International practices of organ donation.

Organ donation and transplant rates vary widely across the globe, but there remains an almost universal shortage of deceased donors. The unmet need for transplants has resulted in many systematic approaches to increase donor rates, but there have also been practices that have crossed the boundaries of legal and ethical acceptability. Recent years have seen intense interest from international political organizations, led by the World Health Organization, and professional bodies, led by The Transplantation Society. Their efforts have focused on the development of a series of legal and ethical frameworks, designed to encourage all countries to eradicate unacceptable practices while introducing programmes that strive to achieve national or regional self-sufficiency in meeting the need for organ transplants. These programmes should seek to reduce both the need for transplantation and also develop deceased donation to its maximum potential. Living donation remains the mainstay of transplantation in many parts of the world, and many of the controversial--and unacceptable--areas of practice are found in the exploitation of living donors. However, until lessons are learnt, and applied, from countries with highly developed deceased donor programmes, these abuses of human rights will be difficult to eradicate. A clear international framework is now in place to achieve this.

Efficiency is a legitimate consideration in equitable distribution of cadaveric transplants: development of an efficiency-equality model of equity.

It is proposed that equity is a trade-off, or compromise, between equality and efficiency. The kidney transplant allocation algorithm currently used in the United Kingdom (NAT) was tested in the efficiency-equity model. In an exercise of 2000 past UK donors and a dynamic waiting list of 5000 potential recipients, 4000 transplants were allocated according either by NAT, by equal allocation (EQ) (a lottery), or by efficiency (EF). Diabetic recipients received 7.4% of transplants in NAT, 8.6% in EQ, and 0% in EF; paediatric recipients received 6.8% in NAT, 0.6% in EQ, and 0.7% in EF model. For HLA matching, there were 77.9% favourable or 000 matches in NAT, 3.0% in EQ, and 53.1% in EF. Predicted survival showed better outcomes in EF versus NAT (P < .0001) and in NAT versus EQ (P = .05). The NAT allocation system favours paediatric recipients and does not deny diabetics the chance of a transplant, broadly in line with published public and professional opinions. The NAT scheme achieves better HLA matching than the EF model, and this suggests that the rationale for allocation based primarily on HLA matching could be reexamined.

The UK National Potential Donor Audit.

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.

Diagnostic contribution of renal allograft biopsies at various intervals after transplantation.

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.

Successful removal and prevention of resynthesis of anti-HLA antibody.

The successful removal and prevention of the resynthesis of an anti-HLA antibody by plasma exchange and immunosuppression in a patient awaiting renal transplantation is described. Before treatment, the patient's serum contained a high titer (greater than 1/50) anti-HLA antibody that reacted with 94% of our lymphocyte donor panel and produced positive cross matches with the lymphocytes from 40 cadaver kidneys. Following treatment, her anti-HLA titers fell to less than 1/10 and her sera reacted with 43% of our lymphocyte donor panel and produced negative crossmatches with lymphocytes from the first two cadaver kidney donors she was tested against. She was successfully transplanted with the second of these kidneys and is now well eight months later, with good graft function.

Morphological differentiation between rejection and cyclosporin nephrotoxicity in renal allografts.

In a prospective study of renal dysfunction in 60 consecutive allograft recipients treated with cyclosporin and prednisolone routine renal biopsies at one week and one month after transplantation, as well as for all episodes of renal dysfunction, were performed. The one year graft survival of this group was 88%. In a retrospective clinical analysis of these patients 35 episodes of dysfunction due to rejection, defined by a response to antirejection treatment alone, and 30 episodes due to cyclosporin nephrotoxicity, defined by a response to reduction in cyclosporin dose alone, were identified. The morphological findings from these biopsies were compared with 20 samples from routine biopsies taken from patients with stable renal function. All patients diagnosed as having rejection had a diffuse, interstitial mononuclear cell infiltrate (32 of 35) or arteritis (19 of 35), or both. In contrast, focal mononuclear cell infiltrates were common in both patients with nephrotoxicity and those with stable function (17 of 30 and 14 of 20, respectively). There were no important differences between biopsies from those with nephrotoxicity and those with stable function, except that arteriolar hyalinosis was considerably more common in the nephrotoxic patients than in those with stable function. Many patients with stable function were, in retrospect, in a state of stable mild nephrotoxicity. In our experience rejection should only be diagnosed when there is at least a diffuse interstitial infiltrate or an arteritis. Focal mononuclear cell infiltrates do not denote rejection. The development of arteriolar lesions in the absence of rejection is indicative of nephrotoxicity.

Accidental transplantation of bronchial carcinoma from a cadaver donor to two recipients of renal allografts.

Malignancy was transferred inadvertently to two patients, each of whom received a renal transplant from a cadaver donor who was found at necropsy to have a small, clinically silent carcinoma of lung. Both recipients died with metastatic bronchial carcinoma of the same histological type as the donor's tumour. The literature on transplanted malignancy is reviewed.

Contaminated renal allografts.

