Organ Transplants From Deceased Donors With Primary Brain Tumors and Risk of Cancer Transmission.

Importance: Cancer transmission is a known risk for recipients of organ transplants. Many people wait a long time for a suitable transplant; some never receive one. Although patients with brain tumors may donate their organs, opinions vary on the risks involved. Objective: To determine the risk of cancer transmission associated with organ transplants from deceased donors with primary brain tumors. Key secondary objectives were to investigate the association that donor brain tumors have with organ usage and posttransplant survival. Design, Setting, and Participants: This was a cohort study in England and Scotland, conducted from January 1, 2000, to December 31, 2016, with follow-up to December 31, 2020. This study used linked data on deceased donors and solid organ transplant recipients with valid national patient identifier numbers from the UK Transplant Registry, the National Cancer Registration and Analysis Service (England), and the Scottish Cancer Registry. For secondary analyses, comparators were matched on factors that may influence the likelihood of organ usage or transplant failure. Statistical analysis of study data took place from October 1, 2021, to May 31, 2022. Exposures: A history of primary brain tumor in the organ donor, identified from all 3 data sources using disease codes. Main Outcomes and Measures: Transmission of brain tumor from the organ donor into the transplant recipient. Secondary outcomes were organ utilization (ie, transplant of an offered organ) and survival of kidney, liver, heart, and lung transplants and their recipients. Key covariates in donors with brain tumors were tumor grade and treatment history. Results: This study included a total of 282 donors (median [IQR] age, 42 [33-54] years; 154 females [55%]) with primary brain tumors and 887 transplants from them, 778 (88%) of which were analyzed for the primary outcome. There were 262 transplants from donors with high-grade tumors and 494 from donors with prior neurosurgical intervention or radiotherapy. Median (IQR) recipient age was 48 (35-58) years, and 476 (61%) were male. Among 83 posttransplant malignancies (excluding NMSC) that occurred over a median (IQR) of 6 (3-9) years in 79 recipients of transplants from donors with brain tumors, none were of a histological type matching the donor brain tumor. Transplant survival was equivalent to that of matched controls. Kidney, liver, and lung utilization were lower in donors with high-grade brain tumors compared with matched controls. Conclusions and Relevance: Results of this cohort study suggest that the risk of cancer transmission in transplants from deceased donors with primary brain tumors was lower than previously thought, even in the context of donors that are considered as higher risk. Long-term transplant outcomes are favorable. These results suggest that it may be possible to safely expand organ usage from this donor group.

The Global Impact of COVID-19 on Solid Organ Transplantation: Two Years Into a Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has had a major global impact on solid organ transplantation (SOT). An estimated 16% global reduction in transplant activity occurred over the course of 2020, most markedly impacting kidney transplant and living donor programs, resulting in substantial knock-on effects for waitlisted patients. The increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection risk and excess deaths in transplant candidates has resulted in substantial effort to prioritize the safe restart and continuation of transplant programs over the second year of the pandemic, with transplant rates returning towards prepandemic levels. Over the past 2 y, COVID-19 mortality in SOT recipients has fallen from 20%-25% to 8%-10%, attributed to the increased and early availability of SARS-CoV-2 testing, adherence to nonpharmaceutical interventions, development of novel treatments, and vaccination. Despite these positive steps, transplant programs and SOT recipients continue to face challenges. Vaccine efficacy in SOT recipients is substantially lower than the general population and SOT recipients remain at an increased risk of adverse outcomes if they develop COVID-19. SOT recipients and transplant teams need to remain vigilant and ongoing adherence to nonpharmaceutical interventions appears essential. In this review, we summarize the global impact of COVID-19 on transplant activity, donor evaluation, and patient outcomes over the past 2 y, discuss the current strategies aimed at preventing and treating SARS-CoV-2 infection in SOT recipients, and based on lessons learnt from this pandemic, propose steps the transplant community could consider as preparation for future pandemics.

Real-world Effectiveness of the Pfizer-BioNTech BNT162b2 and Oxford-AstraZeneca ChAdOx1-S Vaccines Against SARS-CoV-2 in Solid Organ and Islet Transplant Recipients.

