Current management of renal anemia in patients with chronic kidney disease at the predialysis stage

OBJECTIVE: Patients with chronic kidney disease (CKD) are frequently complicated by renal anemia as renal function declines. However, clinical guidelines on erythrocyte stimulating agents (erythropoietin : EPO) for such patients have not been established. Current clinical practice for EPO administration is based on the recommendations of the Japanese health insurance regulations, which have not always been supported by clinical evidence. MATERIALS & METHODS: The study subjects were 49 patients with CKD staged above 3 who had developed renal anemia requiring EPO. These patients were treated with EPO S. C. at the dose of 6,000 IU/week together with iron supplementation as deemed necessary for more than 24 weeks. RESULTS: The hemoglobin (Hb) value was 9.2 +/- 1.0 g/dL at the start, 10.9 +/- 1.6 g/dL at the peak (n = 49, p < 0.001 the start vs. the peak), and 9.0 +/- 1.6 g/dL at the commencement of dialysis (n = 49, p < 0.001 the peak vs. the commencement of dialysis). Seventy-one percent (35/49) of the patients achieved Hb levels over 10 g/dL, and 51% (25/49) achieved Hb levels over 11 g/dL. Conversely, 28% (14/49) of the patients failed to reach an Hb level over 10 g/dL. Factors explaining the good response to EPO (good responders were defined as those achieving Hb levels over 11 g/dL) had shown high Hb levels at the start (Logistic multiple regression analysis, p = 0.03) along with low creatinine concentration at the start (Cox's proportional hazard models, p = 0.015). Transferrin saturation (TSAT) at the start was 33.6 +/- 13.6%, 34.0 +/- 19.9% at the peak, and 24.7 +/- 11.6% at the commencement of dialysis, showing a significant reduction in TSAT at the commencement of dialysis compared to that at the start (n = 49, p = 0.0383, the start vs. the commencement of dialysis). Serum ferritin concentration was 140.7 +/- 139.5 pg/mL at the start, 107.9 +/- 110.8 pg/mL at the peak, and 131.9 +/- 112.4 pg/mL at the commencement of dialysis, indicating an absence of significant differences among the three time points. CONCLUSION: The current health insurance regulations in Japan seem to be inappropriate in that the permitted EPO dosage of 6,000 IU/week might not be sufficient to achieve the target Hb level of more than 11 g/dL in most patients with CKD. To more efficiently achieve renoprotection, both early and timely initiation of EPO and reconsideration of the recommended EPO dosage appear to be warranted.     

An underappreciated problem in renal transplant recipients: anemia

PURPOSE: Posttransplant anemia (PTA) is associated with a higher risk of cardiac mortality, which is the most frequent cause of death among renal transplant recipients. In this study, we sought to determine the prevalence and causes of PTA among Turkish patients. PATIENTS AND METHODS: The study included 75 (52 male, 23 female) adults. Anemia was defined as an hemoglobin (Hb) level < or = 13 g/dL for men and < or = 12 g/dL for women. RESULTS: The prevalence of PTA was 49.3% at a mean duration of 60.45 months after renal transplantation. The most frequent causes of PTA were erythropoietin (EPO) and iron deficiency. The mean Hb level of 12.76 +/- 2.31 g/dL was significantly higher in male compared to female patients (13.26 +/- 2.31 g/dL vs 11.64 +/- 1.93 g/dL, P = .005). The Hb value was positively correlated with creatinine clearance and serum albumin level, and negatively correlated with serum creatinine level, the amount of proteinuria, and cyclosporine level. Creatinine clearance and serum albumin level were found to be an independent risk factors for PTA upon multivariate analysis. Only 12 of 37 anemic patients received treatment for anemia: 5 (13.5%) with EPO and 7 (18.9%) with iron preparations. CONCLUSION: PTA a common complication was unfortunately neglected in this setting. Impaired renal allograft function and decreased serum albumin were major risk factors for PTA. Increased cyclosporine levels were also correlated with decreased Hb concentrations.     

