Treatment of anaemia in inflammatory bowel disease with iron sucrose.

BACKGROUND: Inflammatory bowel disease (IBD)-associated anaemia usually responds to intravenous iron. If not, additive treatment with erythropoietin has been proposed. The objective of the present retrospective study was to evaluate the effectiveness of treatment with iron sucrose alone. METHODS: Sixty-one patients with IBD and anaemia (average haemoglobin 97 g/L) were treated with iron sucrose (iron dose 1.4 +/- 0.5 g). The indications for iron sucrose were poor response and/or intolerance to oral iron. Treatment response was defined as an increase in haemoglobin of > or = 20 g/L or to normal haemoglobin levels (> or = 120 g/L). Two independent investigators retrospectively assessed laboratory variables, clinical findings, and concomitant medication. RESULTS: Two patients were transferred to other hospitals after treatment and therefore could not be evaluated. Fifty-four of the remaining 59 patients (91%) responded within 12 weeks. Sixty percent of the patients had responded within 8 weeks. Five patients had no or only a partial response to iron sucrose of which three had prolonged gastrointestinal blood losses. Eight patients with normal or elevated levels of ferritin could be considered to have anaemia of chronic disease, and all of them responded to iron sucrose. During a follow-up period of 117 +/- 85 (4-291) (mean +/- s (standard deviation) (range)) weeks 19 patients (32%) needed at least one second course of iron sucrose because of recurrent disease. CONCLUSIONS: Anaemia associated with IBD can be successfully treated with intravenously administered iron sucrose, provided that bowel inflammation is treated adequately and enough iron is given. Treatment with iron sucrose is safe. Follow-up of haemoglobin and iron parameters to avoid further iron deficiency anaemia is recommended.

The use of pretransplant erythropoietin to normalize hemoglobin levels has no deleterious effects on renal transplantation outcome.

BACKGROUND: The aim of this study was to establish the outcome of renal transplantation in patients given pretransplant erythropoietin (EPO) treatment targeted at reaching a normal hemoglobin concentration (Hb), compared to those given EPO-treatment aimed at maintaining subnormal Hb. METHODS: A total of 416 patients from Scandinavian countries and with renal anaemia were enrolled to examine the effects of increasing Hb from a subnormal level (90-120 g/liter) to a normal level (135-160 g/liter) by EPO treatment. Half of the patients were randomized to have their Hb increased, with the other half randomized to maintain a subnormal Hb. Thirty-two patients from the normal Hb group and 24 patients from the subnormal group received a renal graft during the study period. The outcomes of these transplantations were examined prospectively for 6 months. RESULTS: Preoperative Hb levels were 143+/-17 and 121+/-14 g/liter in the two groups, respectively (P<0.0001). The Hb remained higher in the normal Hb group during the first 2 weeks after transplantation. The percentage of patients requiring postoperative blood transfusions in the normal Hb group was 16%, compared with 50% in the subnormal group (P<0.01). No statistically significant difference in the proportion of functioning grafts or in the serum creatinine levels could be detected. No correlation between EPO treatment and creatinine levels after transplantation was found. The frequency of adverse events was similar in the two groups. CONCLUSIONS: EPO treatment aimed at reaching a normal Hb in renal transplant recipients reduces the postoperative requirement for blood transfusions and has no deleterious effects on kidney graft function.

Normalization of haemoglobin concentration with recombinant erythropoietin has minimal effect on blood haemostasis.

