Monitoring the content of reticulocyte hemoglobin (CHr) as the progression of anemia in nondialysis chronic renal failure (CRF) patients

BACKGROUND: We previously showed that the content of reticulocyte hemoglobin (CHr) is a reliable measure of iron status in chronic dialysis patients with erythrocytopoiesis. The CHr was significantly correlated with conventional parameters of iron deficiency in dialysis patients. We attempted to utilize the measurement of CHr levels to monitor iron status and clarify the changes in iron levels that occur as renal anemia progresses in patients with chronic renal failure (CRF). METHODS: We measured CHr, iron parameters, and the intrinsic erythropoietin (EPO) concentration in nondialysis CRF patients who visited our outpatient clinic (n=211). Iron deficiency was defined according to the transferrin saturation (TSAT) and ferritin levels. Conventional red blood cell parameters and CHr levels were measured using an ADVIA120 autoanalyzer (Bayer Medical, USA). RESULTS: The mean CHr value of the nondialysis CRF patients (creatinine clearance less than 70 mL/min) was 32.3 pg, which was not significantly different from that of the dialysis patients. Significant correlations were found between CHr and ferritin levels (r=0.042, p<0.0403) and CHr and TSAT levels (r=0.040, p<0.0157). A positive correlation was observed between the CHr and serum creatinine levels. Nondialysis CRF patients treated with recombinant human EPO (rHuEPO) at a dose of 24,000 U/month exhibited lower CHr levels, compared with those of other patients who received less than 24,000 U/month. CONCLUSION: CHr is an easily measurable and trustworthy marker of iron status in nondialysis CRF patients. Moreover, the CHr level was also sensitive to iron alterations in nondialysis CRF patients receiving rHuEPO treatment, and thus, the CHr value could likely provide useful information regarding the need for iron supplementation.     

Reduction in erythropoietin doses by the use of chronic intravenous iron supplementation in iron-replete hemodialysis patients

BACKGROUND: Iron deficiency is the most common cause of suboptimal response to recombinant human erythropoietin (rHuEPO) in chronic hemodialysis (HD) patients. Iron supply can correct this situation, however, optimal dosage, route of administration, and monitoring of iron status during rHuEPO therapy in maintenance HD patients remains controversial. METHODS: We conducted a 12-month intravenous iron substitution trial in 149 iron-replete chronic HD patients receiving subcutaneous rHuEPO therapy. The available iron pool was maintained with 100 mg iron every 2 weeks or 1 month depending on serum ferritin and transferrin saturation levels, the rHuEPO dosage titrated depending on hematocrit (Hct) levels. RESULTS: After 12-month protocol, the Hct increased (28.7 +/- 4.1 vs 27.7 +/- 2.6, p = 0.003), rHuEPO requirement reduced 25% (46.1 +/- 28.9 vs 61.5 +/- 67.8 U/kg/week, p = 0.006), serum ferritin increased (1,383 +/- 727 vs 930 +/- 857 ng/ml, p < 0.001), so did the transferrin saturation (36.1 +/- 12.7 vs 27.5 +/- 12.8%, p < 0.001). The serum albumin decreased slightly but reached statistical significance (4.1 +/- 0.48 vs 4.2 +/- 0.36 g/dl, p = 0.006), so did the cholesterol levels (166 +/- 41 vs 173 +/- 38 mg/dl, p = 0.044) and pre-dialysis creatinine (11.3 +/- 2.3 vs 11.5 +/- 2.4 mg/dl, p = 0.015). Besides, the iPTH levels did not interfere with the rHuEPO dosage reduction and Hct increment in our patients. CONCLUSION: We conclude that maintaining high levels of serum ferritin and transferrin saturation could further reduce the requirement of rHuEPO in chronic HD patients, but the long-term effect of iron overloading to patients' nutritional status must be further evaluated in contrast to the economic saving.     

