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.     

Disparate outcomes in pediatric peritoneal dialysis patients by gender/race in the End-Stage Renal Disease Clinical Performance Measures project

Associations between achievement of adult Kidney Disease Outcomes Quality Initiative (KDOQI) targets for hemoglobin, adequacy and albumin, and race and gender were determined for pediatric peritoneal dialysis patients from the End-Stage Renal Disease (ESRD) Clinical Performance Measures (CPM) project for the period October 2004-March 2005. Fifty-six percent (427/761) of patients were male. Sixty-six percent (500/761) of patients were White. There were no differences in achievement of targets for adults by gender, and no differences in adequacy parameters by race. Blacks had lower mean hemoglobin levels than did Whites (11.1 +/- 1.6 g/dl vs 11.8 +/- 1.4 g/dl, P < 0.0001). Blacks were more likely to have mean hemoglobin levels < 10 g/dl (24% vs 11%, P < 0.0001) and less likely to achieve mean hemoglobin > 11 g/dl (56% vs 72%, P < 0.0001). Whites were more likely to achieve mean serum albumin levels > 4.0/3.7 g/dl [bromocresol green/bromocresol purple (BCG/BCP)] than Blacks were (35% vs 26%, P = 0.0376). In multivariate logistic regression models, White race was associated with mean hemoglobin levels > 11 g/dl [adjusted odds ratio (adj OR) 2.7, 95% confidence interval (CI) 1.7, 4.3] and mean serum albumin > 4.0/3.7 g/dl (BCG/BCP) (adj OR 1.9, 95% CI 1.3, 2.9]. Further study is needed of factors associated with anemia on peritoneal dialysis and barriers to its correction.     

Evaluation of the impact of a new synthetic vitamin E-bonded membrane on anemia and rHuEPO requirement in ESRD patients with central venous catheters: a pilot study

In the last years, the number of hemodialysis (HD) patients with erythropoietin (rHuEPO) resistance is increasing. Probably, central venous catheters (CVCs) contribute to this resistance by inducing inflammation and oxidative stress. This study was aimed to compare vitamin E-bonded dialyzer (PSVE) versus polyethersulfone membrane. Sixteen subjects with CVCs were included in a prospective two-arm crossover 12-month study. The primary endpoints were the rHuEPO requirement and the erythropoiesis-stimulating agents (ESA) index, which was defined by the ratio between weekly EPO dosage (IU/kg/week) and Hb levels (g/dl). The mean dosages of rHuEPO to maintain hemoglobin between 10.5 and 12 g/dl were 135 ± 59 and 101 ± 57 IU/kg/week with polysulfone and PSVE, respectively (P = 0.14). The ESA indexes were 12.1 ± 5.2 and 8.7 ± 5.2 (P < 0.0001) with polysulfone and PSVE, respectively. A trend towards consensual changes in protein glycoxidation, antioxidant, and inflammatory markers was observed. In conclusion, the study suggests a role for PSVE in the reduction of ESA index in HD patients with CVCs.     

Clinical factors associated with achieving K/DOQI hemoglobin targets in hemodialysis patients