BACKGROUND: Elevation of haemoglobin (Hb) with recombinant erythropoietin (rHuEpo) in patients with chronic renal failure has raised concern of increased risk of thromboembolic diseases. In this study, a substudy of the Scandinavian multicentre trial, we examined the influence on haemostatic parameters of normalization of Hb levels from subnormal levels in patients with chronic renal failure. METHODS: Twenty-six patients, 17 males (before study start Hb 113+/-6 g/l) and nine females (Hb 111+/-8 g/l), with end-stage renal disease were included. Both dialysis and predialysis patients were included. After 3 months of rHuEpo therapy Hb levels reached 136+/-14 g/l for males and 128+/-13 g/l for females, and after 1 year 142+/-11 g/l and 126+/-14 g/l respectively. The increase in Hb was significant both at 3 months and 1 year, compared to baseline. At baseline, after 3 months and 1 year haemostatic and prothrombotic parameters were measured, including prothrombin complex test, activated partial thromboplastin time, platelet aggregation and retention, von Willebrand factor antigen, antithrombin, protein C, total and free protein S, activated protein C resistance, FV-Leiden mutation, D-dimers, plasminogen activator inhibitor-1 and prothrombin fragments 1+2 (PF 1+2). RESULTS: The only statistically significant change was a transient decrease in total levels of protein S at 3 months from 131 to 120% (P=0.0093). The free and active form of protein S showed no significant change. After 1 year the difference was not seen. CONCLUSIONS: Apart from a transient and clinically insignificant decrease in total protein S, we found no prothrombotic changes after normalization of Hb from subnormal levels. Our findings indicate that rHuEpo treatment may aim at normalizing Hb levels without significant effects on haemostatic parameters in patients with chronic renal failure compared to patients with subnormal Hb levels.

Effect of normalization of hematocrit on brain circulation and metabolism in hemodialysis patients.

Full correction of anemia with recombinant human erythropoietin (rhEPO) has been reported to reduce the risk of cardiovascular morbidity and mortality and improve the quality of life in hemodialysis (HD) patients. Effects of normalization of hematocrit on cerebral blood flow and oxygen metabolism were investigated by positron emission tomography. Regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), oxygen extraction ratio (rOER), and metabolic rate for oxygen (rCMRO2) were measured in seven HD patients before and after correction of anemia and compared with those in six healthy control subjects. In addition, blood rheology before and on rhEPO therapy was measured in HD patients, which included blood viscosity, plasma viscosity, erythrocyte fluidity, and erythrocyte aggregability. The results showed that plasma viscosity was high (1.51+/-0.19 mPa x s) and erythrocyte fluidity was low (85.8+/-4.8 Pa(-1) x s(-1)), while whole blood viscosity was within the normal range (3.72+/-0.38 mPa x s) before rhEPO therapy. After treatment, the hematocrit rose significantly from 29.3+/-3.3 to 42.4+/-2.2% (P<0.001), accompanied by a significant increase in the whole blood viscosity to 4.57+/-0.16 mPa x s, nonsignificant decrease in erythrocyte fluidity to 79.9+/-7.4 mPa(-1) x s(-1) and nonsignificant change in plasma viscosity (1.46+/-1.3 mPa x s). Positron emission tomography measurements revealed that by normalization of hematocrit, rCBF significantly decreased from 65+/-11 to 48+/-12 ml/min per 100 cm3 (P<0.05). However, arterial oxygen content (caO2) significantly increased from 5.7+/-0.7 to 8.0+/-0.4 mmol/L (P<0.0001), rOER of the hemispheres significantly increased from 44+/-3 to 51+/-6% (P<0.05) and became significantly higher than healthy control subjects (P<0.05). In addition, rCBV significantly increased from 3.5+/-0.5 to 4.6+/-0.6 ml/100 cc brain tissue. The results showed that oxygen supply to the brain tissue increased with normalization of hematocrit, but it was accompanied by increased oxygen extraction in the brain tissue. This may be assumed to be related to the decrease of erythrocyte velocity in the cerebral capillaries as a result of the decreased blood deformability and the increased plasma viscosity.

Kinetic analysis of 52Fe-labelled iron(III) hydroxide-sucrose complex following bolus administration using positron emission tomography.

