Influence of Blood Flow on Adsorption of β2-Microglobulin onto AN69 Membrane

Abstract: Adsorption onto the dialyzer membrane is a contributing factor to the elimination of β₂-microglobulin (β₂M) from the sera of uremic patients. The purpose of this prospective study was to ascertain the influence of the blood flow rate on adsorption of β₂M onto the polyacrylonitrile (AN69) hollow-fiber dialyzer membrane in 8 pa tients during regular hemodialysis (HD). Blood first passed through a low-flux polysulfone dialyzer and then through an AN69 dialyzer, which was not in contact with the dialysis fluid. During the investigation period (first hour of the HD session), the blood flow rate was 100 ml/min (first part of the study), 200 mumin (second part of the study), and 300 ml/min (third part of the study). Ultrafiltration was not performed during the investigation period. At the start of the HD sessions, the serum concentration of β₂M in the afferent blood line did not differ significantly among the 3 parts of the study. Serum β₂M was measured in samples taken from the afferent and efferent blood lines of the AN69 dialyzer at 5,10, 15, 30, 45, and 60 min. The serum β₂M concentration decreased significantly in blood that had passed through the AN69 dialyzer. This decrease, indicating membrane adsorption, was maximal during the first part and minimal during the third part of study. The decrease in the contact time between the blood and the AN69 could be the underlying cause. The calculated quantities of β₂M adsorbed onto the AN69 membrane (44.2 ± 10.2, 43.2 ± 12.1, and 42.6 ± 17.3 mg) did not differ significantly among the 3 parts of the study. These results suggest that an increase in blood flow rate from 100 to 300 ml/min did not significantly affect the quantity of β₂M adsorbed onto the AN69 membrane.     

Long-Term Clinical Evaluation of an Adsorbent Column (BM–01) of Direct Hemoperfusion Type for (β2–Microglobulin on the Treatment of Dialysis-Related Amyloidosis

Abstract: The clinical efficacy and safety of a β₂–microglobulin (β₂M) adsorbent column, BM–01, on the treatment of dialysis-related amyloidosis were investigated in 7 hemodialysis patients for more than 6 months. The percent reduction of serum β₂M was more than 60–70%, and the level at the end of each session was less than 10 mg/L in almost all patients. The amount of β₂M removed was calculated as more than 200–300 mg/session. The results demonstrated that BM–01 performed very well for removing β₂M, was capable of maintaining less than 25 mg/L of time average concentration (TAC) for β₂M, and improved the clinical symptoms. Clinically severe side effects were not observed. We recommend that BM–01 should undergo further evaluation for its usefulness in the long-term treatment of dialysis-related amyloidosis, though treatment with the column may not be successful in preventing the onset of the disease.     

β2-Microglobulin and Low-Flux SyntheticDialyzers

Abstract: The aim of this study was to compare the effect on β₂-microglobulin (β₂-M) plasma levels of dialyzers with 3 low-flux synthetic membranes and regenerated cellulose (Cuprophan) in 12 chronic dialysis patients. The synthetic membrane materials chosen were low-flux polymethylmethacrylate (PMMA), low-flux polysulfone (PS 400), and polycarbonate-polyether (Gambrane). Adequate and comparable removal of small solutes was provided by dialyzers with all 4 membrane materials used under similar conditions. A significant reduction of β₂-M plasma levels was seen only with Gambrane while the other 2 synthetic membrane materials gave rise to increases similar to those known to occur with Cuprophan. After correction for the hemoconcentration caused by ultrafiltration, dialysis with Gambrane showed a 24% lower plasma β₂-M level while the β₂-M concentrations with the other 3 membrane materials were practically unchanged. In addition, the efficiency of Gambrane dialyzers in β₂-M removal was able to significantly lower the predialysis plasma β₂-M levels after only 5 dialysis sessions. The hemocompatibility of the 3 synthetic low-flux membranes as judged by the white blood cell (WBC) count and complement activation was similar and therefore cannot be used to explain the different β₂-M plasma levels. In anticipation of gaining further insight into the mechanisms of accumulation and deposition of β₂-M in dialysis patients, a worthwhile approach may be to use a low-flux membrane such as Gambrane which combines removal with protection against potential activating factors in the dialysis fluid.     

