Rapid removal of DFO-chelated aluminum during hemodialysis using polysulfone dialyzers

Aluminum (Al) removal following deferoxamine (DFO) therapy in hemodialysis patients was evaluated in a paired-fashion comparing cuprophane (Travenol 12.11) and polysulfone (Fresenius F-80) dialyzers. QB and QD were held constant at 250 and 500 ml/min, respectively. The polysulfone dialyzer increased total plasma Al clearance from 20.0 +/- 2.8 to 80.5 +/- 7.6 ml/min (P less than 0.01), and reduced the t 1/2 of plasma Al during hemodialysis from 538 +/- 113 to 112 +/- 12 min (P less than 0.01). The polysulfone F-80 dialyzer increased Al removal during the first hour of hemodialysis from 518 +/- 191 to 1812 +/- 720 micrograms/hr (P less than 0.01). During a four hour hemodialysis the F-80 dialyzer returned plasma Al levels to pre-DFO values (103 +/- 36 vs. 93 +/- 23, P less than 0.05), suggesting complete removal of the DFO chelated Al complex. In one patient Al removal was evaluated using cuprophane, F-40, F-60 and F-80 dialyzers and the t 1/2 for Al removed decreased from 484.6 to 276.1 and 108 to 99 minutes, respectively. These data show the Fresenius F-80 polysulfone dialyzer effects the rapid removal of DFO-Al complexes. We propose use of the Fresenius F-80 dialyzer in conjunction with reduced DFO doses and i.m. administration of DFO the day prior to dialysis to limit DFO exposure as a method to decrease DFO-related side-effects in hemodialysis patients.     

Deferoxamine and coated charcoal hemoperfusion to remove aluminum in dialysis patients

We studied the in vitro and in vivo characteristics of aluminum (Al) removal by coated charcoal hemoperfusion (HP) in combination with intravenous deferoxamine (DFO). DFO enhanced the clearance of Al by HP in vitro after 180 minutes of perfusion with a solution containing 403.3 +/- 14.0 ng/ml of Al at 150 ml/min. The Al clearance was 139 +/- 1.0 ml/min with DFO and 49 +/- 10.0 ml/min (P less than 0.001) without DFO. Addition of DFO enhanced in vitro Al removal from 5.5 +/- 0.9 mg to 10.0 +/- 1.2 mg (P less than 0.05). During our in vivo studies, an HP device was in series in the dialysis circuit after a Cuprophan hemodialyzer. Eight patients with Al toxicity were studied on twelve occasions. Patients received DFO (40 mg/kg) 40 hours before the study. The total Al clearance with the combined hemodialysis (HD) and HP devices was higher than that obtained by the dialyzer alone at 30 minutes (62 +/- 4.9 ml/min vs. 25 +/- 2.5 ml/min, P less than 0.02) and after 180 to 210 minutes (32 +/- 3.0 ml/min vs. 19 +/- 2.9 ml/min, P less than 0.02). After 120 minutes the Al clearance by the HP device alone was significantly lower than the initial Al clearance by HP. Combined HD plus HP removed 2.9 +/- 0.4 mg of Al, whereas the total removal of Al by HD alone was 1.5 +/- 0.3 mg (P less than 0.01).     

Pharmacokinetics of vancomycin in patients undergoing hemodialysis with polyacrylonitrile