Efficacy of erythropoietin administration in the treatment of anemia immediately after renal transplantation

Anemia negatively impacts cardiovascular comorbidity and hospitalization. In animals, recombinant erythropoietin (RhuEPO) leads to faster recovery after acute tubular necrosis. This study evaluates the effect of RhuEPO (Recormon, Hoffman-La Roche, Basel, Switzerland) on the correction of anemia and kidney function after renal transplantation. Patients receiving a renal transplant were randomized to receive or not receive RhuEPO 100 U/kg three times per week if the hemoglobin (Hb) level was less than 12.5 g/dL. The time to reach an Hb level greater than 12.5 g/dL was 66.5+/-14.5 days versus 52.6+/-23.7 days in the non-EPO and EPO groups, respectively (P=0.05). After 3 months, Hb levels were not different between the non-EPO and EPO groups (12.6+/-1.5 g/dL vs. 12.0+/-1.5 g/dL, respectively), although there was a higher increase in the EPO group (4.1+/-1.1 g/dL vs. 3.2+/-1.1 g/dL, P=0.02). In a Cox regression analysis, EPO use (relative risk 7.2, P=0.004) and dose (relative risk=0.63, P=0.04) were retained as independent variables predicting the time to reach an Hb level greater than 12.5 g/dL. In the EPO group, 14 of 22 patients reached the target Hb level of more than 12.5 g/dL versus 12 of 18 patients in the non-EPO group (P=not significant). Serum creatinine levels were not different between groups. RhuEPO in the immediate posttransplantation period seems to have no relevant clinical impact on the correction of anemia. There was no difference in the evolution of serum creatinine levels. In view of the cost, the use of RhuEpo in the posttransplantation period should be limited to high-risk patients.     

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.     

Characteristics and clinical relevance of chronic anemia in adult heart transplant recipients

BACKGROUND: Mild chronic anemia following heart transplantation (HTX), with hemoglobin (Hb) values of 10-14 g/dL in men and 10-12 g/dL in women, is frequent. It has continued to be of uncertain etiology yet clinical relevance. Nonetheless, therapeutic immunosuppression has been regarded as a major cause of chronic anemia in HTX patients. METHODS: Sixty outpatients were observed over a period of 5 yr after HTX. Laboratory values related to anemia such as Hb, erythropoietin (EPO), ferritin, transferrin, iron, and vitamin levels were obtained and analyzed monthly. Patients were divided into two groups retrospectively. Patients with persistent anemia for more than 1 yr were compared with non-anemic patients. RESULTS: Forty-three (72%) of the 60 patients were anemic. Anemia was normochromic, normocytic, and slightly anisocytic. Anemic and non-anemic patients showed EPO levels within the expected range as defined by Erslev (Erythropoietin. N Engl J Med 1991: 324: 1339). Reticulocyte counts were found to be normal in all patients. Iron deficiency and deficiency of vitamin B12 or folic acid were not observed. Patients with persistent anemia showed a significantly shorter survival period than non-anemic patients (p<0.02). CONCLUSIONS: Mild anemia following HTX shows the same characteristics as anemia in chronic diseases. Persisting mild anemia used to be associated with a shorter life expectancy. There is no evidence that standard immunosuppression causes anemia.     

Endogenous erythropoietin levels and anemia in long-term renal transplant recipients