Lixelle Adsorbent to Remove Inflammatory Cytokines

It is the goal of this section to publish material that provides information regarding specific issues, aspects of artificial organ application, approach, philosophy, suggestions, and/or thoughts for the future.
A β₂-microglobulin (β₂M) selective adsorbent (Lixelle) for direct hemoperfusion has been used for the treatment of hemodialysis patients with the long-term complication of dialysis related amyloidosis (DRA), but there is no significant correlation between the serum level of β₂M and the occurrence of DRA. Inflammatory cytokines such as interleukin (IL)-1, IL-6, and tumor necrosis factor alpha (TNFα) are related to the development of DRA. We studied the adsorptive rates of cytokines in vitro using the Lixelle adsorbent. The adsorptive rates were 98. 5% for IL-1β, 98.0% for interleukin-1 receptor antagonist (IL-1RA), 82.9% for IL-6, 99.9% for IL-8, 31.2% for TNF α, and 46.1% for soluble TNF receptor (sTNFr), respectively. As the molecular weights of cytokines increase, the adsorptive rates decrease. The Lixelle column adsorbed β₂M and various inflammatory cytokines as well. Therefore, the removal of both β₂M and inflammatory cytokines may play an important role in the treatment of DRA.     

Protein Adsorption by Artificial Membrane Materials Under Filtration Conditions

Abstract: Elevated plasma levels of numerous low molecular weight proteins (LMWP) in renal insufficiency are likely to contribute to the uremic syndrome. Dialysis-related amyloidosis, caused by the accumulation of β₂-microglobulin (β₂M), has highlighted the need for a renal replacement therapy that allows the elimination of LMWP in addition to small solutes. Synthetic membrane materials employed under hemofiltration conditions proved to be most effective in lowering elevated β₂M plasma levels. In addition to convection, protein adsorption to artificial membrane materials is an important mechanism for β₂M removal. Using an in vitro setup, 12 commercially available hemofilters representing 11 different membrane materials were perfused with human blood containing ¹²⁵I-labeled plasma proteins. Under filtration conditions, total protein adsorption ranged from 338–2,098 mg/m² of membrane surface, and the fraction of adsorbed LMWP varied between 14–70% of total protein adsorption and was negatively correlated to total protein adsorption. β₂M adsorption showed up to an 8-fold difference between membranes, and was negatively correlated with total protein adsorption and positively correlated with the adsorption of LMWPs.     

Adsorption of Human Recombinant Erythropoietin on Dialysis Membranes In Vitro

Abstract: The adsorptive characteristics of 5 dialysis membranes for recombinant human erythropoietin (EPO) were studied in vitro in a closed circuit system. For 120 min, EPO added with bovine serum was significantly adsorbed by polymethylmetacrylate (PMMA) and polyacry–lonitrile (PAN) membranes but not by Cuprophan, ethylene vinyl alcohol (EVAL), or polysulfone (PS) membranes. In addition the EPO adsorptive rate, as well as that of β₂–microglobulin (β₂–MG), was greater with a PMMA membrane than with a PAN membrane. EPO was not detected in the ultrafiltrate at 15 min with 5 membranes. These results indicate that EPO was eliminated by membrane adsorption only with some dialysis membranes.     

Clinical Evaluation of a New Dialyzer, FLX-12 GW, with a Polyester-Polymer Alloy Membrane

Abstract: The performance of a membrane in renal failure therapy is determined by its structure, its overall mass transfer properties, and its blood compatibility. In this regard. removal of β₂-microglobulin (β2M) has become a major objective of dialysis therapy. In the present study, a newly developed high-flux membrane composed of a polyester-polymer alloy (PEPA) with the components of polyarylate and polyethersulfone (dialyzer FLX-12 GW; Nikkiso Co., Japan) has been evaluated with regard to both hiocompatibility and elimination capacity for β2M during hemodialysis of 8 stable chronic uremic patients. The clearance values of low molecular weight solutes were in the same range as those reported for high-flux dialyzers of comparable surface area. There was no drop in leukocyte counts and only a minimal fall in platelet counts nearly in the same range as has been observed by other investigators using polyamide membrane. C3a Des Arg generation was low, and C5a Des Arg formation was not significantly influenced. There was a sharp drop in the serum β2M level (-35%) during dialysis with a clearance between 59.7 ± 5.6 ml/min ( Q_B 200 ml/min) and 70.1 ± 9.7 ml/min ( Q_B 300 ml/min), respectively. Accordingly, the sieving coefficient was calculated to be 0.2 at 30 min after start of dialysis and 0.6 1 h later. The membrane was able to remove 184.0 ± 22.3 mg/4 h due to an apparent rate of adsorption during the first hour of treatment in combination with high transmembrane transfer in the following time.     

