Chris J. Rudge

Pregnancy after organ transplantation: a report from the UK Transplant pregnancy registry.

Background. Maternal and fetal complications in pregnancies after renal transplantation have been highlighted in several reports, but information on their main predisposing factors is limited. The U.K. Transplant Pregnancy Registry was established in 1997 to obtain detailed information on pregnancies in female organ transplant recipients across the U.K. Methods. For each female kidney, liver, or cardiothoracic organ transplant recipient who had had a recent pregnancy, data on maternal and fetal factors and pregnancy outcomes were collected using forms completed by their transplant follow-up and obstetric units. For kidney transplant recipients, the factors that influence pregnancy outcome were studied using logistic regression, and the effect of pregnancy on graft function was analyzed. Results. There were live births in 83%, 69%, and 79% of pregnancies in cardiothoracic organ, liver, and kidney recipients, respectively. In 50% of live births from renal patients, delivery was preterm (<37 weeks), with 83% of the preterm infants delivered via caesarean. Preterm delivery was associated with maternal drug-treated hypertension and impaired renal function. A matched case–control study showed no evidence of increased renal allograft loss after pregnancy. A univariate survival analysis, however, suggested an association between drug-treated hypertension during pregnancy and poorer postpregnancy graft survival. In patients with prepregnancy serum creatinine (SCr) >150 &mgr;mol/L, a trend toward increased postpregnancy SCr was identified. Conclusions. Pregnancy is likely to end in a live birth in a majority of organ transplant recipients. In patients with greater prepregnancy SCr and/or drug-treated hypertension during pregnancy, however, subsequent renal function may be adversely affected.

Potential for organ donation in the United Kingdom: audit of intensive care records

Abstract Objectives To determine the true potential for solid organ donation from deceased heartbeating donors and the reasons for non-donation from potential donors. Design An audit of all deaths in intensive care units, 1 April 2003 to 31 March 2005. The study was hierarchic, in that information was sought on whether or not brain stem testing was carried out; if so, whether or not organ donation was considered; if so whether or not the next of kin were approached; if so, whether or not consent was given; if so, whether or not organ donation took place. Setting 341 intensive care units in 284 hospitals in the United Kingdom. Participants 46 801 dead patients, leading to 2740 potential heartbeating solid organ donors and 1244 actual donors. Main outcome measures Proportion of potential deceased heartbeating donors considered for organ donation, proportion of families who denied consent, and proportion of potential donors who became organ donors. Results Over the two years of the study, 41% of the families of potential donors denied consent. The refusal rate for families of potential donors from ethnic minorities was twice that for white potential donors, but the age and sex of the potential donor did not affect the refusal rate. In 15% of families of potential donors there was no record of the next of kin being approached for permission for organ donation. Conclusions Intensive care units are extremely good in considering possible organ donation from suitable patients. The biggest obstacle to improving the organ donation rate is the high proportion of relatives who deny consent.

A New UK 2006 National Kidney Allocation Scheme for deceased heart-beating donor kidneys.

Introduction. In 2004, it was agreed that a new allocation scheme for kidneys from deceased heart-beating donors was required in the United Kingdom to address observed inequities in access to transplant. The 2006 National Kidney Allocation Scheme (2006 NKAS) was developed to meet agreed objectives and preparatory work included a review of the criteria for human leukocyte antigen (HLA) matching and simulation evidence about the effectiveness of alternative schemes. Algorithm for 2006 NKAS. The 2006 NKAS gives absolute priority to all 000 HLA-A, -B, -DR–mismatched patients and well-matched pediatric patients (<18 years), and then a points score defines priorities for allocation with waiting time being most influential. Points for age and HLA mismatch are linked in a novel approach to ensure well-matched transplants for younger patients while recognizing that HLA matching is less important for older patients as retransplantation is less likely to be required. To improve equity for difficult to match patients, rare HLA specificities were defaulted to more common, related specificities. Impact of 2006 NKAS. After 3 years, the scheme is already making good progress in achieving its objectives, with overall results similar to those observed in the simulations. There has been a significant benefit for patients waiting more than 5 years for transplant. A number of other advantages of the scheme are also apparent with equity of access improving in many respects, including the achievement of equity of access to transplant for HLA-DR homozygous patients, but geographical inequity of access will take a number of years to address fully.

Renal Transplantation in the United Kingdom for Patients From Ethnic Minorities

Background. To investigate any differences in access to transplant and post-transplant outcomes for ethnic minority patients in the United Kingdom, national data on ethnicity of patients on the waiting list, those receiving a transplant, and deceased donors were analyzed. Methods. Adult patients and donors were included. Ethnic origin was classified as white, Asian, black, or “other.” National data were analyzed, and 2001 U.K. National census data were used for comparative purposes. Median waiting times to transplant were obtained from Kaplan-Meier estimates for patients registered 1998–2000. Transplant survival was estimated for patients transplanted from 1998 to 2003. Results. A total of 92% of the U.K. population was white, compared with 77% of waiting list patients, 88% of transplant recipients, and 97% of deceased donors. Median waiting time to transplantation for white patients was 719 days (95% confidence interval 680–758) compared with 1368 (1131–1605) days for Asian patients and 1419 (1165–1673) days for black patients. The degree of human leukocyte antigen matching achieved was inferior for Asian and black patients. There is some evidence of inferior 3-year transplant survival for black patients compared with white and Asian patients (P=0.03). Conclusions. There are imbalances in the ethnic make up of the waiting list, the donor pool, and renal transplant recipients. There are significant differences in both post-transplant outcomes and time to transplantation between patients of different ethnic origin. Waiting times are influenced by allocation schemes, and the 2006 U.K. National Kidney Allocation Scheme is designed to achieve greater equity of access to transplant for all patients, regardless of geography, blood group, or ethnicity.

