Nutritional anaemia in pregnant coloured women in Johannesburg

A nutritional anaemia survey was carried out in 224 pregnant coloured first-time attenders at Coronation Hospital antenatal clinic in Johannesburg during the second quarter of 1986. None had received any form of nutritional supplementation during pregnancy. Haemoglobin concentrations less than 11 g/dl were present in 18.9% of women in the third trimester of pregnancy, while 64% had a saturation of transferrin value of less than 16% and 68% a serum ferritin level less than 12 micrograms/l. Calculations suggested that mean iron stores in the first trimester were 228 mg, with 37.5% of women having absent stores. Comparable figures in the second and third trimesters were 74 mg and -92 mg respectively. The fact that many were iron deficient in the first trimester indicates a high frequency of iron deficiency in non-pregnant women in this population group. Although 20.8% of the women had red cell folate values below the normal range for non-pregnant subjects, folate deficiency did not appear to be a significant problem. Vitamin B12 deficiency was very uncommon.     

Intravenous iron supplementation for the treatment of anaemia in pre-dialyzed chronic renal failure patients.

BACKGROUND: Intravenous iron is a recognized therapy of anaemia in chronic haemodialyzed patients, especially in those receiving erythropoietin (Epo), while its role in the anaemia of pre-dialyzed chronic renal failure (CRF) patients is much less clear. This study attempted to evaluate the effects of intravenous iron in anaemic pre-dialyzed patients. METHODS: Sixty anaemic (haemoglobin<11 g/dl) non-diabetic patients with moderate CRF [32 males, 28 females; mean age 52.2+/-12.5 years; mean glomerular filtration rate 36.2+/-5.2 ml/min], without iron deficiency, iron overload or inflammation, without concomitant erythropoietin treatment and without any previous iron therapy were enrolled. Intravenous iron was administered as iron sucrose, 200 mg elemental iron per month for 12 months, with 1 month pre-study survey and 1 month follow-up after the last iron dose. RESULTS: Intravenous iron supplementation was associated with a significant increase in haemoglobin (from 9.7+/-1.1 at the baseline to 11.3+/-2.5 g/dl after 12 months, a mean increase of 1.6 g/dl), a further 36% of patients reaching the target haemoglobin of 10 g/dl. There was a significant increase in serum iron from 73.9+/-17.2 to 101.8+/-12.2 microg/dl, in serum ferritin from 98.0 (24.8-139.0) to 442.5 (86.0-496.0) microg/l and in transferrin saturation from 21.6+/-2.6 to 33.6+/-3.2%. No worsening of renal function, no increase in blood pressure and no other side effects were noted. CONCLUSIONS: Intravenous iron therapy in pre-dialysis patients with no Epo seems often to ameliorate the anaemia, avoiding the necessity of Epo or blood transfusions in one-third of pre-dialyzed non-diabetic patients. Intravenous iron supplementation appears to be an effective and safe treatment for anaemia in pre-dialysis CRF patients.     

Low-dose subcutaneous erythropoietin corrects the anaemia of renal transplant failure.

Although erythropoietin (Epo) is known to correct anaemia in dialysis and pre-dialysis patients, there is limited experience with its use in immunosuppressed patients suffering from chronic renal graft dysfunction. We report the results of a pilot study of Epo in seven patients with failing grafts and normocytic normochromic anaemia attributable to renal failure. All entering patients had controlled blood pressure and serum ferritin greater than 100 micrograms/l. Three patients were taking triple immunotherapy (prednisone/azathioprine/cyclosporin), two patients prednisone/azathioprine, and two patients CsA monotherapy. Study duration mean was 15 +/- 2 (SEM) weeks, and Epo was started at 4000 units subcutaneously (s.c.) once weekly, adjusted to achieve a target haemoglobin (Hb) of 100 g/l. Mean Hb at initiation was 68 +/- 5 g/l and significantly increased to 96 +/- 6 at end of follow-up, P less than 10(-4). All patients responded. Maintenance Epo dosage was 120 +/- 32 U/kg bodyweight/week, roughly 4000 units/week. There was no significant change in serum creatinine: pre-study 392 +/- 45 mumol/l; post-study 430 +/- 62 mumol/l. There were no complications but blood pressure did rise significantly: pre- 124 +/- 11/74 +/- 4 mmHg to post- 142 +/- 10/86 +/- 3, P less than 0.05 for systolic and diastolic. Low-dose s.c. Epo effectively corrects anaemia in graft failure despite azathioprine and/or CsA therapy, without obvious acceleration of graft failure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increase of body iron stores estimated by the increase of serum ferritin concentration during a treatment of 200 mg Fe++ daily after gastrointestinal surgery

