Renal function during erythropoietin therapy for anemia in predialysis chronic renal failure patients

Recombinant human erythropoietin (r-HuEPO) therapy for anemia in chronic renal failure patients could have unfavorable renal effects since reversal of anemia can raise blood pressure and accelerate experimental glomerular injury. Thus, the effects of r-HuEPO on renal and systemic hemodynamics and the progression of renal disease were studied in predialysis chronic renal failure patients. The clearances of inulin and p-aminohippurate, fractional excretions of albumin and immunoglobulin G, cardiac output, plasma renin activity and aldosterone concentration were assessed at baseline, after short-term r-HuEPO (n = 4) or placebo (n = 4) therapy, and after long-term r-HuEPO for all patients (n = 8). In addition, the slope of l/serum creatinine with time was determined before and during continued r-HuEPO therapy. In contrast to placebo therapy, hematocrit increased with r-HuEPO from 32 to 37% after 7.6 +/- 2.7 weeks (mean +/- SD). Antihypertensive drug therapy was increased in 2 patients in each group. Renal function, cardiac output, plasma renin activity and aldosterone did not change significantly in either group. After 18 +/- 9 weeks of therapy for all patients, hematocrit increased from 31 to 39%. Antihypertensive drug therapy was increased in 5 patients and decreased in 1. Renal function decreased while proteinuria tended to increase. Cardiac output, plasma renin activity and aldosterone did not change. During 37 +/- 22 weeks of r-HuEPO therapy, the slope of l/serum creatinine did not worsen in any patient.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of recombinant human erythropoietin on renal function in humans

To assess the effect of recombinant human erythropoietin (r-HuEPO) treatment on renal function, the slopes of the regression lines of the reciprocal of serum creatinine versus time were compared in 26 patients with renal insufficiency (serum creatinine ranged from 2.3 to 11.7 mg/dl) followed for a period of 2.7 to 24 months. Ten patients received r-HuEPO and the anemia was corrected (Group I). Sixteen patients did not receive r-HuEPO. Ten of them were anemic (Group II) and six had normal hematocrits (Group III). All study groups were matched for age, diagnosis and degree of renal insufficiency. All cohorts were followed prospectively (Period B, from the first day of the study to the time of data analysis or dialysis and transplantation); renal function was also examined retrospectively (Period A, from the first day of the study to the time of first renal function measurement). Hematocrit was lowest in Group II control patients, 27%, highest in the Group III control subjects, 43%, and intermediate in Group I EPO-treated patients, 36%. Serum creatinine uniformly increased in all three groups of patients. The rate of progression, as measured by the slopes of the reciprocal of serum creatinine versus time, however, was similar in all three groups of subjects and during both periods. The mean slopes for Group I patients before and after r-HuEPO were, respectively, -0.0058 and -0.0054, that of the control cohorts with low and normal hematocrit during period B were -0.0063 and -0.0010, respectively. Thus, it appeared that neither r-HuEPO administration nor a normal hematocrit accelerated the deterioration of renal function in these patients with renal insufficiency.     

Blood rheology and hypertension in hemodialysis patients treated with erythropoietin

Fifteen hemodialysis patients suffering from stable anemia were treated with recombinant human erythropoietin (r-HuEPO). Within 16 weeks, hematocrit values increased from 23.7 +/- 1.2 to 35.7 +/- 0.2%. Simultaneously, mean predialytic blood pressure rose significantly from 131/79 to 139/85 mm Hg. Three out of 15 patients developed frank hypertension and had to be put on antihypertensive therapy. When the hematocrit was lowered again from 36.3 +/- 1.8 to 30.5 +/- 1.2% in these 3 patients, blood pressure was attenuated and the antihypertensive medication could be reduced or abolished. With rising hematocrit values, whole blood viscosity increased at both low (+42%) and high shear rates (+33%) without reaching the values seen in healthy subjects. By contrast, plasma viscosity was already elevated in hemodialysis patients prior to r-HuEPO treatment and showed only a slight, but insignificant increase during r-HuEPO treatment. Since whole blood viscosity is one factor that determines vascular resistance, it is conceivable that the development of hypertension during correction of the renal anemia is, at least partly, due to an increment of blood viscosity.     

