The effects of nandrolone decanoate on nutritional parameters in hemodialysis patients

AIMS: Malnutrition with hypoalbuminemia is an independent predictor of mortality in end-stage renal disease patients. Anabolic steroids reduce protein catabolism and therefore may improve nutritional parameters. This study was undertaken to determine the effects of the anabolic steroid nandrolone decanoate on the nutritional status of hemodialysis patients. Secondary endpoints were to examine the effects of androgen therapy on hematocrit and erythropoietin (EPO) dose. PATIENTS AND METHODS: Medical records of chronic hemodialysis patients who received nandrolone decanoate for greater than 30 days were reviewed. Data collected included: demographics, dose, frequency, duration of treatment and cumulative dose of nandrolone. Baseline albumin, transferrin, dry weight, phosphorus, creatinine, hematocrit and erythropoietin dose were obtained for comparison with values after treatment. RESULTS: Of the 9 patients evaluated (mean +/- SD: age 55+/-28 years, 4/9 male), 2 patients received nandrolone doses of 25 mg intramuscularly (i.m.) every week, while the remaining 7 patients received 100 mg i.m. every 2 weeks. The mean +/- SD duration of treatment was 96+/-43 days, with a mean +/- SD cumulative dose of 656+/-371 mg. The mean +/- SD baseline albumin was 2.9+/-0.6 mg/dl which increased to 3.3+/-0.4 mg/dl after treatment (p = 0.045). Dry weight increased from a mean +/- SD of 64.4+/-11.7 kg to 66.0+/-10.9 kg after nandrolone therapy (p = 0.028). Mean +/- SD hematocrit at baseline was 28.2+/-4.5% and increased to 33.2+/-5.1% (p = 0.033). The dose of EPO was reduced in 4 patients (44%) during nandrolone therapy. CONCLUSIONS: Nandrolone significantly improved markers of nutritional status in our hemodialysis patients. This therapy may also enhance the hematopoietic effects of EPO.     

Intravenous ascorbic acid administration for erythropoietin-hyporesponsive anemia in iron loaded hemodialysis patients

Intravenous ascorbic acid administration (IVAA) could override recombinant human erythropoietin (rHuEPO) resistance in hemodialysis patients with iron overload. We investigated the hematopoietic response to IVAA in iron-overloaded hemodialysis patients. We included 36 patients whose ferritin levels were higher than 500 microg/L and who needed more than 100 U/kg/week of rHuEPO. The study included an initial phase (500 mg IVAA twice weekly was administered to all of the patients for 8 weeks) and a maintenance phase (patient groups were formed; Group 1 received IVAA 500 mg/week for 8 weeks and Group 2 received no therapy). We observed a significant increase in hematocrit and transferrin saturation and a decrease in the percentage of hypochromic red cells and ferritin levels at the end of the initial phase. The total weekly-required rHuEpo dose and rHuEpo/hemoglobin also fell significantly after the initial phase. The response remained stable in patient groups during the maintenance phase. In 6 nonresponders, the hypochromic red cells were <10%. In conclusion, IVAA effectively overrides rHuEPO resistance in iron-overloaded hemodialysis patients.     

Effects of resistance exercise training and nandrolone decanoate on body composition and muscle function among patients who receive hemodialysis: A randomized, controlled trial

Patients who are on hemodialysis commonly experience muscle wasting and weakness, which have a negative effect on physical functioning and quality of life. The objective of this study was to determine whether anabolic steroid administration and resistance exercise training induce anabolic effects among patients who receive maintenance hemodialysis. A randomized 2 x 2 factorial trial of anabolic steroid administration and resistance exercise training was conducted in 79 patients who were receiving maintenance hemodialysis at University of California, San Francisco-affiliated dialysis units. Interventions included double-blinded weekly nandrolone decanoate (100 mg for women; 200 mg for men) or placebo injections and lower extremity resistance exercise training for 12 wk during hemodialysis sessions three times per week using ankle weights. Primary outcomes included change in lean body mass (LBM) measured by dual-energy x-ray absorptiometry, quadriceps muscle cross-sectional area measured by magnetic resonance imaging, and knee extensor muscle strength. Secondary outcomes included changes in physical performance, self-reported physical functioning, and physical activity. Sixty-eight patients completed the study. Patients who received nandrolone decanoate increased their LBM by 3.1 +/- 2.2 kg (P < 0.0001). Exercise did not result in a significant increase in LBM. Quadriceps muscle cross-sectional area increased in patients who were assigned to exercise (P = 0.01) and to nandrolone (P < 0.0001) in an additive manner. Patients who exercised increased their strength in a training-specific fashion, and exercise was associated with an improvement in self-reported physical functioning (P = 0.04 compared with nonexercising groups). Nandrolone decanoate and resistance exercise produced anabolic effects among patients who were on hemodialysis. Further studies are needed to determine whether these interventions improve survival.     

