Lisa Mumford

Comparison of the Incidence of Malignancy in Recipients of Different Types of Organ: A UK Registry Audit

An increased incidence of malignancy is an established complication of organ transplantation and the associated immunosuppression. In this study on cancer incidence in solid organ transplant recipients in Britain, we describe the incidence of de novo cancers in the allograft recipient, and compare these incidences following the transplantation of different organs. Data in the UK Transplant Registry held by NHS Blood and Transplant (NHSBT) were linked with data made available by the cancer registries in England, Scotland and Wales. Incidence rates in the transplanted population were then compared with the general population, using standardized incidence ratios matched for age, gender and time period. The 10‐year incidence of de novo cancer in transplant recipients is twice that of the general population, with the incidence of nonmelanoma skin cancer being 13 times greater. Nonmelanoma skin cancer, cancer of the lip, posttransplant lymphoproliferative disease and anal cancer have the largest standardized incidence ratios, but the incidence of different types of malignancy differs according to the organ transplanted. Patterns in standardized incidence ratios over time since transplantation are different for different types of transplant recipient, as well as for different malignancies. These results have implications for a national screening program.

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.

Pancreas Transplantation From Donors After Circulatory Death From the United Kingdom

This study reports the comparative short‐term results of pancreas transplantation from donors after circulatory death (DCD) (Maastricht III & IV), and pancreases from brainstem deceased donors (DBD). Between January 2006 and December 2010, 1009 pancreas transplants were performed in the United Kingdom, with 134 grafts from DCD and 875 from DBD. DCD grafts had no premortem pharmacological interventions performed. One‐year pancreas and patient survival was similar between DCD and DBD, with pancreas graft survival significantly better in the DCD cohort if performed as an SPK. Early graft loss due to thrombosis (8% vs. 4%) was mainly responsible for early graft loss in the DCD cohort. These results from donors with broader acceptance criteria in age, body mass index, premortem interventions, etc. suggest that DCD pancreas grafts may have a larger application potential than previously recognized.

The use of marginal heart beating donor livers for transplantation in the United Kingdom

Background. This study investigated the use of deceased heart-beating donor livers offered for transplantation during a 10-year period, during which there has been an increasing disparity between organ supply and demand in the United Kingdom. Methods. Summary data from the National Transplant Database were analyzed on all 7107 heart-beating cadaveric donor livers offered for transplantation in the United Kingdom between 1996 and 2006, with particular attention to livers that were not retrieved, not transplanted, or that subsequently failed to function after transplantation. Results. The difference between the number of patients registered for liver transplantation in the United Kingdom and those transplanted increased from 132 in 1996 to 333 in 2006, leading to a 77% increase in the number of waiting list deaths. Mean donor age increased by 6.1 (5.7−6.6) years during the period studied, in part because of a reduction in the proportion of donors arising from road fatalities. Despite this, the rate of primary nonfunction remained low (1.7% during 1996–2006). The absolute risk increase of primary nonfunction arising from receipt of a moderately as opposed to mildly steatotic organ was 2.6%, which translates to a “number needed to harm” of 41 patients. Conclusions. The decline in both the number and the quality of livers offered for transplantation in the United Kingdom during the past 10 years has not been associated with a change in the rate of primary nonfunction. In these times of acute donor shortage, these data may justify a more liberal use of marginal grafts.

Kidney transplant outcomes from older deceased donors: a paired kidney analysis by the European Renal Association-European Dialysis and Transplant Association Registry