A 6-week iron therapy of 200 mg Fe++ daily was given to 13 men and 12 women who had previously undergone various kinds of common gastrointestinal surgery and who had empty iron stores estimated from low serum ferritin concentration. The results were compared with those of a control group corresponding to the study group in respect of sex, number of patients, primary disease, previous operation, empty iron stores (serum ferritin), blood hemoglobin, serum iron, sedimentation rate, blood leukocytes, serum transferrin, folate and vitamin B12. The iron therapy restored the lack of body iron, for the serum ferritin concentrations increased from 12 +/- 7 to 30 +/- 11 micrograms/l (p less than 0.001) in the men and from 10 +/- 6 to 30 +/- 12 micrograms/l (p less than 0.001) in the women, whereas the corresponding changes in the control group were from 10 +/- 9 to 11 +/- 8 micrograms/l and from 11 +/- 8 to 13 +/- 11 micrograms/l in the men and women, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inflammation and pruritus in haemodialysis patients.

BACKGROUND: Pruritus is a common symptom among patients on haemodialysis (HD). We studied 68 HD patients to assess the role of iron deficiency, anaemia, inflammation and other common serum and dialysis parameters in pruritus. METHODS: The patients were questioned about the occurrence of pruritus at home, quantified according to frequency ('never', 'occasionally' and 'every day') and intensity ('absent', 'moderate' and 'severe'). The blood and serum variables considered were: haemoglobin, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, hypochromic red blood cells (RBC), hyperchromic RBC, microcytic RBC, macrocytic RBC, reticulocytes, iron, ferritin, transferrin, transferrin saturation, C-reactive protein (CRP), urea, creatinine, calcium, phosphorus, albumin, total protein and glucose. We also analysed Kt/V, age and time on HD treatment. Patients were divided into 3 groups according to the frequency or intensity of their pruritus, and we analysed and compared the variables between the 3 groups. RESULTS: Half (50%) of the patients reported never having pruritus, 32.4% occasionally and 17.6% every day. Pruritus was moderate in 41.2% of them and severe in 8.8%. None of the parameters considered revealed any statistically relevant differences between the three pruritus frequency groups, except for mean serum transferrin level (mg/dl) ('never'=268+/-64 vs 'occasionally'=244+/-40 vs 'every day'=217+/-56, P<0.05). As for the intensity of the symptom, mean serum transferrin (268+/-64 vs 247+/-39 vs 174+/-31, P<0.001) and median ferritin levels (mg/dl) (83 (11-420) vs 98 (11-1121) vs 293 (111-471), P<0.05) showed statistically significant differences between the 3 groups, as did albumin levels (g/dl) (4.3+/-0.4 vs 4.2+/-0.4 vs 3.7+/-0.4, P<0.05). Median CRP values (mg/dl) tended to be higher in patients with more frequent (0.4 (0.3-5.5) vs 0.7 (0.3-11.4) vs 0.9 (0.3-13.5)) and more severe pruritus (0.4 (0.3-5.5) vs 0.7 (0.3-4.0) vs 2.1 (0.3-13.5)), but those differences were not statistically significant. CONCLUSIONS: Iron deficiency and anaemia seem to play no part in HD-related pruritus, whereas lower serum transferrin and albumin levels and higher ferritin values are consistent with the possible role of inflammation in the development and severity of pruritus.     

Post-transplantation anaemia in adult and paediatric renal allograft recipients-Guy's Hospital experience.

