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     

Increased visfatin in hemodialysis patients is associated with decreased demands for recombinant human erythropoietin

Abstract

Background: Studies detected an association between visfatin and markers of iron metabolism in patients with insulin resistance. In this study, such a relation was evaluated in hemodialysis (HD) patients. Also relations between visfatin and hepcidin, demands for recombinant human erythropoietin (rHuEpo), inflammation, and situations characterized by insulin resistance were evaluated. Methods: After a four-week washout period from iron treatment, 33 HD patients and 20 healthy volunteers enrolled in the study. Serum visfatin, hepcidin, and interleukin-6 (IL-6) were assessed by means of enzyme-linked immunosorbent assay. Hemoglobin, serum iron, ferritin, and transferrin saturation (TSAT) were also measured. Results: Visfatin was markedly increased in HD patients. Visfatin levels did not differ between diabetics and non-diabetics. No relation was detected between visfatin and body mass index or IL-6 in HD patients. From the markers of iron metabolism, the hepcidin included, visfatin was related only to TSAT. A strong positive relation was revealed between visfatin and hemoglobin, whereas visfatin was inversely related to rHuEpo dose. Resistance to rHuEpo index was inversely and independently of TSAT related to visfatin. Conclusion: Visfatin is increased in HD patients and it is associated with decreased demands for rHuEpo.     

Iron therapy in the pediatric hemodialysis population

Iron therapy maintains iron stores and optimizes the response to recombinant human erythropoietin (r-HuEPO) in patients with end-stage renal failure. Information is limited, however, regarding the preferential route of iron administration in pediatric patients receiving hemodialysis. Therefore, we prospectively randomized 35 iron-replete patients (aged >1 to <20 years) to receive up to 16 weeks of maintenance IV (n=17) or daily oral (n=18) iron. Eligible patients had received hemodialysis for >2 months, had a baseline transferrin saturation [TSAT] >20%, and were receiving maintenance r-HuEPO. Treatment arms were evenly distributed with respect to baseline demographic and clinical characteristics, with no statistically significant differences in baseline hemoglobin (Hb), hematocrit (Hct), reticulocyte Hb content (CHr), serum ferritin (SF), TSAT, or r-HuEPO dose. In the 35 patients, IV iron dextran and not oral iron was associated with a significant increase (138.5 to 259.1 ng/ml, P=0.003) in SF. A comparison of the change in SF between the IV iron group and the oral iron group was also significant (P=0.001). Whereas only IV iron was associated with a significant decrease in the dose of r-HuEPO (234.0 to 157.6 U/kg per week, P=0.046) and an increase of the CHr (29.2 to 30.1 pg, P=0.049), these changes were not significantly different from those experienced by patients in the oral iron group. In both groups, the Hct remained stable and in neither group was there a significant change in the TSAT. In summary, although both oral and IV iron maintained patients in an iron-replete state in this short-term study, only IV therapy allowed for a significant improvement in iron stores.     

Effect of an intravenous iron dextran regimen on iron stores, hemoglobin, and erythropoietin requirements in hemodialysis patients

Iron deficiency is a common cause of delayed or diminished response to erythropoietin (EPO) in hemodialysis patients. Although oral iron is often prescribed to replete iron stores, this approach to iron supplementation may not be adequate with chronic EPO therapy. Intravenous (IV) iron dextran may be an effective alternative approach to replete iron stores and may facilitate more cost-effective use of EPO. The purpose of this study was to evaluate an IV iron dextran regimen that consisted of a loading dose phase followed by monthly maintenance doses of iron dextran. The effect of this regimen on iron stores, hemoglobin, and EPO doses was evaluated. This was an open prospective study in adult hemodialysis patients who were iron deficient as defined by a serum ferritin less than 100 ng/mL or transferrin saturation (TSAT) of less than 20%. Patients were loaded with 1 g iron dextran in five divided doses and then received monthly maintenance doses of 100 mg for the 4-month study period. Values of serum ferritin, TSAT, hemoglobin, and EPO dose were followed for the 4-month study period. Thirty hemodialysis patients receiving EPO were identified as being iron deficient and were enrolled in the study. The mean serum ferritin increased significantly from 49 ng/mL at baseline to 225 ng/mL at the end of the study period (P < 0.0001). Mean TSAT also increased significantly from 27% to 33% (P = 0.002). Values for hemoglobin did not change significantly during the study period; however, there was a significant reduction in EPO dose from a mean baseline dose of 112 U/kg/wk to 88 U/kg/wk at the end of the study period (P = 0.009). Seventeen patients experienced an increase in hemoglobin or a decrease in EPO dose. Economic analysis showed that approximately $580 (Cdn) per patient per year could be saved by use of IV iron dextran. The administration of the IV iron dextran regimen in the iron-deficient hemodialysis population was effective at repleting and maintaining iron stores and reducing EPO use.     