Measuring the content of reticulocyte hemoglobin (CHr) in predialysis chronic renal failure (CRF) patients

We showed that the content of reticulocyte hemoglobin (CHr) is a reliable measure of iron status with regard to erythrocytopoiesis in chronic dialysis status. The mean CHr level was 32.3 +/- 2.2 pg in dialysis patients and CHr was significantly correlated with the conventional parameters of iron deficiency. We aimed to utilize the measurement of CHr levels to monitor iron status in clinical practice. We measured CHr, iron parameters, and the intrinsic EPO concentration in non-dialysis CRF patients to clarify the alterations in CHr levels that occur as renal anemia progresses. CRF patients who visited our out-patient clinic (n = 189) were included in the study. Iron deficiency was defined by the transferrin saturation and ferritin levels. Conventional red blood cell parameters and CHr levels were measured using an ADVIA120 autoanalyzer (Bayer Medical, USA). The mean CHr value of the non-dialysis patients (creatinine clearance less than 70 ml/min) was 32.7 pg, which did not differ significantly from that of the dialysis patients. Significant correlations were found between CHr and TSAT (r = 0.032, p < 0.0177), unlike the correlation with intrinsic EPO levels. Overall, 11% of the patients were diagnosed as having iron deficiency. There was a positive correlation between CHr and serum creatinine levels. Non-dialysis CRF patients treated with rHuEPO at the dose of 24,000 U/month showed different CHr levels compared with other patients (less than 24,000 U/month). It is possible that rHuEPO treatment in non-dialysis patients affects iron dynamics. In conclusion, CHr is an easily measurable and reliable marker of iron status in non-dialysis CRF patients. Moreover, the CHr level was also sensitive to iron alternations in non-dialysis CRF patients under rHuEPO treatment. Accordingly, if long-acting EPO is available for non-dialysis CRF patients, the CHr value is likely to be indicative of the need for iron supplementation.     

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.     

The relationship between reticulocyte hemoglobin content with C-reactive protein and conventional iron parameters in dialysis patients

Adequate iron stores are a prerequisite for successful erythropoietin (EPO) therapy in hemodialysis (HD) patients. Nevertheless, iron status estimation in HD patients remains problematic, as most parameters are influenced by inflammation. The reticulocyte hemoglobin content (CHr) has recently been proposed as a useful tool in iron status assessment. However, the effect of inflammation on CHr remains unstudied. This study aimed to assess the relationship between CHr with other parameters of iron status as well as with C-reactive protein (CRP). This relationship was studied in all the patients (n=61) at our dialysis unit. CHr was significantly and positively related to transferrin saturation (TS) (rho=0.26; p<0.05) and inversely to the percentage of hypochromic red blood cells (%Hypo) (rho=-0.63; p<0.0001), but not to serum ferritin. CHr was strongly and inversely related to log CRP (rho=-0.50; p<0.0001). Despite the use of maintenance intravenous (i.v.) iron doses and relatively high serum ferritin levels, a large percentage of patients were in a state of functional iron deficiency (%Hypo > or = 6 in 41% of patients and CHr < or = 29 pg in 13% of patients). This percentage was far lower in patients with CRP levels below the detection limit (2 mg/L) (26% and 0%, respectively). In conclusion, CHr is related to both TS and %Hypo, but not to serum ferritin, and is strongly influenced by the presence of inflammation (as determined by CRP). In patients with elevated CRP levels, it is very difficult to reach target iron status levels without exceeding the upper limits for serum ferritin.     

Soluble transferrin receptors and reticulocyte hemoglobin concentration in the assessment of iron deficiency in hemodialysis patients