Subcutaneous recombinant human erythropoietin in chronic renal allograft dysfunction

We investigated the efficacy and safety of subcutaneous recombinant human erythropoietin (rHuEpo) in 25 children with chronic renal allograft dysfunction (13 girls, 12 boys, mean age 15.8±4.2 years) for a treatment period of 9 – 162 (median 43) weeks. rHuEpo was started once weekly at a dose of 105±25 U/kg per week in 16 children, twice weekly at a dose of 175±70 U/kg per week in 6 children, and three times weekly at a dose of 270±28 U/kg per week in 3 children. The hematocrit increased in 21 children from 23.2%±3.1% to 33%±3.1% within 7.2±4.9 weeks at a mean rate of 1.98%/week. The hematocrit increase and rHuEpo starting dose were linearly related (delta hematocrit/week = 0.8+0.08 U/kg per week, r = 0.44, P <0.05). The maintenance dose was 74±23 (43 – 114) U/kg per week. Four children failed to reach the target hematocrit, most likely due to noncompliance. Seventeen recurrences of anemia (“anemic episodes”) during rHuEpo therapy were identified in 12 children, mostly associated with acute or insidious deteriorations in graft function. There was no acceleration of progression of graft dysfunction with rHuEpo treatment. We conclude that subcutaneous rHuEpo at a single weekly dose of 100 IU/kg per week is highly effective in children with chronic graft dysfunction. Children who appear to be rHuEpo resistant or experience rHuEpo-resistant episodes should be assessed for noncompliance, changes in graft function since the last dosage adjustment, and blood loss, such as seen in dysfunctional uterine bleeding in adolescent girls. Received February 13, 1997; received in revised form and accepted June 26, 1997     

A comparison between epoetin omega and epoetin alfa in the correction of anemia in hemodialysis patients: a prospective, controlled crossover study

The objective of the study was to evaluate and compare the safety and effectiveness of epoetin omega (produced in baby hamster kidney cells) and epoetin alfa (produced in Chinese hamster ovary cells) in sustaining the correction of anemia in maintenance hemodialysis patients. The study, a prospective and controlled crossover, was completed in 38 stable patients treated with both epoetins for 24 weeks. Group A (17 patients) started with epoetin omega, and Group B (21 patients) started with epoetin alfa. After 24 weeks, a 4 week crossover (wash out) was made: Group A was switched to epoetin alfa and group B to epoetin omega for the next test period of 24 weeks. Both epoetins were administered subcutaneously after each dialysis. Doses were adjusted with the aim of maintaining a target hemoglobin level between 10 and 12 g/dl (hematocrit 30% to 35%). The mean weekly dose of epoetin omega/kg body weight (BW) was 67 +/- 43 U. The mean weekly dose of epoetin alfa/kg BW was 86 +/- 53 U. The average of all mean values of hemoglobin (Hb) during treatment with epoetin omega was 11.4 +/- 0.7 g/dl (hematocrit 34 +/- 2%), and during treatment with epoetin alfa was 11.3 +/- 0.7 g/dl (hematocrit 33 +/- 2%) (not significant). Thromboses of vascular access occurred in 3 patients during an epoetin omega treatment and in 3 patients during epoetin alfa treatment. At the site of injection, only 1 patient described a mild pain when treated with epoetin omega and only 6 patients when treated with epoetin alfa. In conclusion, both epoetin omega and epoetin alfa were effective in correcting the anemia of all studied patients. However, lower doses of epoetin omega were needed to maintain the same target hemoglobin level. No serious side effects with either epoetin were noted. The authors believe that additional comparisons of different epoetin preparations should be performed and will provide better insight into their biological activity and clinical responsiveness.     