Bioavailability of iron in hemodialysis patients treated with erythropoietin: evidence for the inhibitory role of aluminum

The dose of recombinant human erythropoietin (r-HuEPO) required to correct the anemia of end-stage renal disease (ESRD) varies among patients. The response to r-HuEPO is impaired if absolute or relative iron deficiency exists. Aluminum may cause a microcytic anemia in patients with ESRD, but the mechanism remains incompletely defined. Twenty-two patients in the Canadian Multicentre EPO trial were studied for 6 months. In this randomized double-blind placebo-controlled trial, free erythrocyte protoporphyrin (FEP) was used as an indicator of iron-deficient deficient erythropoiesis. The relationship of FEP to the estimates of iron availability (serum iron, transferrin saturation, ferritin) and iron utilization (corrected reticulocyte count, hemoglobin) was evaluated by multiple linear regression analysis. The effect of aluminum on FEP was evaluated by adjusting the statistical model for this variable. All patients were iron replete as assessed by serum ferritin. FEP was not related to serum aluminum before administration of r-HuEPO, but it was significantly correlated with aluminum in the treated group. In hemodialysis patients treated with r-HuEPO, the proportion of the variability explained by the parameters of iron utilization and iron availability was 0.27. The effect of aluminum increased this to 0.59. In hemodialysis patients not receiving r-HuEPO, the proportion of variability in FEP explained by the model increased from 0.16 to 0.28 by adjusting for aluminum. The data support the hypothesis that aluminum interferes with the bioavailability of stored iron for erythropoiesis and thus may result in a microcytic anemia in patients with ESRD or may blunt their response to r-HuEPO therapy.     

Therapy of iron deficiency anemia in patients on maintenance dialysis.

A controlled, prospective study compared the effectiveness of oral ferrous sulfate to intravenous iron dextran, each with and without concurrent intramuscular androgen for therapy of iron deficiency anemia in patients with chronic renal failure treated with maintenance hemodialysis. During the 12-week period of therapy, the patients who received oral ferrous sulfate and androgens showed an increment in their mean hematocrit of 16.3% and those who received oral ferrous sulfate alone had an increase of 8.3%. Patients treated with intravenous iron dextran androgens showed an increment in their mean hematocrit of 9.4% and those given iron dextran alone showed an increase of 3.5%. Serum ferritin levels increased with iron repletion but correlated inversely with the erythropoietic response. The serum ferritin assay provides a simple and reliable method to demonstrate iron repletion, and oral ferrous sulfate is the preferred method of iron repletion in compliant patients.     

Improved sexual function in hemodialysis patients on recombinant erythropoietin: a possible role for prolactin

As it was reported that correction of anemia in long-term hemodialysis patients by recombinant human erythropoietin (r-HuEPO) is associated with improved sexual function, we conducted the present study to further delineate the mechanism(s) by which this is brought about. Serum prolactin, testosterone, and parathyroid hormone (PTH) levels were followed during 4 months of r-HuEPO therapy. Within 4 months of treatment with r-HuEPO, hematocrit values rose from 23.7 +/- 1.2 to 35.7 +/- 0.2% and hemoglobin increased from 7.3 +/- 0.3 to 11.3 +/- 0.4 g/100 ml. In parallel, serum prolactin values decreased significantly from 66.9 +/- 9.3 to 9.6 +/- 2.6 ng/ml in females and from 39.5 +/- 10.5 to 10.3 +/- 1.0 ng/ml in male dialysis patients. Testosterone concentrations were low in male patients and remained unchanged during r-HuEPO therapy. Baseline PTH values were elevated (1,880 +/- 220 pg/ml) in patients of both sexes and declined to 1,410 +/- 180 pg/ml during treatment with r-HuEPO. However, this difference did not reach statistical significance. Sexual function improved in 4 out of 7 males and 5 out of 9 female patients began to menstruate regularly again. It appears that treatment of anemia in end-stage renal disease by r-HuEPO improves sexual function via normalization of elevated serum prolactin concentrations.     

