1 Department of Internal Medicine Division of Nephrology2 Clinical Laboratory3 Research Unit Hospital Virgen de la Concha Zamora4 Seter Dialysis Center Zamora5 University Hospital Service of Nephrology Salamanca, Spain Email: jdeira{at}saludalia.com
Sir,
We read with much interest the original article by Tarng and Huang [1] in the June 2002 issue of Nephrology Dialysis Transplantation. The interests of these authors were dual: on one hand, the lack of a marker of functional iron that is sensitive and easy-to-handle in haemodialysis (HD) patients, and secondly, the fact that soluble transferrin receptor (sTfR) levels are increased in non-uraemic ferropenic patients [2]. In their cross-sectional study, with univariate analyses (Spearman correlation coefficients) they found that sTfR levels are strongly correlated with erythropoietic stimulation (sEPO) levels (r= 0.60, P< 0.001) and the percentage of hypochromic red cells (% HRC) (r= 0.60, P< 0.001), and significantly with serum ferritin (r= 0.29, P< 0.01), transferrin saturation (TS) (r= 0.27, P< 0.05), the dose of recombinant human erythropoietin (rHuEPO) administered (r= 0.27, P< 0.05), haematocrit (Hct) (r= 0.26, P< 0.05), red blood cell counts (r= 0.23, P< 0.05) and reticulocyte counts (r= 0.24, P< 0.05). Multivariate regression analysis disclosed that sEPO, % HRC and serum ferritin were the three independent predictor of sTfR level accounting for 58.8% of the variability in sTfR. The authors conclude that sTfR levels quantitatively reflect the integrated effects of iron availability (% HRC), iron reserves (serum ferritin) and sEPO; they suggest that sTfR levels may be useful in monitoring iron status for HD patients undergoing steady-state erythropoietic stimulation.
We recently published the results of a prospective longitudinal study [3], in which we assessed erythropoiesis activity by sTfR and ferrokinetic measurements in 23 stable patients on HD. sTfR levels were determined at the start of treatment with rHuEPO and at 15, 30, 45, 60, 90 and 120 days. sTfR levels were determined by an enzyme-linked immunosorbent assay (Quantikine in vitro diagnostic from R&D Systems). rHuEPO significantly increased all the parameters involved in erythropoietic activity: Hct, the reticulocyte count, plasma iron turnover, erythron transferrin uptake and sTfR levels. We found a positive correlation (Pearson correlation coefficients) between sTfR levels and Hct (r= 0.53, P= 0.001) and the reticulocyte count (r= 0.24, P= 0.001) and a negative correlation with ferritin (r= 0.33, P= 0.002) and TS (r= 0.28, P= 0.01). We believe that the data reflect both an efficient activation of erythropoiesis during treatment with rHuEPO and the passage of iron from deposits to the functional pool, rather than the functional iron status. Thus, we found no significant differences in sTfR levels regardless of whether the patients had greater (serum ferritin >100 ng/ml) or smaller (serum ferritin <100 ng/ml) iron reserves. Later, using multiple regression analysis (unpublished data) in 34 patients on HD with normal reactive protein C levels, we observed that the two most determinant parameters in sTfR levels were the reticulocyte count (r= 0.62, P< 0.001) and TS (r= 0.36, P< 0.001), accounting for 41 and 13% of the variability, respectively (54% overall), without serum ferritin being an independent predictive variable as regards sTfR levels. Recently, in 71 patients with an absolute iron deficiency or occult iron deficiency treated with parenteral iron (2 mg/kg/week), Chiang et al. [4] have also reported a positive correlation between sTfR levels and an increase in erythropoiesis. More importantly, they observed that during the course of iron therapy sTfR levels increased rather than declined (as should have happened if sTfR levels were a marker of iron deficit) and stated that the results of their study failed to reveal any difference in sTfR levels between iron-deficient and non-iron-deficient patients. Accordingly, like other authors, [4] we believe that sTfR levels are a good marker of erythropoietic activity [2], although they are unable to differentiate the status of iron availability in chronic HD patients receiving maintenance rHuEPO therapy.
Conflict of interest statement. None declared.
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