The pharmacokinetics of vancomycin in patients undergoing dialysis with cuprophane membranes are well known, however little has been reported of the use of polyacrylonitrile membranes in dialysis. We studied, in a crossover design, eight dialysis patients (7 men, 1 woman) aged 30 to 66 years who prospectively received 1 gram of vancomycin i.v. before first dialysis and were subsequently hemodialyzed with cuprophane every second day for a total of three times. A month later trial was repeated using polyacrylonitrile. A mono-compartment model was used to calculated pharmacokinetic parameters. Mean +/- standard deviation of vancomycin clearance varied from 5.2 +/- 2.1 ml/min in the interdialysis period to 9.7 +/- 2.7 ml/min during dialysis with cuprophane and to 58.4 +/- 15.6 ml/min during dialysis with polyacrylonitrile (p less than 0.001). Vancomycin half-life varied from 71.5 +/- 23.0 to 35.9 +/- 9.8 and to 6.1 +/- 1.4 hours, respectively (p less than 0.001). Fractional removal of vancomycin increased from 4% using the cuprophane dialyzer to 34% using the polyacrylonitrile dialyzer (p less than 0.001). Serum vancomycin levels at 100 and 168 hours were higher with cuprophane than with polyacrylonitrile (7.0 +/- 2.2 vs 3.9 +/- 1.2 micrograms/ml) (p less than 0.001). Moreover, the mean levels at 100 hours were suboptimal on polyacrylonitrile. Approximately 208 +/- 53 mg of vancomycin were removed during one polyacrylonitrile dialysis. Thus, those patients who undergo dialysis with polyacrylonitrile and are treated with vancomycin may need supplementary doses post dialysis or to lessen dosage intervals than those traditionally used for dialysis patients since clearance of the drug is significantly higher than with cuprophane dialyzers. Continuous monitoring of vancomycin levels is also recommended.     

Removal of aluminoxamine and ferrioxamine by charcoal hemoperfusion and hemodialysis.

We studied the removal of aluminoxamine (AlO) and ferrioxamine (FO) by (i) hemoperfusion/hemodialysis using an AluKart in combination with either a Cuprophan F-120 or a Hemophan FH-160 membrane, or (ii) hemodialysis with a high-flux F-60 polysulfone membrane. The same six dialysis patients underwent in a random order dialysis by the three set-ups after i.v. infusion of 30 mg/kg of desferrioxamine (DFO) during the last half an hour of the preceding dialysis session. The mean +/- SD plasma AlO and FO clearances of the AluKart combined with either a F-120 or FH-160 membrane were 194.3 +/- 25.8 ml/min (AlO) and 164.2 +/- 41.3 ml (FO) at the start of dialysis declining to respectively 76.6 +/- 27.3 and 68.5 +/- 42.6 ml/min at the end of dialysis. With a high-flux dialysis membrane the intra-dialytic plasma clearance remained constant at 81.5 +/- 6.8 ml/min for AlO and 60.0 +/- 2.8 ml/min for FO. In the presence of an AluKart combined with a FH-160 up to 84 +/- 27% and 84 +/- 19% of the available AlO and FO could be removed during a four-hour hemoperfusion/hemodialysis session. During the first hour of dialysis, respectively 59 and 58% of the total amount of AlO and FO extracted by the AluKart was removed compared to only 9 and 16% during the last hour.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effective anticoagulation by a low molecular weight heparin (Fragmin) in hemodialysis with a highly permeable polysulfone membrane.

The efficacy and kinetics of a low molecular weight heparin fragment (LMWH-fragment, Fragmin) were studied during one hemodialysis session with a highly permeable polysulfone membrane and compared to a second dialysis session using a conventional cuprophane membrane. All patients received 5000 U of Fragmin given as an injection into the arterial line at start of dialysis. The anticoagulative efficacy was evaluated by measuring plasma fibrinopeptide A concentrations. LMWH-fragment concentrations in plasma and ultrafiltrate were determined by an amidolytic activity assay and by a radioimmunoassay using a monoclonal antibody. During hemodialysis with cuprophane and polysulfone membranes the fibrinopeptide A concentrations were low indicating adequate anticoagulation. LMWH concentrations in plasma did not differ in the two membranes at any time. The LMWH-fragment in the ultrafiltrate could neither be detected with the amidolytic assay nor with the radioimmunoassay. We conclude that a single injection of Fragmin effectively prevents clotting during hemodialysis with a highly polysulfone membrane. No significant amounts of the anticoagulant are lost over the dialysis membrane.     

Biocompatibility of dialysis membranes: effects of chronic complement activation

The ability of three dialysis membranes (cuprophane, cellulose acetate, and polymethylmethacrylate) to activate complement was studied prospectively in ten chronic dialysis patients using new and reused membranes. Patients were dialyzed for 1 month with each type of membrane. New cuprophane membranes caused the most intense activation, while polymethylmethacrylate (PMMA) surfaces caused the least degree of complement activation. Reuse decreases the capacity of the cuprophane membrane to activate complement but does not significantly alter the capacity of cellulose acetate membranes. The extent of complement activation paralleled the ability of these membranes to induce neutropenia. Recurrent dialysis with new cuprophane and cellulose acetate membranes leads to a decrease in pre-dialysis and "rebound leukocytosis" neutrophil count, as well as a more intense activation of complement and an enhanced endogenous clearance of products of complement activation. The clinical sequelae of recurrent complement activation are discussed.     