As the median age of deceased kidney donors rises, updated knowledge of transplant outcomes from older deceased donors in differing donor-recipient age groups is required. Using ERA-EDTA Registry data we determined survival outcomes of kidney allografts donated from the same older deceased donor (55-70 years), and transplanted into one recipient younger and one recipient of similar age to the donor. The recipient pairs were divided into two groups: group 1; younger (median age: 52 years) and older (60 years), and group 2; younger (41 years) and older (60 years). 1,410 adults were transplanted during 2000-2007. Compared to the older recipients the mean number of functioning graft years at 10-years was six months longer in the group 1 and group 2 younger recipients (p <0.001). Ten-year graft survival was 54% and 40% for the group 1 younger and older recipients, and 60% and 49% for the group 2 younger and older recipients. Paired Cox regression analyses showed a lower risk of graft failure (group 1 younger; adjusted relative risk [RRa]:0.57, 95%CI:0.41-0.79, and group 2 younger; RRa:0.63, 95%CI:0.47-0.85) in younger recipients. Outcomes from older deceased donor allografts transplanted into differing donor-recipient age groups are better than previously reported. These allografts remain a valuable transplant resource, particularly for similar-aged recipients. This article is protected by copyright. All rights reservedAs the median age of deceased kidney donors rises, updated knowledge of transplant outcomes from older deceased donors in differing donor–recipient age groups is required. Using ERA‐EDTA Registry data we determined survival outcomes of kidney allografts donated from the same older deceased donor (55–70 years), and transplanted into one recipient younger and one recipient of similar age to the donor. The recipient pairs were divided into two groups: group 1; younger (median age: 52 years) and older (60 years) and group 2; younger (41 years) and older (60 years). A total of 1410 adults were transplanted during 2000–2007. Compared to the older recipients, the mean number of functioning graft years at 10 years was 6 months longer in the group 1 and group 2 younger recipients (P < 0.001). Ten‐year graft survival was 54% and 40% for the group 1 younger and older recipients, and 60% and 49% for the group 2 younger and older recipients. Paired Cox regression analyses showed a lower risk of graft failure (group 1 younger; adjusted relative risk [RRa]:0.57, 95% CI:0.41–0.79, and group 2 younger; RRa:0.63, 95% CI:0.47–0.85) in younger recipients. Outcomes from older deceased donor allografts transplanted into differing donor–recipient age groups are better than previously reported. These allografts remain a valuable transplant resource, particularly for similar‐aged recipients.

Pancreas Transplantation From Donors After Circulatory Death From the United Kingdom: Pancreas Transplantation From Donors

Our report on DCD pancreas transplantation in the United Kingdom (2) was based upon information supplied by the centers to the UK Transplant Registry. The assumption stated in our paper of a maximum of 60 min from withdrawal to cardiac arrest reflected a general consensus amongst the centers involved in DCD pancreas transplantation in the United Kingdom and we accept both that this is an arbitrary stipulation and that there were exceptions to this rule.

Early Outcomes of the New UK Deceased Donor Kidney Fast-Track Offering Scheme

Background The UK Kidney Fast-Track Scheme (KFTS) was introduced in 2012 to identify kidneys at high risk of discard and to rapidly facilitate transplantation. A retrospective analysis of kidneys transplanted through the KFTS was undertaken. Methods UK Transplant Registry data were collected on deceased donor kidneys implanted between November 1, 2012, and April 30, 2015, (donation after brain death [DBD] donors) and March 1, 2013, and April 30, 2015 (donation after circulatory death [DCD] donors). Posttransplant outcomes included 1-year estimated glomerular filtration rate and death-censored graft survival (DCGS). Results Over the study period, 523 deceased donor kidneys were transplanted through the KFTS and 4174 via the standard National Kidney Allocation Scheme (NKAS). Kidneys in the KFTS were more likely to be from older diabetic donors, had a higher frequency of poor ex vivo perfusion, had longer cold ischemic times, and were transplanted into older recipients. One-year DCGS of KFTS and NKAS DBD donor kidneys was similar (94% vs 95%; P = 0.70), but for DCD donor kidneys, DCGS was lower in those allocated via the KFTS (91% versus 95%; P = 0.04). Median 1-year estimated glomerular filtration rate for DBD donor kidneys was lower in those allocated via the KFTS (49 vs 52 mL/min per 1.73 m2; P = 0.01), but for DCD kidneys, there was no difference (45 vs 48 mL/min per 1.73 m2; P = 0.10). Conclusions Although KFTS kidneys have less favorable donor, graft, and recipient risk factors than NKAS kidneys, short-term graft and patient outcomes are acceptable. National schemes that identify and rapidly offer kidneys at high risk of discard may contribute to minimizing the unnecessary discard of organs.