BACKGROUND: Few studies have assessed treatable factors associated with achieving the Kidney Disease Outcomes Quality Initiative (K/DOQI) guideline of hemoglobin values of 11 to 12 g/dL in anemic hemodialysis patients. METHODS: This was a retrospective study of 30,029 prevalent hemodialysis patients with mean hemoglobin values less than 11 g/dL between January 1 and March 31, 1999. We studied the associations between demographic characteristics, comorbid conditions, disease severity, urea reduction ratio, epoetin doses, intravenous iron doses, and mean hemoglobin values in the ensuing 3 months. RESULTS: Approximately half (51.3%) of patients reached a mean hemoglobin value of at least 11 g/dL. By multiple logistic regression, the major factors showing a positive association with this outcome included a urea reduction ratio greater than 75% (odds ratio [OR], 1.23; P < 0.0001) and intravenous iron (OR: for 0 vials/month, 1; for < 1, 1.22; for 1 to 1.9, 1.36; 2 to 2.9, 1.48; for 3 to 3.9, 1.61; for > or = 4, 1.79; P < 0.0001), while a negative association with hemoglobin response, possibly representing epoetin resistance, was shown for initial severity of anemia (OR: for initial hemoglobin value < 7 g/dL, 0.06; for 7 to 7.9 g/dL, 0.12; for 8 to 8.9 g/dL, 0.23; for 9 to 9.9 g/dL, 0.45; for 10 to 10.9 g/dL, 1; P < 0.0001) and epoetin doses in the highest quintile (OR for > 38,000 units/wk, 0.76; P < 0.0001). CONCLUSION: In patients with persistently low hemoglobin values, optimizing urea clearance and a proactive approach to intravenous iron therapy may enhance epoetin responsiveness.     

The effects of higher hemoglobin levels on mortality and hospitalization in hemodialysis patients

BACKGROUND: The introduction of recombinant human erythropoietin for the treatment of anemia of chronic renal failure provided the opportunity to correct anemia in this patient population. The optimal target hemoglobin for patients with end-stage renal disease (ESRD) remains controversial. A large database of hemodialysis patients was analyzed to determine whether increasing hemoglobin level above the current Kidney Dialysis Outcomes Quality Initiative (K/DOQI) recommendations was associated with increased risk of mortality and hospitalization. METHODS: A longitudinal study of hemodialysis patients in Fresenius Medical Care-North America facilities was performed. Selection was restricted to patients in the census for 6 consecutive months from July 1, 1998 through June 30, 2000. Patient mean hemoglobin and other covariates measured during the initial 6 months were related to survival, number of hospitalizations, and length of stay over the subsequent 6 months of follow-up. RESULTS: Patients with hemoglobin <9 g/dL had an adjusted relative risk of death of 2.11 compared to those patients with 11 /=13 g/dL had an adjusted length of stay of 9.6 days compared to 10.9 days for those with 11 12 g/dL.     

Protocolized anemia management with erythropoietin in hemodialysis patients: a randomized controlled trial

Treatment of the anemia of chronic renal failure with exogenous recombinant human erythropoietin (rHuEpo) is well established. The objective of this randomized clinical trial was to evaluate an anemia management team protocol in hemodialysis patients, using subcutaneous rHuEpo and intravenous iron. A total of 215 patients were randomized to either usual care or the protocol. The primary outcome was the proportion of patient hemoglobin (Hgb) values between 11.0 and 12.5 g/dl over the final 8 wk. The study was halted after 240 d because of an institutional change to intravenous rHuEpo. The proportion of Hgb values in the target range increased from 47.4% to 62.8% overall (P = 0.001); there was no difference between treatment groups. The proportion of baseline Hgb values between 11.0 and 12.5 g/dl increased from 44.6% in patients who had enrolled within the first 3 mo of study inception to 75.0% in those who started later (P = 0.017), suggesting a Hawthorne effect. A nonsignificant decrease in rHuEpo dose was observed in the protocol group; subgroup analysis in patients who were enrolled for at least 5 mo demonstrated a reduction in the rHuEpo dose of 2788 units/wk in the protocol group (P < 0.05), independent of intravenous iron dose. Multivariate analysis demonstrated that a higher transferrin saturation and albumin and protocol group assignment were associated with a lower final rHuEpo dose. This study demonstrated that a protocolized approach to anemia management in hemodialysis patients results in comparable Hgb levels and may reduce rHuEpo requirements, independent of iron use.     