Reduction of recombinant human erythropoietin maintenance dose by supplementation with a low-dose iron preparation, given intravenously

Background. In chronic hemodialysis patients who showed iron deficiency, we investigated whether the maintenance dose of recombinant human erythropoietin (rHuEPO) could be reduced by long-term intravenous supplementation with a low-dose iron preparation. Methods. In 26 chronic hemodialysis patients who were receiving treatment with a maintenance dose of rHuEPO, without an iron supplement, who showed iron deficiency, the intravenous administration of 40 mg of chondroitin sulfate-iron colloid once per week after dialysis was initiated. We observed the patients' course for 1 year and investigated the reduction in the rHuEPO dose. Results. In the 26 patients, the rHuEPO dose was reduced by 25% after 6 months, and the reduction increased to 32% in the twelfth month. The patients were divided, according to the maintenance dose of rHuEPO received before the iron supplementation into high-, intermediate-, and low-dose groups (9000, 4500, and 2250 IU/week, respectively), and the results were analyzed. A marked reduction of the rHuEPO dose, of 46% in the twelfth month, was obtained in the intermediate-dose group. In the high- and low-dose groups, the reductions of the rHuEPO dose were low. Conclusions. In chronic hemodialysis patients with iron deficiency who are being treated with a maintenance dose of rHuEPO, the intravenous administration of a low dose of iron (40 mg/week) led to a reduction in the rHuEPO dose. This effect was marked in patients in the intermediate-dose rHuEPO group, i.e., 4500 IU/week, which is the most frequently employed maintenance dose in Japan. This therapeutic method can be recommended from a health-care economics perspective. Received: April 5, 2001 / Accepted: August 22, 2001     

CERA conversion to darbepoetin alfa in 154 hemodialysis patients

Purpose

Anemia is a common complication in dialysis patients, usually treated with erythropoietin (EPO). Among available EPOs and analogs, continuous erythropoietin receptor activator (CERA) and darbepoetin alfa (DA) are the only two agents with a long duration of action, although they have almost never been formally compared in terms of efficacy. We took advantage of an accidental disruption in CERA supply to study the effect of its replacement with DA in the same patients.

Methods

The clinical and biological characteristics of 154 hemodialysis patients were retrospectively reviewed during the last 3 months on CERA compared to the first 4 months after replacement by DA, both ASE being administered by IV route. The comparison included EPO doses, hemoglobin levels, factors interfering with anemia (iron status assessment, iron doses, inflammation, quality of treatment) and was performed under the Bayesian paradigm.

Results

We found no significant differences between the two EPOs in terms of doses or hemoglobin concentrations. Factors that could potentially influence hemoglobin concentrations also did not differ under CERA or DA. The stability of hemoglobin was identical with both EPOs. We provide a conversion factor which allows comparison of cost according to local prices.

Conclusions

We conclude that, in this observational “real life” study, the two EPOs are to be considered as equivalent.

     

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.     

Reticulocyte hemoglobin content as a marker of iron status in patients receiving maintenance hemodialysis

Background. Patients with renal anemia who show a poor response to erythropoietin might have iron insufficiency. Reticulocyte hemoglobin content (CHr) was measured in hemodialysis patients, and its potential as a marker for iron status was assessed by comparing CHr with ordinary markers. Methods. Ninety-one patients receiving maintenance hemodialysis were enrolled. Venous sampling was performed twice, at a 3-month interval. During the interval, none of the patients received any iron agent and there was no alteration in their erythropoietin doses. CHr was measured with an automated blood cell counter. Simultaneously, ordinary markers for iron status, such as hematocrit (Ht), mean hemoglobin content (CH), serum iron (Fe), ferritin (Fr), and transferrin saturation (TSAT), were measured. CHr was compared with these markers. Results. CHr randed from 24.1 to 34.7 pg, with a mean of 31.0 pg. CHr correlated with CH (P < 0.001), Fr (P < 0.01), Fe (P < 0.001), and TSAT (P < 0.001), but not with Ht. When patients were divided into two groups according to the CHr : CH ratio (CHr : CH ≧ 1 and CHr : CH < 1), there was no difference in any parameter between the two groups in the first measurement. In the second measurement, done after a 3-month interval, patients with CHr : CH ≧ 1 showed significantly higher values for CHr (P < 0.001), CH (P < 0.01), Fe (P < 0.05), and TSAT (P < 0.05) than patients with CHr : CH < 1. Conclusions. It was suggested that the CHr : CH ratio would predict changes in the state of iron supply. CHr might be a potential marker for monitoring renal anemia. Received: March 28, 2001 / Accepted: May 31, 2002     

