Lipoprotein abnormalities in renal transplant recipients with chronic vascular rejection.
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Biomedical subjects
Publications and source records attributed to G Tufveson.
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This report summarises the outcome of 90 combined kidney/pancreatic grafts performed in Europe in 1986. Data for the combined kidney/pancreas grafts were obtained by a special questionnaire. The one-year patient and kidney graft survival is compared to the results of a group of 389 patients with diabetic nephropathy on the EDTA Registry data file who received kidney grafts alone. The recipients of combined kidney-pancreas grafts were younger, whereas a greater proportion of males received kidney graft alone. Patient survival at one year after transplantation was similar: 89% in recipients of combined transplants compared to 90% in recipients of kidney grafts alone. Kidney graft survival was 78% at one year for recipients of combined grafts versus 76%. It is concluded that pancreas transplantation has little effect on the fate of concomitant kidney grafts. The procedure should-in experienced hands and in selected patients-be almost as safe as kidney grafting alone.
The immunomodulator LS-2616 (Linomide) induces rejection of cyclosporine-protected rat cardiac allografts. The aim of this study was to characterize this rejection in the presence of CsA and to test LS-2616 in other models of permanent graft acceptance in the rat. PVG rat hearts were transplanted heterotopically to Wistar/Kyoto (Wi/Ky) rat recipients on day 0. The recipients were treated orally on days 0-9 with CsA (10-40 mg/kg) and/or with LS-2616 (2.5-160 mg/kg) starting at different times (day -7 -+5) until the day of complete rejection. The addition of LS-2616 (day -1--stop) to CsA (10 mg/kg) resulted in a dose-dependent antagonism of the immunosuppressive effect of CsA with daily doses of 2.5-160 mg/kg. Furthermore, the results were similar, irrespective of whether LS-2616 treatment (160 mg/kg) was started on day -7, -1, +1, +3, or +5. LS-2616 (160 mg/kg) pretreatment of the recipient for 7 days before transplantation was considerably less effective. CsA (20 mg/kg) for 14 days after a PVG to DA transplantation resulted in permanent graft survival. This was not abrogated by LS-2616. Neither was rejection induced in long-term surviving grafts of RT1.C incompatible Lewis recipients. Our data suggest that LS-2616 activates already stimulated and sensitized T cells that are otherwise controlled by CsA.
Following 0, 5, or 18 h of cold ischemia in the University of Wisconsin or Sacks' solution syngenic small bowel transplantation was performed to the renal vessels. Mucosal injury during ischemia or at reperfusion was evaluated microscopically using a grading scale from 0 to 8. The series subjected to small bowel transplantation without cold ischemia showed superficial damage to the tips of the villi (median grade 2) with no further exacerbation at reperfusion and complete healing 24 h thereafter. Moderate villous injury (median grade 3) was demonstrated following 5 h of cold ischemia. This injury was exacerbated to grade 4 (p less than 0.05) following reperfusion but was almost completely healed 24 h later. Grade 4 tissue injury was seen following 18 h of cold ischemia without further exacerbation at reperfusion and no clear tendency to healing 24 h later.
The following study describes cold ex vivo or intravenous infusion of monoclonal antibodies (MCAB) for lymphocyte target cells of rat small-bowel grafts. The MCAB Ox8, directed against CD8+ T lymphocytes, is used here as a model antibody. We demonstrate that Ox8 antibodies administered during cold ex vivo perfusion are able to reach the target cells in the small-bowel mucosa and the mesenteric lymph nodes of rat small-bowel grafts. Thus, cold perfusion of the vascular system for 20-60 min resulted in good labelling of the CD8+ T cells as analysed on cryostat tissue sections using immunoperoxidase staining. Rats treated with Ox8 intravenously 60 min before taking of specimens showed similar labelling. Additional staining of the tissue sections with Ox8 antibody resulted in no further labelling, thus indicating that nearly all CD8+ T cells were labelled both after ex vivo perfusion and after intravenous treatment of the donor. It is concluded that MCAB can, as an alternative to the intravenous route, be administered ex vivo after organ harvesting.
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The disturbed coagulation state seen in patients with uremia has been suggested to contribute to thrombotic events in kidney grafts following transplantation. Primary haemostasis, plasmatic coagulation and fibrinolysis were investigated in eight patients before and during four weeks after kidney transplantation. In spite of an improved renal function there was postoperatively still a depressed platelet aggregation and the prostacyclin concentrations in plasma were low. The plasma coagulation seemed to be activated according to short activated partial thromboplastin time, high levels of FVIII:C and prothrombin complex. The fibrinolysis was increased and the PAI-1 levels were decreased. It is concluded that the overall haemostatic balance is characterized by a high degree of activation in uremic patients and that this activation persisted four weeks after transplantation.
