Postmortem and living organ donation in Europe: transplant laws and activities.
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Biomedical subjects
Publications and source records attributed to W Land.
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AIM OF THE STUDY: The frequency of acute renal failure (ARF) after preservation and kidney transplantation is rather high. The etiology of an ARF is an interaction of multiple mechanisms as donor conditions, explantation procedure, duration of ischemia and reperfusion injury. Different experiments demonstrated, that the damage produced by reperfusion can be prevented by the scavenger of free radicals, the enzyme superoxide dismutase (SOD). PATIENTS AND METHODS: After a double blind study, using consecutive intraarterial bovine SOD (n = 100) in kidney transplantation, showing a trend in favour to the SOD treated group, especially when long-time stored kidneys (> 30 h) had been grafted, a second study was designed to evaluate the efficiency of intravenous recombinant human SOD in the protection from ARF. This study (n = 180) was split into two different trials, double blind and randomized in itself: (A) grafts with cold ischemia time lower or equal 30 hrs., (B) cold ischemia more than 30 hrs. All grafts were preserved with Euro-collins. The study substances were either placebo or 200 mg rh-SOD (Grünenthal GmbH, FRG), given 10-2 minutes prior reperfusion intravenously. Parameters causing an ARF were equal and well comparable in both groups. RESULTS: Concerning early graft function there was no difference in study A between placebo and rh-SOD group. In study B the average and median of the day creatinine dropped the first time without interference of hemodialysis, showed a trend in favour to the rh-SOD group. If placebo was given only 19% of the grafts gained function within the first week, when rh-SOD was applied 47% functioned in the first week. The lack of significant benefit from SOD treatment could be explained by the dependency of the proportion of the total injury caused by reperfusion compared with the proportion resulting from ischemic injury per se. The rh-SOD group showed a better 3 years graft survival rate (+16%). CONCLUSIONS: It seems rh-SOD is able to augment the early graft function and is helpful to reduce the ARF frequency when long-time stored cadaveric kidneys have to be transplanted. These promising results encourage us to continue the study in protocol B to get greater numbers and definitive results.
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This study reports the course of diabetic retinopathy in 25 patients (41 eyes, 9 one-eyed patients) who had undergone successful renal and pancreatic transplantation. The mean duration of follow-up was 38 months (range, 15-71 months). Visual acuity improved in 13 eyes (32%), remained stable in 19 (46%) and deteriorated in 9 (22%); only 2 of the latter 9 eyes (5%) sustained severe visual loss according to the definition of the Diabetic Retinopathy Study Group. The frequency and severity of vitreous hemorrhage improved in 19 eyes (46%), remained unchanged in 18 (44%) and worsened in 4 (10%). In comparison with other modes of treatment such as intensified conventional insulin therapy and artificial insulin-delivery systems, the combined renal and pancreatic transplantation seems to have advantages concerning the course of proliferative diabetic retinopathy.
Our pancreatic transplantation programme was initiated in 1979. Since then a total of 102 pancreas transplantations have been performed, blocking exocrine secretion using the duct occlusion technique with prolamine. Early non-immunological complications are frequent. The long-term results (9 years) in combined pancreas and kidney transplanted patients are satisfying: the survival rate for pancreas is 38% and 54% for kidney. Patient survival rate in this period is 85%. Beyond the first year post-transplant the exocrine activity disappears whereas the endocrine function remains well preserved.
Nineteen patients with endstage renal failure due to Type 1 (insulin-dependent) diabetes mellitus received simultaneous pancreas/kidney transplants using bladder drainage technique. Another group of 25 Type 1 diabetic patients received pancreas/kidney transplants by the duct occlusion technique. We observed a higher incidence of rejection episodes in the patients of the bladder drainage group than those in the duct occlusion group, 14 of 19 patients (74%) vs 7 of 25 (28%) respectively. Anti CD3 antibodies (OrthocloneR, OKT3) as a part of induction treatment was used more often in the bladder drainage group (58%) than in the control group (20%).
