Serum sTfR Concentrations Research Articles

Association of Serum Soluble Transferrin Receptor Concentration With Markers of Inflammation: Analysis of 1001 Patients From a Tertiary Rheumatology Center.

Soluble transferrin receptor (sTfR) is considered to be a useful biomarker for the diagnosis of iron deficiency, especially in the setting of inflammation, as it is thought to not be affected by inflammation. We analyzed the relationship between sTfR levels and inflammatory markers in patients with known or suspected inflammatory rheumatic disease (IRD). Blood samples of 1001 patients with known or suspected IRD referred to a tertiary rheumatology center were analyzed. Study participants were classified as patients with active IRD and patients with inactive IRD or without IRD. Correlation analyses were used to explore the relationship between sTfR levels and inflammatory markers (ie, C-reactive protein [CRP], erythrocyte sedimentation rate [ESR]). We applied multiple linear regression analysis to evaluate the predictive value of CRP levels for sTfR concentrations after adjustment for potential confounding factors. There were positive correlations between inflammatory markers (CRP, ESR) and serum sTfR levels (ρ 0.44, ρ 0.43, respectively; P < 0.001), exceeding the strength of correlation between inflammatory markers and the acute phase reactant ferritin (ρ 0.30, ρ 0.23, respectively; P < 0.001). Patients with active IRD demonstrated higher serum sTfR levels compared to patients with inactive or without IRD (mean 3.99 [SD 1.69] mg/L vs 3.31 [SD 1.57] mg/L; P < 0.001). After adjustment for potential confounding factors, CRP levels are predictive for serum sTfR concentrations (P < 0.001). The study provides evidence against the concept that sTfR is a biomarker not affected by inflammation.

Iron Status of a People Living with HIV in Sub-Saharan Africa Using a Multi-Criteria Approach Based on the Determination of Blood Ferritin, sTfR, CRP and sTfR-F Index

Background: The assessment of iron status using a single biomarker of iron metabolism is not enough sensitive and specific to reliably diagnose iron deficiency associated with multiple comorbidities. The objective of this study was to describe the iron status of people living with HIV in sub-Saharan Africa using a multi-criteria approach based on the determination of blood ferritin, sTfR, CRP and the calculation of sTfR-F index. Methods: This study was conducted using a retrospective panel of 933 sera/plasmas. We determined serum ferritin concentration, serum sTfR concentration, and C-reactive protein (CRP) by immunoturbidimetry for each subject. The sTfR-F index was determined by calculating the sTfR/log ferritin ratio. The statistical test used was Chi2. Results: Regardless of the inflammatory syndrome, we determined 3.80%, 30.29%, and 42.70% iron deficiency based on the separate interpretation of ferritin concentration, sTfR, and sTfR-F calculation, respectively. We used those biomarkers in addition to CRP in an algorithm for the diagnosis of iron deficiency. Subjects without inflammatory syndrome, had iron deficiency of 2.89% (n = 26). Taking into account the presence of an inflammatory syndrome, the frequency obtained was n = 88 (9.78%). Overall, iron deficiency was diagnosed in 114 (12.67%) patients when we used the diagnostic algorithm. Conclusion: The use of diagnostic algorithms combining several biomarkers of iron metabolism and taking into account the presence or absence of an inflammatory syndrome is a good approach to detect a large number of iron deficiencies in a population. Therefore, an assessment of the effectiveness of different diagnostic algorithms is necessary.

Analytical evaluation of three soluble transferrin receptor measurement systems for diagnosis of iron deficiency anemia: A retrospective study.