The effects of ACE inhibitor treatment and ACE gene polymorphism on erythropoiesis in chronic hemodialysis patients

Aggravation of anemia in chronic renal failure patients by angiotensin-converting enzyme inhibitors (ACEIs) has been attributed to the inhibition of angiotensin II which facilitates erythropoietin(Epo) production. This study was aimed at evaluating whether ACEIs aggravate anemia in maintenance hemodialysis patients and to investigate the influence of ACE gene polymorphism on erythropoiesis in these patients. Ninety-one hemodialysis patients were divided into 2 groups, based on whether or not they were administered ACEIs, into the ACEI group(n = 24) and the non-ACEI group(n = 67), and comparisons were made of the doses of recombinant human Epo(rHuEpo) administered, the hematocrit(Hct) and the plasma Epo concentrations. Among the patients in the non-ACEI group, only 17 did not receive rHuEpo, while all of the patients in the ACEI group received rHuEpo. The average dose of rHuEpo was 102.7 +/- 45.4 IU/kg/week in the ACEI group and 57.8 +/- 55 IU/kg/week in the non-ACEI group and the difference between the two groups was statistically significant. A statistically significant difference in the Hct was also observed between the two groups: the mean Hct in the ACEI group was 28.7 +/- 2.9% while that in the non-ACEI group was 31.1 +/- 3.7%. The plasma Epo concentrations were significantly lower in the ACEI group than in the non-ACEI group. No significant differences in the rHuEpo dose and Hct were observed between the three ACE genotype classes in either the ACEI or the non-ACEI group, however, there was a significant difference among the three genotypes in the non-ACEI group in regard to the plasma Epo concentrations; patients with the DD genotype had higher concentrations than those with the DI or II genotypes. These data suggest that anemia in maintenance hemodialysis patients is worsened by ACEIs as a result of the suppression of Epo production. Although it has been suggested that the endogenous Epo concentrations in maintenance hemodialysis patients are associated with ACE gene polymorphism, no significant influence of the ACE genotype on the rHuEpo dose or Hct was evident. Therefore, it is possible that exacerbation of anemia by ACEIs in the patients receiving rHuEpo is a result of an inhibited bone marrow response to Epo.     

The prevalence of insulin resistance and its relationship between anemia, secondary hyperparathyroidism, inflammation, and cardiac parameters in chronic hemodialysis patients

BACKGROUND: Insulin resistance (IR) frequently accompanies end-stage renal disease (ESRD). There is a positive correlation between IR and cardiovascular pathologies that plays a role in mortality and morbidity on patients with ESRD. We aim to research the prevalence and evaluability of homeostasis model assessment-insulin resistance (HOMA-IR) in hemodialysis (HD) patients and also to evaluate the relationship of this value with various clinical parameters. MATERIAL AND METHODS: 57 ESRD patients, regularly undergoing HD were enrolled in the study. Obese patients (BMI > 25 kg/m2) and ESRD patients with diabetic etiology were excluded. Twenty-nine patients were men (50.9%), and 28 patients were women (48.1%); the mean age was 45.9 +/- 13.6 years. Results were recorded after evaluated by HOMA-IR. In addition to calculating the HOMA index, anthropometrical parameters, plasma levels of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), hematocrit (hct), parathyroid hormone (PTH), calcium (Ca), phosphorus (P), C-reactive protein (CRP), fasting glucose, and insulin plasma levels were measured by standard methods in all subjects. The systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure were recorded, and left ventricle posterior wall thickness was measured by echocardiography. All patients completed the study. The minimum HOMA-IR value was 0.11, maximum value was 5.18, and the cut-off point was 1.23. According to this value, the patients were classified into two groups: HOMA-IR positive that were equal or higher than 1.23 (group 1), and HOMA-IR negative that were under this value (group 2). RESULTS: We established that 18 of 57 (31.6%) patients were HOMA-IR positive and 39 of 57 (68.4%) patients were negative. In group 2, hct levels were higher than in group 1 and the weekly requiring dose of rHuEpo was significantly low in group 2 compared with group 1 (p < 0.05). Interestingly, the Ca x P products (> or =55 mg/dL) were significantly higher in group 2 than in group 1 (p < 0.05). There was not any significant correlation between HOMA-IR and anthropometrics measurements, hemodialysis adequacy, plasma PTH level, cardiac parameters, and inflammation markers. We established the prevalence of IR as 31.6% in our HD patients' cohort. CONCLUSIONS: There was a positive correlation between low HOMA-IR value with target hct levels and administration of the rHuEpo. Because insulin resistance is an independent risk factor of cardiovascular mortality in ESRD patients, it was accepted that being able to correct the insulin resistance could be a novel therapeutic approach in this cohort.     

