RETICULOCYTE HEMOGLOBIN CONTENT PREDICTS FUNCTIONAL IRON-DEFICIENCY IN HEMODIALYSIS-PATIENTS RECEIVING RHUEPO

Early detection of iron sufficiency at the level of the erythropoietic cell is necessary to optimize management of uremic anemia with recomb inant human erythropoietin (rHuEPO). ''Absolute'' and ''functional'' i ron deficiency are the most important factors causing resistance to ad ministered rHuEPO. Transferrin saturation and serum ferritin measureme nts have been noted to be insensitive and inaccurate measures to detec t functional iron deficiency. Recently, the reticulocyte hemoglobin co ntent (CHr) has been shown to be a sensitive and specific indicator of functional iron deficiency in nondialysis patients treated with rHuEP O. The purpose of this study is to compare CHr with currently used ind ices of iron sufficiency in rHuEPO-treated hemodialysis (HD) patients. In study 1, 364 stable HD patients were studied at two outpatient dia lysis centers. CHr was normally distributed, with a mean value of 28.3 pg, and was consistent over two consecutive monthly samples in each c enter. CHr was weakly but consistently correlated with transferrin sat uration and serum ferritin, CHr and reticulocyte number were inversely correlated with red blood cell (RBC) number, suggesting that the eryt hropoietic stimulus of routinely administered rHuEPO may have resulted in functional iron deficiency. Month-to-month changes in CHr correlat ed weakly with changes in serum iron and percent transferrin saturatio n, but not at all with changes in serum ferritin. When we analyzed tho se patients with baseline CHr less than 26 pg, a level strongly sugges tive of functional iron deficiency, these correlations strengthened, a nd in addition, month-to-month changes in CHr correlated strongly and directly with concomitant changes in RBC count, hemoglobin, and hemato crit, suggesting that rising CHr was indicative of an erythropoietic r esponse. In study 2, 79 patients received a single-dose infusion of 50 0 mg iron dextran. After intravenous iron, CHr rose within 48 hours, p eaked at 96 hours, and then fell toward baseline. Patients who were ir on deficient by standard measures (serum ferritin < 100 ng/mL or trans ferrin saturation less than 20%) had a greater and a sustained CHr res ponse to intravenous iron dextran. A CHr less than 28 pg at baseline p redicted functional iron deficiency, defined as a corrected reticulocy te increase of greater than 1% to iron dextran, more accurately than t ransferrin saturation, ferritin, or their combination. Eighty-two perc ent of individuals who were iron deficient at baseline responded to in travenous iron with an increase in CHr of greater than 2 pg. Sixty per cent of patients who were iron sufficient by usual iron indices also r esponded to intravenous iron with a CHr rise of greater than 2 pg, sug gesting that they were, in fact, functionally iron deficient despite ' 'normal'' conventional iron parameters. We conclude that CHr may be a more sensitive marker of functional iron deficiency in rHuEPO-treated hemodialysis patients than percent transferrin saturation and ferritin , particularly in those with ''normal'' conventional iron parameters. (C) 1997 by the National Kidney Foundation, Inc.