Recombinant human erythropoietin independence in chronic hemodialysis patients: clinical features, iron homeostasis and erythropoiesis

AIMS: Recombinant human erythropoietin (r-HuEPO) is widely used to correct renal anemia in uremic patients. Interestingly, some chronic hemodialysis (HD) patients can maintain high hemoglobin level without the need of r-HuEPO. The aim of this study is to investigate clinical features, iron metabolism and erythropoiesis of these r-HuEPO-independent HD patients. METHODS: r-HuEPO independence was defined in dialysis patients as hemoglobin greater than 12 g/dl and no use of r-HuEPO for at least 6 months. An age- and sex-matched group was selected for comparison. Their underlying diseases, duration of hemodialysis therapy, efficacy of dialysis (Kt/V), normalized protein catabolic rate (nPCR) and body mass index (BMI) were recorded. Laboratory data including: hemoglobin, albumin, high sensitivity C-reactive protein, serum iron, total iron binding capacity, transferrin saturation, ferritin, intact parathyroid hormone, soluble transferrin receptor (sTfR), serum EPO, cortisol, testosterone, aluminum and leptin levels were measured. Renal sonography was also performed in each patient to evaluate renal cyst formation. RESULTS: About 2.3% of all HD patients (21/888; M : F = 18 : 3) were r-HuEPO-independent. These patients had significantly longer HD duration and higher serum EPO and sTfR levels, and lower transferrin saturation rate than dependent groups. Correlation analysis revealed that hemoglobin level strongly correlated with HD duration, serum sTfR and EPO levels. Levels of sTfR were positively related with serum EPO levels and BMI. Multivariate regression analysis showed that level of sTfR was the only independent factor related to r-HuEPO independence. CONCLUSION: R-HuEPO independence is rare among chronic hemodialysis patients. Factors contributing to this dependence are complex and multiple. Level of serum sTfR parallels erythropoiesis and is the most significant factor associated with r-HuEPO independence in chronic HD patients.     

Alterations in sex hormones and sexual function of patients with renal failure treated with recombinant human erythropoietin.

Since it has been reported that correction of anemia in long-term hemodialysis patients by using human recombinant erythropoietin (r-HuEPO) is associated with improve sexual function, we conducted the present study to evaluate the changes in sex hormones as well as sexual function after r-HuEPO administration (1500 to 4500 IU per dialysis) for a year in patients on regular hemodialysis. Thirteen patients receiving regular hemodialysis entered this study. Their median age was 43 years. Along with correction of anemia (the hematocrit increased from 20 to 28%), testosterone (T) increased from 2.4 +/- 0.1 to 2.6 +/- 0.2 ng/ml, follicular stimulating hormone (FSH) increased (29 +/- 5 to 73 +/- 7 mIU/ml), luteinizing hormone increased (69 +/- 14 to 160 +/- 21 IU/ml) and prolactin decreased (all changes are significant at p less than 0.05). However, the improvement of sexual function was not remarkable. Only 25% of the uremic patients treated with r-HuEPO showed amelioration of this function. From the present data, it does not seem likely that therapy with r-HuEPO induces directly amelioration of sexual function through changes in sex hormones.     