BACKGROUND: The commonest cause of renal transplant loss is death with a functioning graft, usually from an excess of cardiovascular disease (CVD). Anaemia is becoming increasingly recognized as a reversible risk factor for the development of CVD. The purpose of this study was to estimate the prevalence of post-transplantation anaemia (PTA) in a large population of stable adult and paediatric renal transplants in one centre and to correlate the estimated glomerular filtration rate (eGFR), iron indices and the use of immunosuppressants with the prevalence of anaemia. METHODS: Every adult and paediatric patient with a functioning renal transplant and more than 3 months post-engraftment at Guy's hospital, London, as of 31 December 2004 and who had a valid creatinine and haemoglobin, in the period 1 September-31 December 2004 inclusive, was identified. A large database of clinical and biochemical indices was built up on the basis of medical notes and electronic patient records. Results were analysed for the prevalence of anaemia and risk factors for its development. Anaemia was defined according to the WHO criteria. All patients on treatment with an erythropoiesis stimulating agent were classified as anaemic, irrespective of haemoglobin. RESULTS: A total of 878 adults and 73 children were identified. Mean haemoglobin in adults was 12.9 +/- 1.6 g/dl and 11.8 +/- 1.4 g/dl in the children. Mean eGFR was 49.3 +/- 20.1 ml/min in adults and 65.7 +/- 18.8 ml/min in the paediatric cohort. Haemoglobin correlated positively with the eGFR in both cohorts (R = 0.33 and 0.29 in adults and children, respectively (P < 0.0001 for both)). We identified anaemia in 45.3% of adults and 22% in children. Ferritin levels were lower in children than in adults (79 +/- 93 vs 204 +/- 353 mg/l), but were higher in both cohorts among the non-anaemic populations than in those with anaemia. 58% of adults taking mycophenolate mofetil (MMF) were anaemic compared with 22% of children. One child, and 68 adults, were on recombinant erythropoietin. Multiple regression analyses identified age, female gender, eGFR and serum ferritin levels as independent predictors of haemoglobin in adult subjects. CONCLUSIONS: The prevalence of PTA was high in both adult and paediatric cohorts while comparatively few patients were being treated with erythropoiesis stimulating agents. The strongest predictors of haemoglobin in this cohort of patients were age, female sex and graft function. Immunosuppression including MMF or sirolimus was associated with a higher prevalence of anaemia, but this was likely to be the result of poorer graft function in these subjects. Iron deficiency did not seem to be a causative factor for anaemia in this population.     

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.     

Dietary iron overload in southern African rural blacks

A survey conducted in rural southern African black subjects indicated that dietary iron overload remains a major health problem. A full blood count, erythrocyte sedimentation rate, serum concentrations of iron, total iron-binding capacity, ferritin, C-reactive protein (CRP), gamma-glutamyltransferase (GGT) and serological screening for hepatitis B and human immunodeficiency virus (HIV) infections were carried out in 370 subjects (214 inpatients and 156 ambulatory Mozambican refugees). The fact that the geometric mean (SD range) serum ferritin concentration was much higher in the male hospital patients than in subjects living in the community [1,581 micrograms/l (421-5,944 micrograms/l) and 448 micrograms/l (103-1,945 micrograms/l) respectively] suggested that dietary iron overload was not the only factor raising the serum ferritin concentration. The major additional factor appeared to be inflammation, since the geometric mean (SD range) serum CRP was significantly higher in male hospital patients [21 mg/l (8-53 mg/l)] than in subjects in the community [3 mg/l (1-5 mg)]. Alcohol ingestion, as judged by history and by serum GGT concentrations, was also associated with significantly raised serum ferritin concentrations. This finding was ascribed to the fact that traditional brews are not only associated with alcohol-induced hepatic damage but are also a very rich source of highly bio-available iron. The role of iron overload in the genesis of the raised serum ferritin concentrations are confirmed in the diagnostic liver biopsy study. The majority of biopsies showed heavy siderosis, with varying degrees of hepatic damage.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of body iron stores on serum aluminum level in hemodialysis patients.

To evaluate the influence of body iron stores on the serum aluminum (Al) level, we studied the correlation between iron status (the serum ferritin, serum iron and transferrin saturation) and serum Al levels in 68 severely anemic hemodialysis patients. Among them, 36 underwent the desferrioxamine (DFO) mobilization test. These 68 patients were divided into three groups according to their serum ferritin level. The basal Al level in the patient group was 41.4 +/- 37.4 micrograms/l (control, 4.1 +/- 2.4 micrograms/l). The serum Al level after DFO infusion of the patient group was 111.1 +/- 86.8 micrograms/l. A significantly higher basal Al and peak Al level after DFO infusion were found in group 1 patients (serum ferritin less than 300 micrograms/l) when compared to group 2 (serum ferritin 300-1,000 micrograms/l) and group 3 (serum ferritin greater than 1,000 micrograms/l) patients. A significant negative correlation between serum ferritin and basal serum Al (r = -0.544, p = 0.0001), as well as peak serum Al after DFO infusion (r = -0.556, p = 0.0001), was noted. Similarly, a negative relationship between serum Al (both basal and peak) and either serum iron or transferrin saturation was noted. However, there was no correlation between the serum Al level and the dosage of aluminum hydroxide. In conclusion, serum ferritin, serum iron and transferrin saturation were inversely correlated with serum Al in our hemodialysis patients. Iron deficiency may probably increase Al accumulation in these patients.     

