Multiple varieties of bionic support in kidney transplantation.
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Biomedical subjects
Publications and source records attributed to V Bonomini.
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A search for antibodies against hepatitis C virus (HCV) was performed in 185 patients on chronic hemodialysis by means of 1st and 2nd generation ELISA tests. Immunoblot assays were performed on positive sera. This study shows a 38% prevalence of HCV-positive patients in our dialysis population according to the 2nd generation ELISA test which shows a higher specificity and sensitivity when compared to the 1st generation one (38 vs. 20%). A correlation was found between the prevalence of HCV-positive patients and how long they had been on dialysis and how many blood transfusions they had received.
An experimental model of hypertrophic pyloric stenosis was made by suture of the pyloric wall and gastrostomy in 10 rabbits under general anesthesia. Blood sampling indicated severe alkalosis and hypochloremia 3h 30 min after surgery. To correct the derangement, we tested an ion exchange resin (Dowex SAR), coated with a methacrylic hydrogel. A cartridge containing 18 g of this resin was inserted in an extracorporeal circuit. This chloride charged resin achieved uptake of HCO3- ions, and elution of Cl- ions. The electrolytic balance was fully restored after 10 min of treatment.
This study reports on 12 patients with acute renal failure due to biopsy-proven rapidly progressive glomerulonephritis and signs of systemic disease in whom antineutrophil cytoplasmic autoantibodies (ANCA) were detected by indirect immunofluorescence (IIF) on alcohol-fixed neutrophils and assessed in serial determinations by ELISA. The diagnosis was: Wegener's granulomatosis in nine patients who showed a diffuse cytoplasmic pattern at IIF (c-ANCA), and microscopic polyarteritis in three where a perinuclear pattern (p-ANCA) was seen. All patients underwent a course of plasma exchange - PE - (3-10 sessions per patient) associated with steroids and cyclophosphamide. The ANCA titer dropped steeply during PE in all cases and was followed by disappearance of systemic symptoms and renal function improvement within four weeks. After a follow-up period of 50 +/- 31.2 months all patients were alive without signs of disease activity; ten had stable renal function, with serum creatinine 1.8 +/- 0.7 mg/dl; two had entered regular dialysis treatment after 44 and 82 months. Our results suggest that the rapid removal of ANCA by means of PE can help control disease activity and reduce the risk of death or end-stage renal disease.
This paper reports a 2-year experience of more than 5,000 cross-match tests for renal transplantation. Tests were performed by means of both standard light microscopy and an innovatory method based on flow cytometry, an up-to-date investigative technique for computerized analysis of individual cell characteristics. Flow cytometry allowed a better detection of weak positive reactions (false-negative cross-matches) than light microscopy, thus reducing the risk of selecting candidates with donor presensitization. Transplant clinical outcome supported the value of this original and advanced technological method.
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Cellular immunity represents an interesting biological model for biocompatibility evaluation of artificial materials owing to its sensitivity to contact with the external environment and its capability of modulating response reactions to foreign agents. Advanced methodologies such as flow cytometry and the immunoenzyme techniques in particular have given new insights into lymphocyte structure and functions, enabling analysis of the in vivo modification of these cells. By means of these sophisticated techniques we investigated lymphocyte activation and proliferation during one single haemodialysis session. Findings clearly show that increases in HLA antigen density (class I and II), DNA synthesis, and interleukin-2 receptor serum concentration (Il-2R) take place during the dialysis procedure, and reach their maximum during the first hour of extracorporeal circulation. The relationship between dialysis procedure and cellular immunity appears noticeable and is of potential value in the evaluation and quantification of the biocompatibility of different dialysis membranes.
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Plasma exchange has been used in our renal transplantation programme for over ten years to treat 86 patients divided into four groups. Five patients had preformed cytotoxic antibodies before transplantation (group A); 13 sensitized patients (greater than 60% PRA) underwent prophylactic plasma exchange in the immediate post-operative period (group B); 62 patients were treated for acute vascular rejection (group C); six patients had chronic graft rejection (group D). Plasma exchange is a valid tool for the treatment of acute vascular rejection, provided that it is started before irreversible graft damage occurs: 75% rejection crises were reversed by plasma exchange and the actuarial graft survival from the rejection episode was 75% at one year, 66% at two and 50% at five years. Serum creatinine before treatment and glomerular thrombosis at graft biopsy correlated with the response to plasma exchange. In sensitized patients and in those with chronic rejection the results were disappointing and suggest that in these clinical conditions plasma exchange should be used only in selected cases.
Present 'techno-medicine' has brought about clinical results that were simply unthinkable only a few years ago. Just how positive these results really are is beginning to emerge today with growing clarity. Yet, typical of techno-medicine is the way it solves certain problems whilst at the same time creating others. Organ replacement therapy clearly illustrates this modern predicament. Nowadays the death of an organ does not necessarily spell death to the individual. But the miracle of survival thus achieved entails a whole series of complex, controversial, or unsolved repercussions (ethical, logistic, clinical, economic). To find a solution to these would require more progressive thinking by our politicians if they are to grasp the real social importance of technomedicine; and greater humility from our scientists who must be prepared to admit that the widespread application of scientific results hinges entirely on their acceptance by politicians. Such concrete, trusting collaboration between the two orders of politics and science is still utopian. The ethics of living-donor transplantation conform to the rule: results (here moral as well as clinical) following on results (the creation of the renal 'new man' brought about by present techno-medicine).
Recurrent glomerulonephritis and de novo glomerulonephritis may develop in the graft after renal transplantation. Among 59 patients with a pathological diagnosis of glomerulonephritis as original renal disease, 12 (20.3%) showed recurrence of the original lesions in the graft. Two patients with hereditary nephritis developed anti-GBM disease (one patients in two grafts). The disease rapidly progressed to graft loss. A de novo membranous nephropathy was diagnosed in four patients whose original renal disease was not a glomerulonephritis. One patient had been treated with antilymphocyte globulin, another with captopril.
When chronic renal failure becomes advanced, the serum or tissue levels and/or the functions of most hormones are altered because of several interplaying mechanisms involving synthesis, transport, accumulation of inhibitors, abnormality of target organ responsiveness, and impaired renal clearance. As regular dialysis treatment is performed, most of these uremic hormone abnormalities are not reversed, and some of them may even get worse. The main endocrine derangements can be grouped as sexual hormone dysfunction, thyroid abnormalities, growth retardation, hormone-related disorders of metabolism, derangements of pressor substances, gastrointestinal peptide abnormalities, renal osteodystrophy, and anemia. The endocrine abnormalities play a major role as for the clinical and metabolic rehabilitation of dialysis patients.
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To investigate the possibility of slowing down disease progression 27 patients with primary glomerular diseases unresponsive to steroids and cytotoxic drugs were treated with Defibrotide. This drug is a single stranded DNA fraction which has profibrinolytic and deaggregating properties and can promote the generation and release of prostacyclin from vascular tissue. Before treatment all patients showed proteinuria in excess of 1 g/day and 16 had a nephrotic syndrome (59%); 10 patients had serum creatinine above 1.6 mg/dl (37%) and 6 were hypertensive. After therapy a significant decrease in daily proteinuria was observed, although the reduction exceeded 50% of pre-treatment values in only 16 patients (59%). A progressive decrease in serum creatinine occurred in patients with abnormal renal function; serial measurement of renal plasma flow showed a progressive improvement with an average increase of 6 and 12%, after 1 and 3 months of treatment, respectively. These observations confirm the view that drugs improving endothelial function and renal hemodynamics can be of value in the treatment of chronic glomerular diseases and can contribute to the maintenance of renal function.
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