Lymphocyte-mesenchymal cell interaction in acute renal transplant rejection: an electron microscopy study.
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Biomedical subjects
Publications and source records attributed to V Bonomini.
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The present study reports on the effects of plasmapheresis on both cellular (E-rosette receptor- and Fc receptor-bearing lymphocytes) and humoral (antilymphocyte antibodies) immunity in patients with active SLE. Ten untreated patients were studied before and after two plasma exchanges. The E-rosette receptor-positive cells were studied by OKT11 monoclonal antibody and Fc receptor-bearing cells by Leu15 monoclonal antibody. Antilymphocyte antibodies were studied before and after plasma exchange by an indirect immunofluorescence technique on autologous and normal lymphocytes. A reduction in OKT11+ and Leu15+ lymphocytes was observed in all patients before plasmapheresis. Antilymphocyte antibodies were detected in five patients. After plasma exchange, an increase in E-rosette receptor- and Fc receptor-bearing lymphocytes was observed along with a reduction in the amount of antilymphocyte antibodies.
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In transplanted patients graft rejection is the most frequent complication in the first year after surgery. Vascular lesions (necrosis, intimal proliferation, thrombosis) are signs of poor prognosis and lead to irreversible loss of renal function and graft removal in most cases. The problem of vascular rejection is still not solved and the results of therapy unsatisfactory, both because of inadequacy of diagnosis and/or inadequacy of available therapy. The role of prevention, very likely the best approach, is still sub judice. In an attempt to explore the validity of prevention, 22 transplanted patients (group A) were given a new antithrombotic agent (defibrotide) immediately after surgery, and the results were compared with those of a well-matched group of 30 patients on dipyridamole (group B). Follow-up lasted 6-19 months (mean 9.9) for group A; 5-21 months (mean 12) for group B. In group A, 8 patients (36%) had rejection episodes. Antirejection therapy was followed by recovery of renal function in all cases. In group B, 9 patients (29%) had rejection crises and graft removal was necessary in 7 instances due to severe vascular lesions. At the end of follow-up, all patients treated with defibrotide had normally functioning grafts: among the 30 patients on dipyridamole, 22 (73%) had satisfactory graft function.
Thrombotic microangiopathy (TMA) can occur whenever pathogenetic events lead to fibrin deposition in the microcirculation. It has been suggested that intravascular coagulation is important in the development of renal as well as cerebral lesions. The mortality rate in adults varies from 50 to 70%; chronic or progressive renal failure occurs in approximately two thirds of children over 2 years of age. Poor success may be due to therapy being initiated too late or to inappropriate use of antagonistic drugs, or both. In the last 2 years we have treated 8 patients with TMA (5 with thrombotic thrombocytopenic purpura; 3 with hemolytic uremic syndrome) with defibrotide, a new antithrombotic agent extracted from mammalian lungs. At admission all patients had severe renal involvement (serum creatinine 5.3-14.9 mg/dl) and coagulation abnormalities (low platelet count; high levels of circulating fibrin degradation products). There were neurological manifestations in 6 patients. Defibrotide administration was followed in 6 patients by recovery of renal function. In all patients, defibrotide therapy induced the disappearance of neurological manifestations and normalization of coagulation abnormalities. Defibrotide caused no side effects. All patients are alive after 7-22 months of follow-up.
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Biocompatibility of charcoal hemoperfusion was studied in a group of 15 uremic patients, evaluating the effects of long-term treatment on some structural and functional parameters of circulating lymphocytes: in vivo distribution of T-cell subsets; surface T3, T4 and T8 antigen expression, in vivo and in vitro DNA synthesis. A comparative analysis was performed with patients on conventional dialysis using cuprophan membranes.
The present report deals with a medium-term programme using biofiltration on a group of 10 patients, who underwent a regular reduced-time schedule (3 procedures per week, 3 hours duration each) lasting up to 12 months. A polyacrylonitrile AN 69 S membrane was used together with a substitution fluid containing Na and bicarbonate. Hematochemical and nutritional parameters were regularly checked to evaluate the efficacy of treatment. Biocompatibility of materials was evaluated by humoral and cellular immunological tests.