BACKGROUND: Diagnosing iron deficiency in hemodialysis (HD) patients is crucial for correct anemia management. Hypochromic erythrocytes appear to be the best available marker, but they are often unavailable. Transferrin saturation (TSAT) and ferritin are also indicated as reference markers by guidelines. We evaluated the usefulness of soluble transferrin receptor (s-TfR) and reticulocyte hemoglobin concentration (CHr), which have been recently proposed as more sensitive functional iron deficiency indicators. METHODS: A single-center unselected cohort of 39 chronic HD patients underwent a cross-sectional determination of hemoglobin (Hb), hematocrit (Hct), CHr, transferrin, iron, TSAT, ferritin, folate, vitamin B12 and s-TfR. Twenty-nine patients (74.4%) were treated with subcutaneous erythropoietin (EPO) at a dose of 122 +/- 98 U/kg/week and 24 patients (61.5%) were treated with intravenous (i.v.) iron gluconate, 62.5 mg/week. RESULTS: Hb was 11.1 +/- 1.2 g/dL, Hct 34.4 +/- 3.7%, CHr 32.7 +/- 3.8 pg, transferrin 170 +/- 31 mg/dL, iron 60.2 +/- 25.9 mg/dL, TSAT 30 +/- 18%; ferritin 204 +/- 219 ng/mL, folate 4.2 +/- 1.0 mcg/L, vitamin B12 0.58 +/- 0.15 mcg/L, and s-TfR 1.94 +/- 0.83 mg/L. Both TSAT and s-TfR significantly correlated with CHr, but no relationship could be found between s-TfR and TSAT or between s-TfR and ferritin. Dividing the population into two groups based on iron repletion (ferritin >100 ng/mL and TSAT >20%) we found no differences for CHr levels and significantly lower levels of s-TfR in the replete group (s-TfR 1.71 +/- 0.70 vs. 2.29 +/- 0.90 mg/L; p=0.033). Analysis of 2x2 tables demonstrated that 44% of patients with TSAT >20% had elevated (>1.5 mg/L) s-TfR, indicating a possible functional iron deficiency, but covariance analysis showed that TSAT had a better correlation to CHr. CONCLUSIONS: No clear-cut advantages in the use of CHr content and s-TfR levels as single diagnostic tests could be demonstrated by this cross-sectional study. However, our results suggest that the combined use of TSAT <20% and s-TfR >1.5 mg/L (therefore, including all patients with low TSAT, but also patients with high s-TfR despite normal TSAT) could improve functional iron deficiency detection in dialysis patients suspected of having inflammatory conditions.     

Soluble transferrin receptor is correlated with erythropoietin sensitivity in dialysis patients.

BACKGROUND: Iron deficiency is the most common cause of erythropoietin (EPO) resistance in dialyzed patients with renal anemia. Subclinical or functional iron deficiency is difficult to diagnose in these patients. The soluble transferrin receptor (sTf-R) is considered as a sensitive and specific indicator of bone marrow iron availability. PATIENTS AND METHODS: To evaluate the clinical usefulness of this novel marker, we investigated relationships between EPO requirements and various hematological and biochemical parameters of erythropoiesis in 27 pediatric end-stage renal failure patients treated by hemodialysis (HD, n = 11) or chronic peritoneal dialysis (PD, n = 16). Iron was substituted intravenously once or twice per week in HD, and by daily oral administration to PD patients. Serum sTf-R concentrations were measured by an enzyme-linked immunosorbent assay. Serum ferritin and transferrin concentrations were determined using nephelometric assays. Hemoglobin and iron levels were estimated by automated procedures. RESULTS: While neither transferrin saturation nor serum ferritin concentrations were indicative of EPO requirements, a highly significant correlation between the EPO efficacy index (EPO dose divided by hemoglobin concentration) and sTf-R was observed (r = 0.65, p = 0.001). The intravenous iron substitution in HD patients was associated with higher ferritin concentrations compared to the orally substituted PD patients (280+/-100 ng/ml vs. 124+/-83 ng/ml, p<0.002). In contrast, sTf-R concentrations were similar in both treatment groups (25.7+/-7.7 nM vs. 27+/-10.8 nM, n.s.), as were hemoglobin concentrations and EPO requirements. CONCLUSION: Our results suggest that sTf-R is a more sensitive indicator of functional iron deficiency and impaired EPO responsiveness than serum ferritin or transferrin saturation in dialyzed patients. Intensified iron substitution to patients with elevated sTf-R concentrations may considerably improve the cost efficacy of EPO treatment.     

Low-dose intravenous iron administration in chronic hemodialysis patients treated with recombinant human erythropoietin

We conducted a prospective study to determine the effect of intravenous low-dose iron administration in chronic hemodialysis patients treated with recombinant human erythropoietin (rHuEPO). Sixteen hemodialysis patients (8 males and 8 females; mean age 63.1+/-9.8 years) on maintenance rHuEPO therapy were included in the study. Patients with <100 ng/ml of ferritin received 50 mg iron during every hemodialysis session. Patients with 100-200 ng/ml of ferritin were given 50 mg iron fortnightly. Iron was not supplemented in patients with ferritin levels >200 ng/ml. Mean hematocrit, serum iron levels and transferrin saturations were significantly higher at 6 and 12 months. There was a significant reduction in weekly rHuEPO doses between the start and the 6th and 12th months. Our study shows intravenous iron administration of 100 mg/month may be sufficient to achieve a satisfactory iron status in dialysis patients on maintenance rHuEPO therapy.     

