Plasma levels of granulocyte elastase during hemodialysis: effects of different dialyzer membranes

Plasma levels of granulocyte elastase in complex with alpha 1-proteinase inhibitor during hemodialysis were investigated in 15 patients (37.4 +/- 3.2 years) undergoing maintenance hemodialysis (47.0 +/- 12.9 months) with dialyzers made from cellulose hydrate, cuprophan, polymethylmethacrylate, ethylene-vinyl alcohol copolymer, and polyacrylonitrile. Cellulose hydrate membrane caused a maximal increase of the plasma levels of granulocyte elastase in complex with alpha 1-proteinase inhibitor (E-alpha 1PI: 1,659.0 +/- 256.8 ng/ml). Patients dialyzed with polyacrylonitrile dialyzers failed to exhibit comparable plasma levels of granulocyte elastase (E-alpha 1PI: 237.8 +/- 22.9 ng/ml). During hemodialysis plasma E-alpha 1PI values rose to a peak 643.0 +/- 174.7 ng/ml in patients on polymethylmethacrylate dialyzers, to 557.5 +/- 120.0 ng/ml on cuprophan dialyzers, but to only 381.9 +/- 54.0 ng/ml on ethylene-vinyl alcohol copolymer dialyzers. Plasma lysozyme levels decreased significantly in the presence of polyacrylonitrile and polymethylmethacrylate membranes. We conclude that the degree of PMNs stimulation depends on the nature of the dialyzer membrane material. The following membranes induce a reaction of increasing intensity: polyacrylonitrile, ethylene-vinyl alcohol copolymer, cuprophan, polymethylmethacrylate, and cellulose hydrate.     

Plasma levels of main granulocyte components in patients dialyzed with polycarbonate and cuprophan membranes

Plasma levels of granulocyte lactoferrin, granulocyte myeloperoxidase and granulocyte elastase in complex with alpha 1-proteinase inhibitor (E-alpha 1PI) were investigated in regular hemodialysis patients dialyzed with hollow-fiber dialyzers made from polycarbonate (FD 100) or cuprophan (GFS 120 H). Plasma levels of all these main granulocyte components increased significantly during hemodialysis. E-alpha 1PI levels were significantly higher in patients dialyzed with the polycarbonate compared with the cuprophan membrane, whereas the increases of myeloperoxidase and lactoferrin were not different for the two dialyzers. On the other hand, plasma C3a levels were higher in patients dialyzed with the cuprophan compared with the polycarbonate dialyzer. Therefore, granulocyte activation during hemodialysis does not necessarily need complement activation.     

Plasma levels of main granulocyte components during hemodialysis: effects of immunosuppression

Plasma levels of granulocyte lactoferrin, granulocyte myeloperoxidase and granulocyte elastase in complex with alpha 1-proteinase inhibitor were investigated during hemodialysis in oliguric patients following cadaveric renal transplantation (CRT). The results were compared with those of patients undergoing regular hemodialysis treatment (RDT) using different membrane materials. In RDT patients, plasma lactoferrin levels increased from 61.9 +/- 10.2 to 417.9 +/- 96.7 using dialyzers made of cuprophane. Dialyzers made of polymethyl methacrylate induced an increase of lactoferrin from 166.6 +/- 28.5 to 712.5 +/- 165.9 and dialyzers made of polyacrylonitrile an increase from 122.6 +/- 23.5 to 647.7 +/- 203.6 ng/ml. In CRT patients, in contrast, plasma lactoferrin levels increased from 49.1 +/- 10.9 to 199.6 +/- 45.9 (cuprophane), from 30.1 +/- 6.9 to 252.5 +/- 46.9 (polymethyl methacrylate), and from 43.3 +/- 9.1 to 174.2 +/- 39.3 ng/ml (polyacrylonitrile). On the other hand, the plasma levels of myeloperoxidase and elastase in complex with alpha 1-proteinase inhibitor increased comparably in both groups of patients. Our data suggest that immunosuppression might prevent degranulation of specific granules independently of the used dialyzer membrane material, whereas no effect was observed on two main components of azurophilic granules.     