A parallel, comparative study of intravenous iron versus intravenous ascorbic acid for erythropoietin-hyporesponsive anaemia in haemodialysis patients with iron overload

Background: Functional iron deficiency may develop and cause erythropoietin resistance in haemodialysis patients with iron overload. Controversy remains as to whether intravenous iron medication can improve this hyporesponsiveness due to decreased iron availability, or whether iron therapy will aggravate haemosiderosis. Intravenous administration of ascorbic acid has been shown to effectively circumvent resistant anaemia associated with iron overload in a small preliminary study. To elucidate further the possible mechanisms of this resistance, a parallel, comparative study was conducted to compare the effects of intravenous iron and ascorbate therapies in iron-overloaded haemodialysis patients. Methods: Fifty haemodialysis patients with serum ferritin of >500 &mgr;g/l were randomly divided into two protocols. They were further stratified into controls (Control I, n=11) and intravenous iron group (IVFE, n=15) in protocol I; and into controls (Control II, n=12) and intravenous ascorbic acid group (IVAA, n=12) in protocol II. Controls had a haematocrit of >30% and did not receive any adjuvant therapy. IVFE and IVAA patients were hyporesponsive to erythropoietin and functionally iron deficient. Ferric saccharate (100 mg dose) was administered intravenously post-dialysis on five consecutive dialysis sessions in the first 2 weeks; and ascorbic acid (300 mg dose) thrice a week for 8 weeks. Red cell and iron metabolism indices were examined before and following therapy. Results: Mean values of haematocrit and transferrin saturation were significantly lower, and erythropoietin dose was higher in IVFE and IVAA patients compared to controls. Intravenous iron therapy neither improved erythropoiesis nor reduced erythropoietin dose during 12 weeks. Iron metabolism indices significantly increased at 2 and 6 weeks, but decreased at 12 weeks returning to the baselines. In contrast, mean haematocrit significantly increased from 25.8±0.5 to 30.6±0.6% with a concomitant reduction of 20% in erythropoietin dose after 8 weeks of ascorbate therapy. Serum ferritin modestly fell but with no statistical significance. The enhanced erythropoiesis paralleled a rise in transferrin saturation from 27±3 to 48±6% and serum iron from 70±11 to 107±19 &mgr;g/dl (P<0.05). Conclusions: Short term intravenous iron therapy cannot resolve the issue of functional iron deficiency in haemodialysis patients with iron overload. Intravenous administration of ascorbic acid not only facilitates iron release from storage sites, but also increases iron utilization in the erythron. Our study draws attention to a potential adjuvant therapy, intravenous ascorbic acid, to treat erythropoietin-hyporesponsive anaemia in iron-overloaded patients.     

Treatment of Iron Deficiency Anemia in Orthopedic Surgery with Intravenous Iron: Efficacy and Limits: A Prospective Study

Background: Preoperative anemia is frequent in patients undergoing orthopedic surgery. The purpose of this study was to assess the preoperative increase of hemoglobin in iron deficiency anemia patients treated with intravenous iron.

Methods: After obtaining written informed consent, 20 patients with iron deficiency anemia received 900 mg intravenous iron sucrose over 10 days starting 4 weeks before surgery. Changes of hemoglobin and iron status were measured over 4 weeks and at discharge. In the last 11 patients, endogenous erythropoietin was also measured. Data were analyzed using the Friedman test followed by pairwise Wilcoxon signed rank tests with Bonferroni correction.