BACKGROUND: The clinical effectiveness of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in immunosuppressed solid organ and islet transplant (SOT) recipients is unclear. METHODS: We linked 4 national registries to retrospectively identify laboratory-confirmed SARS-CoV-2 infections and deaths within 28 d in England between September 1, 2020, and August 31, 2021, comparing unvaccinated adult SOT recipients and those who had received 2 doses of ChAdOx1-S or BNT162b2 vaccine. Infection incidence rate ratios were adjusted for recipient demographics and calendar month using a negative binomial regression model, with 95% confidence intervals. Case fatality rate ratios were adjusted using a Cox proportional hazards model to generate hazard ratio (95% confidence interval). RESULTS: On August 31, 2021, it was found that 3080 (7.1%) were unvaccinated, 1141 (2.6%) had 1 vaccine dose, and 39 260 (90.3%) had 2 vaccine doses. There were 4147 SARS-CoV-2 infections and 407 deaths (unadjusted case fatality rate 9.8%). The risk-adjusted infection incidence rate ratio was 1.29 (1.03-1.61), implying that vaccination was not associated with reduction in risk of testing positive for SARS-CoV-2 RNA. Overall, the hazard ratio for death within 28 d of SARS-CoV-2 infection was 0.80 (0.63-1.00), a 20% reduction in risk of death in vaccinated patients (P = 0.05). Two doses of ChAdOx1-S were associated with a significantly reduced risk of death (hazard ratio, 0.69; 0.52-0.92), whereas vaccination with BNT162b2 was not (0.97; 0.71-1.31). CONCLUSIONS: Vaccination of SOT recipients confers some protection against SARS-CoV-2-related mortality, but this protection is inferior to that achieved in the general population. SOT recipients require additional protective measures, including further vaccine doses, antiviral drugs, and nonpharmaceutical interventions.

Changes in quality of life (QoL) and other patient-reported outcome measures (PROMs) in living-donor and deceased-donor kidney transplant recipients and those awaiting transplantation in the UK ATTOM programme: a longitudinal cohort questionnaire survey with additional qualitative interviews.

OBJECTIVE: To examine quality of life (QoL) and other patient-reported outcome measures (PROMs) in kidney transplant recipients and those awaiting transplantation. DESIGN: Longitudinal cohort questionnaire surveys and qualitative semi-structured interviews using thematic analysis with a pragmatic approach. SETTING: Completion of generic and disease-specific PROMs at two time points, and telephone interviews with participants UK-wide. PARTICIPANTS: 101 incident deceased-donor (DD) and 94 incident living-donor (LD) kidney transplant recipients, together with 165 patients on the waiting list (WL) from 18 UK centres recruited to the Access to Transplantation and Transplant Outcome Measures (ATTOM) programme completed PROMs at recruitment (November 2011 to March 2013) and 1 year follow-up. Forty-one of the 165 patients on the WL received a DD transplant and 26 received a LD transplant during the study period, completing PROMs initially as patients on the WL, and again 1 year post-transplant. A subsample of 10 LD and 10 DD recipients participated in qualitative semi-structured interviews. RESULTS: LD recipients were younger, had more educational qualifications and more often received a transplant before dialysis. Controlling for these and other factors, cross-sectional analyses at 12 months post-transplant suggested better QoL, renal-dependent QoL and treatment satisfaction for LD than DD recipients. Patients on the WL reported worse outcomes compared with both transplant groups. However, longitudinal analyses (controlling for pre-transplant differences) showed that LD and DD recipients reported similarly improved health status and renal-dependent QoL (p<0.01) pre-transplant to post-transplant. Patients on the WL had worsened health status but no change in QoL. Qualitative analyses revealed transplant recipients' expectations influenced their recovery and satisfaction with transplant. CONCLUSIONS: While cross-sectional analyses suggested LD kidney transplantation leads to better QoL and treatment satisfaction, longitudinal assessment showed similar QoL improvements in PROMs for both transplant groups, with better outcomes than for those still wait-listed. Regardless of transplant type, clinicians need to be aware that managing expectations is important for facilitating patients' adjustment post-transplant.

SARS-CoV-2 infection and early mortality of waitlisted and solid organ transplant recipients in England: A national cohort study.

Patients waitlisted for and recipients of solid organ transplants (SOT) are perceived to have a higher risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and death; however, definitive epidemiological evidence is lacking. In a comprehensive national cohort study enabled by linkage of the UK transplant registry and Public Health England and NHS Digital Tracing services, we examined the incidence of laboratory-confirmed SARS-CoV-2 infection and subsequent mortality in patients on the active waiting list for a deceased donor SOT and recipients with a functioning SOT as of February 1, 2020 with follow-up to May 20, 2020. Univariate and multivariable techniques were used to compare differences between groups and to control for case-mix. One hundred ninety-seven (3.8%) of the 5184 waitlisted patients and 597 (1.3%) of the 46 789 SOT recipients tested positive for SARS-CoV-2. Mortality after testing positive for SARS-CoV-2 was 10.2% (20/197) for waitlisted patients and 25.8% (154/597) for SOT recipients. Increasing recipient age was the only variable independently associated with death after positive SARS-CoV-2 test. Of the 1004 transplants performed in 2020, 41 (4.1%) recipients have tested positive for SARS-CoV-2 with 8 (0.8%) deaths reported by May 20. These data provide evidence to support decisions on the risks and benefits of SOT during the coronavirus disease 2019 pandemic.