Matching Graft Life Expectancy with Patient Life Expectancy

NSHBT Kidney Advisory Group. Introduction One of the key recommendations following a review of the current UK Kidney Allocation Scheme was to match graft life expectancy with patient life expectancy more effectively in order to maximise the lifetime of kidneys transplanted and reduce the incidence of offer declines. Material and Methods Data from the UK Transplant Registry held by NHS Blood and Transplant on 7,628 first adult kidney only recipients of adult deceased donor kidney transplants in the UK 2006-2012 were analysed. Donor factors potentially influencing graft outcome and recipient factors potentially influencing graft and patient outcomes were investigated using Cox regression. A Kidney Donor Risk Index (DRI) and a Kidney Recipient Risk Index (RRI) were derived from the models and validated on an independent dataset. Both indices were divided into quartiles and the combinations of the four donor and four recipient quartiles were used to investigate offer decline rates and post-transplant survival. Results and Discussions Donor factors found to significantly predict poor graft outcome included; older age, shorter height, a history of hypertension, positive CMV result, longer hospital stay before death, lower eGFR at time of offering and male donors. Recipient factors found to significantly predict poor transplant outcome (time to graft failure or death) included; older age, on dialysis at point of registration, diabetic and longer time on dialysis. A DRI based on the 7 significant factors and a RRI based on the 4 significant factors were derived and confirmed to be prognostic of outcome in a validation cohort (concordance statistic 0.64 for both models). Using the combination of the DRI and RRI quartiles it was observed that the poorest donors with the best recipients had the highest offer decline rate (64%) and the best donors with the best recipients had the lowest offer decline rate (23%). For kidneys transplanted from the best donors into the best recipients, 15-year patient survival was 86% compared with 70% graft survival, suggesting that patients are likely to outlive their grafts. Conversely, for the best donors with the poorest recipients, patient survival was 37% compared with 73% graft survival, suggesting that patients are likely to die with a functioning graft (Figure 1). These extreme examples demonstrate the importance of matching graft and patient life expectancies. Figure. No caption available. Conclusions A Kidney Donor Risk Index alongside a Kidney Recipient Risk Index provides a clinically useful tool that can be used in allocation schemes to maximise the lifetime of kidneys transplanted and reduce the incidence of offer declines.

The effect of differing kidney disease treatment modalities and organ donation and transplantation practices on health expenditure and patient outcomes

The Effect of Differing Kidney Disease Treatment Modalities and Organ Donation and Transplantation Practices on Health Expenditure and Patient Outcomes (EDITH) aims to obtain information on long-term kidney transplant outcomes, long-term health outcomes of living kidney donors and detailed outcomes and costs related to the different treatment modalities of end-stage kidney disease. Nine partners from seven European Union countries will participate in this project.

The UK National Registry of ABO and HLA Antibody Incompatible Renal Transplantation: Pretransplant Factors Associated With Outcome in 879 Transplants

Background ABO and HLA antibody incompatible (HLAi) renal transplants (AIT) now comprise around 10% of living donor kidney transplants. However, the relationship between pretransplant factors and medium-term outcomes are not fully understood, especially in relation to factors that may vary between centers. Methods The comprehensive national registry of AIT in the United Kingdom was investigated to describe the donor, recipient and transplant characteristics of AIT. Kaplan-Meier analysis was used to compare survival of AIT to all other compatible kidney transplants performed in the United Kingdom. Cox proportional hazards regression modeling was used to determine which pretransplant factors were associated with transplant survival in HLAi and ABOi separately. The primary outcome was transplant survival, taking account of death and graft failure. Results For 522 HLAi and 357 ABO incompatible (ABOi) transplants, 5-year transplant survival rates were 71% (95% confidence interval [CI], 66-75%) for HLAi and 83% (95% CI, 78-87%) for ABOi, compared with 88% (95% CI, 87-89%) for 7290 standard living donor transplants, and 78% (95% CI, 77-79%) for 15 322 standard deceased donor transplants (P < 0.0001). Increased chance of transplant loss in HLAi was associated with increasing number of donor specific HLA antibodies, center performing the transplant, antibody level at the time of transplant, and an interaction between donor age and dialysis status. In ABOi, transplant loss was associated with no use of IVIg, cytomegalovirus seronegative recipient, 000 HLA donor-recipient mismatch; and increasing recipient age. Conclusions Results of AIT were acceptable, certainly in the context of a choice between living donor AIT and an antibody compatible deceased donor transplant. Several factors were associated with increased chance of transplant loss, and these can lead to testable hypotheses for further improving therapy.