A New Therapeutic Approach to Dialysis Amyloidosis: Intensive Removal of β2-Microglobulin with Adsorbent Column

Abstract: Amyloidosis, in which amyloid protein consists of β₂-microglobulin (β₂-M), is both a common and a serious complication of long-term hemodialysis. The mechanism of its development is not completely understood. Since (β₂-M is an amyloid protein, it is essential to try to remove as much of it as possible. A specific adsorbent of β₂-M has been developed for use in direct hemoperfusion. The adsorbent is a porous cellulose bead to which hydrophobic organic compound is bound covalently. A combination of a high-flux membrane dialyzer and an adsorption column (BM-01) would make it possible to efficiently eliminate β₂-M. Dialysis with a combination of direct hemoperfusion (DHP) and an adsorption column led to the elimination of more than 200–300 mg of β₂-M. We observed 5 patients who received treatment with this column (BM-01) in combination with high-flux dialysis 3 times a week for periods of 1 week (3 patients), 6 months (I patient), or 14 months (1 patient). It is demonstrated that the adsorbent column (BM-01) provides an intensive method to eliminate β₂-M from the blood with no serious adverse effect. It thus has the potential to suppress the progression of dialysis amyloidosis. The use of this adsorbent column (BM-01) in combination with a high-flux dialyzer may present an improved approach to removing β₂-M from the body.     

Uremic pruritus, cytokines, and polymethylmethacrylate artificial kidney

Abstract:  Uremic pruritus is one of the common complications in long-term dialysis patients. Recently, researchers reported that immunohypothesis with high serum level of cytokines could be the cause of uremic pruritus. Polymethylmethacrylate (PMMA) artificial kidney (AK) has been reported to adsorb more serum cytokines than other high-flux AKs. In July 2006, 30 patients with severe uremic pruritus from 300 chronic hemodialysis (HD) patients in a single center entered this prospective study. Their dialyzers were changed to PMMA AK for 4 weeks. The severity of pruritus was evaluated every week using the results of a questionnaire (pruritus score). Laboratory assays including predialysis serum blood urea nitrogen (BUN), creatinine, β2-microglobulin (β2M), calcium, phosphate, intact parathyroid hormone (iPTH), total CO₂, ferritin, hematocrit, high-sensitivity C-reactive protein (hsCRP), IL-1β, IL-2, IL-6, IL-18, tumor necrosis factor-α (TNF-α), Kt / V , and β2M clearance were measured before and at the end of 4 weeks of PMMA AK use. PMMA AK was effective in reducing the pruritus score from 23.46 ± 11.94 to 7.38 ± 6.42 ( P  < 0.001). The effect of uremic pruritus relief appeared after 1 week of PMMA AK use. There were no significant differences in the laboratory assay results including predialysis serum BUN, Cr, β2M, calcium, phosphate, calcium–phosphate product, iPTH, total CO₂, ferritin, hematocrit, hsCRP, IL-1β, IL-2, IL-6, IL-18, TNF-α, Kt / V , and β2M clearance. The mechanism for the beneficial effect of PMMA AK on uremic pruritus remains to be determined. PMMA AK may be a useful adjuvant therapy in chronic HD patients with severe uremic pruritus.     