Long-term normalization of glucose metabolism is necessary to prevent or ameliorate diabetic complications. Although pancreatic grafting is able to restore normal blood glucose and glycated haemoglobin, the degree of normalization of the deranged diabetic metabolism after pancreas transplantation is still questionable. Consequently glucose, insulin, C-peptide, glucagon, and pancreatic polypeptide responses to oral glucose and i.v. arginine were measured in 36 Type 1 (insulin-dependent) diabetic recipients of pancreas and kidney allografts and compared to ten healthy control subjects. Despite normal HbA1 (7.2 +/- 0.2%; normal less than 8%) glucose disposal was normal only in 44% and impaired in 56% of the graft recipients. Normalization of glucose tolerance was achieved at the expense of hyperinsulinaemia in 52% of the subjects. C-peptide and glucagon were normal, while pancreatic polypeptide was significantly higher in the graft recipients. Intravenous glucose tolerance (n = 21) was normal in 67% and borderline in 23%. Biphasic insulin release was seen in patients with normal glucose tolerance. Glucose tolerance did not deteriorate up to 7 years post-transplant. In addition, stress hormone release (cortisol, growth hormone, prolactin, glucagon, catecholamines) to insulin-induced hypoglycaemia was examined in 20 graft recipients and compared to eight healthy subjects. Reduced blood glucose decline indicates insulin resistance, but glucose recovery was normal, despite markedly reduced catecholamine and glucagon release. These data demonstrate the effectiveness of pancreatic grafting in normalizing glucose metabolism, although hyperinsulinaemia and deranged counterregulatory hormone response are observed frequently.
The effect of simultaneous pancreas and kidney transplantation on diabetic retinopathy was studied in a prospective study with 30 patients (57 eyes) and 15 control subjects (26 eyes), patients who lost the pancreas, but preserved kidney function. There was no significant difference between the groups after a mean observation time of more than 35 months (a range of 12 to 96 months). Both populations had a stable retinopathy during follow-up. This seems to be a consequence of the far advanced retinopathy (mean duration of type 1 diabetes was 22 years) and the high percentage of coagulated eyes (81% and 85%, respectively), but is not related to the organ transplantation. A closer look at the few patients who did not receive laser coagulation (14 patient and 6 control eyes), produced a different result. Four control eyes experienced a significant deterioration of the retinopathy which had been stable before rejection. It is the most important and so far never mentioned aspect of this study, that periods of destabilisation are a definite threat for the retinopathy. Nevertheless, it seems questionable whether we will ever be able to make a definite statement on the pancreas-eye relation, as long as the transplantation must be restricted to carefully selected late-stage diabetic subjects.
The influence of successful simultaneous pancreas and kidney transplantation on peripheral polyneuropathy was investigated in 53 patients for a mean observation period of 40.3 months. Seventeen patients were followed-up for more than 3 years. Symptoms and signs were assessed every 6 months using a standard questionnaire, neurological examination and measurement of sensory and motor nerve conduction velocities. While symptoms of polyneuropathy improved (pain, paraesthesia, cramps, restless-legs) and nerve conduction velocity increased, there was no change of clinical signs (sensation, muscle-force, tendon-reflexes). Following kidney-graft-rejection there was a slight decrease of nerve conduction velocity during the first year, which was not statistically significant. Following pancreas-graft rejection there was no change of nerve conduction velocity during the first year. Comparing the maximum nerve conduction velocity of the patients with pancreas-graft-rejection to the nerve conduction velocities of these patients at the end of the study, there was a statistically significant decrease of 6.5 m/s. In conclusion, we believe that strict normalization of glucose metabolism alters the progressive course of diabetic polyneuropathy. It may be stabilized or partly reversed after successful grafting even in long-term diabetic patients.