Supplemented very low protein diet ameliorates responsiveness to erythropoietin in chronic renal failure

BACKGROUND: The aim of this study was to evaluate the relationship between uremic state and erythropoiesis in patients with predialytic chronic renal failure (CRF). METHODS: We monitored for 2 years the erythropoietin (EPO) requirement in patients with advanced CRF (creatinine clearance < or =25 mL/min), randomized to either low protein diet (LPD) group (0.6 g/kg body weight/day, N = 10) or very low protein diet (VLPD) group (0.3 g/kg body weight/day, N = 10) supplemented with a mixture of ketoanalogs and essential amino acids, both kept at target hemoglobin levels. RESULTS: The achieved protein intake after 6 months was 0.79 +/- 0.02 g/kg body weight/day and 0.50 +/- 0.02 g/kg body weight/day in LPD and VLPD, respectively; such a difference was maintained up to the end of follow up. The final hemoglobin values did not differ from the basal values in either group (11.5 +/- 0.2 g/dL and 11.5 +/- 0.3 g/dL). EPO dose, that was similar at baseline (62.4 +/- 9.6 UI/kg body weight/week and 61.8 +/- 8.8 UI/kg body weight/week subcutaneously), remained unchanged in LPD but progressively decreased in VLPD down to the final value of 41.2 +/- 7.0 UI/kg body weight/week (P < 0.0001 vs. basal and LPD). VLPD was associated with a decrease of urinary excretion and serum levels of urea nitrogen and phosphate; however, EPO requirement was not correlated with the changes of these parameters. On the contrary, the variation of EPO dose directly correlated with the modification of parathyroid hormone (PTH) levels, that diminished from 229 +/- 55 pg/mL to 118 +/- 16 pg/mL (P < 0.0001) in VLPD and did not change in LPD. CONCLUSION: In patients with advanced CRF, an effective decrease of protein intake of 0.3 g/kg body weight/day induces a reduction of about 35% of the EPO dose required to maintain the target hemoglobin levels. This effect appears dependent on the correction of a moderate secondary hyperparathyroidism.     

Association of mortality and hospitalization with achievement of adult hemoglobin targets in adolescents maintained on hemodialysis

With the use of data from the Centers for Medicare & Medicaid Services' ESRD Clinical Performance Measures Project (October through December 1999 and 2000) linked with US Renal Data System hospitalization and mortality records, whether achieving adult target hemoglobin (Hb) levels in adolescents who are on hemodialysis (HD) was associated with decreased risk for death or hospitalization was assessed. Of 677 adolescents, 238 were hospitalized and 54 died. In bivariate analysis, 11.7% with Hb <11 g/dl at study entry died versus 5% of those with initial Hb > or =11 g/dl (P = 0.001); 40.3% with baseline Hb <11 g/dl were hospitalized versus 31.1% with initial Hb > or =11 g/dl (P = 0.013). In multivariate analysis, Hb > or =11 g/dl was associated with decreased risk for death (hazard ratio [HR] 0.38; 95% confidence interval [CI] 0.20 to 0.72) but did not show a statistically significant association with decreased risk for hospitalization (HR 0.87; 95% CI 0.66 to 1.15). When Hb was recategorized as Hb <10, > or =10 and <11, > or =11 and < or =12, and >12 g/dl, risk of mortality declined as Hb level increased. At Hb 11 to 12 g/dl (versus Hb <10 g/dl), mortality risk decreased by 69% (HR 0.31; 95% CI 0.14 to 0.65). Risk for mortality was similar for Hb 11 to 12 and >12 g/dl. For hospitalization, no statistically significant difference in risk between Hb categories was found. This observational study of adolescents who are on HD is consistent with adult literature showing decreased mortality in patients who have ESRD and meet adult Hb targets. Further studies in the form of randomized, clinical trials are needed to assess optimal Hb levels for adolescents who are on HD.     