Reference concentrations of serum selenium and manganese in healthy nulliparas

Reference serum selenium and manganese concentrations were established for healthy nulliparas aged 18-23 years resident in Cape Town. Measurements were determined for selenium in 100 female students who had been taking low-dosage triphasic contraceptive medication for a minimum of 3 months and in 100 female students who were not on contraceptive therapy. Manganese concentrations were determined for 25 female students from each group. The mean serum selenium concentrations were 0.988 +/- 0.189 micrograms/l (78 +/- 15 micrograms/dl) and 0.925 +/- 0.177 mumol/l (73 +/- 14 micrograms/l) respectively for females taking and not taking oral contraceptives. The corresponding concentrations for manganese were 21.84 +/- 9.82 nmol/l (1.20 +/- 0.54 micrograms/l) and 21.66 +/- 7.64 nmol/l (1.19 +/- 0.42 micrograms/l) respectively. The differences in selenium were statistically significant (P = 0.0231) but not for manganese (P = 0.910).     

Ascorbic acid does not augment the restoration effect of iron treatment for empty iron stores in patients after gastrointestinal surgery

The effect of a 6-week combined treatment with ferrous sulfate (80 mg Fe++ three times daily) and ascorbic acid (75 mg three times daily) on the empty iron stores in 20 patients after gastrointestinal surgery was examined from changes of serum ferritin. One group of 20 patients with similar clinical characteristics served as controls. The treatment replaced the empty iron stores. Since mean serum ferritin concentrations increased from 9 +/- 8 to 29 +/- 11 micrograms/l (P less than 0.001) in males and from 8 +/- 8 to 26 +/- 10 micrograms/l (P less than 0.001) in the females. Also blood hemoglobin and serum iron concentrations increased significantly (P less than 0.01). Among the controls there were no marked changes in serum ferritin, blood hemoglobin or serum iron concentrations. However, the increase of serum ferritin caused by this combined treatment was similar with that caused previously by pure ferrous sulfate treatment. Thus, it is considered that the combined treatment with ferrous sulfate (80 mg Fe++ three times daily) and ascorbic acid (75 mg three times daily) restores the empty iron stores in patients after gastrointestinal surgery, but that the increase is not augmented by the ascorbic acid. Thus, a pure iron therapy is recommended to fill up the empty iron stores in these patients.     

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.     

Darbepoetin alfa effectively maintains haemoglobin concentrations at extended dose intervals relative to intravenous or subcutaneous recombinant human erythropoietin in dialysis patients.

BACKGROUND: Darbepoetin alfa is a unique molecule that stimulates erythropoiesis by the same mechanism as endogenous erythropoietin. Due to its approximately 3-fold longer half-life and greater biological activity than recombinant human erythropoietin (rHuEpo), darbepoetin alfa maintains effective haemoglobin control at extended dose intervals compared with rHuEpo. This study assessed the efficacy and safety of unit doses of darbepoetin alfa for the treatment of renal anaemia. METHODS: In this multicentre, prospective, open-label study, 1502 dialysis subjects maintained on stable rHuEpo treatment were switched to darbepoetin alfa at extended dose intervals by the same route of administration as previous rHuEpo therapy [intravenous (i.v.), n = 900 or subcutaneous (s.c.), n = 602]. Subjects receiving rHuEpo two (n = 408, 27%) or three times (n = 884, 59%) a week were switched to darbepoetin alfa once a week, and those receiving rHuEpo once a week (n = 210, 14%) were switched to darbepoetin alfa once every 2 weeks. The unit doses of darbepoetin alfa (10-150 microg) were titrated to maintain haemoglobin concentrations of 10-13 g/dl for 24 weeks. RESULTS: Haemoglobin concentrations were maintained effectively in subjects regardless of whether they received darbepoetin alfa once a week or once every 2 weeks. The overall mean change in haemoglobin from baseline to the evaluation period (weeks 21-24) was +0.10 g/dl [95% confidence interval (CI) 0.04+/- 0.17]. The mean haemoglobin concentration increased by 0.19 g/dl (95% CI 0.11+/-0.27) in subjects receiving i.v. darbepoetin alfa, and was unchanged (-0.02 g/dl; 95% CI -0.12 to 0.07) in patients treated with s.c. darbepoetin alfa. Subjects with baseline haemoglobin < 11 g/dl experienced a clinically relevant increase in mean haemoglobin concentration of 0.67 g/dl (95% CI 0.56+/-0.77) from baseline to the evaluation period. The mean weekly i.v. and s.c. darbepoetin alfa dosage requirements during the evaluation period were 19.9 microg/week (95% CI 19.02+/-20.87) and 21.6 microg/week (95% CI 20.36+/- 22.94), respectively. Darbepoetin alfa was well tolerated and the safety profile was consistent with previous trials with darbepoetin alfa in dialysis subjects. CONCLUSIONS: Treating renal anaemia with darbepoetin alfa administered at extended dose intervals is both effective and well tolerated. Moreover, administration of darbepoetin alfa by both the i.v. and s.c. route is associated with stable haemoglobin concentrations.     