BackgroundSoluble transferrin receptor (sTfR) is a promising indicator of iron deficiency anemia (IDA). Here, we investigated the application value of sTfR assays based on three different methods for the diagnosis of IDA.MethodsThe sTfR concentrations in two groups of patient specimens with high‐level and low‐level sTfR concentrations and in quality control materials were measured four times a day for five consecutive days to evaluate the precision of the three methods. We selected patients with IDA, anemia of chronic disease (ACD), or chronic diseases with iron deficiency anemia (CIDA), and apparently healthy subjects, and measured the serum sTfR concentrations in all subjects using the three different methods. The cutoff points for an IDA diagnosis using the three assays and their corresponding clinical sensitivities and specificities were calculated by receiver operating characteristic analysis.ResultsFor the diagnosis of IDA, the cutoff points of sTfR measured by the chemiluminescent, immunoturbidimetric, and immunonephelometric assays were 2.91, 6.70, and 2.48 mg/L, respectively. The corresponding sensitivities were 85.59%, 85.59%, and 85.59%, the specificities were 91.47%, 90.31%, and 90.70%, and area under the curve was 0.943, 0.944, and 0.936, respectively. The sTfR concentrations measured by the different methods were significantly higher in the IDA and CIDA groups than in the other two groups (P < .05).ConclusionsThe sTfR based on the three different measurement methods presented promising analytical performances and met the clinical requirements for sensitivity and specificity. However, the different measurement methods had markedly different cutoff points for IDA diagnosis, which should be critically considered in clinical practice.

Markers of iron status, blood pressure and incident hypertension among Chinese adults

Background and aimsThe evidence on the relationship between markers of iron, blood pressure and hypertension are limited and inconsistent. This prospective cohort study aimed to investigate the relationship of serum ferritin (SF), transferrin, soluble transferrin receptor (sTFR) and haemoglobin on blood pressure and incident hypertension in the China Health and Nutrition Survey (CHNS) study. Methods and resultsWe studied 8337 adults aged 18 years old or above from CHNS in 2009 to investigate the association of markers of iron and blood pressure (BP). Among them, 4509 non-hypertensive participants who completed follow up were included to investigate the association of markers of iron and hypertension development. Linear regression model was used to assess the association between markers of iron and BP. Cox regression model was used to examine the association of markers of iron and hypertension development. SF and serum sTFR concentration had a non-significant effect on incident hypertension. Transferrin and haemoglobin concentrations were positively associated with incident hypertension. Compared to the participants with the lowest tertile of transferrin, those with the highest tertile had a higher risk of developing hypertension [HR: 1.26, 95% CI (1.04, 1.53), P = 0.017]. Similarly, participants with the highest tertile of haemoglobin had a significantly higher risk of incident hypertension [HR: 1.27, 95% CI (1.01, 1.59), P = 0.038]. ConclusionThe current study found that haemoglobin and transferrin levels were positively associated with blood pressure and incident hypertension. Further research in different ethnic groups is required to confirm the association of the full range of markers of iron with BP and incident hypertension.

Analysis of CD177 neutrophil expression in β-thalassemia patients

Ineffective erythropoiesis plays a well established role in the pathophysiology of disease expression in β-thalassemia major and intermedia. CD177 expression was investigated in different clinical conditions. The study aimed to analyze neutrophil expression of CD177 in β-thalassemia patients and its correlation with serum soluble transferrin receptor (s-TfR) concentration as a marker for the extent of erythropoiesis and hence disease severity in these patients. Flow cytometric analysis of neutrophil CD177 expression and enzyme immunoassay measurement of serum s-TfR concentration were assessed in 45 β-thalassemia patients of whom 36 had β-thalassemia major and nine had β-thalassemia intermedia. They were also assessed in 21 age- and gender-matched control children. Neutrophil mean fluorescence intensity ratio (MFIR) of CD177 expression was significantly higher in patients than in controls (p < 0.001). There was highly significant increase in serum s-TfR concentration in β-thalassemia patients than in controls (p < 0.001). There was a highly significant positive correlation between MFIR of CD177 expression and serum s-TfR concentration in β-thalassemia patients (r = 0.59, p < 0.001). Elevated CD177 expression is not only a specific feature of polycythemia rubra vera (PV) but may be also an indicator of increased erythropoietic activity in thalassemia syndromes.