Efficacy and immunogenicity of novel erythropoietic agents and conventional rhEPO in rats with renal insufficiency

Recombinant human erythropoietin (rhEPO) is used to treat anemia in chronic renal insufficiency. Erythropoietin (EPO) immunogenicity can lead to EPO-resistant anemia. Conjugating proteins with polyethylene glycol (PEG) can prolong elimination half-life and diminish protein immunogenicity. We investigated the efficacy of new erythropoietic agents, synthesized by single (Ro 50-3821) and multiple (MIX) integrations of PEG and succinimidyl butanoic acid with rhEPO, in rats with chronic renal insufficiency. Sprague-Dawley rats with surgically induced renal insufficiency received Ro 50-3821 or MIX subcutaneously (s.c.) over 4-12 weeks compared to rhEPO and NaCl. Hemoglobin and antibody levels served as primary efficacy and safety variables. Dosing intervals and dose-response characteristics were investigated. Ro 50-3821 (2.5 microg/kg once weekly) increased hemoglobin levels by 7 g/dl after 4 weeks compared to 1 g/dl in NaCl controls (P<0.05). MIX (2.5 microg/kg once weekly) and rhEPO (0.25 microg/kg three times weekly) increased hemoglobin levels by 3 g/dl. Ro 50-3821 administered for 12 weeks (0.75 microg/kg once weekly) increased hemoglobin levels (from 13 to 19 g/dl) more effectively than rhEPO (0.75 microg/kg once weekly, decline from 13 to 11 g/dl, P<0.05). No antibodies against Ro 50-3821 were detected after 12 weeks of treatment. Antibodies against rhEPO were seen in 69% of animals (P<0.00001). Ro 50-3821 increased hemoglobin levels with once weekly s.c. dosing. Multiple pegylated EPO is less effective. In rats, rhEPO failed to increase hemoglobin levels with once weekly long-term dosing. Antibody formation following rhEPO may explain this finding. Therefore, Ro 50-3821 may provide important clinical advantages compared to unpegylated EPO. It can be administered in longer dosing intervals and has a lower risk of unfavorable immunological responses.     

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     

Prevalence of anemia in erythropoietin-treated pediatric as compared to adult chronic dialysis patients

BACKGROUND: Recent guidelines recommend a target hemoglobin range of 11 to 12 g/dL in pediatric and adult dialysis patients. We compared anemia prevalence in United States Medicare pediatric and adult dialysis patients. METHODS: Prevalent hemodialysis patients (0 to 19 years, pediatric: N= 1692; adult: N= 352,291) and peritoneal dialysis patients (pediatric: N= 597; adult: N= 39,136) treated with recombinant human erythropoietin (rHuEPO) from 1996 to 2000 were selected. Mean annual hemoglobin values were calculated by modality, age, sex, and race. RESULTS: Among hemodialysis patients, mean annual hemoglobin values less than 11 g/dL were present in pediatric and adult patients during 54.1% versus 39.8% patient years, respectively (P < 0.0001); for peritoneal dialysis patients, 69.5% versus 55.1% (P < 0.0001). Mean hemoglobin values increased over time and were 11.2, 11.5, 10.8, and 11.2 g/dL for pediatric and adult hemodialysis and peritoneal dialysis patients, respectively, in 2000. Pediatric hemodialysis patients received intravenous iron less frequently than adults (66.3% vs. 82.5% patient years; P < 0.0001). CONCLUSION: Hemoglobin values in rHuEPO-treated pediatric dialysis patients lagged behind those of adult patients, with pediatric patients achieving target hemoglobin values only a minority of the time (45.9% and 30.5% patient years, respectively, for hemodialysis and peritoneal dialysis). Trends show recent improvement in anemia treatment of children on dialysis. Still, further attention to and analysis of rHuEPO and iron therapy in pediatric dialysis patients is warranted.     