24-hour pulsatile and circadian patterns of cortisol secretion in alcoholic men

Pulsatile and circadian patterns of cortisol secretion during acute (3 to 16 days) and chronic (29 to 39 days) abstinence were examined in alcoholic men with no clinical or laboratory evidence of hepatic dysfunction or nutritional deficiencies. Mean and integrated 24-hour serum concentrations of cortisol determined by sampling the blood every 20 minutes over a 24-hour period were increased in six out of 10 alcoholic subjects during acute abstinence when compared with normal controls. Sustained abstinence in seven subjects with follow-up studies caused significant decreases in the mean maximal cortisol peak amplitude (13 +/- 1.0 SEM acutely vs. 10.3 +/- 0.52 micrograms/dl follow-up; P = 0.01), mean 24-hour serum cortisol concentrations (10.9 micrograms/dl +/- 1.2 vs. 8.5 micrograms/dl +/- 0.26; P = 0.047), interpulse valley mean (9.3 micrograms/dl +/- 0.88 vs. 6.5 micrograms/dl +/- 0.34; P = 0.007), and valley nadir (7.9 micrograms/dl +/- 0.69 vs. 5.4 micrograms/dl +/- 0.30; P = 0.0036) concentrations. Cortisol pulse frequency was normal. Although circadian cortisol rhythmicity was maintained in alcoholics, the timing of the circadian acrophase was delayed significantly (P = 0.006) during acute abstinence (1022 [clocktime] +/- 34 min) as compared with normal controls (0743 [clocktime] +/- 34 min), and the amplitude of circadian cortisol rhythms exceeded normal in five of 10 alcoholics. Analysis of data in one alcoholic subject by a new multiparameter deconvolution method demonstrated increases in secretory burst amplitude (0.64 microgram/dl +/- 0.08 SD), mass of cortisol released per burst (9.8 micrograms/dl +/- 1.2 SD), and daily endogenous cortisol production rate (22 mg +/- 2.4 SD) during acute abstinence. These values were statistically different when compared with seven normal controls and the subjects' values during sustained abstinence (P less than 0.02). In conclusion, the results of the present study suggest increased daily production of cortisol as a possible mechanism underlying the elevated serum cortisol concentrations in chronic alcoholics during acute abstinence. This abnormality is shown to be reversible with sustained abstinence from alcohol.     

Iron, folate and vitamin B12 nutrition and anaemia in black preschool children in the northern Transvaal

The prevalence of anaemia and deficiencies of iron, folate and vitamin B12 were investigated in 140 rural black preschool children aged 3-5 years living in five different villages in the Letaba area, near Tzaneen. Anaemia was highly prevalent, 39.2% of the children having haemoglobin levels below 11.1 g/dl. Approximately 10% were considered to be iron-deficient. On the basis of subnormal red cell folate values, 1 in 4 children was folate-deficient, suggesting the need for intervention at the community level such as enrichment of the staple foodstuff, maize meal, with folic acid.     

Intravenous iron for CAPD populations: proactive or reactive strategies?