Effect of different dialyzers on proteinases and proteinase inhibitors during hemodialysis

The effect of different membrane materials on plasma levels of granulocyte elastase, 'unspecific' proteolytic (azocasein-hydrolyzing) activity, and activity and concentration of the main plasma proteinase inhibitors alpha 1-proteinase inhibitor (alpha 1PI) and alpha 2-macroglobulin during hemodialysis was investigated. Cuprophan (679.6 +/- 80.0 ng/ml) and polymethyl methacrylate (873.0 +/- 20.6 ng/ml) membranes caused a significantly higher maximal increase of plasma levels of granulocyte elastase-alpha 1-proteinase inhibitor (E-alpha 1PI) complex compared with polyacrylonitrile (395.3 +/- 56.0 ng/ml) or polysulfone (295.2 +/- 41.3 ng/ml) membranes (healthy subject 70.3 +/- 4.4 ng/ml). The activity of alpha 1PI increased significantly during hemodialysis using polyacrylonitrile (+36%) or polysulfone (+29%) membranes, whereas this increase was less using cuprophan (+6%) or polymethyl methacrylate (+8%) membranes. The reverse effect, however, was observed analyzing alpha 1PI concentrations (cuprophan +33%, polymethyl methacrylate +23%, polyacrylonitrile +12%, polysulfone +7%). 'Unspecific' proteolytic activity and non-trichloroacetic acid-precipitable small molecular weight plasma protein fraction decreased significantly during hemodialysis in the presence of all four membranes. We conclude that neutral granulocyte proteinases can be released during hemodialysis independent of the change of white blood cells during the 1st h of dialysis therapy.     

Anaphylatoxin formation during hemodialysis: effects of different dialyzer membranes

Measurable complement activation resulting in the formation of both C3a and C5a anaphylatoxins was observed in 12 patients undergoing maintenance dialysis treatment with cuprophan hollow fiber dialyzers. Specific radioimmunoassay measurements demonstrated that these patients displayed significantly elevated levels of C3a antigen in the venous (outflow) line of the dialyzer after only 2 min of dialysis. During hemodialysis, venous plasma C3a levels continued to increase and became maximally elevated after 15 min. Thereafter, C3a concentrations gradually declined, suggesting that the rate of complement activation abates with continued cuprophan hemodialysis. Complement activation, as judged by venous plasma C3a levels, was also temporally correlated with hemodialysis leukopenia. The factor believed to be responsible for pulmonary vascular leukosequestration, C5a, could also be detected in venous plasma, but levels of this antigen were not strikingly elevated until the later stages of dialysis. By contrast, six patients dialyzed with polyacrylonitrile dialyzers failed to exhibit hemodialysis leukopenia and displayed only very modest increases in their plasma C3a levels during the initial phases of hemodialysis. These observations provide direct evidence that anaphylatoxin formation during hemodialysis is a transient phenomenon and indicate that the biocompatibility of dialysis membranes, as reflected by their complement activating potential, may be significantly different.     