Suppression of the renin-angiotensin-aldosterone axis with erythropoietin therapy by a negative feedback loop.

To investigate the pathophysiology of hypertension in patients receiving recombinant human erythropoietin (rHuEpo) we studied its effects on the renin-aldosterone axis of chronic haemodialysis (HD) patients not receiving antihypertensive drugs. Nine severely anaemic normotensive HD patients received rHuEpo 50 U/kg bodyweight, thrice weekly after each HD. The dose was increased by 25 U/kg bodyweight every 4 weeks to a maximum of 100 U/kg or until an increase of Hb or Hct of 2 g/dl or 7% was achieved. Blood samples were taken after 30 min supine rest and while seated 10 min later after gentle ambulation. Results expressed as mean +/- SEM: therapy in normotensive HD patients by a negative feedback loop, before the development of hypertension.     

Aluminium interference in the treatment of haemodialysis patients with recombinant human erythropoietin

In nine chronic haemodialysis patients a desferrioxamine (DFO) load test (40 mg/kg body-weight) was performed 1 year after the beginning of treatment with recombinant human erythropoietin (rHuEpo). The patients were then divided into two groups. Group A comprised five patients with a greater mean aluminium (204 +/- 28 micrograms/l) than the four patients in group B. Group A was given a mean dose of 25.8 g (range 14-39 g) of DFO over 6 months. Group B (aluminium values 112 +/- 36 micrograms/l) was never treated with DFO. During the period of observation, plasma iron, serum ferritin and transferrin, as well as iron supplementation, did not differ between the groups. After DFO treatment a second DFO load test was performed. The mean predialysis aluminium value was significantly reduced in group A (204 +/- 28 vs 111 +/- 72 micrograms/l; P less than 0.05), while remaining unchanged in group B (112 +/- 36 vs 140 +/- 39 micrograms/l; P = ns). In both groups, the doses of rHuEpo necessary to maintain the same haemoglobin values decreased with time, but reduced significantly only in group A (298 +/- 105 vs 110 +/- 61 mu/kg per week; delta -63%; P less than 0.01). Thus, aluminium interferes with the response to rHuEpo in haemodialysis patients, and the correction of aluminium overload with DFO can allow a considerable sparing of rHuEpo.     

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.     

The evaluation of postdialysis L-carnitine administration and its effect on weekly requiring doses of rHuEPO in hemodialysis patients

BACKGROUND: In this study, our aim was to evaluate the effect of postdialysis administration of parenteral L-carnitine supplementations on hematological parameters and also on weekly requiring dose of the recombinant human erythropoietine (rHuEPO) in hemodialysis (HD) patients. MATERIAL AND METHODS: The stable 34 patients (17 male, 17 female) were enrolled in the study who were on rHuEPO therapy and a regular maintenance HD program at 5 h, three times a week with bicarbonate dialysate and with biocompatible membranes in HD Center of Medical Faculty Hospital in University of Dicle. rHuEPO was administered subcutanously at 80-120 U/kg/week. The patients were divided into two groups: Group 1, rHuEPO therapy (n=17) and Group 2, rHuEPO therapy + L-carnitine (n=17). L-carnitine (L-carnitine ampul, Santa Farma) 1 g was injected postdialysis intravenously via venous route of the dialytic set, three times a week. The patient's hemoglobin (Hgb), hematocrit (Hct), serum iron (Fe(+2)), total iron-binding capacity (TIBC), transferrin saturation index (TSI), and serum ferritin (Fer) levels were followed during the 16-week period. The weekly requiring doses of rHuEPO and hematological parameters of patients were recorded at the beginning of the study, at 8 weeks, and at 16 weeks of the study period. RESULTS: In group 1 (n=17, 13 female, four male), the mean age was 38.8 +/- 12.1 years, mean period time on HD therapy was 18.1 +/- 14.9 months, and mean Kt/V value was 1.48 +/- 0.28. In group 2 (n=17, 13 male, four female), the mean age was 48.1 +/- 15.4 years, mean period time on HD therapy was 34.4 +/- 23.0 months, and mean Kt/V value was 1.29 +/- 0.20. The hematological parameters of the groups were found as follows: in group 1, Hgb: 7.9-10.8 g/dl, Hct: 25.3-32.5%; in group 2, Hgb: 10.2-11.8 g/dl, Hct: 30.6-35.4%, respectively (p < 0.05). The target Hgb/Hct values were achieved at the end of the study in both groups. Both groups were the same according to their serum Fe(+2) markers (p > 0.05). But unlike serum Fe(+2) markers, there were significant differences on weekly requiring doses of rHuEPO therapy between groups. While in group 1, the mean weekly requiring dose of rHuEPO was 6529 U/week (120 U/kg/ week) at the beginning of the study, and maintenance weekly requiring dose of rHuEPO was 3588 U/week (66 U/kg/week) at the end of the study, in group 2, they were 4882 U/week (80 U/ kg/week), and 1705 U/week (28 U/kg/week), respectively. According to these values, the total reduction in weekly requiring dose of rHuEPO was 45% in group 1, and 65% in group 2; the net gain was 20% in group 2 (p < 0.05). CONCLUSIONS: If other factors related to anemia are excluded, the postdialysis parenteral L-carnitine therapy can be considered in selected stable patients, which may improve anemia and may reduce the weekly requiring dose of the rHuEPO and also be cost-effective.     