936 Soluble Transferrin Receptor as a Marker of Iron Stores in Fullterm and Preterm Newborns and Infants

Soluble transferrin receptor (sTfR) is a form of tissue transferrin receptor circulating in blood, which is responsible for donation of iron into the cells. The aim of the study was evaluation of sTfR serum concentration in newborns and infants born at term and preterm regarding to classic markers of iron stores like iron and ferritine concentrations and blood counts. The study group was composed of 117 newborns and infants between 1- 21 weeks of chronological age. The children were divided into three groups according to gestational age. Group I was composed of preterms with a gestational age of 24-31 wk (n=32), group II - preterms with a gestational age of 32-37 wk (n=42), group III -newborns and infants born at time (n=43). Our results reviled that fullterm newborns and infants had higher ferritin but lower sTfR concentration than preterms (p< 0.02), specially born before 32 weeks of gestation. The latter had also significantly higher reticulocyte count. The sTfR concentration correlated negatively with gestational age, birth weight, iron and ferritine serum concentrations, and correlated positively with reticulocyte count. On the basis of our investigation it can be concluded that serum sTfR concentration may reflect iron requirement during intensive erythropoesis as well as its intensity.

Circulating soluble transferrin receptor concentration decreases after exercise-induced improvement of insulin sensitivity in obese individuals

Circulating soluble transferrin receptor (sTfR) has been recently found to be associated negatively with insulin sensitivity. To evaluate circulating sTfR concentration after changing insulin sensitivity in obese individuals. Circulating sTfR concentration was evaluated after diet-induced weight loss in obese women (diet (D) group, n=8); after diet-induced weight loss plus resistance training (D+RT group, n=11); and after follow-up without weight loss (control (C) group, n=7). After 16 weeks, insulin sensitivity (HOMA (Homeostasis Model Assessment) value) significantly improved in parallel to weight loss (-7.3%) and reduced total fat mass (evaluated using magnetic resonance imaging) in the D group. Thigh muscle mass decreased significantly (P=0.03). Serum sTfR concentration did not change significantly. In the D+RT group, weight loss (-8.7%) and improvement of insulin sensitivity were of similar magnitude. Thigh muscle mass was preserved (P=0.8). Serum sTfR concentration decreased significantly (P=0.001). Interestingly, higher the thigh muscle volume after weight loss, higher the decrease in circulating sTfR concentration. We also found that higher the increases in leg force at week 16, higher the decrease in circulating sTfR concentration in all individuals as a whole. No significant changes were observed in insulin sensitivity, sTfR concentration or thigh muscle mass in the C group. These findings suggest a long-term regulation of serum sTfR concentration by exercise-induced improvement of insulin sensitivity in obese individuals.

Soluble transferrin receptor and sTfR-F index for assessing concurrent iron deficiency in patients with chronic renal failure

Dear Editor, We read with interest the comments of Dr. Koulaouzidis [1] regarding the results of our study, which was recently reported on the usefulness of the combination index of serum-soluble transferrin receptor (sTfR) and mean corpuscular hemoglobin (MCH) to differentiate coexisting iron deficiency in patients with end-stage renal disease (ESRD) [2]. First, Dr. Koulaouzidis raised a question as to why the sTfR value was used instead of the sTfR-F index (the ratio of sTfR to log ferritin) to evaluate iron deficiency in patients with chronic renal failure. In fact, the sTfR-F index has been suggested as a good estimate of body iron status [3]. Several investigators reported that the sTfR-F index is an additional biochemical marker for identification of irondeficient erythropoiesis [4]. In our study, however, the sTfR-F index was not superior to sTfR value in the correlation coefficients with serum iron (r=−0.22 vs. r=−0.24) and transferrin saturation (r=−0.23 vs. r=−0.27) in the patients with ESRD. The sTfR-F index may reflect the erythropoietic activity, but it seems to depend on the body iron status of subject populations. The relationships between the sTfR-F index and erythropoietic parameters are fairly different from each other between healthy individuals and iron-deficient anemic subjects [5]. In the preliminary test of our study, similar findings were also observed in the patients with rheumatoid arthritis. On the basis of these results, we selected the sTfR value rather than sTfR-F index as an indicator of iron status in the patients with ESRD. Secondly, Dr. Koulaouzidis made a comment on the low cut-off level of sTfR, which was used to diagnose iron deficiency in our study, and emphasized the importance of the normal reference value of sTfR that was obtained from the healthy controls. However, it is likely that there are large differences in sTfR production between healthy subjects and the patients with ESRD, especially under the condition of suppressed erythropoiesis. It is hard to apply the reference intervals of healthy subjects for the patients with chronic renal failure. In our study, mean values of sTfR in the patients with ESRD (1.50±0.97 mg/l) were significantly lower than those in age-matched healthy controls (2.13±0.51 mg/l, p<0.05) [6]. The reason for the low limit of sTfR seems to be that the cut-off point was determined on the basis of the mean sTfR concentrations from the patients with chronic renal failure. Another possible explanation is that the cutoff value of sTfR was defined as a combination index, in conjunction with MCH level in a small number of patients. In healthy subjects, the reference range of serum sTfR concentration shows variances according to investigators. It may reflect the difference of the healthy controls enrolled in the corresponding study. In our experience, fourfold or more Ann Hematol (2008) 87:575–576 DOI 10.1007/s00277-008-0460-5