Kinetic analysis of a single intravenous injection of 100 mg iron(III) hydroxide-sucrose complex (Venofer) mixed with 52Fe(III) hydroxide-sucrose as a tracer was followed for 3-6 h in four generally anaesthetized, artificially ventilated minipigs using positron emission tomography (PET). The amount of injected radioactivity ranged from 30 to 200 MBq. Blood radioactivity, measured by PET in the left ventricle of the heart, displayed a fast clearance phase followed by a slow one. In the liver and bone marrow a fast radioactivity uptake occurred during the first 30 min, followed by a slower steady increase. In the liver a slight decrease in radioactivity uptake was noted by the end of the study. A kinetic analysis using a three-compartment (namely blood pool, reversible and irreversible tissue pools) model showed a fairly high distribution volume in the liver as compared with the bone marrow. In conclusion, the pharmacokinetics of the injected complex was clearly visualized with the PET technique. The organs of particular interest, namely the heart (for blood kinetics), liver and bone marrow could all be viewed by a single setting of a PET tomograph with an axial field of view of 10 cm. The half-life (T1/2) of 52Fe (8.3 h) enables a detailed kinetic study up to 24 h. A novel method was introduced to verify the actual 52Fe contribution to the PET images by removing the interfering radioactive daughter 52mMn positron emissions. The kinetic data fitted the three-compartment model, from which rate constants could be obtained for iron transfer from the blood to a pool of iron in bone marrow or liver to which it was bound during the study period. In addition, there was a reversible tissue pool of iron, which in the liver slowly equilibrated with the blood, to give a net efflux from the liver some hours after i.v. administration. The liver uptake showed a relatively long distribution phase, whereas the injected iron was immediately incorporated into the bone marrow. Various transport mechanisms seem to be involved in the handling of the injected iron complex.

Pharmacokinetics and red cell utilization of iron(III) hydroxide-sucrose complex in anaemic patients: a study using positron emission tomography.

The pharmacokinetics of a single intravenous injection of 100 mg iron hydroxide-sucrose complex labelled with a tracer in the form of 52Fe/59Fe was followed in six anaemic patients for a period ranging from 6 to 8 3 h using positron emission tomography (PET). Red cell utilization of the labelled iron was followed for 4 weeks. PET data showed radioactive uptake by the liver, spleen and bone marrow. The uptake by the macrophage-rich spleen demonstrated the reticuloendothelial uptake of this iron preparation, with subsequent effective release of that iron for marrow utilization. Red cell utilization, followed for 4 weeks, ranged from 59% to 97%. The bone marrow influx rate constant was independent of blood iron concentration, indicating non-saturation of the transport system in bone marrow. This implied that higher doses of the iron complex can probably be used in the same setting. A higher influx rate into the marrow compared with the liver seemed to be consistent with higher red cell utilization. This would indicate that early distribution of the injected iron complex may predict the long-term utilization.

Identification of complement activators and elucidation of the fate of complement activation products during extracorporeal plasma purification therapy.

It has been known for many years that the complement system is activated during extracorporeal plasma purification (ECCP) therapy. In a previous study, we showed that high concentrations of complement activation products (CAPs) are returned to the patient during immunoadsorption treatment. In the present study, we investigated the question of where complement activation takes place with different forms of ECPP equipments as well as the fate of the CAPs. Eleven patients (8 men and 3 women), mean age 52 +/- 18 years, were included in the study. They were treated either with plasmapheresis (PP), immunoadsorption, bilirubin adsorption, or low density lipoprotein (LDL) apheresis. It was found that during all ECPP treatments and after the plasma separation filter, the plasma concentrations of CAPs were increased, and that high concentrations of CAPs were returned to the patients, except with PP. The plasma levels of individual CAPs varied between different types of ECPP. These variations were due to several factors: (1) complement activation (CA) on the plasma separator and a secondary device, e.g., column or membrane; (2) adsorption of specific CAPs to separation columns; and (3) reduction of CAPs due to separation and waste. Since CAPs have inflammatory and immunological effects, it is possible that high serum concentration of CAPs in the treated patients may influence the clinical outcome of the treatment. In conclusion, complement activation is a fact that should not be ignored during performance of any form of an ECPP. It is the plasma separator that plays a key role in the process of complement activation. Different ECPP treatments may have different effects regarding the levels of individual CAPs.

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.

Gender and age differences in transthoracic bioimpedance.