Mitogenic activity on human arterial smooth muscle cells is increased in the plasma of patients undergoing hemodialysis with cuprophane membranes

During hemodialysis on cuprophane membranes, platelets are activated and release in plasma alpha-granule-specific substances such as PF4 or platelet-derived growth factor (PDGF). PDGF is the main source of mitogenic activity found in serum. In vitro, it induces the proliferation of smooth muscle cells (SMC) which is known to be involved in the development of atherosclerotic lesions. Atherosclerosis is one of the major complications of uremic patients undergoing chronic hemodialysis. To investigate whether this complication could be due to the dialysis itself, we measured the mitogenic activity in plasma of 10 patients undergoing hemodialysis on cuprophane membrane, using human arterial SMC in culture. Mitogenic activity in plasma increased about 3-fold during dialysis. These results may provide an argument in favor of a contribution of platelet activation and release of mitogenic activity to atherosclerosis in patients dialysed with cuprophane membranes.     

Beta-2-microglobulin in hemodialysis patients. Effects of different dialyzers and different dialysis procedures

beta 2-Microglobulin (beta 2m) has been identified as the major constituent of dialysis-related amyloid. Although there is no clear correlation between absolute beta 2m levels and amyloidosis-related symptoms, elevated serum levels are thought to be the basis for tissue deposition of beta 2m. Besides diminished renal excretion and insufficient removal during hemodialysis, a dialysis-related induction of beta 2m production is discussed as the major cause of elevated serum beta 2m levels. In order to evaluate the influence of hemodialysis membranes and the hemodialysis procedure on beta 2m levels we determined serum beta 2m levels in patients on chronic intermittent hemodialysis. Polymethylmethacrylate 2.0 m2, cuprophane and cellulose acetate dialyzers led to increasing beta 2m levels during dialysis, which was in excess of what could be accounted for by hemoconcentration. The polymethylmethacrylate 1.6 m2 dialyzer did not result in a significant rise of beta 2m levels during dialysis. This indicates that production of beta 2m is not only dependent on the membrane material but also on the surface area of the dialyzer. The use of polysulfone and hemophane low-flux dialyzers did not induce an increase in beta 2m levels during dialysis but a significant clearance of beta 2m was not demonstrable either. Volume-controlled dialysis with high-flux membranes (polysulfone 0.65 m2 and polysulfone 1.25 m2) lowered beta 2m; clearance values, however, were significantly higher when these dialyzers were used in a hemodiafiltration procedure. We conclude from our study that some dialysis membranes appear to induce beta 2m production, whereas others do not.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oxalate removal by hemodialysis in end-stage renal disease

Because of mounting evidence of precipitation of calcium oxalate in the soft tissues of patients with end-stage renal disease (ESRD) on maintenance hemodialysis, the plasma oxalate concentrations and calculated dialysis removal of oxalate were studied in seven patients without evidence of either primary or absorption hyperoxaluria prior to ESRD. A reversed-phase high-pressure liquid chromatographic method was developed to quantitate serum oxalate. Mean value +/- SE in four healthy controls was 28 +/- 5 mumol/L, and in the seven patients it was 187 +/- 15 mumol/L predialysis and 89 +/- 11 mumol/L postdialysis. Oxalate deposition in the soft tissues of ESRD patients is the consequence of sustained hyperoxalemia. Oxalate removal by dialysis was calculated from the four-hour oxalate clearance. Since the ionic radii of phosphate and oxalate are similar, total oxalate clearance was calculated midpoint of dialysis. Mean oxalate removal/dialysis was 3.01 +/- 0.283 mmol. On a daily basis this value was 1.645 +/- 0.155 mmol, which is about threefold the normal oxalate excretion rate. It is not significantly different from the excretion rate in absorption oxalurias but is less than that in primary hyperoxaluria. Therefore, it is concluded that hyperoxalemia in ESRD results from loss of renal excretion, failure of hemodialysis to remove enough oxalate to maintain a normal serum concentration, and increased intestinal absorption of oxalate and/or increased endogenous production.     

