Anticoagulation and platelet activation in hemodialysis: clinical results with PMMA.
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Biomedical subjects
Publications and source records attributed to S Stefoni.
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Blood-membrane contact in the extracorporeal circuit affects the activation of many biological systems. Among these, phagocytizing activity has been reported to be influenced by the nature of the hemodialysis membrane used, whether cellulosic or synthetic. This work reports on an ex-vivo, comparative test between cellulosics and synthetics concerning the effects of blood-membrane contact on the polymorphonucleate and monocyte phagocytizing function, both during and after the hemodialysis session. By means of flow cytometry, we evaluated the capacity for phagosoma formation and oxidative burst both in polymorphonucleates and monocytes. Ten hemodialysis patients were included in the study. Six separate dialysis procedures for each patient were considered, one per dialyzer (3 cellulosic and 3 synthetic membranes). Tests were performed at 15', 60', 210' and 4 hours after the session end. Comparative evaluation was made according to Student's t test. Polymorphonucleate phagocytosis and oxidative burst activation were globally more marked for synthetic than cellulosic membranes, tending to level out in the post-dialysis. This result could be affected by their functional exhaustion following pulmonary sequestration. Monocyte intradialytic phagocytosis and oxidative burst proved more activated by cellulosic membrane. All differences tended to vanish in the post-dialysis.
A mathematical model of solute kinetics oriented to improve hemodialysis treatment is presented. It includes a two-compartment description of the main solutes (K+, Na+, Cl-, urea, HCO3-, H+, CO2), acid-base equilibrium through two buffer systems (bicarbonate and non-carbonic buffers) and a three-compartment model of body fluids (plasma, interstitial and intracellular). The main model parameters can be individually assigned a priori, on the basis of body weight and plasma concentration values measured before beginning the session. Model predictions are compared with clinical data obtained during 11 different hemodialysis sessions performed on six patients with profiled sodium concentration in the dialysate and profiled ultrafiltration rate. In all cases, the agreement between the time pattern of model solute concentrations in plasma and clinical data turns out fairly good as to urea, sodium, chloride and potassium kinetics. Finally, the time patterns of plasma bicarbonate concentration and pH can be reproduced fairly well with the model, provided CO2 concentration remains constant. Only in two sessions, blood volume was directly measured in the patient, and in both cases the agreement with model predictions was good. In conclusion, the model allows a priori computation of the amount of sodium removed during hemodialysis, and may enable the prediction of plasma volume changes and plasma osmolarity changes induced by a given sodium concentration profile in the dialysate and by a given ultrafiltration profile. Hence, it can be used to improve the dialysis session taking the characteristics of individual patients into account, in order to minimize intradialytic imbalances (such as hypotension or disequilibrium syndrome).
In this study, we have investigated the nature and magnitude of the immunological response after implantation of human aortic segments. Five recipients of aortic segment replacement were studied for anti-HLA antibody production (specificity and Ig class), CD3, CD4, and CD8 T cell subpopulation dynamics, and aortic wall thickness. Mismatch-specific IgG antibodies to HLA class I and HLA class II antigens were first detected 1-3 months after implantation and persisted in high concentrations for at least 1 year. Computer tomography scanning showed a progressive thickness of the aortic wall. Also the absolute number of CD3, CD4, and CD8 positive lymphocytes increased progressively after implantation. In conclusion, as was observed earlier for heart valve allografts, human implanted aortic segments induce a strong anti-HLA antibody response in recipients. We speculate that these antibodies have the potential to harm the implant, for example, by having an impact on luminal narrowing.
The aim of this study was to compare the effect on beta2-microglobulin (beta2-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 beta2-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 beta2-M level while the beta2-M concentrations with the other 3 membrane materials were practically unchanged. In addition, the efficiency of Gambrane dialyzers in beta2-M removal was able to significantly lower the predialysis plasma beta2-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 beta2-M plasma levels. In anticipation of gaining further insight into the mechanisms of accumulation and deposition of beta2-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.
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PURPOSE: While there is general agreement on the need to increase urinary volume in stone formers, contrasting opinions have been expressed about the hardness of water and stone incidence. We evaluate the influence of 3 types of mineral water on urinary analytes in 22 idiopathic calcium oxalate stone formers. MATERIALS AND METHODS: All patients underwent a nutritional and metabolic evaluation at baseline, and after a controlled diet including water with a high, medium or low calcium content. RESULTS: In patients who drank water with high and medium calcium contents calcium excretion increased, although the results did not reach statistical significance. In those who drank water with the highest calcium content oxalate excretion significantly decreased (p = 0.05), as did the oxalate-to-calcium ratio (p = 0.05). Moreover, these modifications did not induce relevant changes in urinary saturation. In patients who drank water with the greatest amount of bicarbonate citrate excretion increased (p = 0.03). CONCLUSIONS: Mineral water with a higher calcium content induced increased calcium excretion but significantly decreased oxalate excretion. These data are in accordance with those of others, who did not find definite evidence that hard water is more lithogenic than soft water. Furthermore, water components other than calcium can modify the tendency toward crystal formation, affecting inhibitory power and/or lithogenic salt excretion.
