Clinical Experience and Model Analysis on Beta-2-Microglobulin Kinetics in High-Flux Hemodialysis

Abstract: Beta-2-microglobulin (β₂M) is associated with amyloidosis. The study of β₂M kinetics can provide information on the elimination of this uremic toxin. A β₂M kinetic model modified from Gotch, considering the volume changes between intracellular, interstitial, and intravascular compartments and the generation stimulation and inhibition during hemodialysis is proposed. The clinical experiments on 8 stable hemodialysis patients treated with polysulfone (F80) and polymethyl methacrylate (PMMA, BK2.1p) 3 times a week were conducted. There was an 18% decrease of β₂M clearance in the period from 30 to 180 min with a time-averaged β₂M clearance of 48 ml/min using polysulfone dialyzers (F80). In PMMA dialyzers, there was a 64% decrease of β₂M clearance from 30 to 180 min with a time-averaged clearance of 56.3 ml/min. During hemodialysis, the generation rate was 0.379 mg/min in polysulfone and 0.828 mg/min in PMMA dialyzers. There was a stimulation generation of 0.309 mg/min in polysulfone and 0.749 mg/min in PMMA during hemodialysis. In conclusion, we provide a β₂M kinetic model including volume changes, polymerization, generation stimulation, and inhibition that is similar to the human physiological condition. This model can be used for further clinical study.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

α1-adrenoceptor stimulation is able to reverse halothaneinduced cardiac depression in isolated rat hearts

Background: Stimulation of myocardial α₁-adrenoceptors has been shown to exert positive inotropic effects through a cyclic AMP-independent mechanism. The purpose of this study was to examine if α₁-adrenoceptor stimulation is able to attenuate myocardial depression produced by exposure to halothane, and to test if α₁-adrenoceptor stimulation alters myocardial oxygen supply-demand balance in hearts exposed to halothane.
Methods: The effects of phenylephrine were examined in 7 isolated perfused rat hearts. Variables measured were: heart rate, isovolumetric peak left ventricular pressure (LVP), LV dP/dt, coronary arterial flow, myocardial O₂ delivery (DO₂), myocardial O₂ consumption (MVO₂) and the ratio of DO₂/MVO₂. Each heart was exposed to phenylephrine cumulatively 0.1 μM, 0.3 μM, 1 μM and 3 μM under the administration of 1% halothane in the presence of propranolol 1μM.
Results: Halothane 1% decreased the heart rate by 9±3%, LVP by 37±3%, and LV dP/dt by 35±2%. Phenylephrine restored these decreases to the baseline levels. Phenylephrine maintained or further enhanced the reductions in coronary flow and DO₂ produced by halothane, resulting in a decrease in the DO₂/ MVO₂ ratio.
Conclusion: α₁adrenoceptor stimulation is capable of restoring direct cardiac depressant effects of halothane with a possible impairment of the oxygen supply-demand balance.     

Respiratory Depressant Action of Tilidine during N2O+O2, Anaesthesia

The respiratory depressant actions of pethidine and tilidine during anaesthesia were compared in 18 surgical patients anaesthetized with N₂O + O₂ after thiopental induction. Five minutes after thiopental, 0.5 mg/kg pethidine or 1.5 mg/kg tilidine were each given intravenously to six patients, the remaining six patients serving as controls.
Minute ventilation, respiratory rate, end-tidal CO₂ and Pco₂ from arterialized venous blood were measured up to 30 min. Pethidine caused the following maximal changes: 0–0.98±0.24 (s.e. mean) 1/min, rate -.5.5 ± 0.7/min, C0_2ET+0.7±0.1 vol % and Pco₂ + 5.7±1.1 mm Hg. These changes occurred within 10 xnin of the injection.
In terms of the above parameters, tilidine caused at least as pronounced a respiratory depression as pethidine. The peak effect of tilidine, however, could not be measured with certainty, since the respiratory depression first became apparent 15 min after the injection, and then increased throughout the study period. The long onset time of tilidine explains our previous failure to demonstrate tilidine-induced respiratory depression.     

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.     