1.25 (OH)2 cholecalciferol pulse therapy and the effects of different dialysis membranes on serum PTH levels of haemodialysis patients

Either oral, intravenous or subcutaneous 1.25 (OH)₂ cholecalciferol is used in the therapy of hyperparathyroidism, which is a serious complication in patients on haemodialysis. We studied a total of 30 patients (10 women and 20 men) and divided them into two groups depending on the different types of dialysis membranes used. In the poly sulfone group, mean age was 43.7±0.97 years and the average dialysis period lasted 29.9±1.23 months. For the 15 cases in which we used cuprophane membrane the mean age was 40.2±1.31 years and the average dialysis period lasted 16.2±0.86 months. The calcium level of the dialysate in both groups was 1.5 mmol/l. According to the study protocol, the determined oral calcitriol dose was 0.07 mg/kg and it was administered intermittently. After one month on high dose calcitriol therapy, treatment was continued with a maintenance dose of 0.03 mg/kg for a further six months. As a phosphate binding agent, daily 3 g calcium carbonate was administered. Before starting this treatment protocol, patients went on a 1 mg/day calcitriol therapy, although the mean PTH level was 424.63 pg/ml and the mean serum alkaline phosphatase level was 290.2 U/l. During the pretreatment period, levels of PTH, alkaline phosphatase, ionized calcium, and total calcium remained significantly within normal limits as a result of the new therapy protocol applied. PTH and phosphorus clearance rates were compared in the patient groups in which different dialysis membranes had been used. PTH and phosphorus clearances were 15.2±3 ml/min and 239.1±19.2 ml/min, respectively, in the polysulfone membrane group, and 1.1±0.3 ml/min and 112.8±9.88 ml/min, respectively, in the cuprophane membrane group (p<0.05).     

Normal T lymphocyte function in patients with end-stage renal disease hemodialyzed with 'high-flux' polysulfone membranes

T lymphocyte function was analyzed in patients hemodialyzed with 'high-flux' polysulfone membranes, which have been reported to improve the patients' overall clinical condition and well-being. For comparison purposes, patients treated by the use of 'low-flux' cuprophane membranes were also studied. Peripheral blood white cell counts, numbers of lymphocytes as well as the numbers of T cells and their CD4 and CD8 subsets were within normal range in both patient groups. The absolute number of B cells was slightly decreased in cuprophane-membrane- but not polysulfone-membrane-treated patients. The proliferative response of T lymphocytes after stimulation with optimal concentration of phytohemagglutinin (PHA) was normal in patients treated with 'high-flux' membrane dialysis but significantly reduced in those treated with cuprophane membranes. The generation of interleukin-2 (IL-2) receptor on T lymphocytes after PHA stimulation was normal in the polysulfone-membrane-treated group and slightly impaired in the cuprophane-membrane-dialyzed patients. Production of both IL-2 and interleukin-1, as well as the natural killer cell activity, in patients treated by 'high-flux' membrane dialysis were also comparable to controls. The levels of serum beta 2-microglobulin were significantly elevated in patients-maintained on 'high-flux' dialysis membranes but did not reach the levels seen in patients dialyzed by cuprophane membranes. The beta 2-microglobulin at levels seen in patients on cuprophane dialysis had no effects on activation and proliferation of control lymphocytes in vitro. These results suggest that impaired functional responses of T lymphocytes seen in end-stage disease patients on prolonged hemodialysis with cuprophane membranes are not seen in similar patients hemodialyzed with polysulfone membranes.     