Evaluation of hemodialysis patients treated with erythropoietin

We evaluated 20 hemodialysis patients who had been treated with erythropoietin (Epo). All patients had hemoglobin levels below 8.5 g/dL. They were randomized to receive either Epo (100 U/kg) or placebo three times per week for 12 weeks. All patients on Epo had a significant (P less than 0.001) elevation of hematocrit levels (19.7% v 35.7%). They also had a significant (P less than 0.05) increase in midweek predialysis blood urea nitrogen (BUN) levels, 27.8 versus 29.6 mmol/L (78 v 83 mg/dL), and serum phosphorus, 1.8 versus 2.1 mm/L (5.7 v 6.6 mg/dL). Protein catabolic rate also increased significantly (P less than 0.05). No changes were seen in the levels of serum creatinine and potassium, but episodes of hyperkalemia were more frequent in patients on Epo. No changes were seen in patients on placebo. When hematocrit increased, the clearance of blood-water for urea decreased 9%, and the clearance of creatinine, potassium, and phosphorus decreased 15%. Patients on Epo increased both their appetite and protein intake. More frequent episodes of hyperkalemia and elevated phosphorus level resulted from a combination of increased intake and decreased dialyzer clearance. We may need blood-water clearance to calculate Kt/V.     

Causes of anemia in renal transplant recipients

Iron-deficiency anemia is one of the major problems encountered in renal transplant recipients. The aim of this retrospective study was to reevaluate the causes of anemia among 100 anemic kidney recipients. Patients with serum creatinine levels greater than 2 mg/dL were excluded from the study. Female patients were considered to be anemic if the hemoglobin was <12 g/dL for males, <13 g/dL. Complete blood count, serum creatinine, serum iron, iron-binding capacity, ferritin, transferrin saturation, erythrocyte folate, and serum vitamin B(12) levels were measured in all patients. Mean hemoglobin value was 10.2 +/- 1.4 g/dL for female and 9.9 +/- 1.3 for male patients, mean corpuscular volume (MCV) 91.3 +/- 4.9 fL. We observed normocytic anemia in 60, macrocytic anemia in 30, and microcytic anemia in 10 patients. A low level of serum folate was observed in 9 (15%) and of vitamin B(12) in 5 (8.8%) of 60 patients with normocytic anemia. Folate deficiency was found in 18 (60%) and vitamin B(12) deficiency in 12 (40%) of 30 patients with macrocytic anemia. All patients with microcytic anemia had iron deficiency. Splenomegaly was seen significantly more often in patients with macrocytic than normocytic anemia (P =.008). Folate and vitamin B(12) deficiency were the major causes of nutritional anemia; oral or parenteral supplementation with these vitamins is likely to cure the anemia in the majority of cases.     

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.     

Postoperative intravenous iron used alone or in combination with low-dose erythropoietin is not effective for correction of anemia after cardiac surgery

OBJECTIVES: The aim of this study was to examine whether intravenous iron III-hydroxide sucrose complex (IHSC) used alone was sufficient to provide rapid correction of anemia after cardiac surgery and whether additional stimulation of erythropoiesis is possible by means of a single low dose of recombinant-human erythropoietin (r-HuEPO) administration. DESIGN: Prospective, randomized, double-blind study. SETTING: The study was conducted in a university hospital. PARTICIPANTS: One hundred twenty American Society of Anesthesiologists II or III patients, who underwent elective cardiac surgery using cardiopulmonary bypass and in whom postpump hemoglobin ranged between 7 and 10 g/dL. INTERVENTIONS: Patients were divided into 3 groups: group I = control; group II received postoperative intravenous iron supplementation with an iron III-hydroxide sucrose complex (IHSC); and group III received IV iron and a single dose of r-HuEPO (300 U/kg). MEASUREMENTS AND RESULTS: No significant difference in transfusion needs was observed among the 3 groups (22%, 25%, and 17% of patients transfused in groups I, II, and III, respectively). Hemoglobin levels, reticulocyte counts, and serum ferritin levels were evaluated at different time intervals (until day 30 postoperatively). No side effects because of iron administration were noted in the study. Reticulocyte counts increased rapidly at day 5 (2.24% +/- 1.11%, 1.99% +/- 1.44%, and 3.84% +/- 2.02% in groups I, II, and III, respectively) and decreased after day 15 in the 3 groups. Ferritin levels increased significantly at day 5 in the 2 treated groups (899.33 +/- 321.55 ng/mL in group II, 845.75 +/- 289.96 ng/mL in group III v 463.15 +/- 227.74 ng/mL in group I). In group I, ferritin levels, after a slight elevation on day 5, decreased at day 15 to lower than baseline levels. No significant difference in hemoglobin increase was noted among the 3 groups. CONCLUSION: Postoperative intravenous iron supplementation alone or in combination with a single dose of r-HuEPO (300 U/kg) is not effective in correcting anemia after cardiac surgery.     

