Organ donation in the United Kingdom.
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Biomedical subjects
Publications and source records attributed to C J Rudge.
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As part of a series of measures designed to improve organ donation rates in the United Kingdom, a potential donor audit has been established by UK Transplant. The audit will identify the number of patients who could be solid organ donors and will establish the obstacles to donation. Results from the first full year of the audit indicate that the overall relative refusal rate for heart-beating solid organ donation is 41.5%. The age and gender of the potential heart-beating donor has little impact on the relative refusal rate, but relatives of ethnic minority groups are more than twice as likely to deny consent than those of white potential heart-beating donors.
While the outcome following organ transplantation in the United Kingdom has never been better, the waiting list has never been longer and the organ shortage is now the most pressing issue. UK Transplant has invested in four initiatives to promote donor and transplant numbers: coordinating the coordinators, establishing donor liaison posts, improving living donor coordination, and encouraging non-heart-beating donation. The Potential Donor Audit to be introduced as soon as possible will clarify the likely maximum number of heart-beating donors. A major review of the legal framework covering donation and transplantation in England and Wales is currently underway. It is hoped that in due course the benefits of these initiatives will be translated into a rise in both donor and transplant numbers.
BACKGROUND: Renal allograft outcome, during an 8 year period (1985-1992), has been assessed in 56 renal transplants performed in 55 patients who had end-stage renal failure as a consequence of urological abnormalities. The abnormalities were: primary vesicoureteric reflux (VUR) or renal dysplasia (26 patients); posterior urethral valves (PUV) (15); neuropathic bladders (6); vesico-ureteric tuberculosis (5); bladder exstrophy (3); and prune belly syndrome (1). Six patients had augmented bladders, and eight transplants were performed in seven patients with urinary diversions. RESULTS: Overall, 1 and 5 year actuarial graft survival was 89 and 66%, with mean creatinine of 154 micromol/l +/- 11 (SE) and 145 +/- 9 respectively. Patients with abnormal bladders or conduits (n = 28) had worse graft function than those with normal bladders (n = 28) although graft survival was not significantly different in the two groups at 1 and 5 years: 93 and 75% with normal bladders vs 86 and 57% with abnormal systems. Symptomatic urinary tract infections were common in the first 3 months after transplantation (63%); fever and systemic symptoms occurred in 39% with normal bladders and 59% with abnormal bladders. Urinary tract infection directly contributed to graft loss in six patients with abnormal bladders, but had no consequences in those with normal bladders. CONCLUSIONS: Abnormal bladders must be assessed urodynamically before transplantation, and after transplantation adequacy of urinary drainage must be re-assessed frequently. Prophylactic antibiotics are now given for the first 6 months and urinary tract infections must be treated promptly. With these measures, good results, similar to those of patients without urological problems, can be obtained.
Although the cousience and character of a good doctor are sufficient on their own to allow us to discuss and make decisions regarding very difficult ethical subjects in transplantation, basic ethical principles commonly used in medicine must also be applied to various aspects of organ donation. Some system has to be adopted that assesses the weight that must be given to various possible solutions. For example, would live donor transplantation still be acceptable if there were a surfeit of cadaveric organs? If animal organs can be transplanted successfully, is that more desirable than using human organs: particularly if human donation involves interventional ventilation or non-heart beating donors? Is interventional ventilation more "ethical" than live donor liver or lung transplantation? No doubt future developments in transplantation, opening more opportunities for the successful treatment of more patients, are likely to produce increasingly difficult ethical issues. Discussions of these issues must be firmly based on principles of medical ethics, although accepting that whilst absolute principles may be available, absolute answers are more difficult to come by.
Renal allograft biopsy is the accepted gold standard for investigating episodes of graft dysfunction in the early posttransplant period. The situation is less clear in late transplant biopsies. Later renal biopsies performed for graft dysfunction or as part of a routine investigative protocol have not been subjected to detailed critical evaluation. Two hundred sixty-three consecutive renal allograft biopsies in a single center were evaluated. They were arbitrarily divided into three groups based on interval after transplantation: group 1, up to 3 months (n=117); group 2, 4-12 months (n=60); and group 3, greater than 12 months after transplantation (n=86). There were no significant differences in demographic factors among the groups. The mean interval after transplantation was 0.8+/-0.1 months in group 1, 6.1+/-0.3 months in group 2, and 40.1+/-3.4 months in group 3. There were six principal diagnostic categories: acute rejection (AR), chronic rejection (CR), cyclosporine (CsA) nephrotoxicity, acute tubular necrosis (ATN), normal, and others. A statistically significant decrease in the frequency of AR (P<0.001) was seen in group 3 (3%) compared with groups 1 (43%) and 2 (37%). In contrast, the frequency of CR was significantly higher (P<0.001) in group 3 (71%) compared with groups 1 (0) and 2 (10%). ATN was seen almost exclusively in group 1. All but one of the 37 patients with ATN were in this group. CsA nephrotoxicity remained an important cause of graft dysfunction in all three groups, with no significant difference in incidence among the three groups. The differences between groups with other histological types were not significant. Patient management was changed based on the biopsy report in 84 patients in group 1 (72%), 45 patients in group 2 (75%), and only 16 patients in group 3 (19%) (P<0.001). In only seven patients in group 3 did the change in management result in a significant change in serum creatinine. All of these seven patients had CsA nephrotoxicity on biopsy and also had a significantly higher level of CsA compared with those with AR or CR. Thus, the diagnosis might have been possible without the need for biopsy. We conclude that late renal allograft biopsies are only rarely helpful in patient management and as such should be an investigation of last resort.