Deferoxamine test and bone disease in dialysis patients with mild aluminum accumulation

Aluminum bone disease is a frequent complication of dialysis patients. The deferoxamine (DFO) test has been advocated as a noninvasive procedure for the diagnosis of AI bone lesion. However most of these studies have been performed in symptomatic patients with significant AI bone disease. Whether this test may provide similar data at an earlier stage of AI toxicity is not known. The present study evaluates prospectively 28 patients with mild AI load. Patients studied ranged in age from 21 to 65 years; duration of dialysis was 5.6 +/- 3.2 years; deferoxamine, 40 mg/kg body weight, was infused at the end of dialysis. Serum AI was measured before DFO administration and before the next dialysis treatment. Bone biopsies were performed in all patients. Cortical bone AI was determined biochemically; trabecular and cortical bone AI were also determined histochemically. Mean basal serum AI (43.2 +/- 30.8 micrograms/L) and cortical bone AI (25.7 +/- 35.2 micrograms/g) were moderately increased. Basal serum AI correlated (r = 0.77) with the increment in serum AI after DFO infusion. After DFO, stainable trabecular and cortical bone AI correlated in a similar manner with both basal serum AI and increment in serum AI. Only biochemically determined cortical bone AI was not significantly related to basal serum AI. Nineteen of the 28 patients had evidence of osteitis fibrosa on bone biopsy. Stained AI surfaces but not trabecular AI were different in patients with low and patients with high bone formation rates. The bone findings, assessed as bone formation rates and resorption surfaces, did not correlate with biochemically or histochemically determined bone AI.(ABSTRACT TRUNCATED AT 250 WORDS)     

High fluoride exposure in hemodialysis patients

The observation of higher plasma flouride levels in our hemodialysis (HD) patients than our continuous ambulatory peritoneal dialysis (CAPD) patients (4.0 +/- 0.5 mumol/L [n = 17] v 2.5 +/- 0.3 mumol/L [n = 17], P less than 0.005) prompted an evaluation of fluoride metabolism during HD. We found that serum fluoride was completely ultrafiltrable across cuprophane membranes (99% +/- 4%) and that HD produced acute changes in plasma fluoride levels that correlated well with the fluoride gradient between plasma and dialysis fluid at the start of dialysis. Our HD fluids contained significantly higher fluoride concentrations than were present in commercially prepared peritoneal dialysis fluid. Our fluids are prepared from fluoridated tap water that is purified by reverse osmosis (RO). We conclude that the different concentrations of fluoride in our dialysis fluids account for the differences in the plasma flouride concentrations between our dialysis groups. Since many HD units rely on RO systems to purify fluoridated tap water, it is likely that many HD patients are being exposed inadvertently to increased concentrations of fluoride.     

Radiolucent bone cysts and the type of dialysis membrane used in patients undergoing long-term hemodialysis.

The relationship between the types of dialysis membrane used and the prevalence and severity of radiolucent bone cysts (which are a main radiological feature of dialysis amyloidosis) was studied in 30 patients on hemodialysis for more than 10 years. One of them was treated exclusively with cuprophane; the other 29 were dialyzed with cuprophane, and then treated with polyacrylonitrile AN 69. In 12 of the 30 patients, radiolucent bone cysts (at least 5 mm in diameter in the wrists and at least 10 mm in the shoulders or hips) were observed. The patients with bone cysts spent significantly more time on cuprophane dialysis and significantly less time on AN 69 dialysis than the group of patients without bone cysts. Nine of the 14 patients who had been treated with cuprophane for more than 8 years had bone cysts; whereas bone cysts were observed in only 2 of the 12 patients dialyzed for more than 8 years with AN 69. The frequency of bone cysts was significantly different for each of the two groups. There was, however, no significant difference in the total duration of dialysis between the two groups. The severity of the cystic bone lesions correlated positively with the duration of dialysis using cuprophane and negatively with the duration of dialysis using AN 69. These findings suggest that the development of osteoarticular amyloidosis may be related to the type of dialysis membrane used. Hemodialysis using AN 69 membranes may prevent, or at least postpone the development of dialysis amyloidosis.     