Centralized On-Line Hemodiafiltration System Utilizing Purified Dialysate as Substitution Fluid

We followed the guidelines of the Kyushu Society for Hemodiafiltration (HDF) Therapy on the purification of dialysate used as substitution fluid and clinically applied HDF using only 20 L or 15 L of substitution fluid in the pre- or postdilution mode, respectively. We used a centralized on-line HDF system consisting of a novel multi-patient dialysate delivery system applying 3 endotoxin (ET) removal filters in series, maintaining the ET level within the criteria limit below 1.0 IU/L (measured at the first filter outlet to be 0.1 IU/L and after the third filter to be below the sensitivity limit) irrespective of the fluctuation in the ET level of the tap water. Low molecular weight proteins (β₂-microglobulin, prolactin, α₁ -micro-globulin, and α1-acid glycoprotein) were more effectively removed in this HDF system than in conventional hemodialysis (HD) using the same dialyzer as that in the HDF system, and the removal of these proteins in the HDF system was enhanced as their molecular weights increased. The clinical effect of the HDF system was demonstrated by a decrease in joint pain accompanied by improvement in joint motion in 6 dialysis patients followed over the long term (100 weeks).     

Biocompatibility study based on differential sequestration kinetics of CD14+CD16+ blood monocyte subsets with different dialyzers

The immune defect in hemodialysis (HD) patients is associated with a monocyte dysfunction, including an increase in the production of proinflammatory cytokines. Blood membrane contact leads to an increase in cellular activation and sequestration into the capillary bed of the lung. The influence of the sequestration on the number of mature monocytes was studied by analyzing the fate of monocytes, particularly, the CD14+CD16+ subpopulation, during HD treatment. In thirty stable HD patients, the distinct cell populations were determined by differential blood counts and flow cytometry. Patients with diabetes or systemic vasculitis, those showing evidence of infectious complications or malignancy, or those taking immunosuppressive medications were excluded from the study. Cells from this study population were analyzed before the start, 30 min thereafter, and at the end of HD treatment, each time using a different dialyzer: hemophan, methylmethacrylate (PMMA), triacetate membrane, cuprophane/vitamin E, acrylonitrile, and sodium methallylsulfonate polymer (AN69). The CD14+CD16+ subset decreased at 30 min and remained suppressed for the course of dialysis. To examine whether currently used biocompatible membranes differ in their effect on the sequestration of monocyte subpopulations, temporal monocytic changes were comparatively analyzed during HD with a different dialyzer. The drop in the first 30 min until the end of HD treatment was significant (p<0.05), very uniform, and sharp in all patients, and was independent upon membrane type. The CD14+CD16+ monocyte subpopulation showed increased and longer margination from the blood circulation during HD. Given the fact that CD14+CD16+ monocytes represent a sensitive marker for inflammation or cellular activation, the depletion of these cells may offer an easily accessible parameter that is more sensitive than complement activation for biocompatibility studies on forthcoming, improved dialyzer membranes.     

Biocompatibility Study Based on Differential Sequestration Kinetics of CD14+CD16+ Blood Monocyte Subsets with Different Dialyzers

The immune defect in hemodialysis (HD) patients is associated with a monocyte dysfunction, including an increase in the production of proinflammatory cytokines. Blood membrane contact leads to an increase in cellular activation and sequestration into the capillary bed of the lung. The influence of the sequestration on the number of mature monocytes was studied by analyzing the fate of monocytes, particularly, the CD14+CD16+ subpopulation, during HD treatment.

In thirty stable HD patients, the distinct cell populations were determined by differential blood counts and flow cytometry. Patients with diabetes or systemic vasculitis, those showing evidence of infectious complications or malignancy, or those taking immunosuppressive medications were excluded from the study. Cells from this study population were analyzed before the start, 30 min thereafter, and at the end of HD treatment, each time using a different dialyzer: hemophan, methylmethacrylate (PMMA), triacetate membrane, cuprophane/vitamin E, acrylonitrile, and sodium methallylsulfonate polymer (AN69).

The CD14+CD16+ subset decreased at 30 min and remained suppressed for the course of dialysis. To examine whether currently used biocompatible membranes differ in their effect on the sequestration of monocyte subpopulations, temporal monocytic changes were comparatively analyzed during HD with a different dialyzer. The drop in the first 30 min until the end of HD treatment was significant (p<0.05), very uniform, and sharp in all patients, and was independent upon membrane type.

The CD14+CD16+ monocyte subpopulation showed increased and longer margination from the blood circulation during HD. Given the fact that CD14+CD16+ monocytes represent a sensitive marker for inflammation or cellular activation, the depletion of these cells may offer an easily accessible parameter that is more sensitive than complement activation for biocompatibility studies on forthcoming, improved dialyzer membranes.     