Circulating Soluble Transferrin Receptor According to Glucose Tolerance Status and Insulin Sensitivity

The relationships between iron metabolism and type 2 diabetes are bidirectional: iron affects glucose metabolism and glucose metabolism impinges on several iron metabolic pathways. The mechanisms of these interactions depend on poorly known factors. We aimed to study the contribution of the serum soluble transferrin receptor (sTfR). Circulating sTfR was evaluated in 221 men (97 with normal glucose tolerance [NGT], 36 with impaired glucose tolerance, and 88 with type 2 diabetes). In a subset of these subjects, glucose tolerance (oral glucose tolerance test [OGTT]), minimal model-derived insulin sensitivity, and sTfR during the OGTT were also evaluated. Men with altered glucose tolerance showed significantly increased sTfR (9.4 +/- 4.4 vs. 8.2 +/- 2.6 microg/ml, P = 0.02) and higher serum ferritin than men with NGT. Serum sTfR was negatively associated with serum ferritin (r = -0.16, P = 0.02). sTfR correlated with several clinical and metabolic variables such as systolic blood pressure, glycated hemoglobin, and glucose and insulin values during OGTT. Insulin sensitivity was also negatively associated with sTfR in NGT and nonobese subjects. BMI (P = 0.01), serum ferritin (P = 0.025), and insulin sensitivity (P < 0.0001) contributed independently to 21% of sTfR variance. Serum sTfR concentration did not significantly change during the OGTT. Both insulin sensitivity and glucose tolerance status are significantly associated with serum sTfR concentrations, although insulin sensitivity predicts independently circulating sTfR, mainly in subjects with NGT. The implications of the interrelationships between iron and glucose metabolism should be investigated further.

Impact of Malaria, Helminths and Anemia on Dietary Iron Absorption in Zanzibari Toddlers

The ability of toddlers to absorb non-heme iron; and the impact of parasitic load on iron absorption and red blood cell stability was assessed in 80 toddlers (age 16.5 ± 24.7 months). Toddlers had been participating in a deworming study in which ½ of those recruited had received mebendazole every 3 months over the previous year. At entry, toddlers had Hb> 7.0 g/dL and no active malarial infections. At baseline a blood sample was taken and 58Fe tracer (1 mg with 6 mg ferrous sulfate) or 57 Fe tracer (7 mg) was given orally. Complete stool collections were obtained over the following three days. At 2 weeks and 90 days post-dosing, blood samples were collected for isotope analysis. Throughout the study, weekly health assessments and home visits were conducted. Iron isotopes were measured with magnetic sector thermal ionization mass spectrometry. Average Hb in those studied was 10.8 and was inversely correlated with serum sTfr concentrations (P <0.0001, R= −0.531, n= 69). In total, 47.14% of subjects were anemic (Hb<10.5 g/dL). Preliminary iron absorption data found iron absorption averaged 29.72 ± 3.47 %, n=3. Those with malaria parasites (n=58) had significantly lower Hb (P<0.05) and significantly higher sTfR (p=0.059) compared to those without malaria parasites (n=11). Additional analyses will assess the impact of iron status and parasitic infection on iron absorption and red blood cell iron stability among this cohort.

