Androgens potentiate the effects of erythropoietin in the treatment of anemia of end-stage renal disease

Since androgens may increase the sensitivity of the erythroid progenitors to erythropoietin, the present studies were designed to investigate the effect of administration of androgens on the actions of exogenous erythropoietin (EPO) in hemodialysis patients. Studies were performed in a group of 15 adult male hemodialysis patients. Seven patients were treated with EPO alone at a dose of 2,000 U intravenously (IV) three times a week. An additional group of eight patients was treated with 2,000 U of EPO three times a week and also received 100 mg of nandrolone decanoate intramuscularly (IM) each week. After 12 weeks of therapy, hematocrit values increased slightly in the group receiving EPO alone, from 25.3 +/- 0.8 to 27.4 +/- 1.5. In contrast, EPO in combination with nandrolone decanoate resulted in a greater increase in hematocrit values, from 24.4 +/- 1.4 to 32.9 +/- 1.8 (P less than 0.001). The results show that the groups receiving low-dose EPO alone had a poor erythropoietic response. In contrast, patients receiving androgen in addition to EPO had a significantly greater increase in hematocrit values with treatment. Transfusions were eliminated in both groups of patients. These data show that androgen therapy significantly augments the action of exogenous EPO such that lower doses of EPO are sufficient for an adequate hematopoietic response.     

A controlled trial of recombinant human erythropoietin and nandrolone decanoate in the treatment of anemia in patients on chronic hemodialysis.

We conducted a prospective, randomized study in chronic hemodialysis patients in order to determine whether the erythropoietic response to low dose recombinant human erythropoietin (rHuEpo) could be enhanced by administration with androgens. Patients received rHuEpo 40 U/kg intravenously three times weekly either alone (Group 1, n = 6) or with weekly intramuscular injection of 2 mg/kg nandrolone decanoate (Group 2, n = 6) for up to 16 weeks. Baseline hct, ferritin, N-terminal parathyroid hormone, and aluminum levels were similar. The mean weekly rate of rise in hct was 0.32 +/- 0.13% in Group 1 and 0.37 +/- 0.11% in Group 2, p = NS. Three of 6 patients in Group 1, but only 1 of 6 patients in Group 2, reached the target hct of 30% within 16 weeks. Two patients in Group 2 requested that the nandrolone decanoate be stopped prior to reaching target hct because of unacceptable side effects (acne). We conclude that many chronic hemodialysis patients appear to respond adequately to rHuEpo at the dose used in our study. Nandrolone decanoate does not enhance the response rate to this rHuEpo dose and is associated with significant side effects.     

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.     

Randomized prospective comparison between erythropoietin and androgens in CAPD patients

BACKGROUND: Anemia and malnutrition are significant complications in peritoneal dialysis (PD) patients. Previous studies in hemodialysis have shown that androgens are effective as therapy for anemia; however, this has not been tested in a randomized prospective trial in PD patients. Furthermore, the anabolic properties of androgens may exert additional benefits on the nutritional status in this population. METHODS: Twenty-seven stable male patients over 50 years who were under maintenance continuous ambulatory peritoneal dialysis (CAPD) therapy were randomized to receive recombinant human erythropoietin (rHuEPO; N = 14) or nandrolone decanoate (ND; 200 mg/week IM; N = 13) as therapy for anemia. The evolution of hematologic parameters and the impact on both nutritional anthorpometric and biochemical variables were evaluated after six months of treatment. RESULTS: Hemoglobin and hematocrit experienced similar increases in both groups: from 8.5 +/- 0.9 g/dL and 25.8 +/- 2.7% to 11.7 +/- 0.6 g/dL and 34.7 +/- 1.6% (P < 0.001) in patients receiving rHuEPO, and from 8.9 +/- 0.8 and 27 +/- 2.2% to 11.8 +/- 0.4 g/dL and 35.1 +/- 1.5% (P < 0.001) in subjects treated with ND. At the end of the study, out of the diverse nutritional variables included in this investigation, only weight and body mass index significantly increased in the rHuEPO group. Conversely, both anthropometric [weight, body mass index, triceps skinfold, mid-arm circumference (MAC) and mid-arm muscle circumference (MAMC)] and biochemical parameters (serum total proteins, albumin, prealbumin and transferrin) were significantly increased in patients treated with ND. In this group, serum urea nitrogen, urea net excretion and protein equivalent of nitrogen appearance significantly decreased. These facts, together with an increase in serum creatinine and no changes in dietary intake during the study, suggest a rise in muscle mass related to an anabolic effect of nandrolone decanoate. Interestingly, serum levels of insulin-like growth factor type 1 (IGF-1) increased in patients on the androgen group compared to subjects treated with rHuEPO. Moreover, there was a positive and significant correlation between the rise in IGF-1 concentrations and the increase in hemoglobin, hematocrit, MAC and MAMC. CONCLUSIONS: Androgens therapy improved the anemia in elderly male CAPD patients in a similar manner to that observed with rHuEPO. Furthermore, compared with rHuEPO, androgen administration was associated with beneficial effects on nutritional status. The mechanism of action of androgens on hematologic and nutritional parameters might be mediated, at least in part, by IGF-1.     