Effect of dialyzer geometry on granulocyte and complement activation

During hemodialysis with cuprophan membranes, the complement system as well as leukocytes become activated. In order to clarify the role of dialyzer geometry, the effect of hollow-fiber versus flat-sheet dialyzers and of different surface areas on C3a generation and leukocyte degranulation was investigated. Plasma levels of leukocyte elastase in complex with alpha 1-proteinase inhibitor were significantly increased after 1 h (+55%) and 3 h (+62%) of hemodialysis with flat-sheet dialyzers as compared to hollow-fiber devices. In addition, plasma levels of lactoferrin, released from the specific granules of leukocytes during activation, were significantly higher (+42%) 3 h after the onset of dialysis treatment with flat-sheet than with hollow-fiber dialyzers. With respect to surface area, larger dialyzers tended to cause more release of leukocyte elastase as compared to dialyzers with smaller surface areas, irrespectively of the configuration of the dialyzer used. On the other hand, activation of the complement system, as measured by the generation of C3a-desarg, did not differ with both types of configurations. The same held true for leukopenia, which was almost identical for hollow-fiber and flat-sheet dialyzers. From these findings two lines of evidence emerge: First, not only the type of membrane material used in a dialyzer may influence its biocompatibility, but the geometry of the extracorporeal device also determines the degree of compatibility. Hence, the extent of leukocyte activation correlated with both configuration of the dialyzer and surface area of the membrane.(ABSTRACT TRUNCATED AT 250 WORDS)     

β-2-Microglobulin and Main Granulocyte Components in Hemodialysis Patients

Plasma levels of granulocyte elastase in complex with alpha 1-proteinase inhibitor (E-alpha 1-PI) increased during hemodialysis from 110 +/- 10 to 506 +/- 66 micrograms/L using dialyzers made of polyamide, from 95 +/- 2.2 to 211 +/- 54 micrograms/ml with hemophane and from 114 +/- 10 to 203 +/- 25 using dialyzers made of polysulfone. Plasma lactoferrin values were also significantly higher during hemodialysis with polyamide (772 +/- 110 micrograms/L) compared with hemophane (268 +/- 2.2) and the polysulfone (278 +/- 31 micrograms/L) dialyzer. After dialysis each dialyzer was rinsed. We found the lowest concentration of lactoferrin (902 +/- 254 micrograms/L) and E-alpha 1-PI (739 +/- 162 micrograms/L) after rinsing polysulfone dialyzers, whereas the highest concentrations were observed after rinsing the polyamide dialyzer (lactoferrin: 2,426 +/- 314; E-alpha 1-PI: 1,134 +/- 144 micrograms/L). Hemodialysis with polysulfone dialyzers caused significantly lower plasma levels of beta-2-microglobulin compared with polyamide or hemophane membranes despite significantly lower levels in the rinsing solutions. Our data indicate that low plasma levels of main granulocyte component observed with polysulfone and hemophane dialyzers are not the result of higher membrane adsorption of E-alpha 1-PI and lactoferrin. These main granulocyte components are not related to beta-2-microglobulin levels of both plasma and rinsing solutions.     

Anaphylatoxin formation during hemodialysis: comparison of new and re-used dialyzers

Hemodialysis of 11 endstage renal failure patients with new cuprophan hollow fiber dialyzers produced significant leukopenia as well as increased plasma levels of both C3a and C5a antigens during the initial phases of the procedure. Formalin-fixed new dialyzers produced quantitatively similar phenomena in eight of these same patients. By contrast, hemodialysis with re-used dialyzers, that is dialyzers exposed to blood prior to formalin sterilization, produced only a 20 to 30% decline in peripheral blood leukocyte counts. Correspondingly, C3a antigen formation within re-used dialyzers was only 20% of that observed in new dialyzers. Re-used dialyzers also differed significantly from either new or formalin-fixed new dialyzers in that C3b antigen could be readily detected within them even after extensive washing. These observations suggest that C3b deposition on the cellulosic membrane surface during first use markedly diminishes the complement activating potential of cuprophan dialyzers when they are subsequently re-used.     

Removal of plasma porphyrins with high-flux hemodialysis in porphyria cutanea tarda associated with end-stage renal disease.

