Effect of high-flux dialysis on the anaemia of haemodialysis patients.

BACKGROUND: Anaemia is one of the major clinical characteristics of patients with chronic renal failure, and has a considerable effect on morbidity and mortality. Adequate dialysis is of paramount importance in correcting anaemia by removing small and medium-sized molecules, which may inhibit erythropoiesis. However, high-molecular-weight inhibitors cleared only by means of highly porous membranes have also been found in uraemic serum and it has been claimed from uncontrolled studies that high-flux dialysis could improve anaemia in haemodialysis patients. METHODS: We therefore planned this multicentre randomized controlled trial with the aim of testing whether the use of a large-pore biocompatible membrane for a fixed 12-week follow-up improves anaemia in haemodialysis patients in comparison with the use of a conventional cellulose membrane. Eighty-four (5.3%) of a total of 1576 adult haemodialysed patients attending 13 Dialysis Units fulfilled the entry criteria and were randomly assigned to the experimental treatment (42 patients) or conventional treatment (42 patients). RESULTS: Haemoglobin levels increased non-significantly from 9.5+/-0.8 to 9.8+/-1.3 g/dl (dP=0. 069) in the population as a whole, with no significant difference between the two groups (P:=0.485). Erythropoietin therapy was given to 32/39 patients (82%) in the conventional group, and 26/35 (74%) in the experimental group (P:=0.783) with subcutaneous administration to 26/32 patients in conventional and to 23/26 patients in experimental group, P:=0.495. Dialysis dose (Kt/V) remained constant in both groups (from 1.30+/-0.17 to 1.33+/-0.20 in the conventional group and from 1.28+/-0.26 to 1.26+/-0.21 in the experimental group, P:=0.242). Median pre- and post-dialysis beta(2)-microglobulin levels remained constant in the conventional group (31.9 and 34.1 mg/dl at baseline) and decreased in the experimental group (pre-dialysis values from 31.1 to 24.7 mg/dl, P:=0.004 and post-dialysis values from 24.8 to 20.8 mg/dl, P:=0.002). Median erythropoietin doses were not different at baseline (70 IU/kg/week in conventional treatment and 90 IU/kg/week in experimental treatment, P:=0.628) and remained constant during follow-up (from 70 to 69 IU/kg/week in the conventional group and from 90 to 91 IU/kg/week in the experimental group, P:=0.410). Median erythropoietin plasma levels were in the normal range and remained constant (from 12.1 to 12.9 mU/ml in the conventional group and from 13.2 to 14.0 mU/ml in the experimental group, P:=0.550). CONCLUSIONS: This study showed no difference in haemoglobin level increase between patients treated for 3 months with a high-flux biocompatible membrane in comparison with those treated with a standard membrane. When patients are highly selected, adequately dialysed, and have no iron or vitamin depletion, the effect of a high-flux membrane is much less than might be expected from the results of uncontrolled studies.     

Chronic hepatitis ameliorates anaemia in haemodialysis patients

Background: Study for influence of chronic hepatitis (CH) on anaemia in haemodialysis (HD) patients remains inconclusive. We aim to characterize the red cell status between CH and hepatitis‐free groups among the HD population. Methods: We retrospectively analysed 80 chronic HD patients from Taipei Medical University Hospital with monthly sampled biochemical study between December 2004 and December 2005. Data classified according to the hepatitis‐free, chronic hepatitis B and C groups were expressed as mean ± standard deviation. Student's t‐test and anova were used to determine the mean difference for continuous variables. Results: Age, Kt/V, systolic or diastolic blood pressure, body mass index, total cholesterol and triglyceride were not different between CH and hepatitis‐free groups. HD duration (P = 0.0002), aspartate (P < 0.0001), alanine aminotransferase (P < 0.0001), alkaline phosphatase (P = 0.04), haemoglobin (P = 0.0066) and haematocrit (P = 0.002) were significantly more elevated in the CH group demanding less erythropoietin dose than in the hepatitis‐free group. Conclusion: Our study demonstrated that lessoned anaemia was observed in CH, which demanded less erythropoietin dose.     