Recurrence of left ventricular hypertrophy following cessation of erythropoietin therapy

The high cardiac output state is considered a major factor for occurrence of left ventricular hypertrophy (LVH). Increased left ventricular mass is a powerful predictor of morbidity and mortality. We analyzed morphologic changes of the heart in dialysis patients during treatment with erythropoietin (EPO) and after cessation of therapy. Fourteen hemodialysis patients were treated with EPO for 1 year. They were above age 18, dialyzed 3 times per week, and with a hematocrit below 28 vol%. EPO was given subcutaneously, at a dose of 20 U/kg body weight 3 times per week, before each hemodialysis session. Anemia was corrected and hematocrit maintained between 30 and 35 vol%. When this part of the study was completed, EPO was stopped in all 14 patients. Echocardiography was performed three times: at baseline, at 12 months of therapy, and 1 year after EPO cessation. Mean hematocrit of the group at these 3 time intervals was 23.78 +/- 2.11 vol%; 33.14 +/- 1.95 vol%; and 25.93 +/- 5.23 vol%, respectively (mean +/- SD). The following echocardiographic changes occurred. End-diastolic volume decreased from 134.8 +/- 25.4 to 113.2 +/- 26.4 ml and increased back to 136.2 +/- 46.2 ml. Left ventricular mass decreased from 296.6 +/- 62.4 to 225.2 +/- 52.7 g and increased again to 311.7 +/- 106 g. Cardiac output decreased from 7,295.8 +/- 2,166.9 to 5,816.4 +/- 1,216.2 ml/min and increased to 6,803.2 +/- 1,646.5 ml/min. Total peripheral resistance increased from 1,360.8 +/- 428 to 1,691.3 +/- 326 and decreased again to 1,242.8 +/- 303.3 dyne x s/cm5. All these changes were significant. Mean arterial pressure increased from 114.7 +/- 13.9 to 119.3 +/- 13.8 mm Hg and decreased to 100.5 +/- 9.3 mm Hg. LVH could be affected severely by the degree of anemia in uremics and was reversible.     

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

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

Effects of nandrolone therapy on forearm bone mineral content in osteoporosis

Forearm bone mineral content (BMC) was measured sequentially on and off anabolic steroid therapy in 52 postmenopausal women with osteoporosis. The steroid used was nandrolone decanoate in a dose of 50 mg every two weeks by intramuscular injection. In 16 of the patients nandrolone was given first (for 6.2 +/- 0.6 months) followed by a control period (6.1 +/- 1.0 months) and in 36 there was an initial control period (9.5 +/- 1.1 months) followed by nandrolone (for 5.8 +/- 0.4 months). Any other therapy was continued unchanged during both treatment and control periods. There was a significant rise in BMC on nandrolone (p less than 0.001) and a nonsignificant fall in BMC off nandrolone. The difference between the rates of change on and off nandrolone was highly significant (+53 vs. -7 mg/cm/year; p less than 0.001).     