Plasma porphyrin levels are markedly increased in patients with porphyria cutanea tarda (PCT) associated with end-stage renal disease. Conventional hemodialysis (CHD) with lower blood flow rates (less than 250 mL/min) and cuprophan or cellulose acetate membranes is ineffective in removing significant amounts of porphyrins in this condition. Changes in plasma porphyrin levels and porphyrin clearances during hemodialysis with higher blood flow rates and more-permeable, high-efficiency cellulose acetate and high-flux polysulfone dialyzers were evaluated in a chronic hemodialysis patient with PCT and markedly elevated plasma porphyrins. The polysulfone membrane achieved significantly better fractional porphyrin removal (P = 0.02) and porphyrin clearances (P less than 0.01) than did the high-efficiency cellulose acetate membrane. After conversion from maintenance CHD with a standard cellulose acetate dialyzer to a 4-wk period of high-flux hemodialysis (HFHD) with a polysulfone dialyzer, predialysis plasma porphyrins fell by 37%. After returning to CHD, plasma porphyrins returned to the higher prestudy levels. These observations suggest that HFHD with more permeable membranes and higher blood flow rates removes porphyrins more effectively than does CHD. HFHD may be a useful adjunct to other measures used in treating dialysis patients with PCT.     

Effect of the hemodialysis membrane on the inflammatory reaction in vivo

BACKGROUND: Increased levels of C-reactive protein (CRP), a marker of systemic inflammation, are associated with myocardial infarction, stroke and the development of peripheral arterial disease. Hemodialysis patients show signs of an inflammatory reaction indicated by elevated plasma levels of CRP and by increased plasma levels of interleukins. PATIENTS AND METHODS: To investigate the effect of the dialysis membrane on the inflammatory reaction, we conducted a randomized study in 18 hemodialysis patients. Patients were subsequently treated with dialyzers containing polyamide, polycarbonate or cuprophan for 8 weeks on each dialyzer in a crossover design. During each treatment period, CRP plasma levels were measured 6 times at weekly intervals. The total content and the spontaneous and lipopolysaccharide- (LPS) stimulated production of interleukin-1beta (IL-1beta), IL-6 and IL-1 receptor antagonist (IL-1Ra) were determined in whole blood samples. RESULTS: CRP plasma levels were significantly higher in hemodialysis patients (all patients, 1.63 +/- 0.23 mg/dl) compared to normals (0.14 +/- 0.02 mg/dl, p < 0.0001). CRP levels were lower when patients were dialyzed with polyamide (1.19 +/- 0.18 mg/dl) compared to the levels when the same patients were dialyzed with cuprophan (1.77 +/- 0.37 mg/dl, p = 0.02) or with polycarbonate (1.34 +/- 0.2 mg/dl, n.s). The whole blood content of IL-1Ra in non-incubated samples was significantly lower in normal subjects (512 +/- 60 pg/ml) compared to hemodialysis patients (980 +/- 80 pg/ml, p < 0.01). The whole blood content of IL-1Ra was higher when patients were dialyzed with cuprophan (1,062 +/- 119 pg/ml) compared to the same patients on polyamide (906 +/- 78 pg/ml, p < 0.05) or on polycarbonate (973 +/- 80 pg/ml, n.s.). Spontaneous and LPS-induced production of IL-1beta and IL-6 was similar for all dialyzers. CONCLUSION: We conclude that the inflammatory reaction in hemodialysis patients is affected by the choice of the dialyzer.     

Neutrophil and eosinophil degranulation during hemodialysis are mediated by the dialysis membrane

During hemodialysis of heparinized blood without having a patient in the circuit, the serum concentrations of lactoferrin, myeloperoxidase (MPO) and eosinophil cationic protein (ECP) steadily increased, indicating neutrophil and eosinophil degranulation. The increments in serum of these granular proteins were more pronounced using plate dialyzers than capillary dialyzers. The release of granule constituents does not seem to reflect merely a sequestration of granulocytes in the dialyzer, since the increase of the serum concentrations of lactic dehydrogenase was very modest. The intracellular contents of lactoferrin, MPO, lysozyme and ECP were reduced after experimental dialysis in the granulocytes isolated from the blood, indicating that the cells in association with degranulation were not entrapped in the dialyzer. The relatively modest increase of the plasma concentrations of lysozyme during experimental hemodialysis, in spite of the reduction of the intracellular content of lysozyme, was explained by the propensity of lysozyme for adhering to the dialysis membrane. Serum samples obtained at different times during dialysis did not induce an enhanced release of granular proteins from isolated granulocytes in vitro. The earlier observed increase during hemodialysis of the serum concentrations of granular proteins in uremic patients can be explained by the dialysis membrane triggering granulocytes to degranulate.     

