High-dose AZA therapy in a triple-drug regimen, monitored by 6-TGN, will keep myelotoxicity within acceptable limits with the benefit of a reduction in acute rejection episodes.
Aortoiliac angiography has always been an integral part of the pretransplantation work-up of renal transplant candidates in Norway. The present study was undertaken to investigate the value of this routine. Based on the angiograms of approximately 1400 patients evaluated for renal transplantation during the 7-year period 1984-1991, 26 were found to have aortic and/or iliac atherosclerosis requiring pretransplant vascular reconstruction. Fifteen of the 26 patients had aneurysm of the abdominal aorta and 11 had extensive aortoiliac occlusive disease. A prosthetic graft was inserted in 25 patients and endarterectomy of the aortic bifurcation was performed in one. The cause of death was coronary heart disease in four of six patients who died before, and in one patient who died after, transplantation. Sixteen patients received a renal transplant while four patients are still on the waiting list. Fifteen of the recipients are alive, 14 with functioning renal transplants. The low yield of patients below 40 years of age requiring vascular reconstruction calls into question the routine use of angiographic investigation of renal transplant candidates below this age. However, we recommend this routine for the higher age groups because it often provides the surgeon performing the transplantation with valuable information. Aortoiliac reconstruction as preparation for renal transplantation is advocated when atherosclerosis of a degree that may preclude transplantation is found. Because of the high risk of myocardial infarction in these patients, one must be especially aware of coronary atherosclerosis when evaluating patients for this procedure.
SDZ CHI 621 is a murine-human chimeric monoclonal antibody (mAb) to the interleukin-2 (IL-2) receptor (CD25) intended for prophylactic immunosuppression against acute rejection in the first several weeks following kidney transplantation. A multicentre, prospective, dose-finding study was conducted in 37 primary, mismatched cadaver kidney transplant patients to assess its tolerability, pharmacokinetics and immunodynamics. Successive cohorts of patients were stratified to receive total doses of 20,30,40 or 60 mg (n = 4,4, 14, 15, respectively) administered as 15-or 20-mg intravenous infusions with the first dose given preoperatively and subsequent doses within the first 10 days posttransplant. Daily mAb serum concentrations were analysed by a radioimmunoassay method and the percentage of peripheral T-lymphocytes expressing CD25 from serial blood samples was determined by FACScan. Intravenous administrations were well tolerated. mAb concentration pro-files exhibited a biphasic decline with an initial t,,* of 14.4 f 14.2 h, terminal t,,, of 13.4 f 6.0 days, distribution volume (V,,) of 6.9 f 3.3 1 and clearance of 17.4 f 7.8 ml/h. The concentration-effect (mAb-CD25) relationship indicated that mAb concentrations exceeding a threshold of about 0.7 pg/ml corresponded to complete suppression of CD25 (4 3 % CD25' T-cells). The threshold mAb concentration was exceeded at all dose levels, whereas the duration above the threshold (and thus of CD25 suppression) rose with increasing dose: 20 mg, 20 -t 7 days; 30 mg, 32 f 6 days; 40 mg, 37 f 10 days; and 60 mg, 53 f 17 days. As mAb concentrations declined below the threshold following the last dose, CD25 expression returned to baseline (18-44 % CD25' T-cells) within a few days.
Twenty-five patients with transplant artery stenosis were identified among 1141 renal graft recipients. Impaired graft function (9 patients), hypertension (4 patients) or both (12 patients) were the indications for arteriography. All were treated by percutaneous angioplasty (PTA). The immediate technical success rate was 88% and actuarial graft survival was 88% and 80% at 2 and 5 years respectively. The long-term success rate on graft function was 67% (median observation time 24 months) and on hypertension 63% (median observation time 23 months). Six patients needed rePTA (8 procedures) and in only one patient was surgical repair performed. No case of graft loss due to PTA was recorded and in only one case did occlusion of a segmental artery lead to impairment of graft function. Minor complications were recorded in four other cases and in no case was surgical intervention necessary. Based on these results we favour PTA as a first-line interventional procedure in transplant renal artery stenosis, and the need for surgical repair has been low.
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