BACKGROUND/AIM: Although anemia is a common complication after renal transplantation (RT), data concerning endogenous erythropoietin (EPO) levels in long-term RT recipients are rare. The goal of this study was to evaluate the prevalence of anemia within 6 months to 5 years after RT and to assess the relationship between the serum concentrations of endogenous EPO, graft function and grade of improvement of anemia. METHODS: 140 patients who had undergone RT were included in the group: 89 males (63.6%) and 51 females (36.4%), with an average age 46.8 +/- 12.8 years. The serum concentrations of EPO and creatinine (Cr) were tested in all the individuals and the values of the red blood component of blood count, serum ferritin (SF), plasma iron concentration, plasma total iron-binding capacity (TIBC), transferrin saturation (TS), folic acid and vitamin B(12) levels in the serum were determined. A statistical analysis of the results was performed using the correlation analysis, Mann-Whitney U test and Duncan's multiple range test. RESULTS: Normal blood count values were found in 91 patients (65%), and a mild grade of anemia with a mean hemoglobin (Hb) 114.4 +/- 11.9 g/l was observed in 45 patients (32.1%), and 4 patients (2.9%) fulfilled the diagnostic criteria for post-transplantation erythrocytosis. Individuals with normal Hb values had a mean EPO serum concentration of 39.3 +/- 12.3 mU/ml (median 37.2) and the mean Cr was 133.8 +/- 36.9 micromol/l (median 122). Patients with anemia (Hb <120 g/l in females, Hb <130 g/l in males) had a mean EPO value of 47.0 +/- 26.6 mU/ml (median 36.0) and a mean Cr of 203.8 +/- 108.9 micromol/l (median 181). The difference in the Cr values was statistically significant (p < 0.0001), while the difference between the EPO concentrations was not significant. No relation of EPO serum concentration with regard to graft function was found in the analysis. A lack of storage iron (SF <10 microg/l in females, SF <22 microg/l in males) was found in 16 patients (11.4%), and a lack of functional iron (TS <20%) was found in 27 patients (19.3%). CONCLUSIONS: Theprevalence of anemia in patients after transplantation was 32.1%. The most common cause of anemia is insufficient graft function development. The achieved values of the red component of blood count have no relation to the endogenous EPO serum concentrations.     

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.     

Continuous intravenous sodium ferric gluconate improves efficacy in the maintenance phase of EPOrHu administration in hemodialysis patients

Although intravenous iron has proved to optimize the efficacy of EPOrHu in hemodialysis patients, hitherto no consensus exists with respect to the best regimen of intravenous iron administration. We started a prospective randomized study in 26 patients undergoing chronic hemodialysis who had adequate iron metabolism indices (serum ferritin >100 microg/l; %TSAT >20%; %HypoE <10% and CHr >26 pg) and were in the maintenance phase of EPOrHu administration (target hemoglobin obtained >10 g/dl). All patients were receiving sodium ferric gluconate (Ferrlecit) intermittently prior to the study and after a 1-month wash-out period where iron was not administered patients were randomized to receive the same previous dose of intravenous iron either in a continuous (6.25-21.3 mg in every hemodialysis session) or an intermittent regimen (62.5 mg every 1-4 weeks, not modifying the previous schedule of administration). At 16 weeks, the continuous group showed a significant increment in serum Hb (11.83 +/- 1.12 g/dl) with respect to baseline (10.96 +/- 1.31 g/dl) (p < 0.05), whereas no differences were obtained in intermittent group (baseline: 11.16 +/- 1.03 g/dl; 16 weeks: 11.14 +/- 0.90 g/dl, NS). In contrast with the intermittent group, serum ferritin increased significantly in the continuous group (16 weeks: 508 +/- 157 microg/l; baseline: 368 +/- 56 microg/l; p < 0.05), whereas %TSAT and CHr did not modified during the study in both groups. %HypoE increased significantly with respect to baseline values in the continuous group (p < 0.05) and close to significantly different in the intermittent group (p = 0.06). Our study suggests that hemodialysis patients in the maintenance phase of EPOrHu administration would obtain further benefit in terms of serum hemoglobin level with a continuous intravenous serum ferric gluconate regimen, at least in the short term.     

Iron deficiency in patients with chronic kidney disease: potential role for intravenous iron therapy independent of erythropoietin