Thoracic impedance consists of a constant baseline component Z0 and a time-variable component delta Z which represents the impedance change related to the cardiac cycle. The maximum part of delta Z [(dZ/dt)max] represents the peak of the ascending aortic blood flow. Measurements of basal thoracic impedance are affected by structural and anatomical differences in the thorax related to sex and ageing. This component is a variable in the denominator of Sramek's formula which is used for calculating stroke volume. The aim of this study was to elucidate the question as to whether the age- and sex-related variation in basal impedance may affect bioimpedance measurements of stroke volume. The study comprised 111 healthy subjects (55 males and 56 females) of ages between 20 and 69 years, divided according to age decades into five groups each of males and females. Stroke volume index (SI), Z0 and (dZ/dt)max were measured in every subject, using transthoracic bioimpedance cardiography. Z0 and (dZ/dt)max had significantly higher values in females than in males in every age group except the oldest one in the case of Z0 and the oldest two groups in the case of (dZ/dt)max. Stroke index showed no significant sex difference, although the higher Z0 in females may underestimate the values of stroke index. Elevation of (dZ/dt)max in females may therefore reflect a positive relation to Z0 rather than higher flow rates. Since Z0 and (dZ/dt)max are variants in opposite positions in Sramek's formula (denominator and numerator, respectively), this functional relationship may keep the bioimpedance measurements from being affected by the sex- and age-related changes in Z0.

Proportional changes in body fluid with hemodialysis evaluated by dual-energy X-ray absorptiometry and transthoracic bioimpedance with particular emphasis on the thoracic region.

Alterations in body composition during extracorporeal hemodialysis (HD) were investigated in 12 hemodialysis patients (9 males and 3 females, mean age 50 +/- 15 years) with a mean ultrafiltration of 2.6 +/- 1.0 L. Analysis was performed using a dual-energy x-ray absorptiometry technique (DXA), which measures 3 principal components of the body: fat mass (FM): lean body mass (LBM), i.e., all soft tissues excluding fat; and bone mineral content (BMC). These 3 components were calculated for the whole body and for different body regions (namely, the thorax, trunk, lower limbs, and upper limbs). The thoracic cage region could be defined manually, separately from the trunk, and its tissue composition was calculated. DXA analysis was performed concomitant with a measurement of the basal thoracic impedance (TFI) by bioimpedance cardiography prior to and 1 h after dialysis. We found a significant decrease in the total LBM, from 55.8 +/- 8.8 to 53.3 +/- 9.3 kg (p < 0.05), but no change in either the FM or BMC. Moreover, there was a disproportional reduction in the LBM in different regions, being significantly greater in the thorax (7.47 +/- 3.7%) than in the other body regions (trunk 4.3 +/- 2.0%, lower limbs 5.4 +/- 2.1%, and upper limbs 4.7 +/- 1.5%). Regarding bioimpedance, a stronger significant correlation was detected between the percentage changes in the TFI and the changes in thoracic fluid (r = 0.80, p < 0.01) than between the changes in the TFI and the changes in the total body fluid (r = 0.63, p < 0.01). The absolute values of the TFI were also significantly and negatively correlated to the thoracic lean mass to fat mass ratio, both before and after HD (r = 0.82, p < 0.001 and r = 0.86, p < 0.001, respectively). In conclusion, DXA is a very sensitive technique to detect fluid changes during HD in the thorax when the thoracic cavity is defined as a region of interest as well as for the whole body. The data also indicate an extracellular compartmental imbalance between different regions with a significantly greater change in the thoracic region. Transthoracic bioimpedance is a useful technique for evaluating the HD induced changes in the thoracic fluid, rather than total body fluid.

Anemia associated with advanced prostatic adenocarcinoma: effects of recombinant human erythropoietin.

BACKGROUND AND METHODS: Nine patients with hormone-refractory metastatic prostatic adenocarcinoma and anemia were treated with recombinant human erythropoietin (rHuEpo) at a median dose of 150 U/kg BW 3 times a week subcutaneously. Baseline hemoglobin (Hb) ranged from 70 to 116 g/L, and the study duration was 12 weeks (median patient participation period was 8 weeks). RESULTS: Four patients demonstrated a median Hb increase of 20 g/L and were considered responders. Three patients showed a median increase of 17 g/L but required blood transfusion once, and were therefore considered as partial responders. Baseline erythropoietic status showed a significant correlation between serum Epo and Hb. Inadequate Epo production, evaluated by the observed/predicted log Epo ratio, was found in two patients. Defective bone marrow activity, demonstrated by low transferrin receptor (TfR), and hypoferremia in spite of abundant iron stores were also shown. Hemorheological investigations showed elevated plasma viscosity. CONCLUSIONS: Our results indicate that suppression of erythropoiesis can be mainly explained by the depressed marrow activity. The altered hemorheology might contribute to the anemia. This anemia could possibly be corrected with rHuEpo.