Soluble Transferrin Receptor and Its Ratio to Erythroblasts in Bone Marrow May Be a New Diagnostic Tool to Distinguish between Aplastic and Refractory Anemia

Myelodysplastic syndromes (MDS), especially refractory anemia (RA) are very heterogeneous diseases regarding their morphological, biological and clinical features. One important clinical problem is the difficulty of diagnosis. Soluble transferrin receptors (sTfRs) reflect the erythropoietic activity in the bone marrow (BM). To establish whether determination of serum sTfR could be useful for the differential diagnosis between RA and aplastic anemia (AA), we measured the serum sTfR concentrations, BM cellularity and BM erythroblast percentages in 14 untreated AA and 7 untreated RA patients. The serum sTfR levels of the RA patients (820.1 ± 402.8 ng/ml) were significantly higher than those of the AA patients (491.1 ± 195.2 ng/ml; p = 0.0207). However, the serum sTfR values of RA and AA patients also overlapped. A new index, the ‘sTfR-E index’ [the ratio of serum sTfR level (ng/ml) to BM cellularity (%) × BM erythroblasts (%)] is proposed, which is expected to reflect the number of transferrin receptors (TfR) on the cell membrane per BM erythroblast. The sTfR-E index values of the 7 RA patients (0.395 ± 0.234) were significantly lower than those of the 14 AA patients (2.669 ± 1.633; p = 0.0003). The sTfR-E index values of AA and RA patients overlapped only marginally. In conclusion, the sTfR-E index may be a useful new diagnostic tool to distinguish between AA and RA patients.

The influence of iron, vitamin B 12, and folate levels on soluble transferrin receptor concentration in pregnant women

Background: Soluble transferrin receptor (sTfR) concentration is high in iron deficiency and in conditions of increased erythropoiesis. In developing countries like Brazil, pregnant women usually have concurrent iron, vitamin B 12, and folate deficiencies. This study investigated the relationship between serum sTfR concentration and iron, vitamin B 12, and folate status in pregnant women. Methods: The concentration of the sTfR, hematocrit (Hct), hemoglobin (Hb), red blood cell (RBC) and white blood cell (WBC) counts, serum iron (SI), total iron-binding capacity (TIBC), transferrin saturation, serum ferritin, zinc protoporphyrin (ZPP), vitamin B 12, and serum and RBC folate were determined in 40 healthy pregnant women who delivered term babies. Results: sTfR concentration was significantly higher when the women had iron deficiency (serum ferritin <10 μg/l, p<0.01), but there was no significant difference in sTfR concentration according to vitamin B 12, serum, and RBC folate concentrations. Women who had serum ferritin <10 μg/l also had lower vitamin B 12 values ( p<0.01). There was no significant correlation between vitamin B 12 and serum folate with sTfR concentration. According to a regression analysis, sTfR concentration was associated with serum iron, serum ferritin, RBC count, and hemoglobin concentration. Conclusion: Iron was the only micronutrient that influenced the sTfR concentration. Vitamin B 12 and folate concentrations were probably not sufficiently low to have an impact on the sTfR concentration.

Serum soluble transferrin receptor reflects erythropoiesis but not iron availability in erythropoietin-treated chronic hemodialysis patients.