Results: Hemoglobin increased significantly (P < 0.0001) after intravenous iron treatment. Overall, the mean maximum increase was 1.0 +/- 0.6 g/dl (range, 0.2-2.2 g/dl). Ferritin increased from 78 +/- 70 to 428 +/- 191 [mu]g/l (P = 0.0001), ferritin index decreased from 2.7 +/- 2.4 to 1.5 +/- 1.0 (P = 0.0001), and soluble transferrin receptor decreased from 4.1 +/- 2.3 mg/l to 3.7 +/- 2.3 mg/l (P = 0.049), whereas transferrin saturation (20.5 +/- 9.0 to 22.9 +/- 9.0%) and serum iron (13.3 +/- 4.6 to 13.1 +/- 4.5 [mu]m) did not change significantly after intravenous iron treatment. Endogenous erythropoietin decreased from 261 +/- 130 pg/ml to 190 +/- 49 pg/ml 2 weeks after intravenous iron treatment (P = 0.050, not significant after Bonferroni correction). No adverse events related to intravenous iron were observed. The maximum increase of hemoglobin was observed 2 weeks after the start of intravenous iron treatment, indicating that administration of intravenous iron 2-3 weeks before surgery may be optimal.     

Continuous intravenous intradialysis versus intravenous postdialysis erythropoietin therapy in chronic haemodialysis patients: a randomized, controlled, crossover study

Background: Subcutaneous recombinant human erythropoietin seems to be more effective than intravenous administration. Local pain, however, may diminish patient compliance with the subcutaneous route. Recently continuous intravenous intradialysis administration of rHuEpo has been reported to be more efficacious in stimulating erythropoiesis than the usual postdialysis intravenous bolus. Methods: We conducted a randomized, controlled, crossover study on stable chronic haemodialysis patients to compare the efficacy of continuous intradialysis rHuEpo therapy with intravenous postdialysis administration. Twenty patients were selected and randomly assigned to receive rHuEpo either postdialysis (control phase) or by continuous intradialysis perfusion (slow Epo phase) for 12 weeks. After this period, patients were switched to the alternative method for 12 additional weeks. The erythropoietin dose remained unchanged during the study. Haematocrit was monitored weekly and iron metabolism, serum Epo, and vitamins were measured monthly. Urea kinetics and iPTH measurements were performed every 3 months. Results: Three patients were excluded because of unrelated problems. The final mean haematocrit was unchanged from previous basal values in both phases and no statistical differences were found for any parameter between the groups. No differences were found in iron metabolism nor in urea kinetic parameters. Conclusions: Continuous intravenous intradialysis administration of rHuEpo is no more effective than an intravenous postdialysis bolus as rHuEpo maintenance therapy in stable chronic haemodialysis patients.     

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.     

Maintenance intravenous iron therapy in pediatric hemodialysis patients

Iron supplementation is required for optimal response to erythropoietin (EPO) in hemodialysis patients. This is due to blood lost in the dialysis tubing after dialysis and the increased demand for iron by EPO therapy. Maintenance intravenous (IV) iron was administered according to a standardized protocol to pediatric patients on hemodialysis in our institution. The effect of this protocol on EPO dose, iron indices, anemia, and medication costs was evaluated. Data on two groups of patients were retrieved from the health records. Group 1 (n=14) consisted of patients treated in the 18 months prior to the protocol. These patients received oral iron supplements and occasional IV iron. Group 2 (n=5) consisted of all patients treated with the IV iron protocol. There was no difference in clinical characteristics and mean values for monthly hemoglobin, serum iron, ferritin, and transferrin saturation between groups. The dose of EPO was significantly reduced in group 2 compared with group 1 (193.9±121.4 vs. 73.9±39.0 units/kg per week, P<0.05). Medication costs were reduced by 26% in group 2. No significant adverse events were seen. Maintenance IV iron reduced the dose of EPO required to maintain blood hemoglobin levels. Our results also suggest that maintenance IV iron is a more-economic method of iron supplementation for pediatric hemodialysis patients. Received: 13 November 2000 / Revised: 23 April 2001 / Accepted: 24 April 2001     

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.     

Sodium ferric gluconate complex maintenance therapy in children on hemodialysis

Intravenous iron therapy is recommended for children and adults who receive hemodialysis (HD) and recombinant human erythropoietin (rHuEPO). However, limited information exists on the use of any maintenance IV iron regimen in children. Therefore, we conducted a prospective, multicenter, open-label trial of maintenance therapy with sodium ferric gluconate complex (SFGC) in iron-replete pediatric HD patients receiving rHuEPO. Patients received SFGC weekly at an initial dose of 1.0 mg kg⁻¹ week⁻¹, not to exceed 125 mg. Doses could be adjusted based on iron indices. Twenty-three patients (mean age: 13.2±2.39 years) were enrolled and received at least one dose of SFGC, while twelve patients completed the study. After 12 weeks of treatment, the mean SFGC dose delivered was 1.0 mg/kg. Mean TSAT and serum ferritin levels remained within NKF-K/DOQI target ranges and the mean Hgb level remained unchanged from baseline. No unexpected or unusual safety risks were associated with SFGC use. In summary, this experience provides evidence for the safety and efficacy of intravenous SFGC and supports the recommendation that the maintenance SFGC starting dose should be 1.0 mg/kg, not to exceed 125 mg, with subsequent adjustments made according to TSAT and/or serum ferritin levels.     