Serum levels of alpha-1 microglobulin and beta-2 microglobulin in bone marrow transplant recipients treated with cyclosporin A

Abstract. The levels of alpha-1 microglobulin (α₁m) and beta-2 microglobulin (β₂m) in serum were estimated in 77 bone marrow transplant recipients. In comparison to pretransplant levels, the highest levels of α₁m and β₂m were found during impairment of renal function, i. e., during cyclosporin-induced nephrotoxicity and during treatment with other nephrotoxic drugs ( P < 0.001). The α₁m levels were less elevated during infections and acute graft-versus-host disease ( P < 0.01), while β₂m levels were markedly elevated during the same conditions ( P < 0.001). The linear correlations between serum creatinine and α₁m and creatinine and β₂m were r = 0.7 and 0.8, respectively ( P < 0.001). The overall correlation between α₁m and β₂m was 0.4 ( P < 0.001). It is concluded that α₁m might be a complement to serum creatinine levels in monitoring renal function after bone marrow transplantation.     

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.     

Principles and Practice of Hemofiltration and Hemodiafiltration

There is growing interest in the convective dialysis therapies, hemofiltration (HF) and hemodiafiltration (HDF). Both require dialysis membranes which are highly permeable to solutes as well as fluid, and in both cases large volumes of ultrafiltration are the condition for convective transport. In HDF the convection is combined with diffusion, and as a consequence, maximum clearance over the entire molecular weight spectrum is achieved. Optimal forms of HDF provide urea clearance 10–15% higher than the corresponding diffusive mode. The larger the solute, the greater is the impact of convection, and β₂-microglobulin (β₂m) levels may be up to 70% reduced. Traditional postdilution HF provides high clearance of medium sized and large molecules. Satisfactory clearance of small solutes requires blood flows in excess of 500 ml/min. With access to practically unlimited volumes of substitution solution through on-line ultrafiltration, predilution HF can now be used. This increases the clearance of small solutes to an acceptable range. For HDF as well as HF, large patient populations consistently treated for longer periods of time are needed to make valid outcome comparisons with other therapies.     

109Near Infrared Spectroscopy of Partial Thickness Burns

Impaired wound healing is a problem for immobilized patients, diabetics, and the elderly. The 43 amino acid angiogenic peptide thymosin β₄ has previously been found to promote accelerated dermal wound repair in rats, aged mice and db/db diabetic mice, and corneal repair in normal rats. It has been found in great abundance in wound fluid. Here, we hypothesized that thymosin β₄ may regulate matrix metalloproteinase (MMP) expression in cells that are involved in wound repair. Western blot analysis of keratinocytes, endothelial cells, and fibroblasts that were treated with increasing concentrations of thymosin β₄ showed changes in the expression of the MMP‐1, −2, and −9. Zymographic analysis of whole excised mouse wounds taken after homogenization also showed changes in MMP‐2 and‐9 expression over a 3‐day period. These results were confirmed in 2‐day‐old wounds by RT‐PCR. We conclude that part of the wound healing activity of thymosin β₄ resides in its ability to increase protease activity. Since thymosin β₄‐induced protease activity can be further controlled by inflammatory cytokines, a regulatory role for thymosin β₄ is proposed in wound healing. These studies suggest that thymosin β₄ may play a pivotal role in extracellular matrix remodeling during wound repair and may be effective in the treatment of chronic wounds in humans.     

Effect of continual light deprivation and alpha-2u-globulin replacement therapy on serum concentration of gonadotropins and testicular activity in rats

Summary. Prolonged darkness caused a fall in testicular 17 β-hydroxysteroid dehydrogenase (17β-HSD) activity and diminished spermatogenesis, serum levels of gonadotropins, testosterone and α_2u-globulin.
Administration of α_2u-globulin at a dose of 1.5 mg rat⁻¹ per day for 7 days after 68 days of light deprivation, reversed the 17β-HSD activity and serum levels of gonadotropins, testosterone and α_2u-globulin, while spermatogenesis was restored to normal.
The animals kept in prolonged darkness for 68 days and then received saline (7 days in light-dark cycle, 14 L: 10 D), showed no significant changes of testicular activity, serum levels of gonadotropins, testosterone and α_2u-globulin, when compared with dark-exposed animals (68 days) receiving rabbit serum (7 days in light-dark cycle, 14 L: 10 D). These results suggest that α_2u-globulin plays an important role in testicular function in dark-exposed rats by inducing gonadotropins and testosterone secretion.     