By using biotin-labeled proteoglycan core protein and an avidin-enzyme system, hyaluronic acid (HA) was visualized in rat kidney. In the normal kidney, HA was localized in the extracellular space of the inner medulla and increased markedly towards the papillary tip. No staining for HA was seen in the interstitial tissue of the cortex or the outer medulla. During the development of rejection of allogeneic renal grafts, a progressive increase in accumulated HA was seen in the interstitial tissue of the cortex and outer medulla. The extractable amounts of HA increased, on average, 40 times in the cortex and outer medulla; no increase was measured in the inner medulla and papilla. The relative water content of the cortex and outer medulla also increased progressively and correlated with the HA accumulation. The extractable amounts of HA in syngeneic grafts increased by day 2 and then leveled off, indicating that surgical trauma may induce some transient HA accumulation after transplantation. Interstitial accumulation of HA, a glycosaminoglycan with unique water-binding qualities, would presumably influence water transport and osmotic activity and should thereby be implicated in the normal papillary function, but also in the development of the interstitial edema of the cortex and outer medulla during rejection of renal grafts.
The demographic data on the use of continuous peritoneal dialysis in Europe for children starting renal replacement therapy under the age of 15 years was obtained from data collected by the Registry of the European Dialysis and Transplant Association--European Renal Association (EDTA Registry) on individual patient questionnaires 1980-1986. Continuous ambulatory peritoneal dialysis (CAPD) and its variants appeared to be increasingly utilised as treatment for children with end-stage renal failure (ESRF) and accounted for approximately 25% of all renal replacement therapy (RRT). Important differences in its use in various European countries are demonstrated. The proportional contribution of CAPD to treatment was higher during the first year of RRT and gradually decreased thereafter. No significant sex differences existed in the use of this treatment. Approximately 70% of all patients on CAPD were older than 6 years of age, but it is in those under 6 years that the highest proportion are put on CAPD as first method of treatment for end-stage renal failure. The most common cause of abandonment of this treatment was peritonitis, which contributed 50% of the drop-out rate.
This paper reports the results of 98 first kidney transplantations in patients with oxalosis as the primary renal disease as recorded by the EDTA Registry. There were 79 patients who received a cadaveric (CAD) graft and 15 patients with a living related donor (LRD) graft; the type of donor was not recorded for four patients. Initial graft survival appeared to be better after LRD as compared to CAD grafts but at 3 years the poor survival was similar with 23% for LRD and 17% for CAD grafts. CAD graft survival did not differ between children and adults and was not affected by the waiting time on dialysis. A slight improvement was observed in grafts performed in the years 1983-1986 as compared to grafts performed in earlier years. The causes of failure reported were mainly rejection (33%) and recurrence of primary renal disease (31%). In view of the poor results related to recurrence of oxalosis in the graft, the potential of combined kidney and liver transplantation is discussed.
In a retrospective case control study the prevalence of signs and symptoms of dialysis osteoarthropathy was analysed. Cases and controls had received over 9 years of maintenance haemodialysis uninterrupted by peritoneal dialysis or transplantation. The cases comprised 55 patients treated predominantly with polyacrylonitrile (AN69) dialysers. They were compared to a matched group dialysed exclusively with cellulosic membranes. Over 60% of all patients, cases and controls, showed one or more signs of disabling osteoarthropathy, with joint pains occurring more frequently in the older age groups. Twenty-seven of the 55 cases who had received less than 2 years of cellulosic membrane dialysis followed by 7-12 years of AN69 dialysis tended to have a lower prevalence of joint pains, carpal-tunnel syndrome and bone cysts. However, no statistically significant differences were obtained compared to the matched control group dialysed exclusively on cellulosic membranes (mostly cuprophane). The remaining 28 cases, who had been treated for more than 2 years with cellulosic membranes preceding the longer treatment period with polyacrylonitrile dialysers, showed a prevalence similar to that of their cellulosic controls. This study thus shows little, if any, influence of the two types of membranes on the prevalence of signs and symptoms of beta 2-microglobulin amyloidosis.
Multiple vascular access failure is a frequent problem and we report our experience with 32 Hemasite devices implanted in 28 patients with end-stage renal disease. All of the patients were on maintenance haemodialysis or haemofiltration with a range of treatment of 1-17 years. Their mean age was 58 +/- 14 years (range 28-72 years). The main indication for using this device as an alternative vascular access was the presence of high-risk patients with a high incidence of previous access failure (1-8 accesses per patient). The majority of the patients were considered as high risk, due either to old age (more than 60 years) (60%) or to the presence of diabetes mellitus (29%). The results of 5 years' experience and follow-up showed that the Hemasite device could be successfully used as a secondary vascular access in high-risk patients who have problems of multiple access failures. The 1-year cumulative survival of the device (55%) was affected by complications such as thrombosis and infection (47% and 16%) which were noted mostly among patients with diabetes mellitus. These complications are the major ones endangering the longevity of the Hemasite implant and were important causes of implant loss (31% and 6% respectively). Being needleless and painless, the Hemasite was well-accepted by the patients and it functioned well, with adequate blood flow. We conclude that the Hemasite device is a valuable alternative when vascular access becomes a problem in haemodialysis patients.