Inequity in Access to Transplantation in the United Kingdom.

BACKGROUND AND OBJECTIVES: Despite the presence of a universal health care system, it is unclear if there is intercenter variation in access to kidney transplantation in the United Kingdom. This study aims to assess whether equity exists in access to kidney transplantation in the United Kingdom after adjustment for patient-specific factors and center practice patterns. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this prospective, observational cohort study including all 71 United Kingdom kidney centers, incident RRT patients recruited between November 2011 and March 2013 as part of the Access to Transplantation and Transplant Outcome Measures study were analyzed to assess preemptive listing (n=2676) and listing within 2 years of starting dialysis (n=1970) by center. RESULTS: Seven hundred and six participants (26%) were listed preemptively, whereas 585 (30%) were listed within 2 years of commencing dialysis. The interquartile range across centers was 6%-33% for preemptive listing and 25%-40% for listing after starting dialysis. Patient factors, including increasing age, most comorbidities, body mass index >35 kg/m2, and lower socioeconomic status, were associated with a lower likelihood of being listed and accounted for 89% and 97% of measured intercenter variation for preemptive listing and listing within 2 years of starting dialysis, respectively. Asian (odds ratio, 0.49; 95% confidence interval, 0.33 to 0.72) and Black (odds ratio, 0.43; 95% confidence interval, 0.26 to 0.71) participants were both associated with reduced access to preemptive listing; however Asian participants were associated with a higher likelihood of being listed after starting dialysis (odds ratio, 1.42; 95% confidence interval, 1.12 to 1.79). As for center factors, being registered at a transplanting center (odds ratio, 3.1; 95% confidence interval, 2.36 to 4.07) and a universal approach to discussing transplantation (odds ratio, 1.4; 95% confidence interval, 1.08 to 1.78) were associated with higher preemptive listing, whereas using a written protocol was associated negatively with listing within 2 years of starting dialysis (odds ratio, 0.7; 95% confidence interval, 0.58 to 0.9). CONCLUSIONS: Patient case mix accounts for most of the intercenter variation seen in access to transplantation in the United Kingdom, with practice patterns also contributing some variation. Socioeconomic inequity exists despite having a universal health care system.

Novel Organ Perfusion and Preservation Strategies in Transplantation - Where Are We Going in the United Kingdom?

This review article focuses on current clinical outcomes with novel perfusion strategies in organ transplantation. Broadly, these approaches can be divided into in situ regional perfusion in the donor and ex situ machine perfusion of individual organs. In both settings, hypothermic and normothermic techniques are in clinical use. Evidence from full text articles, abstracts, and data presented at scientific meetings has been considered. Animal studies have been excluded. The review focuses on kidney, liver, pancreas, heart, and lungs. The level of evidence ranges from quasi-experimental work in human pancreas to multiple meta-analyses of Randomized Controlled Trials for hypothermic machine perfusion of kidneys. The data in this review were presented to experts in organ perfusion and preservation at the National Health Service Blood and Transplant Preservation and Perfusion Future Strategy Summit in London in October 2018. The outcomes of the meeting are discussed in the review after due consideration of the available evidence base.

Recipient Comorbidity and Survival Outcomes After Kidney Transplantation: A UK-wide Prospective Cohort Study.

BACKGROUND: Comorbidity is increasingly common in kidney transplant recipients, yet the implications for transplant outcomes are not fully understood. We analyzed the relationship between recipient comorbidity and survival outcomes in a UK-wide prospective cohort study-Access to Transplantation and Transplant Outcome Measures (ATTOM). METHODS: A total of 2100 adult kidney transplant recipients were recruited from all 23 UK transplant centers between 2011 and 2013. Data on 15 comorbidities were collected at the time of transplantation. Multivariable Cox regression models were used to analyze the relationship between comorbidity and 2-year graft survival, patient survival, and transplant survival (earliest of graft failure or patient death) for deceased-donor kidney transplant (DDKT) recipients (n = 1288) and living-donor kidney transplant (LDKT) recipients (n = 812). RESULTS: For DDKT recipients, peripheral vascular disease (hazard ratio [HR] 3.04, 95% confidence interval [CI]: 1.37-6.74; P = 0.006) and obesity (HR 2.27, 95% CI: 1.27-4.06; P = 0.006) were independent risk factors for graft loss, while heart failure (HR 3.77, 95% CI: 1.79-7.95; P = 0.0005), cerebrovascular disease (HR 3.45, 95% CI: 1.72-6.92; P = 0.0005), and chronic liver disease (HR 4.36, 95% CI: 1.29-14.71; P = 0.018) were associated with an increased risk of mortality. For LDKT recipients, heart failure (HR 3.83, 95% CI: 1.15-12.81; P = 0.029) and diabetes (HR 2.23, 95% CI: 1.03-4.81; P = 0.042) were associated with poorer transplant survival. CONCLUSIONS: The key comorbidities that predict poorer 2-year survival outcomes after kidney transplantation have been identified in this large prospective cohort study. The findings will facilitate assessment of individual patient risks and evidence-based decision making.

