Early prediction of response to intravenous iron supplementation by reticulocyte haemoglobin content and high-fluorescence reticulocyte count in haemodialysis patients

Background. Optimal response to recombinant human erythropoietin (rHuEpo) in haemodialysis (HD) patients requires provision of sufficient available iron. However, a balance between iron requirements and supplements remains a challenge in clinical practice. Reticulocyte parameters, i.e. reticulocyte haemoglobin content (CHr) and reticulocytes in a high-fluorescence intensity region (HFR), have been shown to be accurate predictors of iron-deficient erythropoiesis as compared with traditional markers. Therefore, the aim of this study was to appraise the diagnostic power of these two parameters in the early prediction of response to intravenous iron (IVFE) medications in HD patients receiving rHuEpo. Methods. Sixty-five HD patients with a serum ferritin level of < 500 μg/l and on rHuEpo therapy for > 6 months were enrolled for IVFE supplementation (100 mg iron saccharate three times a week for 4 weeks, then 100 mg every 2 weeks for 5 months). Haemoglobin, haematocrit, serum ferritin, transferrin saturation, reticulocyte count, percentage of hypochromic red cells, CHr and HFR were measured before and following iron supplementation. Response was defined as a rise in haematocrit of > 3% and/or a reduction in rHuEpo dose of > 30% over the baseline values at the end of the study. Results. Forty-two patients had a dramatic response to IVFE therapy with a 13.5% increase in mean haematocrit and a 38% reduction in rHuEpo dose at the end of the study (P < 0.001). This paralleled a statistically significant rise in CHr and HFR (P < 0.001). Univariate analyses showed that ferritin (P < 0.010) and CHr (P < 0.001) at baseline, changes in CHr (ΔCHr_2W, P < 0.001) and HFR (ΔHFR_2W, P < 0.010) at 2 weeks, as well as changes in CHr (ΔCHr_4W, P < 0.001) and HFR (ΔHFR_4W, P < 0.001) at 4 weeks, strongly correlated with response to IVFE supplementation. Stepwise discriminant analysis disclosed that ΔCHr_4W in conjunction with ΔHFR_4W exhibited an r² value of 0.531 (P < 0.001) to predict response to IVFE therapy. Analyses by receiver operating characteristic curves and logistic regression further revealed that ΔCHr_4W at a cut-off value of > 1.2 pg and ΔHFR_4W of > 500/μl were more specific to the status of iron-deficient erythropoiesis following IVFE medications. Combined use of the two cut-off values allowed for the highest accuracy in the early prediction of the response to IVFE therapy, with a sensitivity of 96% and a specificity of 100%. Conclusions. Our study shows that changes in CHr and HFR at either 2 or 4 weeks are superior to the conventional erythrocyte and iron metabolism indices and may serve as reliable parameters to detect iron-deficient erythropoiesis in HD patients undergoing rHuEpo therapy. During aggressive IVFE treatment, early identification of non-responsiveness and subsequent discontinuation of treatment can avoid the inadvertent iron-related toxicity due to over-treatment.