Online hemodiafiltration versus acetate-free biofiltration: a prospective crossover study

Online hemodiafiltration (online HDF) and acetate-free biofiltration (AFB) are 2 innovative renal replacement therapies. Convincing evidence has shown that both techniques are superior to conventional hemodialysis in many aspects. The aim of the present investigation was to compare online HDF and AFB in 12 stable maintenance hemodialysis patients in a prospective, randomized crossover trial. Twelve stable dialysis patients, age 49.7 +/- 11.3 years and on dialysis for 83.5 +/- 76.7 months, were treated prospectively and randomly by either AFB, predilution HDF (pre-HDF), or postdilution HDF (post-HDF) for a total of 36 weeks using exclusively F60S high-flux dialyzers. Routine blood biochemical tests, bone metabolism parameters, and clearance for both small and larger molecular weight substances were measured at defined intervals. During the trial period inter- and intradialysis symptoms, e.g., hypotensive episodes and intradialysis arterial blood gas analyses, were recorded. Both online HDF and AFB were well accepted by the overwhelming majority of patients and also by the dialysis staff. Pretreatment sodium, total and ionized calcium, chloride, bicarbonate, and urea did not differ within or between the 3 treatment groups. Potassium increased slightly in HDF patients while phosphate and beta2-microglobulin (beta2-M) decreased in all groups. After dialysis, AFB patients exhibited a significantly higher bicarbonate concentration and lower potassium level when identical potassium concentrations in dialysate were used. Patients receiving AFB manifested less intradialysis partial pressure of oxygen drop and partial pressure of carbon dioxide rise than those on HDF treatments. HDF treatments could afford higher single-pool and double-pool Kt/V, higher effective urea and beta2M clearance, and lower total interdialysis symptom scores than the AFB treatment method. While bone metabolism parameters did not differ between the 3 dialysis modalities, some parameters such as deoxypyridinoline in HDF and osteocalcin, pyridinoline, and deoxypyridinoline in AFB deteriorated at the end of the crossover study. Aluminum concentration decreased progressively to about one-third of prestudy values at the end of the study with all 3 treatments. AFB was associated with a lower predialysis mean arterial pressure (MAP), a smaller drop in MAP during treatment, and similar hypotension episodes compared with the 2 HDF treatments. Albumin concentration showed a trend to decrease during the first 2 months of the trial period followed by a slight increase thereafter but still significantly lower than initial value at the end of crossover. Both online HDF and AFB share most of the features of optimal renal replacement therapy. Online HDF is superior to AFB in such aspects as increased delivered dialysis dose both for small and larger molecular weight toxins and less interdialysis symptoms. On the other hand, AFB is associated with a smaller effect on arterial blood gas values and improved intradialysis hemodynamic tolerance. Some dialysis-related symptoms and complications in the case of our AFB practice could be attributable, at least in part, to low dialysate calcium level.     

High- and low-flux acetate-free biofiltration: experimental assessment of calcium mass balance and intact parathyroid hormone behaviour

We studied total calcium mass balance and plasma intact parathyroidhormone behaviour in 10 uraemic patients who underwent acetate-freebiofiltration carried out in accordance with six different dialyticschedules, where either a polyacrylonitrile or a polysuiphonemembrane was used. Schedules 1 and 2 involved a reinfusion flowrate of 33.3 ml/mm with a dialysate calcium concentration (DCa)of 1.75 and 2 mmol/l respectively; in schedule 3, 4, 5 and 6reinfusion flow rate amounted to 50 ml/mm and DCa was respectivelyof 1.75, 2, 2.25 and 2.5 mmol/l. Dehydration remained unchangedin all schedules: 700 g/h. Finally high- and low-flux acetate-freebiofiltration are able to induce different Ca mass balance whichmay suit different therapeutic contexts. Ca mass balance waseither positive or negative depending on reinfusion flow rateand DCa. With a reinfusion flow rate of 33.3 ml/mm a DCa ofat least 2 mmol/l was necessary to obtain a positive mass balance,while with a reinfusion flow rate of 50 ml/mm DCa had to equal2.25 mmol/l. In high-flux acetate- free biofiltration, the estimationof predialytic Ca²⁺ and DCa values, using a simple formula,allows prediction of the mass balance that will be attained.At the end of acetate-free biofiltration, intact parathyroidhormone always decreased when a polyacrylonitrile membrane wasemployed while it increased, in the presence of negative Camass balance with a polysulphone membrane.     