Cross-over study of fat-corrected forearm mineral content during nandrolone decanoate therapy for osteoporosis

We have previously reported an increase in forearm bone mineral content (BMC) during therapy for osteoporosis with the anabolic steroid, nandrolone decanoate. However, it has recently been claimed that part of this increase is spurious, due to a decrease in forearm fat during the treatment. We have therefore analyzed the data from a cross-over study of the effects of this agent on 70 osteoporotic women, using the fat correction procedure supplied by the manufacturer of the forearm densitometer. There was a significant rise (p less than 0.001) in the mean fat-corrected BMC (BMC[fc]) on nandrolone decanoate (50 mg intramuscularly every 2 or 3 weeks) and a non-significant fall in mean BMC[fc] off the drug. The mean time-weighted rate of change in the fat-corrected value was +29 +/- 5 mg/cm/year on nandrolone decanoate and -5 +/- 5 mg/cm/year off nandrolone decanoate (p less than 0.001). Nandrolone decanoate produces a significant gain in forearm mineral content even after allowing for changes in forearm fat content during therapy.     

Vitamin B(6) therapy does not improve hematocrit in hemodialysis patients supplemented with iron and erythropoietin

BACKGROUND/AIM: Pyridoxine deficiency may be the cause of failure to respond appropriately to iron and erythropoietin (EPO) administration in hemodialysis patients. METHOD: We studied 36 patients on chronic hemodialysis amply supplemented with iron and EPO, who failed to raise hematocrit levels >33%. Patients were divided into three equal groups and evaluated for 6 months as follows: Group A -- no additional therapy; group B -- supplemented with oral pyridoxine 50 mg/day, and group C received 100 mg/day pyridoxine orally. RESULTS: In all our patients, erythrocyte pyridoxine levels were initially within reference range for a healthy population and did not vary significantly during the study period. Likewise, ferritin levels and iron saturation values remained normal and constant. Hemoglobin and/or hematocrit levels remained practically unchanged in all three groups. CONCLUSIONS: The results indicate that in hemodialysis patients with normal pyridoxine status who, despite appropriate supplementation of iron and EPO, fail to reach optimal hematocrit levels, additional pyridoxine treatment does not produce any hematocrit elevation.     

Skeletal effects of erythropoietin in hemodialysis patients

AIMS: To assess the effects of erythropoietin (EPO) on bone metabolism in patients receiving chronic hemodialysis (HD). METHODS: Forty one patients were divided into two groups whether they required the administration of EPO to treat renal anemia or not. Serial measurements of predialysis blood samples and bone mineral density were performed prospectively over a year. RESULTS: The administration of EPO was associated with an increased serum creatinine (11.9 +/- 0.4 to 12.5 +/- 0.4 mg/dl, p < 0.05), insulin-like growth factor binding protein (3.0 +/- 0.2 to 3.4 +/- 0.2 micrograms/ml, p < 0.05) as well as decreased iron level (112 +/- 7 to 88 +/- 7 micrograms/dl, p < 0.005). Furthermore, in EPO-treated group, exogenous EPO doses correlated with the increments in 1,25-dihydroxy-vitamin D (r = 0.38, p < 0.05), intact osteocalcin (r = 0.42, p < 0.05) and bone alkali-phosphatase (r = 0.53, p < 0.005), but not intact parathyroid hormone (r = 0.09). Both metacarpal index (0.47 +/- 0.02 to 0.47 +/- 0.02) and the summation of gray scale/diameter (2.68 +/- 0.06 to 2.61 +/- 0.07 mmAl), bone mineral density parameters, remained unchanged. CONCLUSION: The present data provide evidence that EPO may modulate the production of 1,25-dihydroxy-vitamin D in HD patients. Furthermore, our findings suggest that EPO therapy activates insulin-like growth factor system in HD patients, possibly through its actions on metabolism.     