Evaluation of reticulocyte hemoglobin content,percentage of hypochromic red blood cells,and ratio of serum transferrin receptor level/serum iron level as markers of iron-deficiency erythropoiesis in patients undergoing hemodialysis

Reticulocyte hemoglobin content(CHr), percentage of hypochromic red blood cells(%HRC, level of serum transferrin receptor(sTfR), and sTfR/serum iron ratio(sTfR/Fe) were measured in 132 hemodialysis patients. On univariate analysis, CHr was positively correlated with serum amyloid A(SAA) and negatively correlated with Kt/V. %HRC showed a positive correlation with the recombinant human erythropoietin(rHuEPO) dosage. The dependency of each iron-status index on 5 variables, SAA, sFt, TS, KtN, and dose of rHuEPO administered, was determined by stepwise multiple regression analysis. CHr was influenced only by TS, while %HRC, sTfR and sTfR/Fe were influenced by both logrHuEPO dosage and TS. Patients whose hemoglobin concentration increased by more than 1 g/dl following iron supplementation were defined as Iron-Responders, and the remaining patients were defined as Iron-Nonresponders. Fifteen out of 20 patients responded to 10 consecutive intravenous administrations of 80 mg of saccharated ferric oxide at each dialysis session, while five did not. The baseline CHr was significantly lower in Iron-Responders than Iron-Nonresponders. The baseline %HRC, sTfR, and sTfR/Fe were significantly higher in Iron-Responders than Iron-Nonresponders. The baseline CHr, %HRC, and sTfR/Fe were correlated with the degree of change in Hb concentration at 4 weeks of iron supplementation. The absolute change in CHr at 2 weeks of iron supplementation was positively correlated with the absolute change in Hb concentration over the first 4 weeks. CONCLUSION: (1) In assessing the iron metabolic status of dialysis patients, CHr, %HRC, and sTfR/Fe were unique indices compared with the ordinary indices, particularly in diagnosing the functional iron deficiency state. (2) CHr was a valuable marker of iron deficiency anemia and could predict the degree of increase in Hb level following iron supplementation. (3) The %HRC and sTfR/Fe seemed to reflect both erythropoiesis induced by rHuEPO and the iron supply to erythropoietic cells.     

A randomized trial of iron deficiency testing strategies in hemodialysis patients.

BACKGROUND: Diagnosis of iron deficiency in hemodialysis patients is limited by the inaccuracy of commonly used tests. Reticulocyte hemoglobin content (CHr) is a test that has shown promise for improved diagnosis in preliminary studies. The purpose of this study was to compare iron management guided by serum ferritin and transferrin saturation to management guided by CHr. METHODS: A total of 157 hemodialysis patients from three centers were randomized to iron management based on (group 1) serum ferritin and transferrin saturation, or (group 2) CHr. Patients were followed for six months. Treatment with intravenous iron dextran, 100 mg for 10 consecutive treatments was initiated if (group 1) serum ferritin <100 ng/mL or transferrin saturation <20%, or (group 2) CHr <29 pg. RESULTS: There was no significant difference between groups in the final mean hematocrit or epoetin dose. The mean weekly dose of iron dextran was 47.7 +/- 35.5 mg in group 1 compared to 22.9 +/- 20.5 mg in group 2 (P = 0.02). The final mean serum ferritin was 399.5 +/- 247.6 ng/mL in group 1 compared to 304.7 +/- 290.6 ng/mL in group 2 (P < 0.05). There was no significant difference in final TSAT or CHr. Coefficient of variation was significantly lower for CHr than serum ferritin and transferrin saturation (3.4% vs. 43.6% and 39.5%, respectively). CONCLUSIONS: CHr is a markedly more stable analyte than serum ferritin or transferrin saturation, and iron management based on CHr results in similar hematocrit and epoetin dosing while significantly reducing IV iron exposure.     