Equity-Efficiency Trade-offs Associated With Alternative Approaches to Deceased Donor Kidney Allocation: A Patient-level Simulation.

BACKGROUND: The number of patients waiting to receive a kidney transplant outstrips the supply of donor organs. We sought to quantify trade-offs associated with different approaches to deceased donor kidney allocation in terms of quality-adjusted life years (QALYs), costs, and access to transplantation. METHODS: An individual patient simulation model was developed to compare 5 different approaches to kidney allocation, including the 2006 UK National Kidney Allocation Scheme (NKAS) and a QALY maximization approach designed to maximize health gains from a limited supply of donor organs. We used various sources of patient-level data to develop multivariable regression models to predict survival, health state utilities, and costs. We simulated the allocation of kidneys from 2200 deceased donors to a waiting list of 5500 patients and produced estimates of total lifetime costs and QALYs for each allocation scheme. RESULTS: Among patients who received a transplant, the QALY maximization approach generated 48 045 QALYs and cost £681 million, while the 2006 NKAS generated 44 040 QALYs and cost £625 million. When also taking into consideration outcomes for patients who were not prioritized to receive a transplant, the 2006 NKAS produced higher total QALYs and costs and an incremental cost-effectiveness ratio of £110 741/QALY compared with the QALY maximization approach. CONCLUSIONS: Compared with the 2006 NKAS, a QALY maximization approach makes more efficient use of deceased donor kidneys but reduces access to transplantation for older patients and results in greater inequity in the distribution of health gains between patients who receive a transplant and patients who remain on the waiting list.

Variation in Practice Patterns for Listing Patients for Renal Transplantation in the United Kingdom: A National Survey.

BACKGROUND: Despite the availability of guidelines for the evaluation of candidates for renal transplantation, variation in access to transplantation exists. This national survey investigates whether center variation exists in the assessment of patients for renal transplantation in the United Kingdom. METHODS: An online survey, informed by qualitative interviews, was distributed to all UK renal centers. This survey examined center approaches to chronic kidney disease service provision, transplant recipient assessment, education provision, and waitlisting decision making processes. Center reevaluation policies for patients already listed and priorities for future development were also examined. RESULTS: All 71 renal centers responded. Of these, 83% reviewed predialysis patients in a low clearance clinic. In 26% of the centers, transplantation was not discussed as a treatment option with all patients. Fourteen centers reported having a dedicated transplant assessment clinic, whereas 28% did not have a formal assessment protocol. Age was an exclusion criterion for listing in 3 centers, all of which had a cutoff at 75 years. Eighty-three percent of the centers excluded patients with a high body mass index. Cardiac investigations were risk-stratified in 90% of centers. Surgical involvement varied with 11% of centers listing patients without formal surgical review. There was no formal protocol in place to reevaluate listed patients in 62% of centers. CONCLUSIONS: There is wide variation in UK practice patterns for listing patients for renal transplantation, though its impact on access to transplantation is unclear. The extent to which center-specific and patient-specific factors affect access to transplantation requires further analysis in a prospective cohort of patients.

Estimating Health-State Utility Values in Kidney Transplant Recipients and Waiting-List Patients Using the EQ-5D-5L.

OBJECTIVES: To report health-state utility values measured using the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) in a large sample of patients with end-stage renal disease and to explore how these values vary in relation to patient characteristics and treatment factors. METHODS: As part of the prospective observational study entitled "Access to Transplantation and Transplant Outcome Measures," we captured information on patient characteristics and treatment factors in a cohort of incident kidney transplant recipients and a cohort of prevalent patients on the transplant waiting list in the United Kingdom. We assessed patients' health status using the EQ-5D-5L and conducted multivariable regression analyses of index scores. RESULTS: EQ-5D-5L responses were available for 512 transplant recipients and 1704 waiting-list patients. Mean index scores were higher in transplant recipients at 6 months after transplant surgery (0.83) compared with patients on the waiting list (0.77). In combined regression analyses, a primary renal diagnosis of diabetes was associated with the largest decrement in utility scores. When separate regression models were fitted to each cohort, female gender and Asian ethnicity were associated with lower utility scores among waiting-list patients but not among transplant recipients. Among waiting-list patients, longer time spent on dialysis was also associated with poorer utility scores. When comorbidities were included, the presence of mental illness resulted in a utility decrement of 0.12 in both cohorts. CONCLUSIONS: This study provides new insights into variations in health-state utility values from a single source that can be used to inform cost-effectiveness evaluations in patients with end-stage renal disease.