The prevalence of iron deficiency and its contribution to the anemia of end stage renal disease has been extensively studied, but much less is known about the role of iron deficiency in the pathogenesis of the anemia of chronic kidney disease in predialysis patients. All new hemodialysis patients entering a single hemodialysis unit between July 1999 and April 2002 were included in the study. The admission laboratory tests and the Health Care Financing Administration (HCFA) 2728 form were examined to determine the prevalence of erythropoietin use, anemia (Hb < 11 g/dl), and iron deficiency (ferritin < 100 ng/ml and transferrin saturation % < 20%). In a second part of the study, the effect of intravenous iron gluconate replacement in patients with stage III & IV chronic kidney disease was examined. Anemia was present in 68% of all patients starting hemodialysis. Iron deficiency was a common feature occurring in 29% of patients taking erythropoietin (49% of all patients) and 26% of patients without erythropoietin (51% of all patients). Following the administration of intravenous iron gluconate to four patients, there was a significant rise in hemoglobin levels from 10.6 ± 0.19 to 11.7 ± g/dl (p = 0.02). Conclusion: Iron deficiency is common in predialysis patients. Replenishing iron stores in anemic patients with chronic kidney disease significantly increases hemoglobin levels and should be considered as an integral part of the therapy for treating anemia in the predialysis population.     

Sodium ferric gluconate complex in sucrose: safer intravenous iron therapy than iron dextrans.

Use of recombinant human erythropoietin in patients with end-stage renal disease has highlighted iron deficiency as the major cause of resistant anemia. The current mainstay of intravenous (i.v.) iron replacement therapy, iron dextran, has been shown in prior studies to have a risk of serious life-threatening anaphylaxis of just under 1 per 100 patients exposed. The current study assessed the safety profile of an alternative i.v. iron, sodium ferric gluconate complex in sucrose (Ferrlecit), as compared with iron dextrans. Sodium ferric gluconate complex in sucrose, a unique chemical preparation, has been in use since 1959, principally in Europe, at a rate of approximately 2.7 million i.v. doses per year (1992 to 1996) in Germany and Italy alone. For iron dextran, usage in the United States was comparable--principally renal hemodialysis--and estimated from market sources at 3.0 million doses per year (1995). From 1976 to 1996, there were 74 allergic adverse events reported for sodium ferric gluconate complex in sucrose to the World Health Organization (WHO), German Health Bureau, and the manufacturer (all combined). For the years 1992 to 1996, sodium ferric gluconate complex in sucrose had an allergy event reporting rate of 3.3 allergy episodes per million doses per year compared with a similar rate of 8.7 reported allergy events per million doses per year for iron dextran in the United States in 1995. Case fatalities for sodium ferric gluconate complex in sucrose and iron dextran within these reports were then compared. For sodium ferric gluconate complex in sucrose, there were no reports of deaths over the entire period (1976 to 1996). However, for iron dextrans, there were 31 fatalities among 196 allergy/anaphylaxis cases reported in the United States between 1976 and 1996, yielding a case-fatality rate of 15.8%. These data show that sodium ferric gluconate complex in sucrose, when compared with iron dextrans in comparably sized patient usage populations with similar total rates of reporting of allergic events, has a significantly lower reported mortality rate (P < 0.001). Thus, the data justify usage of sodium ferric gluconate complex in sucrose as the safer iron replacement therapeutic agent.     

Serum erythropoietin concentrations and responses to anaemia in patients with or without chronic kidney disease.

BACKGROUND: Renal anaemia is caused by a relative erythropoietin (EPO) deficiency. Due to difficult interpretation of serum EPO concentrations adapted to anaemia and renal function, the diagnostic value of measuring serum EPO concentrations is limited. METHODS: We retrospectively analysed the relationship between haemoglobin and serum EPO concentrations routinely measured in in- and out-patients of our university hospital from 2001-04. Patients under EPO substitution or those with acute renal failure, polycystic kidney disease, renal carcinoma or polycythaemia due to pulmonary disease were excluded. The study population (n = 500) was then stratified according to the presence or absence of chronic kidney disease (CKD) and to the stage if CKD was present. EPO concentrations were expressed in percentiles corrected for the severity of anaemia and based on the EPO response in patients without CKD. RESULTS: In patients without CKD (n = 167) there was a strong parametric correlation between severity of anaemia and increase in EPO (r = -0.81). Linear regression of the log-transformed EPO values revealed the equation log EPO (mIU/ml) = -0.135 x Hb (g/dl) + 2.821 (r(2) = 0.65). With increasing stages of CKD the correlation between haemoglobin and EPO concentrations was gradually attenuated and was completely lost in CKD stage four and five. In anaemic patients with Hb < 11 g/dl, relative EPO deficiency defined as EPO concentrations below the 25th percentile was present in 38%, 67%, 93% and 100% of the patients with CKD stages 1-5, respectively. CONCLUSIONS: Expression of EPO concentrations in percentiles improves the diagnostic value of measuring EPO concentrations for diagnosing relative EPO deficiency and renal anaemia.     