Dialysate iron therapy: infusion of soluble ferric pyrophosphate via the dialysate during hemodialysis

BACKGROUND: Soluble iron salts are toxic for parenteral administration because free iron catalyzes free radical generation. Pyrophosphate strongly complexes iron and enhances iron transport between transferrin, ferritin, and tissues. Hemodialysis patients need iron to replenish ongoing losses. We evaluated the short-term safety and efficacy of infusing soluble ferric pyrophosphate by dialysate. METHODS: Maintenance hemodialysis patients receiving erythropoietin were stabilized on regular doses of intravenous (i.v.) iron dextran after oral iron supplements were discontinued. During the treatment phase, 10 patients received ferric pyrophosphate via hemodialysis as monthly dialysate iron concentrations were progressively increased from 2, 4, 8, to 12 micrograms/dl and were then sustained for two additional months at 12 micrograms/dl (dialysate iron group); 11 control patients were continued on i.v. iron dextran (i.v. iron group). RESULTS: Hemoglobin, serum iron parameters, and the erythropoietin dose did not change significantly from month 0 to month 6, both within and between the two groups. The weekly dose of i.v. iron (mean +/- SD) needed to maintain iron balance during month 6 was 56 +/- 37 mg in the i.v. iron group compared with 10 +/- 23 mg in the dialysate iron group (P = 0.001). Intravenous iron was required by all 11 patients in the i.v. iron group compared with only 2 of the 10 patients receiving 12 micrograms/dl dialysate iron. The incidence of adverse effects was similar in both groups. CONCLUSIONS: Slow infusion of soluble iron pyrophosphate by hemodialysis may be a safe and effective alternative to the i.v. administration of colloidal iron dextran in maintenance hemodialysis patients.     

Intravenous iron treatment of renal anemia in children on hemodialysis

Treatment of anemia in children with end-stage renal disease (ESRD) has been greatly facilitated by the introduction of recombinant human erythropoietin (rHuEPO). A major limiting factor in the treatment of renal anemia is sufficient iron supplementation. Eight children (aged 10–17 years) receiving hemodialysis were treated with intravenous iron (1 mg/kg per week) for 3 months. Hemoglobin (Hb), hematocrit (Hct), and serum ferritin levels were measured regularly. The mean Hct increased from 25% to 30%, the mean Hb increased from 7.8 g/dl to 9.2 g/dl, and the mean ferritin level from 200 to 395 mg/dl. The mean EPO dosage could be tapered from 6,500 IU to 6,150 IU. No adverse side-effects were noted. Hence, in this uncontrolled study intravenous iron was an effective treatment for iron deficiency during rHuEPO therapy in children with ESRD on hemodialysis. Received: 30 October 1997 / Revised: 17 November 1998 / Accepted: 18 November 1998     

Nutritional effect of nandrolone decanoate in predialysis patients with chronic kidney disease.

OBJECTIVE: The study objective was to examine the nutritional effect of nandrolone decanoate, an androgen derivative, in predialysis patients with chronic kidney disease (CKD). DESIGN: This was a prospective and experimental study. SETTING: The study was performed at the institutional level of clinical care. PATIENTS: Twenty-nine predialysis patients with CKD, with a glomerular filtration rate between 5 and 30 mL/min and moderate to severe malnutrition, were included and randomly divided into control (n = 13) and nandrolone decanoate (NAN, n = 16) groups. INTERVENTION: Patients in the control group received optimally conventional treatment of CKD. Patients in the NAN group, in addition to the conventional treatment, were intramuscularly injected with nandrolone decanoate at the dose of 100 mg per for 3 months. MAIN OUTCOME MEASURE: Nutritional markers, including lean body mass (LBM), normalized protein catabolic rate, serum albumin, and lipids, were determined at baseline and 3-month periods. RESULTS: Baseline parameters in both groups were not different. After 3 months, the patients in the NAN group had increased LBM (P < .01) and decreased serum albumin levels (P < .05), but no changes in the values of normalized protein catabolic rate, serum lipids, hematocrit, and glomerular filtration rate. No alterations in all parameters were identified in the control group. Changes in LBM in the NAN group were significantly higher than in the control group (P < .05). Minor adverse effects were observed in a few patients in the NAN group. CONCLUSION: Nandrolone decanoate expresses an anabolic effect on LBM without altering the renal function and thus would provide nutritional benefit in predialysis patients with CKD.     