A comparison between the soluble transferrin receptor,transferrin saturation and serum ferritin as markers of iron state in hemodialysis patients

An adequate iron management is important in the treatment of anemia and in hemodialysis (HD) patients. Serum ferritin and transferrin saturation (TS) may be influenced by the presence of inflammation. Recently, the soluble transferrin receptor (s-TfR) has been advocated as a parameter of iron status in HD patients. The aim of the present study was to assess firstly the relation between serum ferritin, TS, and s-TfR in HD patients and to predict their agreement (assessed by kappa) in the diagnosis of iron deficiency, and, secondly, to assess the influence of inflammation on the relation between the parameters of iron state. Iron deficiency by either marker was respectively defined as ferritin <100 microg/l, TS <20%, or s-TfR >2.4 microg/ml. In the overall group of patients, TS and s-TfR were significantly related (r = -0.38), whereas s-TfR and serum ferritin were not. Both serum ferritin and TS were related to CRP (r = 0.50 and -0.34; p < 0.05), whereas s-TfR was not. The kappa value for agreement between serum ferritin and TS in the diagnosis of iron deficiency was 0.24 (p = 0.07), 0.12 (p = NS) for the agreement between TS and s-TfR and 0 for that between serum ferritin and s-TfR. In patients with CRP levels 相似文献   

Acute-phase response predicts erythropoietin resistance in hemodialysis and peritoneal dialysis patients

We defined erythropoietin (EPO) resistance by the ratio of the weekly EPO dose to hematocrit (Hct), yielding a continuously distributed variable (EPO/Hct). EPO resistance is usually attributed to iron or vitamin deficiency, hyperparathyroidism, aluminum toxicity, or inflammation. Activation of the acute-phase response, assessed by the level of the acute-phase C-reactive protein (CRP), correlates strongly with hypoalbuminemia and mortality in both hemodialysis (HD) and peritoneal dialysis (PD) patients. In this cross-sectional study of 92 HD and 36 PD patients, we examined the contribution of parathyroid hormone (PTH) levels, iron indices, aluminum levels, nutritional parameters (normalized protein catabolic rate [PCRn]), dialysis adequacy (Kt/V), and CRP to EPO/Hct. Albumin level serves as a measure of both nutrition and inflammation and was used as another independent variable. Serum albumin level (deltaR2 = 0.129; P < 0.001) and age (deltaR2 = 0.040; P = 0.040) were the best predictors of EPO/Hct in HD patients, and serum albumin (deltaR2 = 0.205; P = 0.002) and ferritin levels (deltaR2 = 0.132; P = 0.015) in PD patients. When albumin was excluded from the analysis, the best predictors of EPO/Hct were CRP (deltaR2 = 0.105; P = 0.003) and ferritin levels (deltaR2 = 0.051; P = 0.023) in HD patients and CRP level (deltaR2 = 0.141; P = 0.024) in PD patients. When both albumin and CRP were excluded from analysis in HD patients, low transferrin levels predicted high EPO/Hct (deltaR2 = 0.070; P = 0.011). EPO/Hct was independent of PTH and aluminum levels, PCRn, and Kt/V. High EPO/Hct occurred in the context of high ferritin and low transferrin levels, the pattern expected in the acute-phase response, not in iron deficiency. In well-dialyzed patients who were iron replete, the acute-phase response was the most important predictor of EPO resistance.     

Transferrin saturation versus reticulocyte hemoglobin content for iron deficiency in Japanese hemodialysis patients

BACKGROUND: Iron deficiency is a frequent cause of recombinant human erythropoietin (rhEPO)-resistant anemia in hemodialysis patients. Both reticulocyte hemoglobin content (CHr) and transferrin saturation (TSAT) have been proposed as markers of iron deficiency, but it is unclear which parameter is superior. METHODS: To compare the efficacy of CHr and TSAT as an indicator for treatment of iron deficiency, we conducted a single-center, open-label, prospective, randomized, controlled trial at the Kidney Center in Shinraku-en Hospital of 197 Japanese patients on chronic hemodialysis. After 4 weeks of run-in period during which iron supplementation was suspended, 100 patients who were randomized to the CHr group received 240 mg iron colloid intravenously over 2 weeks when CHr less than 32.5 pg, and 97 patients who were randomized to the TSAT group received the same doses of iron colloid when TSAT less than 20%. We measured the rhEPO dose needed to maintain prestudy hematocrit levels, hematocrit, CHr, TSAT, serum ferritin, percentage of hypochromic red blood cells, and total iron administered. RESULTS: Sixteen weeks later, 94 patients in the CHr group and 89 patients in the TSAT group finished the study. The doses of rhEPO required decreased by 35.8% (4081 to 2629 U/week, P < 0.005) in the TSAT group, but not significantly in the CHr group (4121 to 3606 U/week). Although CHr increased promptly after the iron administration in both groups, TSAT increased only in the TSAT group. CONCLUSIONS: Although CHr reflects the iron status more sensitively, TSAT is a better clinical marker for iron supplementation therapy.     