Sodium ferric gluconate complex in sucrose is safe and effective in hemodialysis patients: North American Clinical Trial.

A new intravenous (i.v.) iron compound, sodium ferric gluconate complex in sucrose (Ferrlecit, R&D Laboratories, Inc, Marina Del Rey, CA), was administered over 8 consecutive dialysis days in equally divided doses to a total of either 0.5 or 1.0 g in a controlled, open, multicenter, randomized clinical study of anemic, iron-deficient hemodialysis patients receiving recombinant human erythropoietin (rHuEPO). Effectiveness was assessed by increase in hemoglobin and hematocrit and changes of iron parameters. Results were compared with historically matched controls on oral iron. High-dose i.v. treatment with 1.0 g sodium ferric gluconate complex in sucrose resulted in significantly greater improvement in hemoglobin, hematocrit, iron saturation, and serum ferritin at all time points, as compared with low-dose i.v. (0.5 g) or oral iron treatment. Despite an initial improvement in mean serum ferritin and transferrin saturation, 500 mg i.v. therapy did not result in a significant improvement in hemoglobin at any time. Eighty-three of 88 patients completed treatment with sodium ferric gluconate complex in sucrose: 44 in the high-dose and 39 in the low-dose group. Two patients discontinued for personal reasons. The other three discontinued because of a rash, nausea and rash, and chest pain with pruritus, respectively. In comparison with 25 matched control patients, adverse events could not be linked to drug therapy, nor was there a dose effect. In conclusion, sodium ferric gluconate complex in sucrose is safe and effective in the management of iron-deficiency anemia in severely iron-deficient and anemic hemodialysis patients receiving rHuEPO. This study confirms the concepts regarding iron therapy expressed in the National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI) that hemodialysis patients with serum ferritin below 100 ng/mL or transferrin saturations below 18% need supplementation with parenteral iron in excess of 1.0 g to achieve optimal response in hemoglobin and hematocrit levels.     

Sodium ferric gluconate therapy in renal transplant and renal failure patients

Intravenous infusion of sodium ferric gluconate (Ferrlecit) has been reported to be effective and safe in pediatric and adult hemodialysis patients with iron depletion. We sought to expand on the previous studies by treating 13 consecutive pediatric renal failure and renal transplant patients with sodium ferric gluconate doses that were higher than previously reported. Efficacy was defined as: (1) an increase in hematocrit of ≥3 vol% with no change or a decrease in erythropoietin dose or (2) a stable hematocrit with a decrease of ≥25% in the erythropoietin, 2 weeks to 2 months after sodium ferric gluconate infusion. Two dosing strategies were employed: (1) high dose, where single dose sodium ferric gluconate (mg) ≈ calculated iron deficit, and (2) sodium ferric gluconate, 62.5 mg/dose for children <40 kg, 125 mg/dose for children >40 kg, infused on eight consecutive hemodialysis runs. There was only one self-limited adverse reaction in 60 doses. Three patients with previous adverse reactions to iron dextran tolerated sodium ferric gluconate without adverse effect. Sodium ferric gluconate was efficacious in eight out of ten patients that received a cumulative dose >5 mg/kg. The mean hematocrit increased 30.3±7.8 to 36.4±4.4 vol% (P=0.04) and the mean erythropoietin dose decreased 251.5±149.1 to 100.7±113.0 units/kg/week (P=0.02). Although sodium ferric gluconate appears to be effective and safe at the doses used, multicenter, prospective pharmacokinetic and clinical trials of sodium ferric gluconate should be conducted in children. Received: 29 February 2000 / Revised: 20 June 2000 / Accepted: 27 June 2000     

Hemoglobin normalization trials in chronic kidney disease: what should we learn about quality of life as an end point?