Correction of chronic metabolic acidosis in haemodialysed patients by acetate-free biofiltration does not influence parathyroid function

In eight patients remaining acidotic after more than 1 yearof bicarbonate haemodialysis, we studied the effect of correctingthe chronic metabolic acidosis using acetate-free biofiltrationfor 4 months on the course of secondary hyperparathyroidism.An AN69 capillary membrane was employed with a bicarbonate infusionrate initially set at 1.8 l/h in all patients and then adjustedin each one to obtain a predialysis bicarbonate of 23 mmol/l.Standard blood chemistry parameters were determined every 2weeks. Measurements of PTH, calcifediol and calcitriol, as wellas calcium-PTH curves were determined at the beginning and endof the study. While acetate-free biofiltration appears to be an adequate techniquefor the correction of chronic metabolic acidosis when bicarbonatedialysis fails, this study indicates that it does not influencesecondary hyperparathyroidism in haemodialysed patients. Thelevel of intact PTH did not vary significantly and the calcium-PTHcurves at 0 and 4 months were superimposable with no significantdifferences in the set point and the slope of the curves.     

A prospective multicentre study of the role of anaemia as a risk factor in haemodialysis patients: the MAR Study.

BACKGROUND: Retrospective studies have shown hospitalization and mortality rates during haemodialysis (HD) to be associated with anaemia. METHODS: The prospective, multicentre Morbidity-and-mortality Anaemia Renal (MAR) study was designed to establish the burden of anaemia by controlling for other risk factors. Charlson index was used for comorbid adjustment. Finally, 1428 patients from 119 centres (60% men, aged 64.4 years, time on HD 15.3 months, Charlson comorbidity index 6.5 +/- 2.3) completed follow-up. They had hypertension (75.8%), diabetes mellitus (25.9%), heart failure (13.9%) and coronary disease (16.7%). Of the total patients, 94.8% were receiving erythropoietin (111.6 +/- 70.6 U/kg/week) and 76.7% i.v. iron, and haemoglobin (Hb) at inclusion was 11.7 +/- 1.5 g/dl. RESULTS: Hospitalization rate was 1.1 admissions/patient/year. Yearly mortality was 12% [35% cardiovascular (CV)]. The relative risk and confidence interval (CI) for hospitalization and death were 0.86 (0.81-0.91) and 0.82 (0.73-0.91), respectively, per 1 g/dl increase in initial Hb after adjustment for comorbidity, vintage, aetiology, access type, albumin and Kt/V. The probability of remaining free from hospitalization (CI) was 0.34 (0.27-0.41) for initial Hb <10 g/dl, 0.47 (0.41-0.53) for Hb 10-11 g/dl, 0.54 (0.49-0.59) for Hb 11-12 g/dl, and 0.63 (0.59-0.67) for Hb >12 g/dl. Same analysis for patient survival was 0.77 (0.71-0.83) for Hb <10 g/dl vs 0.82 (0.77-0.87) for Hb 10-11 vs 0.89 (0.86-0.92) for Hb 11-12 vs 0.92 (0.90-0.94) for Hb > 12 g/dl, P < 0.001. The Cox regression model for hospitalization-free survival included the risk factors initial Hb (relative risk 0.86 per 1 g/dl increase, P < 0.001) Charlson, albumin and prior CV event. CONCLUSION: Hb level predicted 1-year-survival and hospitalization. This effect persisted after adjustment for comorbidity and other prognostic factors.     

Effectiveness of weekly darbepoetin alfa in the treatment of anaemia of HIV-infected haemodialysis patients.

BACKGROUND: Anaemia is aggravated by the coexistence of chronic kidney disease (CKD) in patients infected with human immunodeficiency virus (HIV). Darbepoetin alfa effectively alleviates CKD-associated anaemia with less frequent dosing than recombinant human erythropoietin (EPO). The current study aimed to determine the efficacy, safety and cost-effectiveness of darbepoetin alfa compared with erythropoietin alfa (EPO-alfa) for treatment of anaemia in HIV-infected subjects receiving haemodialysis. METHODS: An open label, single arm, prospective study of 12 haemodialysis subjects with HIV infection was conducted for a duration of 6 months after switching from intravenous (i.v.) EPO-alfa two/three times weekly to i.v. darbepoetin alfa once weekly. The primary end point was the proportion of patients maintaining haemoglobin (Hb) levels>or=11 g/dl while a weekly dose of darbepoetin alfa was a secondary end point. RESULTS: Darbepoetin alfa, as effectively as EPO-alfa maintained the proportion of the subjects having Hb levels>or=11 g/dl at an average weekly dose of 40.60 microg compared with an equivalent dose of 51.84 microg for EPO-alfa. Antiretroviral therapy and HIV infection stage remained the same for each specific patient throughout the study period, including the last 6 months of EPO-alfa therapy. No difference in the incidence of adverse effects was observed after switching from EPO-alfa to darbepoietin alfa. CONCLUSIONS: Lower doses of darbepoetin alfa at extended dosing interval is as safe and effective as EPO-alfa for treating anaemia, suggesting that darbepoetin alfa is a more cost-effective therapeutic alternative to EPO-alfa in the management of anaemia associated with HIV infection in subjects receiving haemodialysis.     