Treatment of homozygous familial hypercholesterolemia with low density lipoprotein apheresis: a 4 year follow-up study.

Hypercholesterolemia and elevated lipoprotein (a) (Lp[a]) levels are considered to be risk factors for the development and progression of premature atherosclerosis. The purpose of our report is to describe the effects of low density lipoprotein (LDL) apheresis (Liposorber system, Kanegafuchi Chemical Industrial Company LTD, Osaka, Japan) on serum lipoprotein concentrations and the clinical status in 2 male patients with homozygous familial hypercholesterolemia. Compared with pretreatment values, the posttreatment concentrations of total cholesterol, LDL cholesterol, and Lp(a) were significantly reduced by 50-60% (p < 0.0001). The concentration of high density lipoprotein (HDL) cholesterol was slightly affected. After one treatment session, LDL cholesterol and Lp(a) were decreased on average by 65% and then increased to reach about 70-75% of the pretreatment values before the next session. Prior to the treatment with LDL apheresis, each patient had suffered one myocardial infarction and had had 2 coronary angiographies. After treatment with LDL apheresis, neither cardiac complaints nor myocardial infarction were observed. The xanthomas were much decreased during the treatment or disappeared. We conclude that LDL apheresis can be continued safely and without major technical problems for several years. Apheresis effectively lowers the serum levels of total and LDL cholesterol. Furthermore, it reduces Lp(a), which is not influenced by lipid-lowering drugs. The reduction of LDL cholesterol and Lp(a) may delay the progression of the atherosclerotic process, thereby helping to reduce the risk of new episodes of coronary heart disease and thus extending the life expectancy in these patients.

Assessment of erythropoiesis following renal transplantation.

Ten patients, who received cadaveric kidneys, were followed for 24 wk with serial measurements of serum erythropoietin (S-Epo), transferrin receptor (S-TfR) and iron variables. The mean pretransplant creatinine clearance was 8.2 (range 0-22) ml/min and the mean haemoglobin (Hb) level was 99 +/- 18.6 (range 66-124) g/l. Nine patients demonstrated a gradual increase in S-Epo levels, which reached a peak, and was accompanied by a parallel increase in S-TfR levels with a median lag period of 3 wk between both peaks. Hb correction followed the S-TfR peak after a second lag period (median 7 wk). Elevated S-Epo and S-TfR did not result in correction of anaemia in 1 patient due to impaired graft function. Within 4 months, S-Epo levels reached the normal range while TfR levels were higher than normal. Follow-up of iron status demonstrated the development of iron deficiency in 5 patients, which was corrected spontaneously. Improvement in erythropoiesis after renal transplantation seems to occur by means of expansion of the erythroid marrow, as detected by increasing S-TfR levels, subsequent to a S-Epo peak. This expansion precedes Hb normalization. A nonuraemic environment is probably a prerequisite for the correction of anaemia but not for the increase in S-Epo or S-TfR levels. Iron deficiency may occur after transplantation due to an increase in iron utilization.

Effects of LDL apheresis on blood rheology in two patients with homozygous familial hypercholesterolaemia.

Changes in haemorheological and lipid variables were investigated in 2 patients with homozygous familial hypercholesterolaemia (FH) treated with low-density lipoprotein (LDL) apheresis using dextran sulphate adsorbent. The immediate effect of LDL apheresis was a fall in plasma fibrinogen by 50%, total and LDL cholesterol by 60%, plasma viscosity by 12% and whole blood viscosity by 17%. Before the 12th treatment session, plasma fibrinogen concentration remained reduced by 22%, whole blood viscosity by 17% and the plasma viscosity by 11% compared with the initial values. Total and LDL cholesterol in plasma also remained reduced by about 50%. We conclude that LDL apheresis, using dextran sulphate adsorbent, improves blood rheology. The decrease in plasma fibrinogen concentrations, plasma viscosity and LDL cholesterol might be factors contributing to the improved haemorheological properties.

Effects of extracorporeal hemapheresis therapy on blood rheology.