This editorial review takes an in-depth look to the effect of hemoglobin (Hb) normalization with erythropoietin on quality of life (QoL) in chronic kidney disease (CKD). The analysis of the current available data shows major inhomogeneities in the tools used for assessment of QoL and in data reporting. Furthermore, the major trials on Hb normalization were generally not primarily designed to analyze QoL as a specific end-point. However, current data suggest that only partial correction of anemia with EPO may improve QoL, whereas correction of Hb to above 12 g/dL does not exert any positive effect. Finally, the authors provide recommendations on a more rigorous assessment of QoL in future trials in CKD patients.     

Prevalence of anemia and chronic kidney disease in cancer patients: clinical significance for 1-year mortality

Prevalence of anemia, stratified by severity grades, and chronic kidney disease (CKD) was studied in cancer patients receiving chemotherapy. In addition, their relevance to 1-year survival was estimated. We investigated the demographics and clinical findings of 231 cancer patients (male : 142, female : 89) who were admitted to the Division of Chemotherapy at the Cancer and Infectious Disease Center, Tokyo Metropolitan Komagome Hospital between April and September, 2008. Mean age was 63.6 +/- 12.7 years. Anemia was defined as a hemoglobin (Hb)level less than 12 g/dL and the anemia severity grades were classified according to the Anemia Toxicity Scales. Estimated glomerular filtration rate was calculated based on the formula of the Modification of Diet in Renal Disease modified for the Japanese. CKD was defined as stage 3 or more according to the K/DOQI criteria. To assess the clinical relevance of anemia and CKD to 1-year survival, we drew Kaplan-Meier curves, stratifying patients according to the anemia severity grades and the presence or absence of CKD. The joint impact of anemia grades and presence of CKD on 1-year mortality was assessed using the Cox proportional hazard analysis, adjusted for age and gender. Prevalence of anemia was 81% : 6.9% for grade 4 (Hb < 6.5 g/dL); 13.9% for grade 3(6.5 = Hb < 8.0 g/dL); 29.0% for grade 2 (8.0 = Hb < 10.0 g/dL); 31.2% for grade I (10.0 = Hb < 12.0 g/dL) and 19.0% for non-anemia cases. Prevalence of CKD was 25%. Survival probability of the overall or non-CKD cancer patients with anemia severity > or = grade 2 significantly decreased, as compared to that with no anemia. Survival probability of patients with CKD significantly decreased, as compared to that with no CKD. Statistically, the hazard ratio of mortality for patients with both grade 4-anemia and CKD was 14-fold higher than that for patients with neither anemia nor CKD. In conclusion, the prevalence of anemia and CKD were unexpectedly high in cancer patients. The combination of high-grade anemia and CKD is likely to be a significant risk factor for 1-year mortality of these patients.     

Intravenous iron and recombinant erythropoietin for the treatment of postoperative anemia

PURPOSE: To determine if early recovery from severe post-operative anemia is accelerated by iv iron therapy alone or in combination with recombinant erythropoietin (EPO). METHODS: In this double-blinded, placebo-controlled randomized study, consenting adult patients without preoperative anemia whose hemoglobin concentration (Hb) was 70 to 90 g x L(-1) on the first day after cardiac or orthopedic surgery (POD 1) were assigned to one of three groups: control, iv iron alone (200 mg of iron sucrose on POD 1, 2, and 3) or in combination with EPO (600 U x kg(-1) on POD 1 and 3). The primary outcome was increase in Hb (adjusted for red blood cell transfusions) from POD 1 to 7. Analysis was by intention-to-treat in patients for whom the primary outcome was available. Group effect was analyzed by the ANOVA test, and between-group differences were specified with a Duncan multiple-range test. RESULTS: The primary outcome was available in 31 of 38 randomized patients. The average POD 1 Hb was 84 +/- 4 g x L(-1). There were no between-group differences in outcomes except for higher reticulocyte counts on POD-7 in the combination group. The average adjusted one-week increases in Hb were 7 +/- 8 g x L(-1) in the control group (n = 10), 9 +/- 9 g x L(-1) in the iv iron group (n = 11), and 10 +/- 14 g x L(-1) in the combination group (n = 10). The average adjusted six-week increases in Hb were 37 +/- 14 g x L(-1) in the control group, 40 +/- 7 g x L(-1) in the iv iron group, and 45 +/- 12 g x L(-1) in the combination group. CONCLUSION: Early postoperative treatment with iv iron alone or in combination with EPO does not appear to accelerate early recovery from postoperative anemia.     