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We have evaluated the incidence of infection in patients with kidney transplant, their effect on graft function and on patient outcome. Factors important for the development of infections in the post-transplant course in this group of patients have been analyzed, as well as factors affecting graft and patient survival. The prevention of infection is the main aim in this patient population, as every episode of clinical infection requiring treatment carries the potential for lethal consequences, and every effort should be made to assure appropriate screening of the prospective renal recipient.
This study examined whether renal parenchymal imaging using 99mTc DMSA scintigraphy with tomography is a sensitive measure of renal scarring in renal transplant recipients with an abnormal lower urinary tract and whether such scars correlate with impairment of renal function. Three groups of patients were compared: group 1, patients with an abnormal lower urinary tract and deteriorating renal function (n = 9); group 2, abnormal lower urinary tract and stable renal function (n = 5); and group 3, normal lower urinary tract and deteriorating renal function (n = 8). Eight of the nine patients in group 1 had multiple scars visible on 99mTc DMSA scans and this correlated with histology when a renal biopsy was performed; the only patient without scars had a transplant glomerulopathy. The presence of scars was associated with either raised intravesical pressures or recurrent urinary tract infections (UTIs). Only one patient in each of groups 2 and 3 had visible scars and both these patients had a history of recurrent UTIs. Patients in group 3 with deteriorating renal function due to chronic rejection documented by biopsy did not have cortical scars visible with 99mTc DMSA tomography. 99mTc DMSA scanning with tomography is a useful investigation in the management of renal transplant patients with declining renal function; multiple scars may indicate abnormal lower urinary tract function and are not seen in chronic rejection.
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Because doubts remain about the safety and efficacy of renal transplantation for patients with primary urological abnormalities, we have studied the outcome of transplantation in a large group of such patients. Between 1977 and 1989, 69 renal transplants were completed in 62 patients with abnormal lower urinary tracts (29 primary vesicoureteric reflux, 13 posterior urethral valves or bladder outflow obstruction, 6 vesicoureteric tuberculosis, 5 neuropathic bladders, and 9 miscellaneous causes). Graft survival in this urological group was similar to that in 150 allograft recipients (157 grafts) with end-stage renal failure of a non-urological cause. No aetiological subgroup had poorer graft survival than the others, although patients with recurrent urinary-tract infections and a history of outflow obstruction tended to have worse graft function. 9 patients (10 transplants) had renal transplantation into a urinary diversion (8 ileal conduits, 1 rectal bladder). These patients had graft survival and renal function comparable with those of the whole urological group. We found no effect of immunosuppressive treatment (cyclosporin or azathioprine), type of kidney donor (living or cadaveric), or donor or recipient age on graft survival time or renal function. Thus, renal transplantation in patients with abnormal lower urinary tracts is safe and effective; patients with ileal conduits do well and have few substantial difficulties. Preoperative assessment of bladder emptying and urodynamics are important in these patients.
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Resistant continuous ambulatory peritoneal dialysis (CAPD) peritonitis (recurrent or persistent infection) is traditionally treated by removal of the CAPD catheter and a period off peritoneal dialysis. In a pilot study we have treated 8 patients with recurrent staphylococcal peritonitis and 3 patients with persistent staphylococcal peritonitis by stopping CAPD for a 2-week period, the CAPD catheter being left in-situ. All 8 patients with recurrent peritonitis and 2 of the 3 patients with persistent peritonitis had resolution of their infection; the third patient required catheter removal to clear the infection. There were no acute problems associated with stopping CAPD, and there was no evidence of loss of peritoneal filtration capacity on restarting CAPD. This novel approach to the treatment of resistant CAPD peritonitis should reduce the number of CAPD catheters replaced and therefore diminish the risks and inconvenience to patients that such replacements entail.
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Organ donation for transplantation involves intensive care staff in extra time and work. However, the results of renal, cardiac and hepatic transplantation are now so good (over 80% success) that every effort should be made to refer all suitable organ donors to the local transplant unit.
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Forty-four renal allograft recipients were biopsied routinely one month and one year after transplantation. All patients received cyclosporin and prednisolone. Fifteen patients had at least one rejection episode, while 29 patients never underwent rejection. At one year there were no specific histological features that enabled these two groups to be distinguished. Between one month and one year, interstitial cellular infiltrate and vascular pathology regressed, and renal function steadily improved. Interstitial fibrosis, however, was either unchanged or mildly increased in all patients. There was no correlation between the amount of interstitial fibrosis at one year and either the total dose of cyclosporin or the mean concentration during the first 3 months. Our results suggest that trough, whole blood cyclosporin concentrations, at the upper level of the therapeutic range (800-200 ng/ml), may be safely tolerated during the first 3 months, with little evidence of chronic damage at one year. At one year maintenance doses of cyclosporin can be achieved that are associated with almost normal plasma creatinine concentrations and minimal tubular atrophy and interstitial fibrosis. We expect that such doses may be continued indefinitely.