The Effects of a Polyacrylonitrile Membrane and a Membrane Made of Regenerated Cellulose on the Plasma Concentrations of Erythropoietin During Hemodialysis

In vitro studies have shown that some dialysis membranes significantly adsorb erythropoietin (EPO), a fact that might have an effect on anemia in long-term hemodialysis (HD) patients and on anemia treatment with recombinant human EPO. The purpose of the study was to determine whether the ability of adsorption demonstrated in vitro also has an effect on EPO concentrations in vivo. In a crossover study, the plasma concentrations of EPO were examined in 11 patients on chronic HD during HD using a polyacrylonitrile (AN69) membrane (high in vitro adsorption) plus EPO administered subcutaneously after the HD session, HD using a Cuprophan membrane (low in vitro adsorption) plus EPO administered subcutaneously after the HD session, HD using an AN69 membrane plus EPO administered subcutaneously after the HD session plus EPO administered intravenously immediately before HD, or HD using a Cuprophan membrane plus EPO administered subcutaneously after the HD session plus EPO intravenously immediately before HD. The intradialysis plasma concentrations of EPO (not detectable in the dialysate) determined at the dialyzer inlet and outlet at Minutes 5 and 240 of the procedure did not differ significantly after its subcutaneous administration from its predialysis concentrations with either the Cuprophan or AN69 membrane. A comparison of EPO concentrations between AN69 and Cuprophan did not reveal marked differences either. The course of concentrations after additional EPO intravenous administration was similar with no statistically demonstrable difference between the 2 membranes. In conclusion, under clinical conditions, AN69 and Cuprophan membranes do not differ in their effects on plasma EPO concentrations. The differences in EPO adsorption between AN69 and Cuprophan, demonstrated in vitro, do not seem to be of clinical importance.     

Quantifying the interaction of vecuronium with enflurane using closed-loop feedback control of vecuronium infusion

The influence of different levels of enflurane anaesthesia on infusion requirements of vecuronium was studied in 40 adult surgical patients. Ninety percent neuromuscular block was maintained by computer controlled infusion of vecuronium. During the first 90 min study period all patients received fentanyl-nitrous oxide-oxygen (2:1) anaesthesia. For the following 90 min the patients were randomly assigned to receive enflurane at different end-tidal concentrations: group I, control, fentanyl-nitrous oxide anaesthesia; group II, enflurane 0.3%-nitrous oxide; group III, enflurane 0.6%-nitrous oxide; group IV, enflurane 0.9%-nitrous oxide. Every patient served as his/her own control and the changes of vecuronium infusion requirements were determined individually. When the administration of enflurane was started, vecuronium infusion requirements decreased progressively until 90 min. In group II the infusion rate lowered from 80±28 to 56±20 μg . kg^-1 . h ^-1, in group III from 61 ±29 to 34±17 μg . kg^-1 . h^-1 and in group IV from 65±20 to 30± 14 μg . kg^-1 . h^-1. In the control group the infusion rate decreased during the three hour study period from 69± 17 (first 90 min period) to 59± 16 μg . kg^-1 . h^-1 (second 90 min period). Enflurane reduces the dose requirements of vecuronium administered by continuous infusion in a dose- and time-dependent manner.     

End-stage renal failure in New Zealand Maori: an analysis of circulating transforming growth factor-β1

SUMMARY: There is a high incidence of end-stage renal disease in New Zealand Maori. Reasons for this have not been established. Transforming growth factor-β, (TGF-β₁) is a profibrogenic cytokine, which stimulates the secretion of extracellular matrix components, and has been implicated in the pathogenesis of kidney failure. the aim of this study was to examine TGF-β₁ in the serum of haemodialysis patients at our institution, in order to determine whether there was an upregulation of TGF-β₁ in Maori. A TGF-Prspecific sandwich enzyme-linked immunosorbant assay was used to measure active TGF-β from the sera of 74 haemodialysis patients, and 19 healthy Maori without renal disease, diabetes or hypertension. In addition, clinical and laboratory markers were examined in the haemodialysis patients studied. There was no association between TGF-β₁ and ethnicity in the groups studied. Transforming growth factor-β₁ protein appeared to be inversely related to age. but was not associated with parameters of survival on dialysis such as serum albumin or measures of dialysis adequacy. Although there was a significantly higher incidence of type II diabetes mellitus in the Maori ( P < 0.001) in comparison to European patients, the glycaemic control was comparable between the groups, as were all other laboratory and clinical parameters studied. This is the first study to examine the fibrogenic growth factor TGF-β₁ in New Zealand Maori. Thus, an endogenous increase in TGF-β₁ in Maori does not appear to be implicated in the increased incidence of end-stage renal disease in this population.