A randomized, controlled trial comparing IV iron sucrose to oral iron in anemic patients with nondialysis-dependent CKD

BACKGROUND: Although iron deficiency frequently complicates anemia in patients with nondialysis-dependent CKD (ND-CKD), the comparative treatment value of IV iron infusion and oral iron supplementation has not been established. METHODS: In a randomized, controlled multicenter trial, we compared the efficacy of iron sucrose, given as 1 g in divided IV doses over 14 days, with that of ferrous sulfate, given 325 mg orally thrice daily for 56 days in patients with ND-CKD stages 3 to 5, Hb < or =11 g/dL, TSAT < or =25%, and ferritin < or =300 ng/mL. Epoetin/darbepoetin therapy, if any, was not changed for eight weeks prior to or during the study. RESULTS: The proportion of patients achieving the primary outcome (Hb increase > or =1 g/dL) was greater in the IV iron treatment group than in the oral iron treatment group (44.3% vs. 28.0%, P= 0.0344), as was the mean increase in Hb by day 42 (0.7 vs. 0.4 g/dL, P= 0.0298). Compared to those in the IV iron group, patients in the oral iron treatment group showed a greater decline in GFR during the study (-4.40 vs. -1.45 mL/min/1.73m2, P= 0.0100). No serious adverse drug events (ADE) were seen in patients administered IV iron sucrose as 200 mg IV over two to five minutes, but drug-related hypotension, including one event considered serious, occurred in two females weighing less than 65 kg after 500 mg doses were given over four hours. CONCLUSION: IV iron administration using 1000 mg iron sucrose in divided doses is superior to oral iron therapy in the management of ND-CKD patients with anemia and low iron indices.     

Intravenous iron without erythropoietin for the treatment of iron deficiency anemia in patients with moderate to severe congestive heart failure and chronic kidney insufficiency

OBJECTIVES: Iron deficiency anemia is a frequent finding in many patients with congestive heart failure (CHF). The purpose of this study was to assess the effect of intravenous (i.v.) iron on the anemia of CHF patients and on cardiac remodeling, New York Heart Association (NYHA) classification and renal function. METHODS: Thirty-two patients with well-treated CHF which was NYHA class III-IV, and with hemoglobin (Hb) persistently <11 g/dL, were treated with i.v. iron over 26 weeks. Echocardiographic, hematological and renal parameters were measured at the beginning and end of the study. RESULTS: Hb increased significantly from 10.7 +/- 0.4 g/dL to 13.7 +/- 0.4 g/dL and from 9.4 +/- 0.6 g/dL to 12.7+/- 0.8 g/dL in the NYHA III and IV groups respectively. Posterior wall thickness, septal thickness (ST), left ventricular (LV) end diastolic volume and diameter, LV end systolic volume and diameter, LV mass index and LV ejection fraction (LVEF) were all abnormal initially. All of these parameters improved significantly in the NYHA III patients, and all but ST and LVEF improved significantly in the NYHA IV patients. NYHA classification improved from III to II in 9 of 19 NYHA III patients (47.4%) (p<0.01) but did not improve in any of the 13 NYHA IV patients. CONCLUSION: Intravenous iron causes a marked increase in hemoglobin in anemic CHF patients, and this is frequently associated with an improvement in cardiac remodeling and NYHA classification.     