Characterization of a murine monoclonal antibodv specific for swine β1 integrin

Abstract: Murine monoclonal antibodies were raised against porcine platelets in order to provide tools for investigating interactions of human blood cells and natural antibodies with porcine tissues. Hybridomas were screened by cellular ELISA on porcine platelets and endothelial cells. Positive clones were tested by flow cytometry for reactivity with isolated endothelial cells. One clone, NaM160–1A3, produced an antibody that stained porcine but not human endothelial cells and lymphocytes. The antibody bound to a 116 kDa glycoprotein on Western blot of both platelets and endothelial cells. The antigen was purified from a platelet lysate by affinity chromatography, first on a ConA column and then on a column presenting the immobilized NaM 160–1 A3 antibody. Two glycoproteins were obtained: one (116 kDa) was recognized by the antibody and one (150 kDa) was not. The 116 kDa protein had an internal decapeptide identical with human β₁ integrin, and the 150 kDa protein had an internal amino acid sequence belonging to porcine α₂ integrin. Therefore, the NaM 160–1 A3 antibody was directed against porcine β₁ integrin and allowed the purification of the complex α₂β₁ also termed Very Late Antigen 2 (VLA-2). It did not recognize human β₁ integrin.     

Localization of integrin β1, α1, α5 and α9 subunits in the rat testis

Very late activation ( VLA, β₁; α₁; α₅, α₉) integrins were studied by immunoblotting and immunohistochemistry in the testes of sexually mature rats. All integrin subunits were present in membrane fractions of homogenized testes. Immunohistochemistry revealed that the anti β₁ antibody recognized peritubular cells and the basement membrane of blood vessels. Immunoreactivity was also demonstrated in the lamina propria, basement membrane, and the basal cytoplasm of Sertoli cells. In elongating spermatids, β₁ integrin was localized to the acrosome. The α₁ subunit was expressed in peritubular cells and in the lamina propria. In the adluminal compartment, round spermatids were stained diffusely for the α₁ subunit. Immunoreactivity for α₁ integrin was found additionally in the acrosomes of elongating spermatids shortly before their release into the seminiferous tubule lumen. The α₅ subunit was expressed in the acrosomes of elongating spermatids as well as in their distal cytoplasm during stages III–VI; the cytoplasmic lobes of elongate spermatids and/or residual bodies also appeared to be immunostained in seminiferous tubules at stages VII–VIII. The α9 subunit was immunolocalized only in the basement membrane and in peritubular cells. These data suggest that integrins are involved in spermatogenesis, in particular in the process of spermatid maturation.     

Dialysis-related amyloidosis: Pathogenetic aspects and therapeutic considerations

Summary: Beyond renal transplantation and the provision of symptomatic relief, approaches to treat dialysis-related amyloidosis (DRA), an important long-term complication in patients on regular dialysis, must be based on the knowledge of the underlying pathogenetic process. Retention of beta₂-microglobulin (β₂m) is the prerequisite; biochemical alterations of β₃₂m increasing its amyloidogenicity, and local predisposing tissue factors together with age appear to be relevant. A growing body of evidence points toward the importance of pro-inflammatory effects of dialysis (blood-membrane interactions, pyrogen-related priming of cytokine producing mononuclear cells) in the development of DRA. Advanced glycation endproduct formation (AGE-β₂m) may represent a central element in the pathogenesis of DRA. For non-transplant therapy of DRA, the main goals must be the optimization of β₂m removal (high-flux haemodialysis, haemofiltration, especially pre-dilution haemofiltration) and reduction of pro-inflammatory effects of dialysis (use of non-complement activating biocompatible membranes, pyrogen free dialysate). At least patients at high risk for DRA should be treated according to these guidelines.     