Long-term effects on quality of life in haemodialysis patients of correction of anaemia with erythropoietin

Quality of life assessments were performed in 24 haemodialysispatients (10 males, 14 females, age 45 ±15 years) undergoingrHuEpo treatment. The results in the rHuEpo-treated patientswere compared with those in eight haemodialysis patients noton rHuEpo and with the results of a nationwide study of dialysispatients in Sweden (carried out before rHuEpo was registered).Survey questionnaires (112 items, divided into three dimensions,i.e. physical, social, and emotional wellbeing) were completedbefore treatment (Hb 73± 1.1 g/1), when the target Hbvalue of 10 g/dl was reached (1–7 months) and in 14 patients1 year after correction of the anaemia. Before treatment, therHuEpo group had significantly more complaints about poor appetite,fatigue, and irritability than the controls. After the anaemiawas corrected, the rHuEpo group had significantly improved physicaland emotional wellbeing. The most significant changes occurredin satisfaction with health, physical activities of daily life,and fatigue. Alterations in emotional symptoms, such as depressionand apathy, were less pronounced. Only minor changes were observedin their social wellbeing. One year after correction of theanaemia, the improvements in physical and emotional wellbeingwere still present in the rHuEpo-treated patients. A positiveeffect was also noted on hospitalization rate. Scores for thesubdimensions of satisfaction with health, sexual adjustment,physical symptoms, and emotional wellbeing improved in the rHuEpo-treatedgroup and reached a level that was the same, or even higher,than the scores in the dialysis patients in the nationwide study.In conclusion, the quality of life improved during rHuEpo treatment.The greatest changes were seen in satisfaction with health,physical activity, and emotional wellbeing. The positive effectsobserved after the correction of anaemia persisted after morethan a year on rHuEpo treatment.     

Recombinant human erythropoietin corrects anaemia during the first weeks after renal transplantation: a randomized prospective study

BACKGROUND.: Studies on the effect of recombinant human erythropoietin (rHuEpo)on haematopoiesis in patients with kidney transplants, havebeen limited to progressive chronic graft failure, late aftertransplantation. In the present prospective randomized study,the efficacy of rHuEpo in the correction of anaemia during thefirst weeks after renal transplantation (RTP) was evaluated. METHODS.: Patients were allocated to either an Epo-(n=14) or a non-Epo-treatedgroup (n=15). Epo (150 U/kg.week s.c.) was started at a haematocrit(Hct) <30% and was increased at weekly intervals by 30 U/kg.week,as long as Hct remained <25%. RESULTS.: In the Epo group, Hct increased from a nadir of 22±4%2 weeks after RTP to 30±4% at week 4 and to 36±4%at week 6 (P<0.001 and P<0.0001 respectively vs week 2).Corresponding values in the non-Epo group were 25±6%,28±6% (P=NS) and 32±6% (P<0.05 vs week 2) (overallevolution Epo vs non-Epo: P=0.038 by variance analysis). Thedifferences in Hct between the Epo and non Epo group were evenmore marked in patients without major complications (varianceanalysis P=0.009). The Epotreated patients required fewer post-surgicalblood transfusions (0.005 vs 0.014/days follow-up, P<0.05),in spite of greater post-surgical blood losses, especially atday 1 (P<0.05) and the presence of more major complications(7 vs 4) and a higher number of ganciclo vir-treated patients(4 vs 0; P<0.05). The maximum Epo dose after RTP was >2xhigher than the one required before RTP (197.1±45.1 vs85.0±76.0 U/kg.week; P<0.05). CONCLUSIONS.: It is concluded that rHuEpo during the first weeks after RTPis of benefit in the correction of the Hct in the early post-surgicalperiod, in spite of relative Epo resistance.     

Anaemia and mortality in haemodialysis patients: interaction of propensity score for predicted anaemia and actual haemoglobin levels.