Intravenous ascorbic acid in hemodialysis patients with functional iron deficiency: a clinical trial

BACKGROUND: Hemodialysis (HD) patients with functional iron deficiency (FID) often develop resistance to recombinant human erythropoietin (rHuEpo). In these patients, iron therapy may be a hazard, leading to iron overload and consequently to hemosiderosis. Recent studies suggest that intravenous ascorbic acid (IVAA) may circumvent rHuEpo resistance. The aim of our study was to show the effects of IVAA on FID and whether this results in a better correction of anemia in HD patients with stable hemoglobin (Hb) concentration and FID. METHODS: Twenty-seven HD patients with serum ferritin >300 microg/l, transferrin saturation (TS) <20% and hemoglobin (Hb) <10 g/dL were selected andrandomly divided into two groups to enter a cross-over trial with IVAA. In group I IV vitamin C 500 mg was administered three times a week for three months and discontinued in the next three months of the study. Vitamin C was not given the first three months in group II (control group, first three months of the study), who then received 500 mg IV three times a week for the next three months. RESULTS: Hb and TS% significantly increased (baselines vs 3 months, Hb 9.2 +/- 0.2 vs 10.0 +/- 0.3 g/dL, TS% 17.5 +/- 0.6 vs 25.7 +/- 1.7, respectively p < 0.01 and p <0.001) in group I after three months; ferritin fell significantly from 572 +/- 40 to 398 +/- 55 microg/L (p<0.004). Ten patients completed the study: mean Hb and TS% fell significantly (3 months vs final, Hb 9.9 +/- 0.3 vs 8.9 +/- 0.2 g/dL, TS% 25.1 +/- 1.2 vs 19.1 +/- 1.1, respectively p < 0.01 and p <0.001), while mean ferritin did not change. Mean Hb, ferritin and TS% remained unchanged in group II after three months. Hb and TS% mean values rose significantly (3 months vs final, Hb 9.0 +/- 0.2 vs 9.9 +/- 0.2 g/dl, TS% 18.4 +/- 1.0 vs 27.0 +/- 1.0, respectively p < 0.005 and p <0.001), and ferritin markedly decreased from 450 +/- 50 to 206 +/- 24 microg/L (p < 0.001) at the end of the study. The rHuEpo dose was kept unchanged throughout the study. Differences were analyzed after three months. Mean Hb rose (0.8 +/- 0.2 g/dL) in group I but dropped (-0.1 +/- 0.1 g/dL) (p< 0.009) in group II. Ferritin dropped in both groups (group I vs group II, -173 + /-48 vs - 33 +/- 21 microg/L) (p < 0.01) while TS% increased (group I vs group II, 8.2 +/- 1.5 vs 0.4 +/- 0.7) (p < 0.001). CONCLUSION: IVAA may partially correct FID and consequently help rHuEpo hyporesponsive anemia.     

Total dose iron infusion: safety and efficacy in predialysis patients

Iron deficiency anemia is not uncommon in predialysis patients. Oral iron often cannot maintain adequate iron stores. Hence we evaluated the safety and efficacy of total dose infusion (TDI) of iron in these patients. Anemic predialysis patients were screened and those with Hb < 7.0 g/dL and serum ferritin < 200 ng/mL were selected. Patients with active bleeding and acute liver disease were excluded. All patients were on oral iron 100 mg/day. None of the patients were on erythropoeitin. 11 patients (6 males and 5 females), aged 45.9 +/- 15 yrs, were suitable. Hb was 5.9 +/- 1.0 g/dL and serum ferritin was 89.5 + 50 ng/mL. The preparation used was iron dextran. A test dose of 25 mg in 100 mL normal saline was administered over 1 hr to all patients. One patient had fever and chills during the test dose and was not given TDI. 10 patients received TDI. None of these patients had any problem during the infusion. The dose of iron administered was 900 + 316.2 mg. One patient who received 1600 mg had arthralgia-myalgia and another patient had thrombophlebitis following TDI. One month after TDI, Hb was 8.0 + 1.0 g/dL and serum ferritin was 362 ng/mL. We feel that TDI is a safe and effective method of correcting iron deficiency in predialysis patients.