Effects of intravenous ascorbic acid on erythropoiesis and quality of life in unselected hemodialysis patients

BACKGROUND: Intravenous ascorbic acid (IVAA) administration is reported to enhance erythropoiesis in hemodialysis (HD) patients with functional iron deficiency. We explored the effects of IVAA on erythropoiesis and health-related quality of life (HRQOL) in unselected HD patients. METHODS: Sixty-one HD patients were divided into two groups; 30 patients received 100 mg of IVAA (IVAA group) and 31 patients did not (control group) after each dialysis session. Hematocrit (Hct), reticulocyte hemoglobin content, transferrin saturation, ferritin, weekly recombinant human erythropoietin (rHuEPO) dosage, weekly intravenous iron (IVFE) dosage, and MOS Short Form 36 (SF-36) scale scores were measured at baseline and after 6 months of treatment. RESULTS: Mean changes in Hct in the IVAA and control groups were -0.5 and -0.6 mg/dL, respectively, while mean changes in SF-36 scale scores were: physical functioning -1.6 in the IVAA group and 0.38 in the controls; role physical (RP) 3.8 and 9.4; bodily pain 9.7 and 0.81; general health perception 3.7 and -0.68; vitality 4.3 and -7.5; social functioning 2.7 and 0.43; role emotional (RE) 6.9 and 4.9; mental health 3.6 and -1.7. The IVAA group showed significantly higher adverse events (chest pain: n=1, nausea: n=2 and fatigue: n=2) compared to the controls (no event). CONCLUSIONS: The beneficial effects of IVAA on erythropoiesis and HRQOL were not demonstrated in unselected HD patients. Indication of IVAA for HD patients leaves room for further study.     

Intravenous iron dextran and erythropoietin use in pediatric hemodialysis patients

Recombinant human erythropoietin (rHuEPO) is an effective treatment for the anemia of chronic renal failure. However, adequate availability of iron is necessary for an optimal response. We prospectively evaluated the effect of an intravenous iron protocol in a pediatric hemodialysis unit. Patients with either a serum ferritin less than 150 ng/ml or transferrin saturation (TSAT) less than 20% received intravenous iron dextran during ten consecutive dialysis sessions. The administration of rHuEPO was adjusted using a protocol designed to maintain patient hematocrit between 33% and 36%. Thirteen courses of intravenous iron were evaluated. Patients received 4 mg/kg of iron dextran (maximum of 100 mg) during each of ten consecutive dialysis sessions. In 12 cases there was a decrease in rHuEPO use 2 months after completing the course of intravenous iron. The mean rHuEPO dose decreased from 3,784 units to 2,115 units (P<0.005). Based on the criteria of response to intravenous iron, a percentage iron saturation of less than 20% had a high specificity for detecting iron deficiency. All patients who received a course of intravenous iron had a TSAT less than 20%. The measurement of serum ferritin was less useful in our patients.     

The prevalence of iron deficiency among patients presenting with colorectal cancer

OBJECTIVES: To examine prospectively the prevalence of iron deficiency among new patients presenting with colorectal cancer and to compare transferrin saturation and serum ferritin as markers of iron deficiency in this group of patients. PATIENTS AND METHODS: Data were gathered on all patients presenting with a new diagnosis of colorectal cancer over a 12-month period. Iron status was estimated and, when possible, confirmed by measurement of serum ferritin concentration and transferrin saturation. Iron status was further examined in relation to tumour site and Dukes' stage. RESULTS: During the study 157 patients presented with a new colorectal cancer. Of these, 130 could be evaluated and 78[60%] had evidence of iron deficiency. Transferrin saturation was below the reference range in 55 patients, but serum ferritin was below in only 18 patients. Among the 49 patients with right-sided cancers, 39[80%] were iron deficient. Iron deficiency was significantly more likely in patients with right sided cancers compared with those with cancers at or distal to the splenic flexure (chi2 = 13, P < 0.001). CONCLUSION: The majority of patients with a new diagnosis of colorectal cancer are iron deficient at presentation. In such patients transferrin saturation measurement is a more sensitive marker of iron deficiency than serum ferritin. The potential role of measuring serum transferrin saturation as an adjunct to faecal occult blood screening should be explored further.     