BACKGROUND: Haemoglobin levels in haemodialysis patients could represent unknown comorbidities, more severe levels of known comorbidities, as well as therapeutic choice. Thus, integrating factors predictive of anaemia with actual haemoglobin levels might improve prognostic discrimination. METHODS: We retrospectively studied 93,087 patients who started haemodialysis between 1998 and 2000. Clinical and treatment factors from months 4 through 9, derived from Medicare claims, were used to develop propensity scores for anaemia (mean haemoglobin <11 g/dl). Tertiles of propensity scores were interacted with five levels of actual mean haemoglobin to form 15 groups, ranging from low (anaemia) probability with (mean) haemoglobin <10 g/dl to high probability with haemoglobin >or=13 g/dl. Cox proportional hazards regression evaluated mortality and first hospitalization among these groups. RESULTS: The anaemia propensity score improved overall prognostic discrimination. Propensity score adjustment significantly improved prediction of mortality (P<0.0001) after covariate adjustments including haemoglobin. For mortality, the highest and lowest adjusted hazard ratios (AHR) appeared in these groups, respectively: high probability with haemoglobin <10 g/dl (AHR 1.64 [1.54, 1.75], P<0.0001), and low probability with haemoglobin 12 to <13 g/dl (AHR 0.79 [0.74, 0.85], P<0.0001). Higher haemoglobin levels were associated with lower mortality even after propensity score adjustment. Similar patterns resulted for first hospitalization; however, the interaction was significant only for hospitalization (P = 0. 0212). CONCLUSIONS: Integrating factors predictive of anaemia improves overall prognostic discrimination. Propensity score adjustment refines the prognostic association of haemoglobin levels in haemodialysis patients.     

Efficacy and safety of oral versus intravenous ascorbic acid for anaemia in haemodialysis patients

BACKGROUND: Intravenous (i.v.) ascorbic acid (AA) improves anaemia in iron-overloaded, erythropoietin (rEPO) hyporesponsive haemodialysis patients. While oral AA is readily attainable, the efficacy and safety of oral versus i.v. AA has not been examined. METHODS: We conducted an open-label randomised parallel study on the effects of 8 weeks of 250 mg oral AA (n=10) compared with 250 mg i.v. AA (n=11) 3x/week on haemoglobin (Hb), ferritin and rEPO dose in 21 iron-overloaded haemodialysis patients. We also examined the effect of 3 months of 500 mg oral AA 3x/week (n=70) compared with no treatment (n=83) on Hb, ferritin and rEPO dose in 153 haemodialysis patients. RESULTS: Patients had severe AA deficiency (mean 2.2+/-SE 0.4 mg/L; normal range, 4.0-14.0). Following treatment, the plasma AA level increased (P<0.001), but was not significantly different between the groups. There was no change in Hb, iron availability and rEPO dose with oral or i.v. AA. There was a significant increase in serum oxalate but no significant changes in left ventricular function or renal calculi formation. In the second study, oral AA had no effect on Hb, rEPO dose and ferritin in the whole group and a subgroup of 30 with anaemia. CONCLUSION: Haemoglobin and iron availability did not improve following oral or i.v. AA in this select small group of iron-overloaded haemodialysis patients or in a larger population of haemodialysis patients given oral AA at a higher dose and for a longer duration. AA supplementation may still be warranted in view of severe AA deficiency in haemodialysis patients.     

Factors influencing anaemia in dialysis patients. A special survey by the EDTA-ERA Registry

The European Dialysis and Transplantation Association—EuropeanRenal Association (EDTA-ERA) Registry conducted a special studyon anaemia in dialysis patients because it seemed importantto elucidate the various factors that influence the degree ofanaemia and the use of regular transfusions in dialysis patientsbefore the introduction of recombinant human erythropoietin(rHuEpo) for larger groups of patients. In a 20% sample of allpatients recorded to have been dialysed throughout 1987, statisticallysignificant associations could be found by multifactorial analysisbetween haemoglobin (Hb) concentration and age, sex, primaryrenal disease, type of treatment, hours of dialysis per week,and number of years on renal replacement therapy. The type ofdialyser membrane did not seem to play a role (although therewas weak evidence of an effect of the dialyser). Mean Hb concentrationfor dialysis patients differed between countries as did thetransfusion policy. In view of the high costs of the rHuEpotreatment and potential side-effects, factors such as methodof dialysis and hours of haemodialysis per week should be takeninto consideration in the treatment of anaemia in dialysis patients.     