Safety and efficacy of erythropoietin in children with chronic renal failure

 A prospective randomized study of the use of recombinant human erythropoietin (rHuEPO) in children with chronic renal disease was conducted to assess dosing requirements and side effects. Forty-four children with chronic renal failure, aged 4 months to 21 years, were studied. Twenty-five patients were pre dialysis, 10 on peritoneal dialysis, and 9 on hemodialysis. Patients received either 150 U/kg per week or 450 U/kg per week divided thrice weekly of rHuEPO for 12 weeks or until target hemoglobin (Hb) was attained. Dose was then adjusted to maintain a normal Hb. Eighty-two percent of patients reached target Hb by 7.9±5.6 weeks (mean±SD); 95% of patients in the high-dose group and 66% in the low-dose group reached target Hb within 12 weeks. The overall median rHuEPO dose at target Hb was 150 U/kg per week. Hemodialysis patients tended to require more rHuEPO to maintain a normal Hb (median 250 U/kg per week). Transfusion requirements and panel-reactive antibody levels decreased during the 12 weeks. Iron deficiency and/or hypertension occurred in 30% of children. In conclusion, rHuEPO at 150 U/kg per week is safe and effective in treating anemia in children with chronic renal disease. Received: 12 March 1998 / Revised: 24 June 1998 / Accepted: 6 July 1998     

Correction of anaemia with darbepoetin alfa in patients with chronic kidney disease receiving dialysis.

BACKGROUND: Darbepoetin alfa is a new recombinant erythropoietic protein with a 3-fold longer half-life than recombinant human erythropoietin (rHuEpo). The optimal starting dose and frequency of administration of darbepoetin alfa were investigated for treating renal anaemia in dialysis patients. METHODS: Two multicentre, sequential dose-escalation studies examined the i.v. route of administration of darbepoetin alfa in haemodialysis patients (n=75) and the s.c. route in peritoneal dialysis patients (n=47). Patients were randomized to receive darbepoetin alfa at doses ranging from 0.075 to 0.75 microg/kg/week administered as either a once weekly or a three-times weekly injection. Patients achieving the primary endpoint of a > or = 1 g/dl increase in haemoglobin after 4 weeks continued darbepoetin alfa for up to 52 weeks. Safety was assessed by adverse event reports, changes in laboratory values and vital signs, and antibody screening. RESULTS: Darbepoetin alfa produced dose-related increases in haemoglobin over the first 4 weeks of treatment in both studies. Two dose levels (0.45 and 0.75 microg/kg/week) increased the haemoglobin by > or = 1 g/dl in 60-80% of patients, and no difference between once weekly and three-times weekly dosing was apparent. For patients who continued treatment up to 52 weeks, haemoglobin was maintained between 10 and 13 g/dl from mean baseline values of 8.4 and 8.7 g/dl. The adverse event profile was similar to that associated with rHuEpo therapy, and no antibodies to darbepoetin alfa were detected. CONCLUSIONS: Darbepoetin alfa is safe and effective for the treatment of anaemia in dialysis patients. The optimal weekly starting dose is 0.45-0.75 microg/kg and once weekly dosing is possible for both the s.c. and i.v. routes of administration.     