Factors Influencing Outcome After Deceased Heart Beating Donor Kidney Transplantation in the United Kingdom: An Evidence Base for a New National Kidney Allocation Policy

Background. Outcomes after deceased heart beating donor kidney transplantation are good, but survival rates vary according to a number of donor-, recipient-, and transplant-related factors. This comprehensive analysis of transplant outcomes was undertaken to inform development of a new Kidney Allocation Scheme. Methods. A complete case analysis of the outcome of kidney-only transplants in the United Kingdom, 1995 to 2001, was undertaken using Cox regression modeling. Seven thousand three hundred eighty-five (77%) of the 9585 transplants reported to the UK Transplant Registry were primary transplants in adults. Regrafts and pediatric patients (age <18 years) were analyzed separately. Transplant and patient survival over 5 years were investigated in addition to causes of prolonged cold ischemia time (CIT). Results. A variety of factors significantly adversely influenced kidney transplant and patient outcome, including older donor age, older recipient age, waiting time to transplant over 2 years, diabetes, and earlier year of transplant. Human leukocyte antigen mismatch and CIT were significant in analyses of transplant but not in patient outcome, and an increased graft failure rate was also identified in adolescent patients. CIT was prolonged by long-distance kidney exchanges between centers (2 hr) and reallocation of kidneys for alternative patients (7 hr). Conclusion. This study identified a number of factors that influence transplant outcome after deceased heart beating donor kidney transplant in the United Kingdom. The findings suggest that the influences of human leukocyte antigen mismatch and CIT are most relevant in considering a revised kidney allocation scheme.

Long-term graft outcome with mycophenolate mofetil and azathioprine : A paired kidney analysis

Background. Randomized controlled trials and U.S. Registry data have demonstrated that mycophenolate mofetil (MMF) reduces acute rejection rates and improves graft survival. We undertook the first paired kidney analysis comparing the effects of MMF and azathioprine on graft outcome in the United Kingdom. Methods. In all, 238 deceased donors from 1999 to 2002 who donated one kidney to a patient treated with MMF and the other kidney to a patient treated with azathioprine were identified from the national transplant database held by U.K. Transplant. Graft function and rates of change of graft function were compared using multiple linear regression analyses adjusting for covariates on an intention-to-treat basis. Incidence of acute rejection and delayed graft function were studied using logistic regression. Patient and graft survival censored for death were evaluated with Cox regression analyses. Results. The MMF-treated patients exhibited a nonsignificant trend towards improved graft function but with increased rejection rates (44% versus 31%, P<0.01). Treatment with MMF did not reduce delayed graft function rates. Univariate analysis showed that graft survival was inferior in MMF-treated patients (90% versus 95%, log-rank, P=0.02) but in multivariate Cox regression models, MMF treatment was not a significant factor. Surprisingly, in the first year 32% of patients achieved daily doses of less than 2 g of MMF compared to 18% of patients who received less than 100 mg of azathioprine (P<0.01). Conclusion. In this real-life study, there was no difference in patient or graft outcome between MMF and azathioprine treated groups despite increased rejection rates in patients receiving MMF therapy.

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.

Geographic disparities in access to organ transplantation in the United Kingdom.

In the United Kingdom, geographic variations in access to transplantation seem to exist—median waiting time to transplantation ranges between 305 and 1,236 days for kidney recipients, 36 and 73 days for liver recipients, and 66 and 667 days for heart recipients (although this latter example must be interpreted with caution). These variations may result from a number of factors. Different patterns of end-stage organ disease are particularly relevant for patients with kidney failure. Protocols for transplant assessment are now available and may reduce inequality. Regional variations in donation rates also exist but are poorly understood.

The UK scheme for mandatory continuous monitoring of early transplant outcome in all kidney transplant centers.

Mandatory continuous monitoring of early transplant outcome with centralized oversight was introduced in 2004 for all 23 UK adult kidney transplant units. Risk-adjusted cumulative sum charts are used to assess 30-day graft and patient survival against past performance for each center, and change in transplant center performance is assessed by tabular cumulative sum charts. The monitoring scheme has performed as predicted from simulations used to establish outcome thresholds and has been validated by comparison with 1- and 5-year outcome data for all UK transplant centers. The value and limitations of the scheme are discussed along with changes that may improve its utility as a tool for self-assessment and central oversight.

How to increase organ donation: does opting out have a role?

Every country needs to increase the number of deceased organ donors and the potential impact of a change to opting-out legislation remains unproven, despite the apparent association between opting out and higher donor rates. However, the Spanish model—so successful in Spain and many other countries—is not based on a requirement for opting out, and, in the UK, deceased organ donation has increased by 25% in 3 years through implementation of a series of recommendations that have transformed the infrastructure of donation. A major review of opting out concluded that it is not appropriate for the UK at this time.