Effect of uremia and hemodialysis on soluble L-selectin and leukocyte surface CD11b and L-selectin

Leukocyte Mac-1 (CD11b/CD18) and L-selectin (CD62L) are implicated in leukocyte adhesion to endothelial cells. In this study, L-selectin and CD11b expression on leukocytes and soluble L-selectin (sL-selectin) serum levels were investigated in 17 nondialyzed patients with chronic renal failure (CRF), in 28 chronic hemodialysis patients before hemodialysis (basal state), and in 32 healthy subjects. These parameters were also monitored during hemodialysis with cuprophane and cellulose diacetate membranes in a crossover study in five patients. Granulocytes from CRF patients displayed lower expression of L-selectin and higher expression of CD11b than granulocytes from healthy subjects. On the other hand, baseline expression of L-selectin and CD11b on leukocytes from hemodialysis patients did not differ from that of healthy subjects. In CRF and hemodialysis patients, sL-selectin levels were significantly lower than in healthy subjects. During hemodialysis, cuprophane membrane induced an upregulation of granulocyte CD11b, a decrease in granulocyte L-selectin, and an increase in sL-selectin serum levels. Conversely, cellulose diacetate caused only a transient increase in granulocyte CD11b and did not modify granulocyte L-selectin and sL-selectin serum levels. High CD11b and low L-selectin expression on granulocytes in CRF patients suggests an activation state, which was not found in hemodialysis patients at the basal state. The lack of activation in hemodialysis patients could reflect the elimination of a uremic toxin by dialysis or a loss of granulocyte responsiveness because of the repetitive stimulation by hemodialysis treatment. The low serum levels of sL-selectin in CRF and hemodialysis patients also suggest granulocyte dysfunction.     

Hemodynamics and Survival of Patients with Acute Renal Failure Treated by Continuous Dialysis with Two Synthetic Membranes

Synthetic membranes are not identical and have specific interactions that may be harmful or beneficial. We have investigated the incidence of hypotension and the outcome of acute renal failure (ARF) in ventilated patients treated by continuous venovenous dialysis with 2 different synthetic membranes. In Study 1, the mean arterial pressure (MAP) and systemic vascular resistance (SVR) were monitored during the first 12 min of dialysis with polyacrylonitrile (PAN). In Study 2, the MAP and survival rates were compared in patients randomly assigned to either PAN or polysulfone. No subjects were receiving angiotensin converting enzyme inhibitors. In Study 1, the MAP decreased due to a reduction in the SVR during the first 6 min of dialysis but returned to the baseline value by 12 min in 22 patients during 27 dialysis treatments. In Study 2, the MAP was lower than the baseline value at 6 min during 233 dialysis treatments in 133 patients randomly assigned to PAN or polysulfone membranes (PAN group, 81.5 ± 15 to 78.7 ± 15.6 mm Hg, p =0.001; and polysulfone group, 81.3 ± 15.4 to 80.0 ± 15.7 mm Hg, p =0.06). Severe reductions in the MAP were seen during 13.2% of the PAN and 7.2% of the polysulfone treatments (χ², p =NS). The age, APACHE II score, MAP, inotrope requirement, and primary diagnosis did not differ according to membrane material in a total of 197 consecutive patients (PAN, n =97; polysulfone, n =100). Patient survival was 29% (PAN) and 27% (polysulfone). In multivariate analysis, APACHE II score, inotrope requirement, and liver failure were significant determinants of survival. In conclusion, PAN and polysulfone membranes were not different with respect to hypotensive reactions or survival in critically ill patients undergoing continuous venovenous hemodialysis.     

Effects of dialysis membranes on beta 2-microglobulin production and cellular expression

We investigated the effects of different dialysis membranes on the production of beta 2-microglobulin (beta 2m) in peripheral blood mononuclear cell cultures (PBMNC) obtained from hemodialysis patients in a prospective cross-over design study. Chronic dialysis with cuprophane membrane leads to an increase in beta 2m production from 129 +/- 11 ng/ml to 192 +/- 23 ng/ml (P less than 0.002). This increase is reversed by the use of a non-complement activating membrane polymethylmethacrylate. In addition, during chronic dialysis with cuprophane membrane, an increasing proportion of these cells display low beta 2m expression on their surface (from 6.1 +/- 0.8% of PBMNC to 16.9 +/- 3.4%, P less than 0.001), concomitant with the emergence of cells with low density of HLA on their surface (from 4.9 +/- 1.2% of cells to 32.9 +/- 7.8% of cells, P less than 0.001). The total content of cell-associated beta 2m is also decreased in dialysis patients in general, and in particular in patients chronically dialyzed with new cuprophane membrane. These effects can be reproduced by incubation of PBMNC with cuprophane membranes, and with the addition of C5a, IL-1 and TNF in vitro. Thus, chronic dialysis with cuprophane membrane may be a factor in the genesis of high beta 2m levels and causes changes in beta 2m and HLA expression on cell surfaces.     

