Title: Does the introduction of a national pre-implantation biopsy histopathology service increase numbers, and improve outcomes, of kidney transplants performed in the UK: a stepped-wedge cluster randomised trial
Funder: Department of Health and Social Care

Abstract: Background Strategies to address demand for kidney transplantation in the UK are focussed on the increased use of elderly deceased-donors, because this is the UK donor pool with currently the greatest untapped potential. However kidneys from elderly donors (so-called expanded-criteria-donors (ECD)) are associated with higher risks of failure, and poor recipient outcome and so are frequently discarded or declined. One strategy that may help inform selection of ECD kidneys that are safe to transplant is the use of pre-implantation biopsy analysis to evaluate the degree of chronic injury present. According to this score, kidneys are implanted, either as a single or as a dual transplant, or are discarded. Although the use of the scoring system has been reported to improve kidney transplant outcomes, whether it increases transplant numbers or instead results in increased kidney discard is not clear. Aims This study will address how the introduction of a National Histopathology Service impacts upon UK kidney transplant practice, and will test the hypothesis: Provision of a national 24/7 pre-implantation biopsy service results, at reasonable cost, in transplantation of a greater proportion of kidneys offered from ECD donors, and/or improves kidney transplant function at one year post-transplant. Numbers of deceased donor kidney transplants performed annually in the UK are consequently significantly increased or improved in quality. The study aims to: Introduce an efficient National Histopathology Service that uses electronic image transfer to rationalise biopsy processing to a limited number of designated transplant centres. Perform a randomised evaluation of this service, by staggering its introduction to all 22 UK renal transplant centres, according to the principles of a stepped-wedge cluster randomised trial. Determine the cost-effectiveness of this service. Model an efficient randomised registry trial, which can be performed for relatively little cost because outcome data is already collected centrally, and which will provide a template for future transplant research. Plan of Investigation This is an open, multicentre, stepped-wedge cluster randomised trial, with concurrent economic evaluation, of the use of pre-implantation histopathology assessment in kidney transplantation. It will compare number of transplants performed, and their outcomes, from first offers of deceased donor kidneys over 60, before and after the centre gains access to urgent histopathology assessment. All UK adult kidney transplant centres will participate. Each transplant centre represents one cluster, and at 3-monthly intervals a newly selected group of clusters (by randomisation) will be given access to the National Histopathology Service, enabling clinicians to then request pre-implantation biopsy analysis to help evaluate the suitability of a particular kidney for transplantation. The study has two primary end-points: a 10% increase in the proportion of ECD circulatory-death deceased kidney offers that are transplanted; and an increase in the eGFR (estimated Glomerular Filtration Rate) of transplanted kidneys of 6mls/min at one year after transplant. eGFR measures kidney function and is routinely used as surrogate for long-term graft survival; its inclusion as end-point assesses whether biopsy availability results in increased transplantation of poorly-performing transplants. Analysis will be performed using a generalised linear mixed model, with a log link, Poisson model with robust standard errors. Potential benefits By providing a mechanism by which kidneys from a largely unused deceased donor cohort can be transplanted safely, the proposal aims to increase kidney transplant numbers substantially; by about 300 transplants during the study period. Implicit in this increase will be improvements in quality of life and a significant survival advantage for the UK kidney waiting-list population, with clear economic benefits. By providing an objective approach to selecting kidneys from higher-risk, marginal donors, it is also hoped that the trial will address current geographical inequity of access to transplantation in the UK.

Lay abstract: There is a great shortage of kidneys for transplantation. All kidneys from deceased donors carry risk to the recipient (risk of not working, or of disease transmission), but donor age is strongly associated with poor function and early failure of the kidney transplant. This is important, because the majority of the pool of potential UK deceased donors are now over 60 years old. Thus, if we can improve our identification of kidneys from older donors that are better quality , we can maximize numbers of transplants performed without compromising transplant outcomes. The use of urgent kidney biopsy (analysis of a small portion under the microscope) to identify age-related damage has been reported to aid selection of those kidneys from older donors that are good enough quality for transplantation. This approach has not been widely adopted in the UK, because the exact impact that the extra information provided by biopsy has on transplant numbers and on transplant outcomes is not clear, and its cost effectiveness remains unproven. Our study will evaluate whether providing an urgent 24 hour National Biopsy Service increases the number and function of kidneys transplanted from donors aged over 60 years. The study is a national trial: every 3 months a randomly-chosen group of UK kidney transplant centres will be offered access to the National Biopsy service (a stepped-wedge randomised cluster trial ). By the end of the trial, all 22 UK centres will have access, and we will then compare results for each centre from before and after the biopsy service was made available as well as evaluating the cost of providing the service. We anticipate that this comparison will show that biopsy availability increases the use of kidneys from elderly donors by about 10%, which equates to an additional 300 kidney transplants performed in the UK.

Research activity codes: 6.4 SURGERY
Health categories: RENAL AND UROGENITAL