The blood flow property is one of the factors determining blood perfusion and oxygen supply. The viscosity of the blood is primarily related to the hematocrit, but also to the amount of fibrinogen and other macromolecules present in the blood. Patients with ischemic heart disease have shown a rapid and safe improvement in their hemorheological state when treated with heparin-induced extracorporeal low-density lipoprotein (LDL) precipitation (HELP). In this study we used two extracorporeal hemapheresis methods, plasmapheresis (PP) and immunoadsorption (IA), in 15 patients (eight patients treated with PP and seven patients with IA) with various diseases. Hemorheological variables and plasma fibrinogen were measured before and after the first and before the third treatment performed at 3 consecutive days. The aim of our study was to investigate the immediate effects of these two treatment modalities on the flow properties of blood. Immediately after the first PP and IA session statistically significant declines in plasma fibrinogen concentration, plasma viscosity, whole blood viscosity, and erythrocyte aggregation tendency were found. These changes persisted before the third treatment session. The erythrocyte fluidity and hematocrit remained unchanged. We conclude that extracorporeal hemapheresis therapy, with plasmapheresis or immunoadsorption, affects the blood rheology by decreasing the plasma viscosity and erythrocyte aggregation tendency. The decrease in plasma fibrinogen is probably the main factor underlying that, but other factors such as a decrease in immunoglobulins may also be of importance.

Computed tomographic measurement of lung density changes in lung water with hemodialysis.

In 10 hemodialysis patients, with an ultrafiltration volume ranging from 1 to 4.5 liters per session, the lung density was measured by computed tomography (CT) and the lung volumes by total body plethysmography. From the CT numbers (difference in X-ray attenuation between lung and water, measured in Hounsfield units, HU), and by using a special computer program, quantitative estimates of the densities of normally inflated (pixels between -1,000 and -500 HU), poorly inflated (pixels between -500 and -100 HU) and noninflated lung tissue (pixels between -100 and +100 HU) were obtained. The sizes of the normally and poorly inflated areas were also measured. The results showed that, after dialysis, the normally inflated area was decreased in density and increased in size, and conversely, the size of the poorly inflated area was diminished but without change in density. This finding implied introduction of more gas into the lung. The above observation was reflected by the results of pulmonary function measurements, in that the total lung capacity and functional residual capacity were significantly increased after dialysis. In conclusion, changes in lung fluid (both intra- and extravascular) with hemodialysis can be measured quantitatively by the changes in lung density as estimated by the CT densitometry technique.

Lung density for assessment of hydration status in hemodialysis patients using the computed tomographic densitometry technique.

The density of the lung reflects the total mass of fluid, air, and dry lung tissue per unit volume of the lung. Lung density can be measured by evaluation of attenuation of an electron beam with computed tomography (CT). This technique has been shown to be sufficiently reliable and sensitive to distinguish normal from abnormal lung water. The aim of this study was to find out whether lung density properly reflects the hydration status in hemodialysis patients in comparison with other standard methods. Fourteen hemodialysis patients, with an ultrafiltration ranging from 0.3 to 4.5 liters per session, underwent CT measurements of lung density, ultrasonographic measurements of the diameter of the inferior vena cava after quiet expiration (IVCe) and quiet inspiration (IVCi), and measurements of the hematocrit and plasma levels of the biochemical hydration markers cyclic guanosine monophosphate (cGMP) and atrial natriuretic peptide (ANP). These measurements were performed before and 3.5 to 4 hours after termination of dialysis. Quantitative estimates of lung density were obtained within pixels with CT numbers ranging between -1000 and -100 Hounsfield Units (HU), and compared with normal data from 18 normal controls. In normal controls, the lung density ranged from -800 to -730 HU. In hemodialysis patients, lung density was significantly higher than normal before dialysis (-678 +/- 96 HU, P < 0.01) and significantly decreased after dialysis (-706 +/- 92 HU, P < 0.05), indicating a decrease in fluid content of the lung. The density was normalized in 5 patients. A significant correlation was found between lung density and IVCe both before and after dialysis (r = 0.8, P < 0.01 for both). Change in density was significantly correlated to amount of ultrafiltration (r = 0.67, P < 0.01) and percent change in blood volume (r = 0.63, P < 0.05), indicating that lung density is greatly affected by changes in the extracellular fluid volume, mainly the intravascular volume. In conclusion, lung water reflects the hydration status in hemodialysis patients and can be monitored by measuring the lung density by CT. Accordingly, normalization of lung density can help to achieve a proper dry weight in these patients.