The diagnosis of iron deficiency using the current commonly used tests is usually difficult in hemodialysis patients. Soluble transferrin receptor (sTfR) has caught the attention of physicians recently as regards its use as a parameter for the evaluation of iron status. This study was conducted in order to evaluate the correlation of serum soluble transferrin receptor (sTfR) concentration with hematological parameters and iron profiles, in the role of identifying iron deficiency among dialysis patients. Seventy-three patients having received chronic hemodialysis and stable maintenance recombinant human erythropoietin (rHuEPO) therapy were included. Iron, total iron-binding capacity, ferritin and sTfR were measured in the first week. Following this, these patients began to receive intravenous iron dextran (2 mg/kg/week) for 4 weeks. The hematocrit (Hct), hemoglobin (Hb) levels and reticulocyte counts were evaluated weekly. At the beginning of fifth week, the sTfR level was measured again. Patients were classified as belonging to one of the following groups: serum ferritin < 100 microg/L - absolute iron-deficient group; initial ferritin level > or = 100 microg/L with an increase in hemoglobin of greater than 1 g/dL at the end of the study occult iron deficiency group; others - non iron-deficient group. Seventy-one patients completed the study. The concentration of sTfR was positively correlated with Hct, Hb and reticulocyte index at the beginning (r = 0.236, p = 0.047; r = 0.257, p = 0.04; r = 0.401, p < 0.01, respectively) and at the end of the study (r = 0.384, p < 0.01; r = 0.338, p < 0.01; r = 0.427, p < 0.001, respectively). After 4 weeks of iron and rHuEPO therapy, the sTfR concentration increased, rather than declined, from 21.85 +/- 8.06 nM to 23.76 +/- 7.42 nM (p = 0.04) and the change was positively correlated with the changes in Hct, Hb and reticulocyte index. The administered rHuEPO doses did not differbetween the iron deficiency group (absolute deficiency, n = 3; occult deficiency, n = 10) and non-iron deficiency group (n = 58). The sTfR levels failed to identify the occult iron deficiency group because there was no difference between occult iron-deficient and non-iron-deficient patients (24.73 +/- 9.09 nM versus 21.60 +/- 7.89 nM, p = 0.34). Instead, transferrin saturation (TS) could be a differential marker between the 2 groups (19.0 +/- 10.9% versus 30.1 +/- 12.7%, p = 0.012). The serum sTfR concentration is indeed an appropriate marker for erythropoiesis. The erythropoitic effect of administered rHuEPO could mask the effect of iron status on the sTfR concentration. This might make the sTfR concentration no longer an appropriate index to identify the presence of occult iron deficiency. Thus, TS and ferritin currently remain better methods for the evaluation of iron status in rHuEPO-treated chronic hemodialysis patients.

Diagnostic significance of serum soluble transferrin receptors in various anemic diseases: the first multi-institutional joint study in Japan.

Serum soluble transferrin receptor (sTfR) has been reported to be higher in patients with iron deficiency or with elevated erythropoiesis. In the present study, serum sTfR was measured in various anemic diseases and their clinical significance was examined in a multi-institutional joint study. Serum sTfRs in patients with the following anemic diseases were markedly higher than those in normal healthy adults: non-treated iron deficiency anemia (IDA) (9.13 +/- 7.04 mg/l, n = 52, p < 0.0001), anemia of chronic disorders (ACD) (3.45 +/- 1.38 mg/l, n = 20, p < 0.0001), hemolytic anemia (HA) (5.57 +/- 3.26 mg/l, n = 17, p < 0.0001), and myelodysplastic syndrome (MDS) (4.03 +/- 2.83 mg/l, n = 20, p < 0.0001). There were significant differences between IDA and ACD (p < 0.0001), between aplastic anemia (AA) (1.58 +/- 1.26 mg/l, n = 16) and MDS (p < 0.001), and between AA and MDS with refractory anemia (MDS-RA) (4.16 +/- 3.40 mg/l, n = 9) (p < 0.02). In patients with chronic renal failure (CRF), serum sTfR levels and serum sTfR/log serum ferritin ratios (sTfR/F index) were compared in the two classified groups according to Muirhead's criteria, as IDA and non-IDA groups with or without recombinant human erythropoietin (rHuEPO) treatment. Significantly high levels of both serum sTfR (p < 0.0001) and the sTfR/F index (p < 0.0001) were observed in IDA without rHuEPO treatment. Especially in CRF with rHuEPO treatment, the sTfR/F index showed marked elevation in the IDA group (p < 0.0001) compared with serum sTfR (p < 0.001), indicating more diagnostic efficacy of the sTfR/F index for CRF with IDA. In conclusion, the serum sTfR concentration is a useful diagnostic tool for discrimination between IDA and ACD, and between AA and MDS-RA, and for the detection of iron deficiency in CRF patients in the Japanese population.