BACKGROUND: The European best practice guideline [Nephrol Dial Transplant 1999; 14 (Suppl 5)] (5A) for the management of anaemia suggests that > 85% of the CAPD population should have a haemoglobin level of > 11.0 g/dl. METHODS: We developed and implemented an outpatient-based protocol for intravenous iron sucrose (IV Fe) and erythropoietin (Epo) in CAPD patients showing iron deficiency despite oral iron therapy. We managed a total of 103 patients over 13 months of study. All CAPD patients were included, regardless of co-morbidity. Treatment developed in two phases: in phase 1 (reactive) (months 1-8), patients with markers of iron deficiency (ferritin < 100 ng/ml or ferritin 100-500 and percentage hypochromic red cells (%HRC) > or =5) were converted from oral iron to IV Fe (300 mg) and reviewed after 4-8 weeks according to haemoglobin (Hb). In phase 2 (proactive) (months 9-13), the criteria for iron therapy were extended: ferritin < 150 ng/ml or ferritin 150-500 and %HRC > or = 2. Patients then received IV Fe (200 mg) and were reviewed after 4 weeks according to Hb. RESULTS: The median haemoglobin increased from 11.0 (Inter quartile range, IQR, 10.1-12.6) g/dl to 11.7 (11.0-12.7) g/dl (P = 0.06). The proportion of patients with absolute iron deficiency (ferritin < 100 ng/ml) decreased from 24 to 2%. The percentage of hypochromic red cells (%HRC) decreased from 4 (2-7) to 1 (1-4) (P < 0.01). CONCLUSIONS:An integrated Epo and IV Fe policy increased the number of patients reaching the European guideline from 50 to 75% with no increase in the population median Epo requirements (42 (IQR, 25-95) IU/kg/week vs 45 (27-101) (P = NS)). This study demonstrates the benefit of early (proactive) intervention in achieving population compliance within current guidelines for renal anaemia.     

Human recombinant erythropoietin treatment in transfusion dependent anemic patients on maintenance hemodialysis

Six anemic hemodialysis patients dependent on regular blood transfusions and with massive iron overload were treated with recombinant human erythropoietin (r-huEPO). The effect on absolute reticulocyte count, hemoglobin and serum ferritin was studied during a twenty-week period. Red-cell volume and red-cell life span were measured with 51Cr-tagged erythrocytes at baseline and after twenty weeks of r-huEPO. Absolute reticulocyte counts and hemoglobin concentration rose markedly (from 55.6 +/- 31.2 to a maximum of 174.9 +/- 31.0 x 10(9)/l at 4 weeks and from 6.8 +/- 0.3 to a maximum of 11.2 +/- 1.3 g/dl at 12 weeks, respectively, p less than 0.001) without any further need for transfusions. Red-cell volumes increased concomitantly (from 58 +/- 4 to 81 +/- 11% of normal, p less than 0.005), in spite of a persistent shortening of red-cell life span (45 +/- 18 and 47 +/- 4 days before and after r-huEPO). Markedly elevated serum ferritin concentrations indicating iron overload decreased slowly from 3,550 +/- 1,615 to 2,721 +/- 1,506 micrograms/l (p less than 0.05). It is concluded that r-huEPO is very effective in treating the anemia of patients maintained on hemodialysis. The favorable effects on hemoglobin and red-cell volumes occur in spite of persistent hemolysis and lead to a slow reduction of iron overload.     

Switching from subcutaneous to intravenous erythropoietin alpha in haemodialysis patients requires a major dose increase.

BACKGROUND: A change in the licensing arrangements for the use of erythropoietin alpha in haemodialysis patients has required a switch in the route of administration from subcutaneous (SC) to intravenous (IV). Previous work suggested that the IV route was less efficacious but studies since the enforced switch have not confirmed this. METHODS: We studied haemoglobin levels and the mean weekly dose of erythropoietin alpha in 86 haemodialysis patients at monthly intervals over the 6 month period before and after a change in the route of administration of erythropoietin alpha from SC to IV. Changes in other parameters known to be associated with erythropoietin response were also monitored. RESULTS: Mean haemoglobin level fell following the switch from 11.9 g/dl+/-1.4 at baseline to 11.3 g/dl+/-1.4 at 1 month (P = 0.001) and to a trough of 11.0 g/dl+/-1.3 at 2 months (P<0.001) before partial recovery to 11.4 g/dl+/-1.2 (P = 0.007) at 6 months. Mean weekly dose of erythropoietin after 2 months was significantly higher than baseline (8791 IU+/-5314 vs 8035 IU+/-4893). The dose continued to increase and by 6 months was 10605 IU (P<0.001), 32% higher than baseline. There was a small reduction in residual renal function, which was an independent predictor of change in dose requirement. There was a small increase in parathyroid hormone levels, but no change in serum ferritin, dosing frequency, total Kt/V, serum albumin, normalised protein catabolic rate, C-reactive protein, hospitalization rate and dialyser reuse rate. CONCLUSIONS: Switching from SC to IV erythropoietin alpha caused a significant fall in haemoglobin levels in the first 2 months. This was partially reversed by 6 months at the expense of a 32% dose increase in the dose of erythropoietin alpha by 6 months. The economic impact may be considerable.     

