Immunosuppression in renal transplantation.
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Biomedical subjects
Publications and source records attributed to V Bonomini.
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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.
Profiled dialysis is a new conceptual approach to patient intradialytic vascular instability. It is based on the continuous modulation of dialysis operative parameters, such as dialysate sodium and UF rate, according to pre-established profiles. The points to be defined for profiled dialysis are: (a) the patient's individual sodium and masses already stated; (b) the patient's individual algorithms to fit the clinically effective intradialytic variations in plasma sodium and sodium mass; (c) a mathematical model from which sodium and UF profiles are automatically worked out at the beginning of each session. The basic concept of profiled dialysis should evolve towards an ongoing "profiling' programme. This is based on the continuous on-line intradialytic adjustment of profiles according to the patient's emerging clinical requirements.
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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.
This paper reports on 3 patients on renal dialysis for crescentic glomerulonephritis associated with microscopic polyarteritis (MPA) and antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase (MPO-ANCAs). They successfully underwent renal transplantation from a cadaver donor 6-63 months after the onset of the disease, despite the persistence of antibodies at high titer. A triple immunosuppressive regimen including steroids, cyclosporin and azathioprine was used. One patient underwent transplantectomy for surgical complications 3 months later, while the serum creatinine was 2.0 mg/dl (178 mu mol/l): the remainder have a well-functioning graft after 21 and 38 months, no clinical sign of disease recurrence, and a MPO titer within the normal range. We conclude that MPA patients can undergo renal transplantation even if ANCAs persist at a high titer in the circulation.
A sudden-onset chyluria after trauma was evaluated giving evidence of a lymphatic-urinary fistula in the right kidney. Treatment with somatostatin normalized the urinary pattern and the result was maintained even after the discontinuation of the therapy.
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A simple mathematical model of the intradialytic relationship between natraemia and dialysate sodium concentration is presented. The model includes a bicompartmental description of sodium, urea and fluid kinetics and an algebraic characterization of diffusive/convective mass-transfer across the dialysis membrane. Its ability to provide realistic responses has been validated comparing model predictions by a priori parameter tuning against quantities measured during in vivo sessions with both constant and variable dialysate sodium concentration. A quantitative analysis of model predictions indicates that the mean deviation between data calculated by the model and those measured in vivo is 1.32 mEq/l for sodium and 0.76 mmol/l for urea, values which do not greatly exceed the measurement errors of current instruments. The model's predictive capacity thus proves reliable. The ability of the model to calculate the amount of sodium removed and the time course of intra-extracellular volumes during the dialysis session makes it possible to forecast the patient's clinical tolerance to a given sodium dialysate concentration.
Organ replacement therapy is one of the three new forms of life (molecular biology, computer science, organ replacement) that modern techno-medicine affords. Of all the organs, the kidney is pre-eminent in quality and quantity of results. The kidney experience, indeed, acts as a teacher to the other organs in terms of organization and clinical practice. Among the various programs used in the treatment of chronic renal failure, transplantation stands first. It is the only non-illusory form of therapy (in clinical, social and economic terms), but it is only possible in 30% of cases, due to the shortage of valid donors. Artificial replacement (hemodialysis or its alternatives), predominates today and will predominate tomorrow, provided the political and economic structures of various countries are able to afford it. Without dialysis, transplantation itself would not be possible in over 95% of cases, and the graft would have failed in 50% after surgery. Thus, without the backup af artificial replacement therapy, transplantation may be an individual solution for individual cases, but not the solution to the problem as a whole in social terms. Although progressive improvements in technology have resulted in improved survival both in dialysis and in transplantation, all the other expectations of high-tech replacement have tended to be disappointing. As a multidisciplinary reality, renal replacement therapy still requires the integration of various sciences. Results so far achieved have shown the discrepancy between expectations and results, and indicated the way to follow to make the treatment biologically closer to man and physiologically closer to the organ.
The present comparative evaluation aims at establishing whether the basic structure of dialysis membrane is able to predict long-term clinical outcome. From a population of 1,256 patients on renal dialysis treatment, treated by the Institute of Nephrology and Dialysis of the St. Orsola University Hospital of Bologna from 1963 to 1993, 122 patients were retrospectively selected for the present study. Patients were divided into two different groups according to the kind of dialysis membrane used--cellulose-based (64 patients) and synthetic-based (58 patients) membranes. The parameters considered were: intradialytic biology, long-term biocompatibility, survival and morbidity, and cost/benefit. The results obtained demonstrate that cellulosic membranes can be said to cause a greater acute intradialytic biological response than synthetics, though not to a significant degree. There are, however, no significant differences in the biological changes from group to group. Nonsignificant differences were noted in long-term survival general morbidity. In terms of sheer cost, synthetic membrane treatment is anything up to 200% dearer than cellulosic.
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