Assessment of iron deficiency in chronic hemodialysis patients: investigation of cutoff values for reticulocyte hemoglobin content

Background. Recently, the usefulness of reticulocyte hemoglobin content (CHr) as a ferrokinetic marker in hemodialysis patients who receive recombinant human erythropoietin (rHuEPO) has been reported. However, a definite index for iron deficiency has not been established. In this study, a CHr cutoff value was investigated. Methods. We retrospectively selected 27 hemodialysis patients by the following criteria: (1) hematocrit (Ht) values less than 30%, (2) patients receiving a stable dose of rHuEPO for at least 3 months, (3) patients who had not received iron supplements for at least 3 months, and had begun receiving iron supplements, (4) the doses of rHuEPO and iron supplements were unchanged for 8 weeks following the start of iron administration. The iron supplement was administered at a dose of 40 mg/week, and Ht, CHr, transferrin saturation (TSAT), and serum ferritin were measured. The difference between the peak Ht value obtained at weeks 4–8 and Ht at baseline was calculated (ΔHt). Patients with a ΔHt of 3% or more were categorized as iron-deficient at baseline (group 1; n = 17). Patients with a ΔHt of less than 3% were categorized as iron-sufficient at baseline (group 2; n = 10). Each parameter was compared between the groups. Results. Significant negative correlations between ΔHt and CHr at baseline, and ΔHt and TSAT at baseline were observed. CHr and TSAT were significantly lower in group 1 than in group 2 at baseline. CHr was less than 32 pg in all patients in group 1, and greater than 32 pg in nine of the ten patients in group 2. If the CHr cutoff value was 32 pg, sensitivity was 100% and specificity was 90%. Conclusions. It is considered that 32 pg is appropriate for the CHr cutoff value. Received: June 5, 2002 / Accepted: November 18, 2002 Correspondence to:K. Mitsuiki     

Influence of inflammation on the relation between markers of iron deficiency in renal replacement therapy

Iron deficiency is an important factor in the management of anemia in both dialysis and transplant patients. Serum ferritin and transferrin saturation (TS) may be influenced by the presence of inflammation. Recently, the soluble transferrin receptor (s-TfR) has been considered to be a marker of functional iron stores. In this study, parameters of the iron state were investigated in terms of agreement (assessed by kappa) with the diagnosis of iron deficiency and with inflammation. The study was performed in 38 hemodialysis, 31 continuous ambulatory peritoneal dialysis, and 21 anemic renal transplant patients. CRP and amyloid A protein (AAP) were studied as markers of inflammation. Iron deficiency was defined as ferritin <100 mg/L, TS <20%, or s-TfR >1.76 mg/mL. We observed that s-TfR levels were significantly related to both dialysis duration (r = 0.28 in dialysis and r = 0.60 in transplant patients, both P <.05) and PTH levels (r = 0.23 in dialysis and r = 0.55 in transplant patients, both P <.05). Among the transplant group, ferritin and TS, as well as TS and s-TfR were significantly related (r = 0.84 and r = -0.64, respectively), but not s-TfR and ferritin. Among the dialysis group, ferritin and TS, and also TS and s-TfR, were significantly related (r = 0.35 and r = -0.30, respectively), whereas s-TfR and ferritin were not. In the transplant group, the kappa value for agreement between ferritin and TS in the diagnosis of iron deficiency was 0.76 (P =.006), and 0.33 (P =.04), respectively. Among patients with CRP levels <0.3 mg/L or AAP levels <6.4 mg/L, the relation between parameters of iron state was more robust. The kappa value for agreement between ferritin and s-TfR was 0.49 (P =.006) in the dialysis group and 1 (P =.002) for that between ferritin and TS in the transplant group. Our results suggest that PTH levels may influence s-TfR levels. Discordance between ferritin, TS, and s-TfR as markers of iron deficiency might be explained by the effects of inflammation.     

