Background: European guidelines stress that iron status should be regularly assessed for the optimal management of renal anemia. These guidelines include the hemoglobin content of reticulocytes and the percentage of hypochromic RBC as markers for functional iron deficiency. Recently, equivalents of these indices have become available on the automated hematology analyzer Sysmex XE-2100, these being reticulocyte hemoglobin equivalent (Ret-He) and DF-HYPO XE, respectively. Methods: In a prospective study, we closely monitored these parameters in dialysis-dependent patients with end-stage renal disease during the switch from a first-generation epoetin (EPO) once weekly to a third-generation EPO [continuous erythropoietin receptor activator (CERA)] once monthly. As a control, patients staying on EPO β were monitored. Results: During follow-up, no changes in erythrocyte indices were noticed in the EPO β group. By contrast, in the CERA group, a decrease in Ret-He and an increase in DF-HYPO XE were transiently found 7–10 days after administration. The transient state of functional iron deficiency could not be prevented by extra intravenous iron. Conclusion: Fluctuations in Ret-He and DF-HYPO XE have to be taken into account when these parameters are used for the assessment of iron-deficient states. We suggest that a fixed time point in the CERA schedule should be chosen for iron monitoring.

1.
Rao M, Pereira BJ: Optimal anemia management reduces cardiovascular morbidity, mortality, and costs in chronic kidney disease. Kidney Int 2005;68:1432–1438.
2.
Winearls CG, Oliver DO, Pippard MJ, Reid C, Downing MR, Cotes PM: Effect of human erythropoietin derived from recombinant DNA on the anaemia of patients maintained by chronic haemodialysis. Lancet 1986;2:1175–1178.
3.
Eschbach JW, Egrie JC, Downing MR, Browne JK, Adamson JW: Correction of the anemia of end-stage renal disease with recombinant human erythropoietin: results of a combined phase I and II clinical trial. N Engl J Med 1987;316:73–78.
4.
Sulowicz W, Locatelli F, Ryckelynck JP, Balla J, Csiky B, Harris K, Ehrhard P, Beyer U: Once-monthly subcutaneous C.E.R.A. maintains stable hemoglobin control in patients with chronic kidney disease on dialysis and converted directly from epoetin one to three times weekly. Clin J Am Soc Nephrol 2007;2:637–646.
5.
Locatelli F, Aljama P, Barany P, Canaud B, Carrera F, Eckardt KU, Horl WH, Macdougal IC, Macleod A, Wiecek A, Cameron S: 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.
6.
Brugnara C, Laufer MR, Friedman AJ, Bridges K, Platt O: Reticulocyte hemoglobin content (CHr): early indicator of iron deficiency and response to therapy. Blood 1994;83:3100–3101.
7.
Brugnara C, Zelmanovic D, Sorette M, Ballas SK, Platt O: Reticulocyte hemoglobin: an integrated parameter for evaluation of erythropoietic activity. Am J Clin Pathol 1997;108:133–142.
8.
Buttarello M, Temporin V, Ceravolo R, Farina G, Bulian P: The new reticulocyte parameter (RET-Y) of the Sysmex XE 2100: its use in the diagnosis and monitoring of posttreatment sideropenic anemia. Am J Clin Pathol 2004;121:489–495.
9.
Brugnara C, Schiller B, Moran J: Reticulocyte hemoglobin equivalent (Ret He) and assessment of iron-deficient states. Clin Lab Haematol 2006;28:303–308.
10.
Maconi M, Cavalca L, Danise P, Cardarelli F, Brini M: Erythrocyte and reticulocyte indices in iron deficiency in chronic kidney disease: comparison of two methods. Scand J Clin Lab Invest 2009;69:365–370.
11.
KDOQI, National Kidney Foundation: II. Clinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease in adults. Am J Kidney Dis 2006;47:S16–S85.
12.
Levin NW, Fishbane S, Canedo FV, Zeig S, Nassar GM, Moran JE, Villa G, Beyer U, Oguey D: Intravenous methoxy polyethylene glycol-epoetin beta for haemoglobin control in patients with chronic kidney disease who are on dialysis: a randomised non-inferiority trial (MAXIMA). Lancet 2007;370:1415–1421.
13.
Jarsch M, Brandt M, Lanzendorfer M, Haselbeck A: Comparative erythropoietin receptor binding kinetics of C.E.R.A. and epoetin-beta determined by surface plasmon resonance and competition binding assay. Pharmacology 2008;81:63–69.
14.
Macdougall IC, Robson R, Opatrna S, Liogier X, Pannier A, Jordan P, Dougherty FC, Reigner B: Pharmacokinetics and pharmacodynamics of intravenous and subcutaneous continuous erythropoietin receptor activator (C.E.R.A.) in patients with chronic kidney disease. Clin J Am Soc Nephrol 2006;1:1211–1215.
15.
Fishbane S, Pannier A, Liogier X, Jordan P, Dougherty FC, Reigner B: Pharmacokinetic and pharmacodynamic properties of methoxy polyethylene glycol-epoetin beta are unaffected by the site of subcutaneous administration. J Clin Pharmacol 2007;47:1390–1397.
16.
Macdougall IC: Poor response to erythropoietin: practical guidelines on investigation and management. Nephrol Dial Transplant 1995;10:607–614.
17.
Drueke T: Hyporesponsiveness to recombinant human erythropoietin. Nephrol Dial Transplant 2001;16(suppl 7):25–28.
18.
Weiss G, Widner B, Zoller H, Schobersberger W, Fuchs D: Immune response and iron metabolism. Br J Anaesth 1998;81(suppl 1):6–9.
19.
Macdougall IC, Cooper AC: Erythropoietin resistance: the role of inflammation and pro-inflammatory cytokines. Nephrol Dial Transplant 2002;17(suppl 11):39–43.
20.
Nemeth E, Ganz T: The role of hepcidin in iron metabolism. Acta Haematol 2009;122:78–86.
21.
Andrews NC: Molecular control of iron metabolism. Best Pract Res Clin Haematol 2005;18:159–169.
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