BACKGROUND: Among dialysis patients in the last 10 years the incidence of intradialytic dysequilibrium syndrome and symptomatic hypotension has increased significantly. Profiled haemodialysis (PHD), a new dialysis technique based on intradialytic modulation of the dialysate sodium concentration according to pre-elaborated individual profiles, has been set up to reduce intradialytic imbalances and the incidence of dysequilibrium syndrome and symptomatic hypotension. The present paper illustrates a new mathematical model for solute kinetics, single-compartment for sodium and two-compartment for urea, aimed at improving the use of PHD. The model allows the sodium profile to be elaborated a priori, before each dialysis session, according to the patient's clinical needs and respecting the individual sodium mass removal and weight gain. METHOD: The mathematical model was first derived and then applied to determining a rational dialysate sodium profile. A procedure which allows the method to be tuned to individual clinical needs on the basis of routine measurements performed before each session is also presented. The proposed method was validated in vivo during seven dialysis sessions, each performed on a different patient. RESULTS: The comparison between data predicted by the model and those obtained in vivo shows a good correspondence in particular concerning the time pattern of blood urea and sodium. The comparison between the model prediction and in vivo determined sodium and urea plasma curves showed standard deviations (2.25 mEq/l for sodium and 0.87 mmol/l for urea) only slightly higher than those attributable to laboratory measurement errors. Moreover, in vivo implementation of PHD by our model enables one to remove an amount of sodium mass comparable with the a priori quantity predicted by the model.
The effects of vessel joint where the both sides have different wall properties on the heart pulse propagation are investigated. Such a local disturbance can influence post-transplantation pathology and evolution of the organ inconsistency. Using a mathematical model, developed in a previous article, we perform analytical analysis and present some qualitative and quantitative estimations. The effects of jointed vessels with different thicknesses and radii on the local concentration of the pressure, radial wall displacement, bending moment and shear force are analyzed in detail. In particular, it is obtained that the bending and shear stresses at a joint sharply and strongly increase in comparison with the uniform vessel ones.
In the last 10 years the percentage of dialysis patients suffering from clinical intradialytic intolerance has greatly increased. Profiled hemodialysis (PHD) is a new technical approach, alternative to standard hemodialysis (SHD) for the treatment of intradialytic symptomatic hypotension. It is based on intradialytic modulation of the dialysate sodium concentration, using a dialysate sodium concentration profile elaborated by a new mathematical kinetic model. The aim of PHD is to reduce the intradialytic blood volume decrease, thanks to a dialysate sodium profile, which allows a reduction in the plasma osmolarity decrease, thereby boosting intravascular fluid refilling. This work aims at clinically validating the PHD technique, by testing its ability against SHD, to maintain a more stable intradialytic blood volume; this evaluation was supported by monitoring some hemodynamic parameters. Twelve dialysis patients on SHD treatment were selected because of their intradialytic symptomatic hypotension. Twelve SHD (one per patient) and 12 PHD sessions (one per patient) were performed to achieve the same sodium mass removal and body weight decrease on both PHD and SHD. During these sessions we monitored the blood volume variation % by the crit-line (a non invasive blood volume monitoring device), the mean blood pressure and heart rate directly and, finally, the stroke volume and cardiac output indirectly by bidimensional doppler-echocardiography. Comparison of the results obtained with the two techniques shows PHD to achieve a significantly more stable blood volume, blood pressure and cardiovascular function than SHD, in particular during the second and the third hour of the dialysis session.
Posttransplant monitoring of anti-HLA antibodies with routine techniques gives unsatisfactory results due to a variety of technical limitations. We investigated how a new alternative technique correlates with posttransplant clinical events. A total of 313 nonselected serum samples from 136 patients were screened by an ELISA utilizing captured soluble HLA class I antigens. We observed the absence of anti-HLA antibody production in acute rejection cases responding to standard antirejection therapy. On the other hand, we showed a clear presence of these antibodies in acute rejection episodes not responding to standard therapy (P<0.0001) and in chronic rejection (P<0.001). We conclude that routine posttransplant monitoring by ELISA offers early risk assessment that is crucial for proper immunosuppression and for antirejection therapy choice.