Usefulness of recombinant human erythropoietin in cardiac surgery with autologous blood transfusion]

The efficacy and method of administration of recombinant human erythropoietin (EPO) in adult cardiac surgical patients when given preoperatively was evaluated. We used EPO intravenously (iv) with 40 mg ferric oxide for a total of consecutive 47 patients. The patients were divided into group A (n = 14; EPO 200 IU/kg iv 3 times a week from 3 weeks prior to surgery to 2 weeks after surgery, donation of 800 ml) and group B (n = 33; EPO 200 IU/kg iv everyday from 8 days prior to surgery to 2 weeks after surgery, donation of 400 ml). Control groups were group AO (n = 11; donation of 835 +/- 33 ml from 14.8 days prior to surgery) and group BO (n = 7; donation of 406 +/- 34 ml at 7.3 days prior to surgery). All the EPO-treated patients received no homologous blood transfusion while 2 of patients in group BO received some homologous blood transfusion. A hemoglobin change between pre-donation and surgery was +0.14 +/- 1.3 (g/dl) in group A, +0.04 +/- 1.0 (g/dl) in group B, -1.7 +/- 1.3 (g/dl) in group AO and -1.0 +/- 0.6 (g/dl) in group BO. In a comparison of post-surgical hemoglobin levels between group A and group B, we demonstrated that the level in group B, +2.1 +/- 1.8 (g/dl) was significantly higher than that in group A, +11.1 +/- 1.6 (g/dl) 2 weeks after surgery. There was no evidence to show an aggravation of anemia in the pre-surgical period in EPO-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Presence and significance of TT virus in Danish patients on maintenance hemodialysis

OBJECTIVES: To determine the prevalence of TT virus (TTV) in a population of Danish hemodialysis patients and evaluate possible relations between TTV infection and elevated levels of C-reactive protein (CRP) and hypo-response to treatment with erythropoietin (EPO). MATERIAL AND METHODS: Patients on maintenance hemodialysis at a single center were invited to participate. Demographic and clinical data were registered. Blood samples for virological and routine biochemical tests were drawn simultaneously. TTV DNA was detected using polymerase chain reaction (PCR). TTV viral load was estimated by means of semi-quantitative PCR. All patients were tested for hepatitis B, hepatitis C and GB virus C. RESULTS: Of 252 patients, 204 (80.9%) gave their written informed consent to participate in the study. The prevalence of TTV was 68% and 50% of TTV-positive patients had a high TTV viral load. TTV-positive patients were significantly older than TTV-negative patients (p = 0.011). No relations were found between TTV infection and elevated levels of alanine aminotransferase (ALT) or CRP or hypo-response to EPO treatment. The mean hemoglobin concentration was 11.24 +/- 1.48 g/dl. Patients with a high TTV viral load had a lower level of hemoglobin (10.86 +/- 1.47 g/dl) than the others (p = 0.01). This trend suggested a positive relation between TTV infection and the number of blood transfusions. A restriction fragment length polymorphism assay suggested that patients were infected with different TTV strains. CONCLUSIONS: TTV is common in patients on maintenance hemodialysis. The presence of TTV is associated with increasing age. Patients with a high TTV viral load had lower levels of hemoglobin than the others. TTV infection is not related to elevated levels of ALT or CRP or to hypo-response to EPO treatment.     

Effects of different treatment methods on renal anemia in maintenance hemodialysis patients with hyperparathyroidism secondary to uremia