Acetate-free biofiltration versus bicarbonate haemodialysis in the treatment of patients with diabetic nephropathy: a cross-over multicentric study

Background: Morbidity and mortality rates in diabetic patients on regular dialysis treatment (RDT) are higher than in non-diabetic-subjects on RDT. Moreover diabetic patients experience an intradialytic morbidity unacceptably higher than in patients with other causes of terminal renal failure. The aim of the present investigation was to compare standard bicarbonate haemodialysis (BHD) with acetate-free biofiltration (AFB) in a group of 41 diabetic patients stable on dialysis treatment for 25±22 months. Methods: Twenty four type II and 17 type I diabetic patients, all requiring insulin therapy, were included and were followed for 1 year in a 6-month cross-over randomized study for both methods. The analysis was carried out on dialysis symptoms, interdialysis symptoms, and nutritional status, and the multivariate analysis of variance for repeated measures on the same subjects in the two techniques was used. Results: AFB significantly reduced dialytic and extradialytic symptoms (P=0.003 and 0.001 respectively). Cardiovascular collapses decreased by 43%, and other dialysis symptoms showed a similar trend (-35%). The interdialysis symptoms decreased by 28% and were accompanied by an increase in subjective wellbeing (39%) when patients were switched from traditional haemodialysis to AFB. Acid-base control was better with AFB (P=0.01), both at the beginning and during the session. Slightly significant differences were also obtained for Kt/V (AFB 1.48±0.29 vs BHD 1.38±0.30), while no significant difference was noted with respect to sodium mass balance, nutritional status, calorie-protein intake, nPCR, blood glucose profile, and insulin requirements. The number of hospital admissions and the mortality rate, which were much lower during the AFB than the BHD period, were not analysed statistically. Conclusions: AFB allows better control of some metabolic aspects, reduces intra- and extradialysis symptoms, and improves patient quality of life. Whether the long-term prognosis can be improved by AFB remains to be established with further studies. Key words: acetate-free biofiltration; bicarbonate haemodialysis; diabetic nephropathy; morbidity rates; RDT      

Erythropoietin to treat anaemia in critical care patients: a multicentre feasibility study

Anaemia is common and associated with poor outcomes during and after critical illness. The use of erythropoietin to treat such anaemia is controversial with older studies showing mixed results. In this study, we aimed to evaluate the feasibility of performing a large multicentre randomised controlled trial of erythropoietin in this setting. We randomly allocated patients staying in the ICU for ≥ 72 h with haemoglobin ≤ 120 g.l^-1 to either a weekly injection of erythropoietin (40,000 iu, maximum of five injections) or placebo (saline). The primary endpoint was feasibility (as measured by recruitment, randomisation and follow-up rates, and protocol compliance). Secondary endpoints included biological efficacy and clinical outcomes. Forty-two participants were recruited and randomly allocated, all participants received the allocated intervention, but one withdrew their consent and refused the use of their data, leaving 20 in the erythropoietin group and 21 in placebo group. Follow-up was completed for all patients who survived. The overall recruitment rate was 73.7% with 8.4 participants recruited on average per month. The last haemoglobin measured before hospital discharge (or death) was similar between the groups with a mean (SD) haemoglobin of 107 (21) vs. 95 (25) g.l^-1, mean difference (95%CI) 11 (-4–26), g.l^-1, p = 0.154. A large, multicentre randomised controlled trial of erythropoietin to treat anaemia in ICU patients is feasible and necessary to determine effects of erythropoietin on mortality in ICU anaemic patients.     

Crossover comparison of intravenous and subcutaneous erythropoietin in haemodialysis patients.

To examine the suggestion that s.c. administration of recombinant human erythropoietin (rHuEpo) may be more effective than i.v. administration, we changed the route of administration in 11 patients, previously established on a stable dose of rHuEpo given twice or thrice weekly, from i.v. to s.c. administration without altering the dose. All patients were iron replete (serum ferritin greater than 100 micrograms/l). In one patient the haemoglobin concentration declined at the time of conversion due to poor compliance, and another patient died shortly after conversion. In the remainder there was a significant increase in haemoglobin concentration from 9.30 (SD 0.78) at the time of conversion to 9.84 (0.59) at 1 month, 10.35 (1.22) at 2 months, and 10.39 (1.42) at 3 months. The increase in haemoglobin concentration was greater than 1 g/dl at 3 months in only five of the patients. Serum ferritin prior to conversion was similar in 'responders' and 'non-responders', but all responders had a transferrin saturation of greater than 16%, whereas three of four non-responders had transferrin saturation of less than or equal to 16%. Subcutaneous administration of rHuEpo is more effective, dose for dose, than i.v. administration, but poor iron mobilization may limit the response.     