Impact of nocturnal home hemodialysis on anemia management in patients with end-stage renal disease

AIM: Anemia is adversely associated with poor uremia control and is an established cardiovascular risk factor in patients with end-stage renal disease (ESRD). Nocturnal home hemodialysis (NHD) is a novel form of renal replacement therapy that offers superior clearance of uremic solutes and improvements in several cardiovascular outcome parameters. We conducted a retrospective cohort study to test the hypotheses that augmenting the dose and frequency of dialysis by NHD would improve hemoglobin (Hb) concentrations and decrease requirement of erythropoietin (EPO) in ESRD patients. METHODS: In 63 patients (mean age: 46 +/- 2 years) receiving NHD (mean duration: 2.1 +/- 0.2 years), Hb, EPO dose, iron saturation, ferritin were determined before and at six monthly repeated intervals after conversion to NHD. For comparison, 32 ESRD patients (mean age: 57 +/- 3 years) who remained on self-care conventional hemodialysis (CHD) were also studied. RESULTS: There were no differences in baseline Hb concentrations, iron saturation, ferritin, or EPO dose between the two cohorts. After transfer from CHD to NHD, there were significant improvements in Hb concentrations (from 115 +/- 2 to 122 +/- 3 (6 months) and 124 +/- 2 (12 months) g/l, p = 0.03) despite a fall in EPO requirement (from 10,400 +/- 1400 to 8500 +/- 1300 (6 months) and 7600 +/- 1100 (12 months) U/week, p = 0.03). In contrast, CHD cohort had no change in EPO requirement (from 8300 +/- 1100 to 8100 +/- 1300 (6 months) and 8600 +/- 1000 (12 months) U/week, p > 0.05) or Hb concentrations (from 110 +/- 2 to 115 +/- 3 (6 months) and 115 +/- 2 (12 months), p > 0.05). There was a higher percentage of ESRD patients who did not require EPO in the NHD cohort (24% vs. 9.4%, p = 0.01). Lower Hb concentrations were noted in the CHD cohort despite higher iron saturation (0.25 +/- 0.01 (NHD) vs. 0.33 +/- 0.02 (CHD), p = 0.02) at the end of follow-up. CONCLUSIONS: Enhancing uremic clearance by NHD resulted in a rise in Hb and a fall in EPO requirement.     

Effect of erythropoietin on ischemia tolerance in anemic hemodialysis patients with confirmed coronary artery disease.

From a total of 81 patients on maintenance hemodialysis who underwent coronary angiography, 8 patients fulfilled the criteria: significant coronary artery disease, hematocrit less than 27%, reproducible (ECG) positive treadmill test, no disturbance of repolarization in ECG at rest. Exercise stress testing was performed at a hematocrit of 25 +/- 2% and following erythropoietin therapy at a hematocrit of 34 +/- 0.5%. Symptom-limited exercise performance increased in all patients (1.10 +/- 0.3 W/kg b.w. vs. 1.44 +/- 0.31 W/kg b.w., p less than 0.01) as well as exercise duration (489 vs. 362 s, p +/- 0.01). ST segment depression during maximal exercise was reduced from a mean of 2.1 to 0.4 mm (p less than 0.01). It is concluded that amelioration of renal anemia by erythropoietin in dialysis patients with significant coronary artery disease reduces exercise-induced myocardial ischemia.     

Recombinant human erythropoietin dosage in children undergoing hemodialysis and continuous ambulatory peritoneal dialysis