Objective To observe the effects of three treatment methods on renal anemia in maintenance hemodialysis patients with hyperparathyroidism secondary to uremia and analyze the influencing factors of erythropoietin (EPO) dosage. Methods A total of 55 maintenance hemodialysis patients with secondary hyperparathyroidism at the hemodialysis center of Huashan Hospital affiliated to Fudan University from January 2015 to December 2016 were retrospectively divided into three groups according to different treatment methods, parathyroidectomy +forearm transplantation group (surgery group, n=16), cinacalcet treatment group (n=6), and calcitriol treatment group (n=33), respectively. The hemoglobin level and erythropoietin dosage were measured before treatment and in the 3rd month, the 6th month and the 12th month after treatment. The changes of hemoglobin and erythropoietin dosage in the three groups before and after treatment were observed, and the mixed effect model was used to analyze the difference of the change of hemoglobin and erythropoietin dosage among three groups. Multiple linear regression analysis was used to analyze the influencing factors of EPO dosage after one year. Results The levels of intact parathyroid hormone (iPTH) in the surgery group and the cinacalcet group before treatment were significantly higher than that in the calcitriol group (both P＜0.05). In the 12th month after treatment, the levels of iPTH decreased significantly in the patients of surgery group and the cinacalcet group compared with those before treatment (both P＜0.05). The levels of serum alkaline phosphatase, serum calcium and serum phosphorus in the surgery group also decreased significantly compared with those before treatment (all P＜0.05). The mixed effect model analysis showed that the hemoglobin level of surgery group was on an upward trend after the treatment, and the overall level was significantly higher than cinacalcet and calcitriol treatment group (P=0.007). There was no significant difference in the dosage change of erythropoietin (EPO) in the three groups over time. However, the intra-group comparison of the mixed effect model showed that the dosage of EPO in the 12th month was significantly lower than that of before the treatment in surgery group (P=0.007). Multiple linear regression analysis showed that dialysis vintage (B=-0.064, P=0.012) and ferritin ≥ 500 μg/L (B=0.645, P=0.032) were independent influencing factors of EPO dosage. The longer the dialysis vintage, the less EPO dosage, and more EPO dosage were observed in patients with ferritin ≥ 500 μg/L. Conclusions Parathyroidectomy and forearm transplantation is more effective in reducing EPO dosage and improving renal anemia in maintenance hemodialysis patients with secondary hyperparathyroidism. Dialysis vintage and ferritin are independent influencing factors for the dosage of EPO.     

Hemoglobin cycling in hemodialysis patients treated with recombinant human erythropoietin

BACKGROUND: Treatment with recombinant human erythropoietin (rHuEPO) has been a major advance for the management of anemia in patients on hemodialysis. Therapy, however, is often observed to be associated with recurrent cyclic fluctuations in hemoglobin levels. The purpose of this analysis was to describe the phenomenology of hemoglobin cycling during rHuEPO treatment. METHODS: Data were analyzed for 281 hemodialysis patients treated at Winthrop-University Hospital Dialysis Centers between 1998 and 2003. Eligible patients' first full 1-year period with less than 10 hospital days was studied. Hemoglobin cycling (cycles with amplitude >1.5 g/dL and duration >8 weeks) and excursions (half of one full cycle) were analyzed. RESULTS: Greater than 90% of patients experienced hemoglobin cycling. The mean number of hemoglobin excursions was 3.1 +/- 1.1 per patient/year. The mean amplitude per hemoglobin excursion was 2.51 +/- 0.89 g/dL. The mean duration of hemoglobin excursions was 10.3 +/- 5.1 weeks. Factors associated with initiation of up excursions included increases in rHuEPO dose (84%), intravenous iron treatment initiation or increase in dose (27%), posthospital discharge (36%), factors associated with down excursions included rHuEPO dose hold (15%) or dose reduction (62%), infection (6%), discontinuation of intravenous iron therapy (5%), and hospitalization (14%). Patients with frequent hemoglobin cycling (>two full cycles per year) were characterized as being more responsive to rHuEPO [index of EPO responsiveness (ERI) 1036 +/- 659 compared to 1992 +/- 701 for other patients] (P = 0.02). CONCLUSION: Hemoglobin cycling is a common occurrence in rHuEPO-treated hemodialysis patients. It is most closely associated with frequent rHuEPO dose changes, hospitalization, and iron treatment practices.     

Treatment of Anemia in Renal Transplantation: Impact of a Stricter Application of Hemoglobin Targets

Objective

The CREATE and CHOIR studies showed a higher risk for cardiovascular events associated with hemoglobin (Hb) values >13 g/dL in patients with stage 3-4 chronic kidney disease. In 2007, a stricter policy on the use of erythropoietin (EPO) was adopted at our center, with an Hb target of 11 to 12 g/dL and withdrawal or reduction of EPO when Hb was >12.5 to 13 g/dL. This study was designed to evaluate this new approach.