Effect of intravenous ascorbic acid medication on serum levels of soluble transferrin receptor in hemodialysis patients

Intravenous ascorbic acid (IVAA) medication has been shown to facilitate iron release from inert depots and subsequently circumvent the defective iron utilization in chronic hemodialysis (HD) patients who are treated with recombinant human erythropoietin (rHuEPO). This study focuses on the effects of IVAA supplementation on serum concentrations of soluble transferrin receptors (TfR) on the basis of the hypothesis that an increase of labile iron in the cytosol will lead to inhibition of TfR expression. First, 138 HD patients were studied to evaluate the interrelation between serum TfR and iron status. In a stepwise multivariate analysis, serum EPO and transferrin saturation (TSAT) were the two independent predictors for serum TfR in HD patients (r(2) = 0.510, P < 0.001). Further analyses showed that the lower the serum EPO and the higher the TSAT, the lower the serum TfR in HD patients who are on maintenance rHuEPO treatment. Second, 36 HD patients were recruited in a randomized, controlled study to receive IVAA (total dose of 2000 mg) or normal saline (placebo) medication. Serum levels of TfR, EPO, and ferritin and TSAT were measured at baseline and within 7 d after starting IVAA or placebo. There were no significant changes in serum EPO and ferritin levels in patients who received either IVAA (n = 18) or placebo (n = 18). Serum TfR levels (P < 0.001) significantly declined with a parallel rise in TSAT (P < 0.05) as compared with presupplemental values within 7 d in IVAA patients before any apparent alteration in hematocrit values, but the changes were not observed in the placebo group. The trend of decreased serum TfR and increased TSAT was similar in IVAA patients with ferritin of <500 microg/L or >500 microg/L. It is concluded that ascorbic acid status can significantly decrease serum TfR concentrations and increase percentage of TSAT, probably through alterations in intracellular iron metabolism.     

Ultrapure dialysate improves iron utilization and erythropoietin response in chronic hemodialysis patients - a prospective cross-over study

BACKGROUND: The impact of ultrapure dialysis on dialysate-related chronic inflammatory status and anemia in uremic patients on maintenance hemodialysis (HD) remains uncertain. We evaluated ultrapure dialysate effects on erythropoietin (EPO) response and inflammatory status in a prospective, randomized, cross-over study. METHODS: Thirty-four HD patients were divided into two groups. One group was treated with conventional dialysate and the other group with ultrapure dialysate for 6 months and crossed over for another 6 months. Bacteria growth and dialysate endotoxin were examined. Parameters including C-reactive protein (CRP), recombinant human erythropoietin (rHuEPO) dose, ferritin, iron saturation and serum albumin were measured at the start, and at 6 and 12 months. RESULTS: The endotoxin levels reduced significantly in the ultrapure dialysate by adding a dialysate ultrafilter. After a 6-month treatment with ultrapure dialysate, there were statistically significant differences in the systemic inflammation markers between both groups. Changing from conventional to ultrapure dialysis fluid significantly reduced CRP (7.01 +/- 5.059 to 4.461 +/- 3.754 mg/L, p<0.05), and resulted in reduced rHuEPO doses (12500 +/- 7060 to 10440 +/- 7050 U/month, p<0.05). Continuous conventional dialysate use was not associated with significant alternations in CRP (from 5.849 +/- 7.744 to 6.187 +/- 7.997 mg/L, p=0.456) and rHuEPO dose (14060 +/- 6210 to 15060 +/- 7250U/month, p>0.05). The ferritin level reduced significantly (422 +/- 183 to 272 +/- 162 mcg/L, p<0.05) in the ultrapure dialysate group. After another 6-month cross-over, the study parameters were reversed among the two groups indicating the beneficial effect of ultrapure dialysis. CONCLUSIONS: Through endotoxin reduction in conventional dialysate, ultrapure dialysis in dialysis patients manifested a reduced inflammatory parameter, reduced rHuEPO dose and improved iron utilization; and therefore, could be beneficial in anemia treatment.