Serum soluble transferrin receptor and the prediction of marrow aspirate iron results in a heterogeneous group of patients.

Serum soluble transferrin receptor (sTfR) concentration has been evaluated in the diagnosis of iron deficiency in otherwise healthy individuals and in patients with rheumatoid arthritis, but has not been studied in a general population of patients with complicated clinical presentations. In this study, 145 anaemic patients with a variety of medical conditions undergoing diagnostic bone marrow aspiration for any reason were tested by a complete blood count, a panel of biochemical tests to evaluate iron status, bone-marrow aspirate iron stain, and serum sTfR concentration. Sixteen per cent lacked stainable iron in the marrow aspirate. All biochemical parameters differed significantly between patients with or without stainable marrow iron. The sTfR assay was significantly more sensitive but less specific than other iron status assays in identifying the absence of stainable iron. Logistic regression analysis demonstrated that only sTfR and ferritin contributed independently to the prediction of marrow iron status. Serum ferritin alone was highly specific but insensitive. A decision algorithm combining serum ferritin and sTfR was as sensitive as TfR and as specific as serum ferritin. The measurement of serum sTfR, especially in conjunction with serum ferritin, is a valuable addition to the existing methods for predicting the results of marrow aspirate iron stains.

TIME COURSE OF MAXIMAL O2 UPTAKE AND TRANSFERRIN RECEPTOR CONSENTRATION AFTER rhEPO ADMINISTRATION

778 The aim of the study was to quantify the effects of moderate supraphysiological doses of recombinant human erythropoietin (rhEPO) on maximal O2 uptake and soluble transferrin receptor (sTfr) concentration. METHODS: Twenty healthy, endurance trained male athletes, age: 24±3 yrs, weight: 75±5 kg, max. O2 uptake: 61.4±4.5 ml kg−1 min−1 (±SD) were matched for sport and training level and randomly assigned to the EPO group (n=10; 5000 IE Recormon (Boehringer Mannheim GmbH) s.c. three times weekly for 30 days or until hematocrit (Hct) reached 50) or the placebo group (n=10; NaCl s.c.). The groups were followed for 4 wks post-administration with regular blood samples and exercise tests. Subjects and laboratory personnel were blinded to the group assignments. Max. O2 uptake was measured in an exercise test on a cycle ergometer (starting load: 100 W, increased by 50 W every 2. min) at the start of the study, 2, 7, 14, 21 and 28 days post rhEPO administration. RESULTS: There was an increase in Hct from 42.7±1.6 before to a maximum value of 50.8±2.0 the day after the end of the rhEPO administration period in the EPO group. Maximal O2 uptake increased from 63.6±4.5 ml kg−1 min−1 (before) to 68.1±5.4 ml kg−1 min−1 (2 days post rhEPO administration; 7% increase, p=0.002 vs before), 67.6±5.2 ml kg−1 min−1 (after 1 wk; p=0.008 vs before), 67.1±6.5 ml kg−1 min−1 (2 wks; p=0.28 vs before), 66.6±4.4 ml kg−1 min−1 (3 wks; p=0.011 vs before), and 65.8±4.7 ml kg−1 min−1 (4 wks; p=0.14 vs before) in the EPO group. The concentration of sTfr increased in the EPO group from 3.1±0.9 mg l−1 (before) to a maximum value of 6.3±2.3 mg l−1 2 days post rhEPO administration. The sTfr increase was significant after one week of rhEPO administration and remained increased for one week post rhEPO administration. The sTfr concentration was higher than the average basal value plus 2 SD after 30 days of rhEPO treatment in 8 out of 10 subjects in the EPO group. There were no significant changes in Hct, maximal O2 uptake or sTfr concentration in the placebo group. CONCLUSION: Serum sTfr concentration may represent a potential screening method for rhEPO doping, but since the effect on performance outlasts the increase in sTfr, pre-competition lesting is necessary.