The efficacy of erythropoietin (EPO) in 11 children on hemodialysis (HD) and 8 on continuous ambulatory peritoneal dialysis (CAPD) (mean age 11.8 years) was compared. The initial EPO dose was 50 U/kg s.c. once a week; the time of observation was 24 weeks. In the CAPD group, the mean hemoglobin (Hb) level increased from 7.7±0.2 to 11.2±0.6 g/dl (P< 0.001) and hematocrit (Hct) from 22.3±1.0 to 32.6±1.4% (P<0.001), while in the HD group the mean Hb rose from 7.7±0.6 to 9.3±0.8 g/dl (P<0.001) and mean Hct from 22.7±2.3 to 27.6±2.8% (P<0.001) after 12 weeks of observation. An increase in Hb to over 10 g/dl was obtained in 87.5% of children on CAPD but in only 10% on HD after 8 weeks of EPO treatment. After 12 weeks of treatment, all children on CAPD had the target Hb level of more than 10 g/dl, while 7 children on HD required increased doses of EPO (100 U/kg per week). We conclude that the EPO dose of 50 U/kg given s.c. once a week is effective for children with anemia on CAPD but is insufficient for children on HD. Received June 17, 1996; received in revised form January 24, 1997; accepted March 4, 1997     

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.     

Correction of Hemodialysis Anemia is Associated with Significant Increase in Serum Concentration of IGF-I in Patients Treated with Erythropoietin: A Randomized Controlled Study

Background: The effect of erythropoietin (EPO) therapy on the serum level of IGF-I among hemodialysis patients is debated. The aim of this study is to study the effect of EPO on the erythropoiesis and the change of serum level of IGF-I among adequately hemodialyzed patients. Patients and methods: Forty patients (25 males and 15 females) who had an adequate level of both hemodialysis and nutrition were randomly allocated into two equal groups. Besides parenteral iron, the first group of patients received a conventional EPO dose regimen of 2000 U subcutaneously (SC) thrice weekly, the second group of patients remained on parenteral iron and ranked as a control group. The patients were subjected to thorough laboratory investigations. IGF-I concentration was measured before and at the end of the study. Results. Both groups were comparable in their demographic, laboratory, dialysis level, and nutritional status. There was no statistical differences in hemoglobin, hematocrit %, iron store indices and serum level of IGF-I at the study entry. We found a significant rise of both hemoglobin and hematocrit as well as IGF-I serum level in the EPO group at the end of the study in comparison to their values at the starting points in comparison to the control group (P< 0.001). Conclusion: Erythropoietin therapy enhances erythropoiesis and modulates the serum concentration of IGF-I.     

Comparison of intravenous ascorbic acid versus intravenous iron for functional iron deficiency in hemodialysis patients

The effect of intravenous ascorbic acid was compared with that of intravenous iron in the treatment of functional iron deficiency, as defined as serum ferritin levels over 300 ng/ml and serum iron levels below 50 microg/dl, in patients on chronic hemodialysis. Thirteen patients on chronic hemodialysis with functional iron deficiency received intravenous injections of ascorbic acid, 100 mg, three times a week, after hemodialysis. The therapy was continued until serum ferritin decreased to below 300 ng/ml (3 months at the maximum). The iron and control group were composed of patients who had serum iron levels below 50 microg/dl within 3 months after serum ferritin rose to over 300 ng/ml. Seven patients with the iron group received more than a total of 10 intravenous injections of saccharated ferric oxide (40 mg/dose) after hemodialysis, and seven patients with the control group received no iron preparation during the 3 months. In the ascorbic acid group, while hemoglobin did not change from 10.9 +/- 0.5 g/dl (mean +/- SE) during the three-month period, serum iron increased significantly from 37 +/- 4 microg/dl to 49 +/- 4 microg/dl after one month (p<0.01), and remained elevated until the end of the three-month period. Serum ferritin decreased significantly from 607 +/- 118 ng/ml to 354 +/- 30 ng/ml after 3 months (p<0.01). In the iron group, hemoglobin and serum iron increased significantly from the respective pre-treatment levels during the 2-month period, and serum ferritin rose significantly after 3 months. In the control group, hemoglobin, serum iron and ferritin levels decreased significantly from the respective pre-treatment levels during the 3 months. The recombinant erythropoietin dose remained stable for three months in the ascorbic acid, iron, and control groups, respectively. These results suggest that in hemodialysis patients with a functional iron deficiency, treatment with intravenous ascorbic acid can prevent iron overload due to treatment with intravenous iron, and provide a useful adjuvant means of maintaining hemoglobin and serum iron levels.