Bacterial contamination of a renal allograft may cause infection of the transplant with eventual loss of the graft and possibly death of the patient. We report two cases that illustrate these complications and that support the suggestion that culture of the transport medium is a valuable investigation prior to transplantation.

Audit of infection in continuous ambulatory peritoneal dialysis.

The major cause of failure of continuous ambulatory peritoneal dialysis is peritoneal or exit site infection with Staphylococcus aureus. From 1989-1992, eradication of nasal and perineal carriage, continued use of an occlusive dressing to the exit site, improved aseptic technique for dressing changes by the patient and avoidance of wetting of the dressing were used in an attempt to reduce staphylococcal infections. By comparison with the 3-year period prior to intervention, a significant increase in the life of the catheters was achieved (removed at 1 year, 13 vs. 28%, P < 0.001) with a reduction in episodes of peritonitis due to S. aureus. The study was not prospectively controlled but there did not appear to be any other factor to account for the sudden and consistent improvement observed.

Avascular necrosis of bone in patients undergoing renal allotransplantation.

Five to forty-three months after renal allotranplantation, thirteen patients (9 male, 4 female) developed avascular necrosis of one or more joints. The dose of corticosteroids used as part of the immunosuppressive therapy was compared to that used in similar patients who did not develop avascular necrosis. No significant difference could be found.

The use of pressimmune in renal transplantation: a four-year study.

Over a three year period, 22 diabetic and 87 non-diabetic patients received 120 cadaver kidney transplants at Dulwich Hospital. Horse antilymphocyte globulin (ALG), azathioprine and low-dose intra-muscular methyl prednisolone were used as immunosuppressive agents. A control group of 98 non-diabetic patients (113 transplants) at Guy's Hospital during the same period were treated with a standard azathioprine and oral steroid regime. Four main findings emerged: Firstly, survival rates for first grafts in the non-diabetic patients were similar in both centers. This suggests that neither the ALG or more conventional immunosuppressive regime holds any advantage in this patient group. Secondly, the first grafts in diabetic patients did significantly worse than similar grafts in the non-diabetics. Thirdly, in patients receiving the more conventional regime, second grafts did significantly worse than first grafts. Fourthly, and in contrast, the ALG regime gave similar survival figures for both first and second grafts. Thus, ALG had no apparent advantage over conventional steroid regimes on the survival of first grafts but it did produce a marked improvement in the outcome of subsequent grafts.

Renal transplantation in sickle cell disease.

A 49 year old West Indian man with sickle cell disease and chronic renal failure was maintained on hemodialysis for 10 months before receiving a cadaveric renal transplant. Nine months post-transplant his renal function is good. His main problem has been high HbS levels needing repeated exchange transfusions. We conclude that hemodialysis and transplantation may be use successfully performed in patients with sickle cell disease with end-stage renal failure.

Treatment of resistant CAPD peritonitis by temporary discontinuation of peritoneal dialysis.

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.

Transplantation of organs: natural limitations, possible solutions--a UK perspective.

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.

Infections after renal transplantation. Recipient factors affecting their incidence.

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.

Haemodialysis access: a single centre UK Experience.

BACKGROUND: The aim of this study was to determine whether the US National Kidney Foundation Disease Outcome Quality Initiative (K/DOQI) guidelines on haemodialysis access could be achieved and to examine its relevance to patients on dialysis in the UK. METHOD: A cross sectional study of chronic haemodialysis patients at our institution which involved case note review and measurements of biochemical parameters and dynamic venous pressure (dVP) was performed. Patients with polytetrafluoroethylene (PTFE) grafts were followed prospectively for 18 months. RESULTS: 262 patients were studied - 12%, 43%, 30% and 15% underwent dialysis through dialysis catheters, radial-cephalic fistulae (rAVF), brachial-cephalic fistulae (bAVF) and PTFE grafts respectively. RAVFs, bAVFs and PTFE grafts were the primary access (i.e. the first access created for the patient) in 58%, 35% and 7% respectively. Compared with patients of Caucasian origin, patients of Afro-Caribbean race were 3.80 times (95% confidence limit: 1.51 - 9.53) more likely to have a PTFE graft. Patients with higher 'dry weights' were more likely to have PTFE grafts (p<0.005 by ANOVA). Dialysis adequacy was similar irrespective of type and site of access. We found that 64% of PTFE grafts, 46% of bAVFs and 13% of rAVF had dVPs greater than 150 mmHg, (p<0.0001 by c2). This threshold recommended by DOQI predicted 12 of 13 dysfunctional grafts, but had a positive predictive value of only 50%. CONCLUSION: We have demonstrated that the K/DOQI guidelines are not only achievable, but that they can be exceeded by a considerable margin. Our data also suggest that the demographic details of patients within a unit will influence the achievable proportion of AVF: PTFE grafts (the proportion of PTFE grafts in Afro-Caribbeans being 3 times higher than in whites). Although a dVP >150 mmHg proved sensitive in predicting future graft dysfunction, it had low specificity.

[Ethical questions concerning organ transplantation, with special reference to Great Britain]. / A szervátültetések etikai kérdései, különös tekintettel Nagy-Britanniára.

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.