Contrib Nephrol. 2008; 161: 247-254Crossref PubMed Scopus (37) Google Scholar Reduction in RBCLS will necessarily entail a reduction in Hgb unless compensated for by increased RBC production rate (in dialysis patients primarily mediated by EPO and iron therapy). When RBC production cannot increase materially, regardless of increases in EPO dose, a short RBCLS becomes the limiting factor in Hgb increase, giving the impression of resistance to EPO. We have determined RBCLS repeatedly in 44 hemodialysis (HD) patients by carbon monoxide measurements4.Strocchi A. Schwartz S. Ellefson M. et al.A simple carbon monoxide breath test to estimate erythrocyte turnover.J Lab Clin Med. 1992; 120: 392-399PubMed Google Scholar and saw an average baseline RBCLS of 70±23 days, which is in keeping with literature data. It is noteworthy that only one of these patients met the criteria of EPO resistance cited by Bamgbola, illustrating how rarely this definition is met. During this period, RBCLS was measured twice in this patient (spaced one month apart) and was found to be 35.9 days and 39.4 days, respectively (Figure 1). Diagnostic workup according to the flowchart in Figure 3 of Bamgbola's review revealed none of the suggested etiologies. As shown by our data and that of others, HD patients exhibit a wide range of RBCLS, with almost one in six patients having an RBCLS below 47 days. RBCLS and EPO responsiveness are closely related—a fact that is often neglected or underappreciated in clinical practice. A consideration of RBCLS is vital for interpretation of EPO responsiveness, particularly in populations with notably variable RBCLS, such as dialysis patients.