A study on hemolysis in hemodialysis patients

In order to investigate the pathogenesis of hemolysis in chronic renal failure, red cell life span and hemolysis starting point (HSP) by coil planet centrifuge method were studied in 32 hemodialysis (HD) patients and 16 healthy subjects. Mean red cell life span was 22.0 days before recombinant human erythropoietin (r-HuEPO) therapy, and prolonged up to 28.1 days after r-HuEPO therapy. Mean HSP in HD patients was significantly elevated than healthy subjects. Mean HSP was 106.7 mOsm before r-HuEPO therapy, and improved to 101.0 mOsm after r-HuEPO therapy. HSP improved from 106.8 mOsm to 100.8 following the correction of bicarbonate level with HD. HSP was negatively correlated to bicarbonate level pre- and post-r-HuEPO therapy, but HSP was not correlated to BUN, serum creatinine, hydrogen ion, anion gap and amount of body water removal during HD. When blood PH in 18 HD patients was adjusted by 7% NaHCO3 from 7.21 to 7.40, HSP improved to normal range in all. These data suggested that osmotic fragility was normal in younger erythrocyte in HD patients, and a decrease of plasma bicarbonate level resulted in an increase of hemolysis.     

Oxidative stress in kidney transplant patients

BACKGROUND: Little information is available about the role of oxidative stress in renal transplant patients. To evaluate the prevalence and severity of oxidative stress in renal transplantation, the authors conducted a cross-sectional study. METHODS: In 112 cadaver or living-donor kidney transplant recipients with a follow-up of at least 6 months and with plasma creatinine less than or equal to 2.5 mg/dL, complete blood count, serum vitamin B12, serum folate (s-F), reactive oxygen species (ROS), thiol groups (-SH), total antioxidant activity (TAOC), serum homocysteine (Hcy), and intraerythrocyte folate (ery-F) were measured. RESULTS: The mean levels of Hcy (21.1 microM vs. <10 microM), ROS (302.7 U. Carr (Carratelli units) vs. 250-300 U. Carr), and TAOC (410.6 micromol/HclO/mL vs. >350 micromol/HclO/mL), were higher than the reference interval, whereas -SH groups, vitamin B12, s-F, and ery-F were within the normal range. In the multivariate model, plasma creatinine (P=0.0062), vitamin B12 (P=0.0121), and TAOC (P=0.0007) were independently associated with oxidative stress. At multiple regression analysis, -SH groups and ROS were directly and inversely related to hematocrit (P=0.0007 and P=0.0073). There was also a negative correlation between -SH groups and blood pressure levels (P=0.0095). CONCLUSIONS: Renal transplant patients have a pattern of increased oxidant stress that is counterbalanced by an enhancement of the antioxidant mechanisms. Besides the well-known risk factors, the authors found that anemia is an independent risk factor for an increase of ROS. Further studies are needed to evaluate whether the correction of anemia might prevent or reduce the oxidative stress in renal transplant patients.     