Erythropoietin therapy in pre-dialysis patients with chronic renal failure: lack of need for parenteral iron

BACKGROUND: During erythropoietin therapy, scant information exists regarding the optimal target percent saturation of transferrin (TSAT), ferritin and the mode and amount of iron supplementation in pre-dialysis patients with anemia due to chronic kidney disease (CKD). HYPOTHESIS: Pre-dialysis CKD patients may have different needs for iron supplementation than end-stage renal disease subjects during erythropoietin therapy. METHODS: Retrospective analysis of pre-dialysis CKD subjects (n = 31) treated with erythropoietin at our institution. RESULTS: In this population our results showed that target hematocrit (33-36%) was achievable with erythropoietin (mean subcutaneous dose 86 +/- 17 [SD] units/kg/week) without parenteral iron therapy. The hematocrit increased from a mean baseline value of 28.4 +/- 2.7 to 33.6 +/- 3.4% at time 1 (4-9 weeks, p < 0.0001), and to 37.7 +/- 4.5% at time 2 (10-20 weeks, p < 0.0001). The hemoglobin concentration increased from 9 +/- 0.9 g/dl at baseline to 10.7 +/- 1.1 g/dl at time 1 (p < 0.0001) and to 12 +/- 1.5 g/dl at time 2 (p < 0.0001). Subgroup analyses of patients prescribed <200 mg oral elemental iron per day (n = 10), those with TSAT <20% and/or ferritin <100 ng/ml (n = 19), and those prescribed erythropoietin <80 units/kg/week (n = 12), all showed a significant increase in hematocrit and hemoglobin. CONCLUSIONS: Our data show that pre-dialysis CKD subjects respond adequately to erythropoietin at or lower than recommended erythropoietin doses without parenteral iron. This response extends even to subgroups with TSAT and/or ferritin levels deemed to indicate iron deficiency in CKD subjects, and may be due to lack of existence of functional iron deficiency in this group of patients.     

蔗糖铁联合使用重组人促红细胞生成素治疗老年髋部骨折贫血的临床疗效观察

目的:分析蔗糖铁联合使用重组人促红细胞生成素治疗老年髋部骨折贫血的临床疗效。方法:自2016年2月至2018年4月行髋部骨折手术96例老年贫血患者根据治疗方式分为3组,3组患者均在术前3 d接受抗贫血治疗,其中A组32例单独使用蔗糖铁,B组32例单独使用重组人促红细胞生成素,C组32例联合使用蔗糖铁和重组人促红细胞生成素治疗,观察比较3组的治疗效果。结果:临床有效率C组显著高于A、B组患者(P0.05)。3组患者围术期失血量比较,差异无统计学意义(P0.05),但C组输血率明显低于A、B组患者(P0.05)。用药前,3组血红蛋白、红细胞计数比较,差异无统计学意义(P0.05),但术后1、3、5 d,C组患者上述指标均明显高于A、B组(P0.05)。用药期间,药物不良反应发生率3组间差异无统计学意义(P0.05)。结论:与单一用药相比,蔗糖铁联合使用重组人促红细胞生成素治疗老年髋部骨折贫血效果确切,不仅能够有效改善患者血红蛋白水平,保障手术顺利进行,还可降低患者的输血率,促进其术后康复。     

Optimization of epoetin therapy with intravenous iron therapy in hemodialysis patients