Efficacy and tolerance of treatment with recombinant-human erythropoietin in chronic renal failure (pre-dialysis) patients

Recombinant-human erythropoietin (r-HuEPO) was administered to 24 anaemic pre-dialysis patients with end-stage renal disease. R-HuEPO was injected i.v. three times weekly during the first two months (correction phase). Fixed dosages of 50 U/kg, 100 U/kg, and 150 U/kg were used, and each dose group consisted of eight patients. During the subsequent six months r-HuEPO was given once weekly and the dose was adjusted to maintain a stable haemoglobin value (maintenance phase). The mean +/- SD haemoglobin increased from 9.3 +/- 0.6 to 11.1 +/- 1.3 g/dl with 50 U/kg, from 7.9 +/- 1.4 to 11.8 +/- 1.7 g/dl with 100 U/kg and from 8.4 +/- 1.0 to 12.1 +/- 1.1 g/dl with 150 U/kg of r-HuEPO. The two highest dose groups showed a marked reticulocytosis and a transient thrombocytosis. During the maintenance phase haemoglobin remained stable (11.9 +/- 1.1 g/dl) at a mean dose of 199 +/- 139 U/kg of r-HuEPO per week. Blood pressure did not increase, but in nine of eighteen previously hypertensive patients antihypertensive medication was increased. One hypertensive patient developed seizures. No accelerated progression of renal failure could be demonstrated. All patients reported an improved sense of well-being. R-HuEPO is an important new therapeutic agent for the treatment of anaemia of end-stage renal failure that is also effective in pre-dialysis patients.     

Incidence of anaemia, and use of epoetin therapy in pre-dialysis patients: a prospective study in 403 patients.

BACKGROUND: Recent American and European guidelines recommend that epoetin therapy should be considered whenever the blood haemoglobin (Hb) level is <10-11 g/dl in dialysis patients and in pre-dialysis patients. Thus, data on the current prevalence of anaemia with respect to the degree of chronic renal insufficiency are needed in order to determine the potential indications of epoetin therapy in the pre-dialysis period. METHODS: We prospectively studied 403 consecutive ambulatory pre-dialysis patients whose serum creatinine (Scr) was 200 micro mol/l or more at their first passage at our out-patient clinic between January 1 and June 30, 1999. Hb and Scr values were determined at each visit until June 30, 2000, or until the start of maintenance dialysis. Patients had a clinical and laboratory evaluation every 2-3 months, and monthly when treated with epoetin. RESULTS: The mean (+/-SD) age of patients was 60.9+/-17.2 years at presentation. The Hb level was <11 g/dl in 62% of patients with Scr > or =400 micro mol/l, and in 58% of patients with an estimated creatinine clearance (Ccr) <20 ml/min/1.73 m(2). The proportion of anaemic patients was higher for any given Ccr value in females than in males. A total of 136 patients were treated with epoetin during the observation period. At the start of epoetin, their mean Hb value was 9.5+/-0.6 g/dl and Ccr level 13.9+/-4.9 ml/min/1.73 m(2). Among the 123 patients who began maintenance dialysis therapy during the observation period, 85 (or 69%) received epoetin therapy before the start of dialysis. Their mean Hb value at the start of dialysis was 10.8+/-1 g/dl compared with 10.5+/-1.1 g/dl in the 41 dialysed patients who did not require epoetin therapy during the pre-dialysis period. CONCLUSIONS: Based on the data gained in a large cohort of patients receiving regular pre-dialysis nephrological care, the proportion of subjects with a Hb level <11 g/dl may be estimated at approximately 60% when the Ccr is <20 ml/min/1.73 m(2). If the Hb level is to be maintained at no less than 11 g/dl, at least two-thirds of patients at this advanced stage of chronic renal failure should require pre-dialysis epoetin therapy.