Evolution of serum prealbumin following hemodialysis: effect of different dialysis membranes.

The effects of hemodialysis on the levels of serum prealbumin (pA) were studied on a crossover basis in 17 uncomplicated patients. Bicarbonate dialysate was used exclusively, and two different membranes, cuprophane and polysulfone, were compared. We aimed to prove the induction of an acute-phase response during the procedure. Serum pA, corrected for hemoconcentration, decreased significantly 24 h after the start of cuprophane hemodialysis and returned to the initial value within 48 h. No such change was observed using polysulfone membranes. These results were seemingly correlated with the effects of the membranes on complement activation. It is concluded that cuprophane hemodialysis is indeed associated with an acute-phase response, probably due to interleukin-1 release during the treatment, and that the membrane composition has some role in inducing it. Thus, serum pA analysis may prove useful as an indicator of the biocompatibility of the dialysis procedure.     

Production and kinetics of interleukin-1 in hemodialysis. In vivo and in vitro study

Interleukin-1-beta (IL-1-beta) was measured in the plasma and peripheral blood mononuclear cell lysates of uremic patients undergoing maintenance hemodialysis by means of either cuprophane or polysulfone membranes. Basal plasma levels of IL-1-beta in hemodialyzed patients were strikingly higher than those of uremic patients on conservative treatment or of healthy subjects. Plasma levels of IL-1-beta in uremic patients increased significantly after 3 and 6 months of hemodialysis. The study of the kinetics of IL-1-beta concentration during a single hemodialysis session revealed that the concentration of IL-1-beta fell to 21 and 22% of the predialysis level with cuprophane and polysulfone, respectively. Hemodialysis patients also had a significantly higher intracellular IL-1-beta level than normal controls. During the hemodialysis session, an increase in cell-associated IL-1-beta was seen regardless of the membrane employed. In a parallel study, normal mononuclear cells were subjected to closed-loop in vitro dialysis with either cuprophane or polysulfone membranes, with or without acetate buffer. After 120 min of recirculation, an increase in cell-associated IL-1-beta was detected, but no changes were seen in the circulating medium. IL-1-beta production was not significantly influenced by either membrane or the dialysate composition. Hemodialysis has been associated with high plasma- and cell-associated IL-1 levels. The kinetics of intradialytic changes of IL-1-beta levels make IL-1 an unlikely cause of acute complications in hemodialysis. On the other hand, a chronic elevation of IL-1 in plasma of patients on maintenance hemodialysis may contribute to the development of some of the long-term complications of this treatment.     

Accelerated removal of deferoxamine mesylate-chelated aluminum by charcoal hemoperfusion in hemodialysis patients

Although deferoxamine mesylate (DFO) is effective in removing aluminum (Al) in hemodialysis patients, treatment with this drug is associated with a number of adverse effects. In order to limit the exposure of patients to DFO-Al complexes, the efficacy of colloidin-coated microencapsulated charcoal cartridges added in series to conventional dialyzers was investigated. The clearances of Al by the sorbent system were initially 116 +/- 4.7 mL/min, but decreased to 42.5 +/- 6.6 mL/min after 120 minutes of treatment. Thereafter, the Al clearances remained constant. In contrast, the Al clearances of the dialyzer were 29.5 +/- 1.8 mL/min initially and did not change during the treatment period. Both the percent and absolute decrease in Al levels after four hours of dialysis were greater with the dialyzers plus carbon cartridges than with the dialyzers alone. This resulted in an increase in the minimum net Al removal from 1,862 +/- 174 micrograms/treatment to 3,007 +/- 43 micrograms/treatment (P less than 0.05). Treatment with sorbent hemoperfusion should be considered in selected hemodialysis patients being treated with DFO for Al overload.