Thirty-nine Type 1 (insulin-dependent) diabetic patients were studied prospectively after simultaneous pancreas and kidney (n = 26) and kidney grafting alone (n = 13) by measuring heart rate variation during various maneuvers and answering a standardized questionnaire every 6 to 12 months post-transplant. While age, duration of diabetes, and serum creatinine (168.1 +/- 35.4 vs 132.7 +/- 17.7 mumol/l) were comparable, haemoglobin A1 levels were significantly lower (6.6 +/- 0.2 vs 8.5 +/- 0.3%; p less than 0.01) and the mean observation time longer (35 +/- 2 vs 25 +/- 3 months; p less than 0.05) in the pancreas recipients when compared with kidney transplanted patients. Heart rate variation during deep breathing, lying/standing and Valsalva manoeuver were very similar in both groups initially and did not improve during follow-up. However, there was a significant reduction in heart rate in the pancreas recipient group. Autonomic symptoms of the gastrointestinal and thermoregulatory system improved more in the pancreas grafted subjects, while hypoglycaemia unawareness deteriorated in the kidney recipients. This study suggests that long-term normoglycaemia by successful pancreatic grafting is able to halt the progression of autonomic dysfunction.
To evaluate the beneficial effect of pancreatic grafting on peripheral microcirculation and long-term clinical outcome, we compared data of 28 Type 1 (insulin-dependent) diabetic patients either given a pancreatic and kidney graft simultaneously or given a solitary kidney graft (n = 17). Peripheral microcirculation was estimated by transcutaneous oxygen pressure measurement (including reoxygenation potential after blood flow occlusion) and erythrocyte flow/velocity by a non-contact laser speckle method. All the measured parameters showed significant differences between diabetic and control subjects in the mean follow-up time of 49 (simultaneous pancreas and kidney transplantation) and 43 (solitary kidney transplantation) months. The data from patients after simultaneous pancreas and kidney transplantation revealed an improvement of transcutaneous oxygen pressure measurement (rise from 46 +/- 2 mm Hg to 63 +/- 3 mmHg), reoxygenation time (fall from 224 +/- 12s to 114 +/- 6s) and laser speckle measurement (rise from 4.2 +/- 1.7 to 5.6 +/- 1.8 relative units). The control group with solitary kidney transplantation did not show a positive evaluation. Data from patients after simultaneous pancreas and kidney transplantation revealed an improvement in transcutaneous oxygen pressure measurement, reoxygenation time and laser speckle measurement whereas the control group with solitary kidney transplantation did not show a positive evaluation. Improved microcirculation was more pronounced in patients with better microvascular preconditions. The results confirm that diabetic microangiopathy is positively influenced by pancreatic transplantation.
Improvement of the quality of life in Type 1 (insulin-dependent) diabetic patients with severe late complications is one of the main goals of pancreas and/or kidney grafting. To assess the influences of these treatment modalities on the different aspects of the quality of life a cross-sectional study in 157 patients was conducted. They were categorized into patients pretransplant without dialysis (n = 29; Group A), pretransplant under dialysis (n = 44; Group B), posttransplant with pancreas and kidney functioning (n = 31; Group C), post-transplant with functioning kidney, but insulin therapy (n = 29; Group D), post-transplant under dialysis and insulin therapy again (n = 15; Group E) and patients after single pancreas transplantation and rejection, with good renal function, but insulin therapy (n = 9; Group F). All patients answered a mailed, self-administered questionnaire (217 questions) consisting of a broad spectrum of rehabilitation criteria. The results indicate a better quality of life in Groups C and D as compared to the other groups. In general the scores are highest in C, but without any significant difference to D. Impressive significant differences between C or D and the other groups were found especially in their satisfaction with physical capacity, leisure-time activities or the overall quality of life.(ABSTRACT TRUNCATED AT 250 WORDS)
Complement activation in 73 renal transplant biopsies was investigated by indirect immunoperoxidase staining using MoAbs reactive with complement-split products. Intense deposition of complement fragments C4d and C3d in peritubular capillaries, indicating activation of the classical pathway, could be detected in the majority of transplanted kidneys with cell-mediated rejections. Abundant deposition of complement-split products was observed in 22 early biopsies from patients with high 'immunological risk' (i.e. previous, rejected transplants and/or circulating antibodies against HLA-antigens). Despite negative results in the crossmatch before transplantation and paucity of immunoglobulins in transplant biopsies, antibodies directed against endothelial cell antigens should be considered as a possible cause of classical complement activation.