Reduction of plasma fibrinogen, immunoglobulin G, and immunoglobulin M concentrations by immunoadsorption therapy with tryptophan and phenylalanine adsorbents.

Immunoadsorption (IA) therapy with tryptophan (TR-350) or phenylalanine (PH-350) adsorbents has been used to reduce the concentration of serum antibodies in human lymphocyte antigen (HLA)-immunized patients. Other forms of plasma purification have been reported to reduce the level of fibrinogen, which affects the blood properties. In this study we investigated the effects of IA therapy using both adsorbents on plasma fibrinogen and immunoglobulins G and M in 13 patients (8 patients were treated with TR-350, and 5 patients were treated with PH-350). During each session I plasma volume (2.8 +/- 0.4 L of plasma) was processed through the immunocolumn and then returned to the patient together with the blood cells. Compared with the pretreatment values, the plasma fibrinogen, IgG, and IgM concentrations were significantly reduced after IA therapy (p < 0.01 for TR-350; p < 0.04 for PH-350). There was a positive correlation between the degree of reduction of plasma proteins and the number of IA treatments given. A nonparametric test (Wilcoxon's signed-rank test or the Mann-Whitney test) was used for statistical analysis. We conclude from our study that IA therapy effectively lowers the plasma levels of fibrinogen, IgG, and IgM and thus can be considered a valuable alternative to other blood purification methods.

Pharmacokinetics of iron(III)-hydroxide sucrose complex after a single intravenous dose in healthy volunteers.

The pharmacokinetics of iron were investigated after intravenous administration to 12 healthy volunteers of iron(III)-hydroxide sucrose complex (Venofer) as a single i.v. dose containing 100 mg Fe. The average predose concentration was 35.7 +/- 12.5 mumol/l. There was no statistically significant difference between the serum iron level before injection (0 h) and the level at 24 h after the injection. The compartment model used includes a Michaelis-Menten term and is in excellent agreement with the observed exchange of iron to transferrin and with the daily iron turnover by transferrin. The intravenously injected iron(III)-hydroxide sucrose complex led rapidly to high serum iron levels. Maximum measured levels averaged 538 mumol/l (30.0 mg/l) at 10 min after the injection. The terminal half-life of the injected iron was calculated to be 5.3 h. Mean total area under the curve (AUC) was 1491 mumol/l h, the mean residence time (MRT) was 5.5 h. The total body clearance was 20.5 ml/min. The volume of distribution of the central compartment (Vc) was 3.21, hence close to the volume of the serum; the volume of distribution at steady state (Vdss) was 7.31; and the volume of distribution during elimination (Vdarea) was 9.21. The calculated amount of iron transported by transferrin was 31.0 +/- 6.6 mg Fe/ 24h. In summary, the data show that the injected iron(III)-hydroxide sucrose complex is quickly cleared from the serum with a terminal half-life of approximately 5-6 h. Renal elimination of iron contributed very little to the overall elimination (in average < 5%). Renal elimination of sucrose averaged about 68 +/- 10% and 75 +/- 11% of the administered dose after 4 h and 24 h, respectively.

Renal anaemia treatment with recombinant human erythropoietin increases cardiac output in patients with ischaemic heart disease.

An increase in blood pressure is common during treatment of renal anaemia with recombinant human erythropoietin (rhEPO). Concomitant findings of a decrease in cardiac output indicate that an increase in the peripheral flow resistance underlies the increase in blood pressure. The aim of this study was to elucidate the haemodynamic changes during rhEPO treatment in patients with ischaemic heart disease (IHD). Haemodynamic variables were assessed by impedance cardiography in 18 consecutive patients with renal anaemia before and after rhEPO treatment. IHD was found in eleven of these patients. The remaining seven served as controls. Before rhEPO treatment, the cardiac index was decreased in the group of patients with IHD, compared with controls and healthy subjects. Due to an increase in stroke index, the cardiac index increased during rhEPO treatment and reached values equal to those in the control group. The blood pressure increased and the increase in mean arterial pressure was correlated to the increase in cardiac index. Apparently the patients with IHD were unable to compensate for anaemia by increasing their cardiac index. Anaemia treatment increased cardiac index, which in turn caused an increase in blood pressure in these patients.