Reduction of the occurrence of acute cellular rejection among renal allograft recipients treated with basiliximab, a chimeric anti-interleukin-2-receptor monoclonal antibody. United States Simulect Renal Study Group

BACKGROUND: A double-blind, placebo-controlled phase III study was performed to assess whether basiliximab, a chimeric anti-interleukin-2 receptor monoclonal antibody, reduced the incidence of acute rejection episodes in renal allograft recipients. METHODS: A total of 348 patients were randomized into two demographically matched, equally sized groups treated with either basiliximab or placebo. The dose of basiliximab-20-mg infusions on day 0 and day 4-was selected to block detection of interleukin-2 receptor on 97% of peripheral blood lymphocytes for 30-45 days. All patients received immunosuppressive therapy with cyclosporine microemulsion (Neoral) and steroids. An intent-to-treat analysis of 1-year data assessed the incidence of posttransplant acute rejection episodes, patient and graft survival rates, and the safety and tolerability of basiliximab. RESULTS: Among the eligible 346 patients equally divided into the two treatment groups, basiliximab reduced the proportion of patients who experienced biopsy-confirmed acute rejection episodes by 28%: 61 (35.3%) basiliximab vs. 85 (49.1%) placebo (P=0.009). Graft losses occurred in 9 (5.2%) basiliximab-treated and 12 (6.9%) placebo-treated patients. Five (2.9%) deaths in the basiliximab group and seven (4.0%) in the placebo group occurred. Compared with placebo, a higher fraction of basiliximab patients produced urine in the operating room, and a significantly lower fraction had renal dysfunction in the first month (serum creatinine > or =5 mg(dl) and between 1 and 12 months (serum creatinine > or =3 mg/dl). During the first 12 months, 94 (54%) basiliximab-treated patients experienced serious adverse events, compared with 106 (61%) who received placebo. CONCLUSIONS: Prophylactic basiliximab therapy is well tolerated, has an adverse event profile comparable to placebo, and significantly reduces the number of acute rejection episodes in renal allograft patients within the first year after transplantation.     

Anemia in pediatric renal transplant recipients

The aim of this study was to establish the prevalence of anemia in stable pediatric renal transplant recipients and to examine the association of anemia with renal function, immunosuppressants, angiotensin converting enzyme inhibitors, and growth, as well as iron, vitamin B₁₂, and folate stores. This is a cross-sectional study of the 50 renal transplant recipients currently followed at our center. Patient data were collected regarding hematological parameters, growth, medications, renal function, underlying renal disease, delayed graft function, episodes of rejection, and iron or erythropoietin therapy post transplantation. The mean hemoglobin level (Hb) was 110 g/l and the overall prevalence of anemia was 60%, including 30% who were severely anemic (Hb<100 g/l). There was a high rate of iron deficiency (34%) and serum iron was the parameter of iron metabolism most closely associated with anemia. Hb in patients with low serum iron was 90.7 g/l versus 114.4 g/l in those with normal serum iron (P<0.01). Both univariate and multiple linear regression determined tacrolimus dose and creatinine clearance to be significant factors associated with anemia. Tacrolimus dose correlated with a 10 g/l reduction in Hb for every increase of tacrolimus dose of 0.054 mg/kg per day (P=0.001). The dose of mycophenolate was positively correlated with Hb, but this was likely to be confounded by our practice of dose reduction in the setting of anemia. Angiotensin converting enzyme inhibitor use was not associated with anemia. Severely anemic patients tended to be shorter, with a mean Z-score for height of –1.8 compared with –0.9 for those with normal Hb (P=0.02). Anemia is a significant and common problem in pediatric renal transplant patients. Deteriorating renal function is an important cause, but other factors like iron deficiency and immunosuppression are involved. Definition of iron deficiency is difficult and serum iron may be a valuable indicator. Medication doses, nutritional status, need for erythropoietin and iron, as well as poor graft function and growth require systematic scrutiny in the care of the anemic renal transplant recipient.     