Materials and Methods

The study included patients under follow-up at the transplant outpatient clinic on December 31, 2006 (n = 725), and December 31, 2007 (n = 768). Data were compared between the study populations concerning renal function, Hb, use of EPO, and associated costs.

Results

No significant differences in creatinine or Hb values were observed between the 2 groups (1.47 ± 0.6 vs 1.42 ± 0.9 mg/dL and 13.7 ± 1.5 vs 13.7 ± 1.6 g/dL, respectively). After implementation of the new protocol, the frequency of severe anemia (Hb <11 g/dL) increased (2% vs 4%; P = .10), the use of EPO decreased (22.1% vs 17.2%; P = .017), and the mean Hb of EPO-treated patients decreased (12.5 ± 1.4 vs 11.9 ± 1.0; P < .001). The Hb target (11-12 g/dL) was met in fewer than one third of patients, with no significant differences between the 2 study times.

Conclusions

A strict policy on EPO application reduces its use and the rate of patients with “excessive” Hb values (which are associated with increased cardiovascular risks), with an acceptable slight increase in severe anemia cases.     

Pentoxifylline improves hemoglobin levels in patients with erythropoietin-resistant anemia in renal failure

It was hypothesized that pentoxifylline might improve the response to recombinant human erythropoietin (rh-Epo) in anemic renal failure patients. Sixteen patients with ESRD and rh-Epo-resistant anemia, defined by a hemoglobin of <10.7 g/dl for 6 mo before treatment and a rh-Epo dose of > or =12,000 IU/wk, were recruited. They were treated with oral pentoxifylline 400 mg o.d. for 4 mo. Ex vivo T cell generation of tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) from the patients was assessed before treatment and 6 to 8 wk after therapy. A total of 12 of 16 patients completed the study. Before therapy, the 12 patients' mean hemoglobin concentration was 9.5 +/- 0.9 g/dl. After 4 mo of pentoxifylline treatment, the mean hemoglobin concentration increased to 11.7 +/- 1.0 g/dl (P = 0.0001). Baseline ex vivo T cell expression of TNF-alpha decreased from 58% +/- 11% to 31% +/- 23% (P = 0.0007) after therapy. Likewise, IFN-gamma expression decreased from 31% +/- 10% to 13% +/- 10% (P = 0.0002). Pentoxifylline therapy may significantly improve the hemoglobin response in patients with previously rh-Epo-resistant anemia in renal failure. This may occur due to inhibition of proinflammatory cytokine production, which could interfere with the effectiveness of rh-Epo.     

Darbepoetin alfa once every 2 weeks for treatment of anemia in dialysis patients: a combined analysis of eight multicenter trials

AIM: Darbepoetin alfa has a longer half-life than epoetin-(EPO) alfa or beta, allowing administration at less frequent intervals for the treatment of renal anemia. The aim of the present analysis was to evaluate the efficacy and tolerability of an every-2-week (Q2W) schedule of darbepoetin alfa in a large cohort of dialysis patients. METHODS: Data were combined from eight similarly designed 24-week phase 3b European studies, in which patients receiving EPO alfa or beta once-weekly were converted to Q2W darbepoetin alfa. Darbepoetin alfa dosage was titrated to maintain hemoglobin (Hb) between 10 and 13 g/dl and efficacy was evaluated during a 4-week evaluation period. RESULTS: In the 1,101 patients assigned to Q2W darbepoetin alfa (i.v., n = 196, s.c., n = 905), mean (SD) Hb levels were 11.53 (0.77) g/dl at baseline and 11.35 (1.04) g/dl at evaluation (mean change in Hb -0.27 g/dl, 95% confidence interval 0.34, -0.20). Hb levels were maintained between 10 and 13 g/dl during evaluation in 85% of patients. Darbepoetin alfa doses were similar at baseline and evaluation, and the i.v. and s.c. routes were associated with similar efficacy and dose requirements. Darbepoetin alfa was well-tolerated. CONCLUSIONS: Q2W darbepoetin alfa is effective in maintaining Hb levels in dialysis patients switched from weekly rHuEPO, regardless of the route of administration and with no notable increase in the weekly equivalent dose.     