Until recently it has been controversial whether plasmapheresis is benefitial in graft rejection therapy. Here we present a controlled trial in 44 kidney transplanted patients with biopsy proven acute vascular rejection and specific anti-HLA-antibodies. 23 randomized patients were treated additionally with plasmaexchange (group A), whereas the remaining 21 received drug therapy only (group B). 7 out of 23 (30%) lost their graft in group A and 17 out of 21 (81%) in group B. Mean serum creatinine and actuarial graft survival underline the significant effect of plasmaexchange therapy which appears especially benefitial when rejection occurs later than one month after surgery.
Plasmapheresis has been employed in the treatment of various immunological disorders, and its efficacy has mainly been attributed to the removal of humoral factors. Besides these effects, plasmapheresis may induce some modifications to the cellular immunological status, contributing to the restoration of altered immunological function. In immunological renal diseases various parameters may be followed to decide the use of plasmapheresis, and to judge the effect of treatment. They include clinical, functional, and morphological investigations. In patients with lupus nephritis the main indications for plasmapheresis are the presence of impaired renal function and histological signs of activity in renal biopsy. In these patients plasmapheresis is able to modify humoral and cellular immunological abnormalities. Renal function and clinical course may improve in most cases. In patients with arteritis and acute renal failure the response to plasmapheresis combined with immunosuppressive drugs is better than the response to drug therapy alone. In acute renal transplant rejection plasmapheresis may be of value in improving the graft prognosis, when humoral factors are demonstrable in the pathogenesis of graft damage and vascular lesions are present in the kidney.
This paper reports the Authors' 8 year experience in the clinical use of charcoal hemoperfusion as a means to reduce the weekly time of treatment in chronic uremic patients. Two different programmes were applied. Programme A (34 patients) which involved substituting the 3 procedures per week of standard dialysis (4 hours duration each) by 2 procedures of combined hemodialysis and hemoperfusion, again of 4 hours duration each. Programme B (18 patients) which involved substituting the 3 procedures per week of 4 hours duration by 3 procedures of 3 hours each, 2 of combined hemodialysis and hemoperfusion, 1 of conventional dialysis. The net weekly reduction was 33% for Programme A and 25% for Programme B. The efficacy of the two Programmes was evaluated by clinical, hematochemical, nutritional and instrumental parameters.
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8 patients with thrombotic microangiopathy were treated with a new antithrombotic agent, defibrotide. This drug displays considerable fibrinolytic and antithrombotic activity, and induces generation and release of a prostacyclin-like substance from vascular tissue. At admission all patients presented severe renal involvement and coagulation abnormalities. Neurological manifestations were present in 6. Defibrotide administration was followed by recovery of renal function in 6, disappearance of neurological symptoms and coagulation abnormalities in all patients. The use of defibrotide was not associated with side effects. On the basis of the results obtained in these patients, we suggest that defibrotide might be considered as a valuable drug in the management of patients with thrombotic microangiopathy.
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It is generally maintained that the variety of endocrine disorders which occur in uraemia and persist in dialysis (above all hormones whose production and/or metabolic clearance are pertinent functions of the kidney) usually abate after successful renal transplantation. However, a retrospective analysis of long-term results in 71 out of 275 cases serially studied by regular checks, indicates that this event occurs in no more than 2/3 of successfully transplanted patients. In the other patients various endocrine abnormalities may be documented: some seem apparently 'inherited' from uraemia (hyperparathyroidism, sexual dysfunction, growth retardation); some are mainly related to steroids (hyperinsulinism), and some have a de novo origin (erythrocytosis, reno-vascular hypertension). These endocrine abnormalities may occur with a normal or reduced graft function, have a baseline or stimulated expression, a clinical or subclinical course, and a reversible or irreversible outcome. A proper grasp of these events in renal transplantation is of clinical significance particularly for the long-term patient and graft prognosis.
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