Factor Deficiency in the Anemia of Renal Transplant Patients With Grade III-IV Chronic Kidney Disease: Baseline Results of the ARES Study

ARES is a multicenter, prospective study of the prevalence, management, and repercussions on the quality of life of anemia in renal transplant patients with a reduced renal function (creatinine clearance according to Cockcroft-Gault: ≤60 and >15 mL/min). The frequency of factor deficiency and its relationship with anemia were analyzed at the baseline time of the study. Of the 500 patients included in the main study, valid data were available for iron metabolism in n = 419 μg/dL; folic acid, n = 205 ng/mL; and vitamin B12, n = 210 pg/mL. Anemia was defined as hemoglobin ≤13 g/dL (men) or ≤12 g/dL (women) and/or use of erythropoietin (EPO). Anemic patients (59.4%) had less sideremia (73.4 vs 81.2 μg/dL; P = .008), but no significant differences were observed for transferrin saturation index (25.9% vs 25.5%), ferritin (167 vs 171 ng/mL), iron insufficiency (26.5% vs 36.2%), pronounced ferropenia (20.4% vs 20.1%), folic acid (7.5 vs 6.6 ng/mL), or vitamin B12 (486 vs 530 pg/mL). Treatment with oral or intravenous iron was much more frequent in anemic patients (31.6% vs 9.9%; P < .001). The logistic regression analysis of factors associated with anemia revealed that renal function and the use of angiotensin-converting enzyme (ACE) inhibitors were significant but not the degree of iron deficiency. In conclusion, iron deficiency in renal transplant patients with chronic nephropathy is frequent and insufficiently treated. Although it may be an aggravating factor, it was not shown to be a determining factor for the presence or absence of anemia in the patients as a group.     

Recombinant human erythropoietin and autologous blood donation

Risks of transfusion are minimized with autologous blood. However, autologous donation programs require 2 to 5 weeks to yield only 2.2 units per patient. Recombinant human erythropoietin (r-HuEPO) has been shown to increase erythropoiesis. This study evaluated the effects of r-HuEPO on an aggressive autologous donation program. Twelve adult male baboons were randomized into two groups of six. All animals were studied three times per week for 5 weeks. A unit of blood was donated when on any study day the hematocrit was greater than 30%. Animals received intravenously either 750 units/kg of r-HuEPO (n = 6) or placebo (n = 6) on each study day. Iron dextran was given intravenously to replace 150% of shed iron. The r-HuEPO group had an earlier onset of reticulocytosis (2.7 vs 5.5 days, p less than 0.01) and donated 35% more blood (13.5 vs 10.0 units, p = 0.01) than the control group. No adverse reactions to r-HuEPO were observed. The data show that an aggressive autologous donation program can yield 10 units of blood over a 5-week period. Further, r-HuEPO increases that yield by an additional 35%. This aggressive autologous donation program with r-HuEPO may significantly reduce the need for homologous transfusion and its attendant risks.     

Anemia and chronic renal failure: a therapeutical approach by reduced glutathione parenteral administration.

Authors report on the effect of reduced glutathione parenterally administered on the anemic status in patients suffering from chronic renal failure and undergoing hemodialysis. Twenty patients were studied for 180 days and were divided into two age- and sex-matched groups. The first group (10 patients) received placebo, the second group (10 patients) received the treatment (1,200 mg of reduced glutathione). Reduced glutathione and placebo were given for 120 days in a randomized double-blind fashion and the following measurements were performed: red blood cells reduced and oxidized glutathione, plasma reduced and oxidized glutathione, hematocrit, hemoglobin, reticulocytes, serum iron, transferrin, indirect bilirubin, urea, creatinine, calcium, phosphate, parathyroid hormone and alkaline phosphatase. In the treated group, during the supplementation period, there was an increase in the levels of red blood cells and plasma reduced glutathione, hematocrit and hemoglobin and a concomitant decrease in plasma oxidized glutathione and reticulocytes with a maximum effect on the 120th day of therapy. In the placebo-treated group there were no significant variations of the parameters considered during the study period. When the therapy, on patients undergoing treatment, was terminated there was a drop in the analyzed parameters, which fell to pretreatment values at the subsequent controls. These findings seem to indicate that reduced glutathione could represent a useful drug in the treatment and management of anemia in patients affected by chronic renal failure.