A new synthetic dialyzer with advanced permselectivity for enhanced low-molecular weight protein removal

Optimizing solute removal at minimized albumin loss is a major goal of dialyzer engineering. In a prospective, randomized, crossover study on eight patients (age 63 +/- 14 years) on maintenance hemodialysis, the new Baxter Xenium 170 high-flux dialyzer (BX), which contains a 1.7-m(2) PUREMA H dialysis membrane, was compared with two widely used reference high-flux dialyzers currently available for hemodialysis in North America, the Fresenius Optiflux 180 NR (FO) and the Gambro Polyflux 170 H (GP). Solute removal and biocompatibility were assessed in hemodialysis for 240 min at blood and dialysate flow rates of 300 and 500 mL/min, respectively. Additional ex vivo experiments detecting the interleukin-1beta (IL-1b) generation in recirculated donor blood were performed to demonstrate the pyrogen retention properties of the dialyzers. The instantaneous plasma clearances were similar for the three dialyzers except for cystatin c (cysc), for which a lower clearance was measured with FO as compared with BX and GP after 30 and 180 min of hemodialysis. The reduction ratios (RRs) corrected for the hemoconcentration of beta(2)-microglobulin and cysc were lower in FO (44 +/- 9 and 35 +/- 9%, respectively) versus BX (62 +/- 6 and 59 +/- 7%, respectively) and GP (61 +/- 7 and 56 +/- 8%, respectively). The RRs of the cytokine tumor necrosis factor alpha and interleukin-6 were not different between the dialyzers. The albumin loss was <300 mg for all filters. No differences between the dialyzers were found in the biocompatibility parameters showing very low leukocyte and complement activation. The ex vivo recirculation experiments revealed a significantly higher IL-1b generation for GP (710 +/- 585 pg/mL) versus BX (317 +/- 211 pg/mL) and FO (151 +/- 38 pg/mL). BX is characterized by a steep solute sieving profile with high low-molecular weight protein removal at virtually no albumin loss and an excellent biocompatibility. This improved performance may be regarded as a contribution to optimal dialysis therapy.     

Beta 2-microglobulin kinetics in maintenance hemodialysis: a comparison of conventional and high-flux dialyzers and the effects of dialyzer reuse

beta 2-Microglobulin (beta 2M) forms synovial and bony amyloid deposits in long-term hemodialysis patients. To define the kinetics of beta 2M during hemodialysis and the effects of dialyzer reprocessing, we measured serum beta 2M, plasma C3a, and neutrophil counts immediately predialysis; 15, 90, and 180 minutes after beginning dialysis; and 15 minutes postdialysis in ten chronic hemodialysis patients. The studies were performed during first and third uses of cuprammonium rayon and polysulfone dialyzers processed by rinsing with water, then bleach, in an automated system (Seratronics DRS 4) and then packed in 1.5% formaldehyde. Mean serum beta 2M (corrected for ultrafiltration) decreased by 16.6% +/- 18.1% with new cuprammonium dialyzers and 57.1% +/- 12.8% with new polysulfone dialyzers. Dialyzer reprocessing had no significant effect on this decline. Predialysis serum beta 2M decreased by 30.4% +/- 15.5% 1 month after switching from cuprammonium to polysulfone dialyzers; these levels remained stable after 3 months of dialysis with polysulfone. Complement activation and neutropenia during dialysis were significantly more marked with cuprammonium, but were not affected by reprocessing of either dialyzer. In vitro adsorption of 124I-beta 2M to polysulfone fibers was greater than to cuprammonium; adsorption was not influenced by dialyzer reprocessing.     

Ofloxacin clearance during hemodialysis: a comparison of polysulfone and cellulose acetate hemodialyzers

The pharmacokinetics of ofloxacin were studied in 13 patients with end-stage renal disease during hemodialysis using two different dialyzers: a polysulfone membrane (Fresenius F6) and a cellulose acetate dialyzer (Nissho Nipro FB-150T). All patients received 100 mg ofloxacin orally per day before dialysis. The hemodialysis clearance per square meter surface area was significantly different, with 5.0+/-0.7 L/h and 3.7+/-1.6 L/h, respectively. The serum concentration was reduced by a 3-hour hemodialysis by 49.6%+/-5.8% per square meter surface area and 45.5%+/-4.8% per square meter surface area. The half-life was 4.2+/-1.8 hours and 4.8+/-1.6 hours during the hemodialysis period and 22.8+/-2.2 hours and 23.3+/-1.7 hours between the dialysis sessions, respectively. Comparing polysulfone and cellulose acetate dialyzers, the material of the membrane influences the half-life, the dialysis clearance, and the percentage of drug extracted during hemodialysis. We conclude that the type of dialyzer used has to be taken into account in dosage recommendations for antimicrobial therapy in hemodialysis patients.