Prospective study of the immune effects of normalizing the hemoglobin concentration in hemodialysis patients who receive recombinant human erythropoietin

Partial correction of anemia by erythropoietin improves hemodialysis (HD)-associated immunosuppression. It is not known whether hemoglobin normalization improves immune status further. The authors prospectively compared the immune function of HD patients with congestive heart failure or ischemic heart disease on erythropoietin therapy randomized to normal versus anemic blood hemoglobin concentration. HD patients were randomized into a normal hemoglobin group (n = 17, target hemoglobin of 14 +/- 1 g/dl) or an anemic hemoglobin group (n = 18, target hemoglobin 10 +/- 1 g/dl). Delayed-type hypersensitivity, CD4 and CD8 counts, anti-tetanus toxoid antibody levels, erythrocyte complement receptor 1 expression, and lymphocyte proliferative responsiveness were measured. The observation period was 1 yr, and the trial was open label. Target hemoglobin was achieved and maintained in both groups. Significantly improved cutaneous reactivity was seen in the normal hemoglobin group (P = 0.003). The prevalence of anergy decreased in the normal hemoglobin group (from 60 to 20%) but increased in the anemic hemoglobin group (from 57 to 86%). The anemic hemoglobin group had higher CD8 counts compared with baseline (P = 0.0001) and compared with the normal hemoglobin group (P = 0.038). Both groups had significant increases in tetanus toxoid antibody levels after vaccination but without significant differences between groups. The anemic hemoglobin group had a progressive increase in erythrocyte complement receptor 1 levels compared with baseline (P = 0.002) and relative to the normal hemoglobin group (P = 0.023). There was no consistent pattern of altered proliferative responsiveness of lymphocytes. The data suggest that certain aspects of immune function, particularly delayed-type hypersensitivity, may be improved in HD patients by normalization of hemoglobin through the administration of increased doses of erythropoietin.     

Anemia, hospitalization, and mortality in patients receiving peritoneal dialysis in the United States

BACKGROUND: The view that hemoglobin levels in peritoneal dialysis patients should be maintained at 11 to 12 g/dL is based largely on the results of studies in hemodialysis patients. METHODS: We studied 13,974 erythropoietin-treated Medicare patients who initiated peritoneal dialysis between 1991 and 1998. Mean hemoglobin levels for the first 6 months of the study and, subsequently, time to first hospitalization and death during a 2-year follow-up were determined. RESULTS: The percentages of patients with hemoglobin levels of <10, 10 to 10.9, 11 to 11.9, and >/=12 g/dL were 24.6%, 40.6%, 27.6%, and 7.2%, respectively. First-hospitalization and death rates, respectively, were 109.5 and 21.6 per 100 patient-years in nondiabetic patients, and 152.9 and 31.5 in diabetic patients. In nondiabetic patients, adjusted hospitalization hazard ratios for hemoglobin levels of <10, 10 to 10.9, 11 to 11.9 (reference category), and >/=12 g/dL were 1.29 (P < 0.0001), 1.15 (P < 0.0001), 1, and 0.98 (NS), respectively. The corresponding adjusted mortality hazard ratios were 1.43 (P < 0.0001), 1.13 (P < 0.05), 1, and 1.14 (NS). In diabetic patients, hazard ratios of 1.26 (P < 0.0001), 1.07 (NS), 1, and 0.82 (P < 0.01) were observed for hospitalization, and 1.34 (P < 0.0001), 1.18 (P < 0.01), 1, and 0.92 (NS) for mortality. CONCLUSION: In peritoneal dialysis patients, anemia is associated with hospitalization and mortality in a manner supporting current Kidney Dialysis Outcomes Quality Initiative (K/DOQI) hemoglobin targets. In addition, hemoglobin levels of >/=12 g/dL are associated with lower hospitalization rates in diabetic patients.