Early effects of parathyroidectomy on erythropoietin production in secondary hyperparathyroidism

BACKGROUND: Secondary hyperparathyroidism (2-HPT) has an adverse effect on renal anemia and may cause a hyporesponsiveness to recombinant human erythropoietin (rHuEpo) in patients with chronic renal failure. The early effects of parathyroidectomy (PTx) on renal anemia, erythropoietin production, and nutritional state were examined. METHODS: Twenty-nine patients under hemodialysis therapy received a PTx for 2-HPT. They were prospectively studied regarding hematological parameters, rHuEpo use, plasma erythropoietin levels, and nutritional condition until 12 months after PTx. RESULTS: The hemoglobin level showed a significant increase from 3 months after PTx (10.2% +/- 1.5% to 11.2% +/- 1.3%; P <0.01), associated with a consistent increase of the reticulocyte count. These changes lasted until 12 months after PTx. The plasma erythropoietin level showed a gradual increase of up to about 5 times the level of the preoperative value, until 12 months after PTx (22.6 +/- 10.1 to 106.3 +/- 112.1 mU/mL; P <0.001). The weekly dose of rHuEpo administration decreased after 3 months. The serum levels of albumin and total protein also significantly and gradually improved until 12 months after PTx. CONCLUSIONS: PTx caused a significant early improvement in renal anemia in patients with secondary hyperparathyroidism. This effect may be caused by an enhanced erythropoietin production and may also be partially due to the improved nutritional state after PTx.     

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.     

The required dose of erythropoietin during renal anaemia treatment is related to the degree of impairment in erythrocyte deformability

Background: Renal anaemia is rapidly corrected by recombinant human erythropoietin (rHuEpo) therapy, but the dose required varies greatly. Since impaired erythrocyte deformability may be one factor contributing to the development of renal anaemia, the interrelationship between that variable and the rHuEpo requirement was examined. Methods: Twenty-five patients treated with hemodialysis and rHuEpo for at least 6 months were included in the study. The Hb value had been stable and the rHuEpo dose unchanged the last two months. Using a rotational viscometer, the fluidity of erythrocytes, separated from plasma and re-suspended in isotonic buffered saline to a standardized haematocrit, was taken as a measure of erythrocyte deformability. Results: The average weekly dose of s.c. epoetin alpha was 186±93 U/kg body weight (range 56-370). The dose was correlated to the reticulocyte fraction (R-0.69, P=0.0001). When the rHuEpo dose was used as dependent variable and blood haemoglobin concentration, serum (S) albumin, S ferritin, S aluminium, S PTH, S urea, Kt/V/week, erythrocyte fluidity, and plasma viscosity were used as independent variables in a stepwise multiple regression analysis, only erythrocyte fluidity remained significantly negatively correlated to the rHuEpo dose (R=0.5, P=0.01). Despite a tendency towards higher doses of rHuEpo in patients with a C-reactive protein concentration exceeding 20 mg/l, the Hb was lower in these patients. Conclusions: We conclude that the interindividual differences in bone marrow response to rHuEpo were small in these patients. Impaired erythrocyte deformability and inflammation seem to be factors associated with increased rHuEpo requirement.     

The role of aluminium and parathyroid hormone in erythropoietin resistance in haemodialysis patients

Recombinant human erythropoietin (rHuEpo) is an effective therapy for anaemia in most patients with end-stage renal disease (ESRD). However, there remain a minority of patients with ESRD who are resistant to the effects of rHuEpo. The present study examined the role of aluminium overload and hyperparathyroidism of the biological effects of rHuEpo. Twenty-two patients aged 26-74 (mean 53 +/- SD 15.5) received rHuEpo 50-200 U/kg per week for 16.5 +/- 8.0 months (range 3-27). Haemoglobin was maintained at 11.5-13.0 g/dl by appropriate dose adjustment. Iron supplements were provided to maintain serum ferritin greater than 200 ng/ml. The mean time to rHuEpo response (Hb greater than 2 g/dl over baseline) was 6.1 +/- 2.6 weeks. Mean pretreatment serum aluminium correlated with time to Hb response (r = 0.48; P less than 0.05) and pretreatment mean corpuscular volume (r = 0.43; P less than 0.05) but not with eventual rHuEpo maintenance dose. PTH did not correlate with either Hb response or eventual maintenance rHuEpo dose. In summary, elevated serum aluminium concentrations were associated with an initial resistance to the biological effects of rHuEpo but had no effect on long-term dose requirements. In contrast, no impact of PTH on either immediate or long-term rHuEpo dose was evident.     

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).