The solute removal characteristics and haemocompatibility of low-flux dialysers containing Cuprophan, cellulose acetate, polymethylmethacrylate (PMMA), and polycarbonate-polyether (Gambrane) membranes were compared in a multicentre cross-over clinical trial. While all four dialysers provided comparable removal of urea and creatinine, the dialyser containing PMMA membrane showed a reduced ability to remove phosphate compared to that containing Cuprophan membrane. Significant beta 2-microglobulin removal was obtained with the dialyser containing Gambrane membrane, whereas the other three dialysers had no impact on plasma beta 2-microglobulin concentrations. The ability to activate complement, measured as changes in the plasma concentrations of C3a des Arg and the terminal complement complex, and to produce leukopenia was greater for the dialyser containing Cuprophan membrane than for the other three. The ability to activate complement and cause leukopenia was not consistent among the remaining three dialysers and the degree of leukopenia could not be predicted from the level of complement activation. Neutrophil degranulation, as indicated by the release of elastase-alpha 1-proteinase inhibitor, occurred to a greater extent with the dialysers containing Cuprophan and Gambrane membranes. None of the dialysers was overtly thrombogenic as judged by changes in platelet count and plasma concentrations of the thrombin-antithrombin III complex. Our results demonstrate that although there are many similarities between dialysers containing low-flux membranes, there are also significant differences. These differences may enable improvements in therapy, while allowing continued use of low-flux dialysers.
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The incidence of intradialytic disequilibrium syndrome and symptomatic hypotension has increased significantly among dialysis patients over the last ten years. Profiled hemodialysis (PHD) is a new technique, based on the intradialytic modulation of dialysate sodium concentration, which aspires to reduce to previous imbalances. This paper presents a new algorithm for the determination of a rational dialysate sodium profile during PHD. A mathematical model of solute kinetics, monocompartmental for sodium and bicompartmental for urea is used. The algorithm allows the sodium profile to be elaborated a priori before each dialysis session, respecting the individual sodium mass removal and weight gain. A procedure allowing the adjustment of the method to the individual characteristics, on the basis of routine measurements performed before each session is also presented. The method was validated during seven dialysis sessions. Comparison between data measured in vivo and those predicted by the model showed standard deviations corresponding to the range of laboratory measurement errors: 1.50 mEq/L for sodium and 0.87 mmol/L for urea. In vivo implementation of PHD by our algorithm allows one to remove an amount of sodium close to that established a priori on the basis of patient's need.
We report on a kidney transplant recipient experiencing an unexpected early acute vascular graft rejection. Retrospective analysis of patient serum samples, utilizing a new ELISA HLA screening technique, revealed that the rejection crisis and the subsequent graft loss were due to a pretransplant donor-specific pre-sensitization caused by a non-complement-fixing antibody of IgG2 class. The case illustrates the clinical significance of non-complement-fixing anti-HLA antibodies. In addition it is shown that ELISA methods are suitable for detecting potentially harmful donor pre-sensitization in waiting-list patients not detectable by standard lymphocytotoxicity techniques. Hence ELISA could be an alternative to flow cytometry for this purpose. It is concluded that screening and cross-matching techniques which detect non-complement-fixing anti-HLA antibodies could improve graft outcome, and should form part of the immunological monitoring of kidney transplant waiting-list patients.
A multicentre trial (11 nephrology centres) was carried out to test the effects of ibopamine, an orally active dopamine-like drug, on the progression of chronic renal failure. For a 2-year period 189 chronic renal failure patients (serum creatinine level 1.5-4.0 mg/dl) were observed. They were homogeneous for basic nephropathy, degree of residual renal function, blood pressure, and proteinuria. The patients were randomly divided into two groups: 96 took ibopamine at a dosage of 100 mg/day (group A) and 93 served as controls (group B). All were on a low-protein diet (mean 0.8 g/kg body weight). By the end of the observation period, the rate of decrease of the renal function indexes in time proved significantly slower (1.8 times) in group A than in group B. The survival curves for renal function (pre-established end points were creatinine level increases equal to or > 20% and equal to or > 40% of the basal values) proved significantly better (p < 0.02 and p < 0.002 respectively) in group A than in group B. The mean plasma creatinine values rose by 17% in group A and by 36% in group B. The creatinine clearance decreased by 5% in treated patients and by 14% in the controls. Statistical analysis ruled out any possible centre effect. The trial suggests that low-dosage ibopamine administration may be used as a valid and safe pharmacological adjunct for retarding the progression of renal failure in patients with mild or moderate chronic renal impairment.