Dialyzer reuse-Part I: Historical perspective

The first apparatus for hemodialysis in animals, made painstakingly by Abel et al. in their laboratory at the beginning of 20th century, was cleaned with acid-pepsin to digest blood, disinfected with thymol, and reused for up to 30 experiments for as long as 8 months. The obvious incentive was saving time. In the early years of hemodialysis in patients, dialyzers and lines were assembled and sterilized immediately before dialysis. Various methods of dry and moist heat sterilization and miscellaneous chemical agents were employed for disinfection. Significant time was required to assemble the dialyzers, so there was an incentive to reuse previously assembled dialyzers to save time, especially for home hemodialysis. Bleach to clean and formaldehyde to disinfect the membranes and lines was used for this purpose. Preassembled dialyzers, commercially introduced in the 1950s, were the most expensive components of hemodialysis systems, therefore reprocessing of these dialyzers was the most effective way to save money. Refrigeration of coil dialyzers with blood, introduced in the mid-1960s, was associated with frequent febrile reactions and was soon abandoned. Preassembled coil and plate dialyzers permitted almost complete return of blood after dialysis and led to the introduction of chemical disinfection for dialyzer reprocessing. A variety of disinfectants have been used. Formaldehyde was the most common disinfectant until the end of the 1970s. Sodium hypochlorite was used to clean the majority of dialyzers and to sterilize dialyzers with polyacrylonitrile membranes. In the early 1980s, peracetic acid and glutaraldehyde started to compete with formaldehyde. By the 1990s, formaldehyde had become less popular than peracetic acid. In the mid-1990s, disinfection and membrane cleaning with acetic acid and heat was introduced. Manual reprocessing was replaced by early reuse machines in the mid-1970s and a more sophisticated second generation of automated hemodialyzer reprocessing machines followed in the late 1970s. Recently disinfection of dialyzers with moist heat has resumed. Saving both time for the patient and money for the provider were the main motivations for designing a new machine for daily home hemodialysis. The machine, developed in the 1990s, cleans and moist-heat disinfects the dialyzer and lines in situ so they do not need to be changed for a month. In contrast, the reuse of dialyzers in home hemodialysis patients treated with other hemodialysis machines has become less popular and is almost extinct.     

Effect of different dialyzers on defensins during hemodialysis

Background. Defensins are antimicrobial peptides that constitute 30% to 50% of total azurophil granule proteins. Although the activation of azurophils during hemodialysis has been reported, including the release of granulocyte lactoferrin, myeloperoxidase, and elastase, the release of defensins during hemodialysis has not been investigated. The purpose of this study was to determine the effects of hemodialysis on defensin release. Methods. Plasma defensin levels and excreted defensins in dialyzer eluates and dialysates during hemodialysis were determined by radioimmunoassay. Thirty hemodialysis patients were divided into three groups, each group using a different dialyzer membrane: cuprophan (CU), polymethylmethacrylate (PMMA), or polysulfone (PS). Results. The postdialysis plasma defensin level in the CU group was significantly increased compared with the predialysis level. In contrast, defensin levels in the PMMA and PS groups showed significant decreases postdialysis. The predialysis neutrophil count and defensin level exhibited a significant positive correlation in all groups. However, postdialysis, a significant positive correlation was found only in the CU group. Interestingly, defensin excretion in the dialyzer eluates of the PMMA group and in the dialysates of the PS group was higher than that in each of the other two groups respectively. Conclusions. No significant statistical correlation between postdialysis neutrophil count and defensin level was observed in the PMMA and PS groups, a finding that may be explained by the increased excretion of defensins during hemodialysis in these groups. These results suggested that plasma defensin level may be a marker for granulocyte activation in patients dialyzed with membranes showing lower levels of excreted defensins. This study also revealed the importance of determining both plasma changes and excreted volumes of granule proteins to define neutrophil degranulation during hemodialysis. Received: January 17, 2000 / Accepted: May 16, 2001     