Iron deficiency limits the efficacy of recombinant human erythropoietin (rhEPO) therapy in end-stage renal disease (ESRD) patients. Functional iron deficiency occurs with serum ferritin >500 ng/ml and/or transferrin saturation (TSAT) of 20 to 30%. This study examines the effects of a maintenance intravenous iron dextran (ivID) protocol that increased TSAT in ESRD hemodialysis patients from conventional levels of 20 to 30% (control group) to those of 30 to 50% (study group) for a period of 6 mo. Forty-two patients receiving chronic hemodialysis completed a 16- to 20-wk run-in period, during which maintenance ivID and rhEPO were administered in amounts to achieve average TSAT of 20 to 30% and baseline levels of hemoglobin of 9.5 to 12.0 g/dl. After the run-in period, 19 patients randomized to the control group received ivID doses of 25 to 150 mg/wk for 6 mo. Twenty-three patients randomized to the study group received four to six loading doses of ivID, 100 mg each, over a 2-wk period to achieve a TSAT >30% followed by 25 to 150 mg weekly to maintain TSAT between 30 and 50% for 6 mo. Both regimens were effective in maintaining targeted hemoglobin levels. Fifteen patients in the control group and 17 patients in the study group finished the study in which the primary outcome parameter by intention to treat analysis was the rhEPO dose needed to maintain prestudy hemoglobin levels. Maintenance ivID requirements in the study group increased from 176 to 501 mg/mo and were associated with a progressive increase in serum ferritin to 658 ng/ml. Epoetin dose requirements for the study group decreased by the third month and remained 40% lower than for the control group, resulting in an overall cost savings in managing the anemia. Secondary indicators of iron-deficient erythropoiesis were also assessed. Zinc protoporphyrin did not change in either group. Reticulocyte hemoglobin content increased only in the study group from 28.5 to 30.1 pg. It is concluded that maintenance of TSAT between 30 and 50% reduces rhEPO requirements significantly over a 6-mo period.     

Impact des comorbidités sur la stabilité de l’hémoglobine chez des patients insuffisants rénaux chroniques en hémodialyse,traités par CERA en pratique courante : l’étude MIRIADE

This national, prospective and multicenter study aimed to describe the real-life impact of comorbidities on hemoglobin stability in patients with chronic kidney disease on hemodialysis, treated with CERA in relay of an erythropoietin stimulating agent. Comorbidities were defined by the Charlson Index (adjusted on age) and hemoglobin stability as a variation of ±1 g/dL after the 6-month treatment period. The 585 analyzed patients were distributed as follows according to the adjusted Charlson index: score ≤ 3 (12% of patients), 4 ≤ score ≤ 5 (17%), 6 ≤ score ≤ 7 (31%) and score ≥ 8 (40%). At CERA start, its median monthly dose was of 100 μg for the overall population, with no changes during the treatment period and with little variation according to the comorbidity score. Patients with stable hemoglobin (56%, 67% if score ≤ 3) were more numerous to reach the therapeutic target range between 10 and 12 g/dL after 6 months (85% versus 43% if not stable hemoglobin). Patients with low C-reactive protein value (≤ 5 mg/L ; P = 0.04), no red blood cell transfusion (P = 0.03), or no/low dose of intravenous iron (≤ 200 mg ; P = 0.03) were more likely to reach stable hemoglobin under CERA after 6 months. Among the 644 CERA-treated patients, 4 patients (< 1%) had one serious adverse event related to treatment. A stable hemoglobin within the therapeutic target was reached in the majority of the patients after 6 months in current practice with a lower CERA dose, regardless of the comorbidities scores of patients on hemodialysis.     

Impact of gender and dialysis adequacy on anaemia in peritoneal dialysis

Purpose

In the general population, haemoglobin (Hb) concentration is higher in men than in women. However, target Hb levels in dialysis patients are set constant regardless of the patient’s sex. The aim of this study was to evaluate Hb concentration and the use of erythropoiesis-stimulating agents (ESA) in peritoneal dialysis (PD) patients taking gender and dialysis adequacy into account.

Methods

The study comprised two parts. The first was a cross-sectional analysis of Hb and ESA in 2180 prevalent PD patients. The second included 88 incident PD patients, followed for 36 months. During this time, the major parameters recorded at 12-month intervals included: Hb concentration, weekly ESA, total, renal, and peritoneal Kt/V. Erythropoietin resistance index (ERI) was calculated as the ratio between ESA dose and achieved Hb.

Results

In prevalent PD patients, Hb concentration was significantly lower in women, (11.2 ± 1.4 vs. 11.5 ± 1.6 g/dl; p < 0.001), despite higher doses of ESA (2691 ± 1821 vs. 2344 ± 1422; p = 0.001). Hb concentrations were related to dialysis adequacy in both cohorts. However, despite significantly higher Kt/V, women were characterized by a lower Hb level. In incident patients, this association was present throughout the observation period, while the ESA dose in women was significantly higher at every time point. In multiple regression analysis, gender was an independent determinant of ERI (b = 0.34; p < 0.05).

Conclusions

Despite higher dialysis adequacy, Hb concentration in women treated with PD is significantly lower, and the ability to correct it impaired, as compared to men.