Effect of dialyser membrane pore size on plasma homocysteine levels in haemodialysis patients.

BACKGROUND: Hyperhomocysteinaemia is a putative risk factor for atherothrombotic cardiovascular disease in the haemodialysis population. High-dose vitamin B therapy does not entirely normalize elevated plasma total homocysteine (tHcy) levels in haemodialysis patients. Alternative therapies to reduce tHcy further are therefore required. Modifications of the dialysis regimen may result in a better removal of Hcy. We examined the effect of dialyser membrane pore size on tHcy levels in vitamin-replete chronic haemodialysis patients. METHODS: Forty-five haemodialysis patients were dialysed during 4 weeks with a low-flux, a high-flux and a super-flux membrane, in random order. Pre-dialysis tHcy was determined at baseline and every 4 weeks. In 18 patients, plasma tHcy before and after dialysis and dialysate tHcy concentrations were measured. RESULTS: Pre-dialysis tHcy decreased significantly during 4 weeks super-flux dialysis (-14.6 +/- 2.8%), whereas it remained stable during high-flux (+0.5 +/- 2.4%) and low-flux dialysis (+1.7 +/- 3.2%). The homocysteine reduction ratio was not different for the three membranes: 0.39 +/- 0.03 for the super-flux, 0.47 +/- 0.02 for the high-flux and 0.39 +/- 0.02 for the low-flux dialyser. The amount of Hcy recovered in the dialysate during a single dialysis session was also similar: 117.5 +/- 3.6 micro mol during super-flux, 95.3 +/- 11.5 micro mol during high-flux and 116.5 +/- 11.6 micro mol during low-flux dialysis. CONCLUSION: Super-flux dialysis significantly lowers tHcy in chronic haemodialysis patients. Improved removal of middle-molecule uraemic toxins with inhibitory effects on Hcy-metabolizing enzymes, rather than better dialytic clearance of Hcy itself, may explain the beneficial effect of the super-flux membrane.     

Economic appraisal of maintenance parenteral iron administration in treatment of anaemia in chronic haemodialysis patients

BACKGROUND.: Iron deficiency is common in haemodialysis patients and adequatesupplementation by the oral or parenteral route has been limitedby drug side-effects, absorption, and cost. Intermittent doses of intravenous iron dextran complex are recommendedin patients with inadequate iron stores despite maximal toleratedoral dose. We conducted a prospective study with economic analysisof a regular maintenance intravenous iron regimen in this groupof patients. METHODS.: Fifty patients comprising one-half of our haemodialysis populationrequired intravenous iron treatment, i.e. they failed to achievean arbitrary goal serum ferritin 100 µg/l despite maximaltolerated oral iron dose. After a loading dose of intravenousiron dextran complex (IV-FeD) based on Van Wyck's nomogram (400±300mg) they received a maintenance dose of 100 mg IV-FeD once every2 weeks. Initial goal serum ferritin was set at 100–200µg/l. If no increase in haemoglobin was achieved at thislevel, transferrin saturation was measured to assess bioavailableiron, and when less than 20%, goal serum ferritin was increasedto 200–300 µg/l. Recombinant human erythropoietin(rHuEpo) was used where needed to maintain haemoglobin in the9.5–10.5 g/l range only if ferritin requirements weremet. RESULTS.: Mean haemoglobin rose from 87.7±12.1 to 100.3±13.1g/l (P<0.001, Cl 7.7–17.9) at mean follow-up of 6 months(range 3–15 months). In patients on rHuEpo, dose per patientwas reduced from 96±59 u/kg per week to 63±41u/kg per week, repres enting a 35% dose reduction (P<0.05,Cl 1–65). An annual cost reduction of $3166 CDN was projected;however, in the first year this is offset by the cost of theloading dose of IV-FeD required at the beginning of treatment.No adverse reactions were encountered. CONCLUSIONS.: Iron deficiency is very common in our haemodialysis population,especially in those patients receiving rHuEpo. A carefully monitoredregimen of maintenance parenteral iron is a safe, effective,and economically favourable means of iron supplementation inpatients with insufficient iron stores on maximum toleratedoral supplements.     

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)