Neutrophil activation in acute renal failure and sepsis

Neutrophils are activated during sepsis. To find out whether granulocytes are further activated during hemodialysis with cellulosic and noncellulosic membranes, we compared the plasma levels of the main granulocyte components in patients with chronic uremia who were undergoing regular hemodialysis treatment and patients with acute renal failure with and without sepsis. During hemodialysis with cuprophane dialyzers, plasma-granulocyte elastase, in complex with alpha-proteinase inhibitor, and lactoferrin levels increased in patients who were undergoing regular hemodialysis treatment, but these levels increased further in patients with acute renal failure who did not have sepsis. Maximal neutrophil degranulation was observed in patients with acute renal failure and sepsis. There was only mild degranulation in all three groups during dialysis with dialyzers made of polysulfone. Our data demonstrate that neutrophil activation is increased in patients with acute renal failure, and it is increased further by superimposed sepsis. Cellulose-containing dialysis membranes introduce a further activation of neutrophils.     

Plasma adrenomedullin levels in patients on hemodialysis

Adrenomedullin (AM) is a hypotensive peptide that has recently been isolated from human pheochromocytoma. In this study, we measured plasma AM concentrations in 54 patients on hemodialysis (HD) and examined the clinical significance. We also evaluated the effects of high-flux and low-flux dialysis membranes on plasma AM levels. The average value of plasma AM at pre-HD (4.44 +/- 0.16 fmol/ml) was significantly elevated compared with that in 44 healthy volunteers (1.31 +/- 1.41 fmol/ml) (p < 0.0001). The plasma AM concentrations at pre-HD showed a negative correlation with age and mean blood pressure (MBP) at pre-HD. The plasma AM concentrations at post-HD showed a negative correlation with MBP at post-HD and a negative correlation with the reduction rate of AM. Multiple regression analysis showed that age and MBP were independent factors associated with plasma AM at pre-HD and that MBP and reduction rate of AM were independent factors associated with plasma AM at post-HD. We investigated the differences between high-flux dialyzers (PS-UW, PS-N and FB-F) and a low-flux dialyzer (AM-BC-F), and we found that high-flux dialyzers removed plasma AM more efficiently than a low-flux dialyzer did. In addition, in 3 patients on HD, plasma AM levels decreased significantly during isovolumic dialysis using a high-flux dialyzer, despite the fact that there were no significant changes in MBP and ANP. In conclusion, elevation in plasma AM level causes a fall in MBP in patients on HD, therefore, removal of AM by HD treatment using a high-flux dialyzer contributes to the stability of blood pressure during HD.     

Role of Dialyzer Contaminants in the Allergic Epiphenomena of Hemodialysis

Abstract: Cuprophan hollow-fiber dialyzers contain contaminants including 1,2,3-propanetriol, carbohydrates, Limulus amebocyte lysate-reactive material, and particulates. In a clinical study, the role of these substances in the allergic-type response seen in some hemodialysis patients was examined. Patients were dialyzed three times per week for 6-week intervals with each of four dialyzer preparations designed to vary the burden of contaminants presented to the patient. Predialysis eosinophil counts and serum immunoglobulin (Ig) E levels were obtained weekly. White cell and platelet counts and plasma C3a and C5a levels were measured during dialysis for each dialyzer preparation. Dialyzer preparation had no effect on predialysis eosinophil counts or IgE levels. All patients demonstrated transient leukopenia and complement activation during dialysis, the magnitudes of which were unaffected by the type of dialyzer preparation. At the levels found in the dialyzers studied, it was questioned whether water-soluble extractables or particulates play any role in the allergic epiphenomena of hemodialysis.     

Effect of RenNew-D as a sterilant on the performance of reused dialyzers

RenNew-D (Alcide), a novel demand-release sporocidal agent, was employed instead of formaldehyde in the reprocessing for reuse of cuprophan hollow fiber dialyzers (Gambro) and the performance of these dialyzers was evaluated over 40 consecutive dialyses in six patients on maintenance hemodialysis. When RenNew-D was part of automated reprocessing performed with 4.3% bleach as specified by the manufacturer (Lixivitron), dialyzer survival was prolonged (16.7 +/- 7.2 uses) and hemodialysis neutropenia was unchanged with reuse. When RenNew-D was part of manual reprocessing conducted in the absence of bleach, marked improvement in dialyzer biocompatibility was observed but with a decreased survival (4.8 +/- 3.0). The majority of dialyzer failures were due to a fall in fiber bundle volume below a 85% set limit. Small solute clearances were maintained with both types of reprocessing. Dialyses were well tolerated throughout. Our data suggest that RenNew-D is a safe and efficacious product which can serve as a valuable alternative to formaldehyde for the purpose of dialyzer reuse.     

Serum growth factors in hemodialyzed patients

The contact of chronic hemodialysis patients' blood with components of extracorporeal circulation leads to mobilization of several systemic reactions. The purpose of this study was to determine the activity of transforming growth factor (TGF-beta1) and platelet derived growth factor (PDGF) in serum of patients on long-term hemodialysis program and to compare these results with ones obtained in healthy volunteers. Twenty-five patients on dialysis carried out on polysulfone membrane dialyzer, and 16 patients on dialysis with the used of cuprophan membrane dialyzer on long-term hemodialysis program participated in the study. TGF-beta1 level in serum of healthy volunteers (12.06 +/- 7.56 ng/mL) was lower than in serum of patients dialyzed on polysulfone membrane dialyzers (26.56 +/- 14.83 ng/mL). Differences in PDGF concentrations in serum of control group and hemodialyzed patients were not statistically significant. The strong correlation between TGF-beta1 and PDGF in serum of both studied groups of patients was demonstrated.     

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.     

High-flux dialysis lowers plasma leptin concentration in chronic dialysis patients

Leptin is a protein produced by fat cells and involved in body weight regulation. Plasma leptin is significantly higher in some hemodialysis (HD) patients than in normal controls. We examined the influence of dialyzer membrane biocompatibility and flux on elevated plasma leptin concentrations in hemodialysis patients. Employing a crossover design, leptin and tumor necrosis factor-alpha (TNF-alpha) levels were serially determined in eight chronic dialysis patients. Patients were dialyzed sequentially on low-flux cellulosic (TAF) dialyzers, low-flux (F8) polysulfone, high-flux (F80B) polysulfone, then low-flux polysulfone and cellulosic dialyzers again. Mean leptin concentrations were similar when low-flux polysulfone or cellulosic dialyzers were employed (141.9+/-24.2 microg/L versus 137.8+/-18.4 microg/L, respectively (P=NS). In contrast, leptin fell significantly on the high-flux polysulfone dialyzer (99.4+/-16.2 microg/L) compared with cellulosic (P < 0.005), and low-flux polysulfone dialyzers (P < 0.02). Leptin clearance by the high-flux polysulfone dialyzer was significantly higher than the low-flux dialyzers (50.4+/-21.5 v -9.6+/-10.3 mL/min; P=0.043), but did not account fully for the 30% decline in plasma leptin during the high-flux arm of the study. Concentrations of TNF-alpha were lower when high-flux polysulfone dialyzers were employed, but there was no correlation of individual TNF-alpha levels with leptin concentrations. High-flux dialysis lowers plasma leptin concentrations an average of 30%, but biocompatibility does not influence leptin levels. The decrease in plasma leptin on high-flux dialysis cannot be explained solely by enhanced clearance.