Barriers to living donor kidney transplantation in the United Kingdom: a national observational study.

BACKGROUND: Living donor kidney transplantation (LDKT) provides more timely access to transplantation and better clinical outcomes than deceased donor kidney transplantation (DDKT). This study investigated disparities in the utilization of LDKT in the UK. METHODS: A total of 2055 adults undergoing kidney transplantation between November 2011 and March 2013 were prospectively recruited from all 23 UK transplant centres as part of the Access to Transplantation and Transplant Outcome Measures (ATTOM) study. Recipient variables independently associated with receipt of LDKT versus DDKT were identified. RESULTS: Of the 2055 patients, 807 (39.3%) received LDKT and 1248 (60.7%) received DDKT. Multivariable modelling demonstrated a significant reduction in the likelihood of LDKT for older age {odds ratio [OR] 0.11 [95% confidence interval (CI) 0.08-0.17], P < 0.0001 for 65-75 years versus 18-34 years}; Asian ethnicity [OR 0.55 (95% CI 0.39-0.77), P = 0.0006 versus White]; Black ethnicity [OR 0.64 (95% CI 0.42-0.99), P = 0.047 versus White]; divorced, separated or widowed [OR 0.63 (95% CI 0.46-0.88), P = 0.030 versus married]; no qualifications [OR 0.55 (95% CI 0.42-0.74), P < 0.0001 versus higher education qualifications]; no car ownership [OR 0.51 (95% CI 0.37-0.72), P = 0.0001] and no home ownership [OR 0.65 (95% CI 0.85-0.79), P = 0.002]. The odds of LDKT varied significantly between countries in the UK. CONCLUSIONS: Among patients undergoing kidney transplantation in the UK, there are significant age, ethnic, socio-economic and geographic disparities in the utilization of LDKT. Further work is needed to explore the potential for targeted interventions to improve equity in living donor transplantation.

Global trends and challenges in deceased donor kidney allocation.

Worldwide, the number of patients able to benefit from kidney transplantation is greatly restricted by the severe shortage of deceased donor organs. Allocation of this scarce resource is increasingly challenging and complex. Striking an acceptable balance between efficient use of (utility) and fair access to (equity) the limited supply of donated kidneys raises controversial but important debates at ethical, medical, and social levels. There is no international consensus on the recipient and donor factors that should be considered in the kidney allocation process. There is a general trend toward a reduction in the influence of human leukocyte antigen mismatch and an increase in the importance of other factors shown to affect posttransplant outcomes, such as cold ischemia, duration of dialysis, donor and recipient age, and comorbidity. Increased consideration of equity has led to improved access to transplantation for disadvantaged patient groups. There has been an overall improvement in the transparency and accountability of allocation policies. Novel and contentious approaches in kidney allocation include the use of survival prediction scores as a criterion for accessing the waiting list and at the point of organ offering with matching of predicted graft and recipient survival. This review compares the diverse international approaches to deceased donor kidney allocation and their evolution over the last decade.

Patient preferences, knowledge and beliefs about kidney allocation: qualitative findings from the UK-wide ATTOM programme.

OBJECTIVE: To explore how patients who are wait-listed for or who have received a kidney transplant understand the current UK kidney allocation system, and their views on ways to allocate kidneys in the future. DESIGN: Qualitative study using semistructured interviews and thematic analysis based on a pragmatic approach. PARTICIPANTS: 10 deceased-donor kidney transplant recipients, 10 live-donor kidney transplant recipients, 12 participants currently wait-listed for a kidney transplant and 4 participants whose kidney transplant failed. SETTING: Semistructured telephone interviews conducted with participants in their own homes across the UK. RESULTS: Three main themes were identified: uncertainty of knowledge of the allocation scheme; evaluation of the system and participant suggestions for future allocation schemes. Most participants identified human leucocyte anitgen matching as a factor in determining kidney allocation, but were often uncertain of the accuracy of their knowledge. In the absence of information that would allow a full assessment, the majority of participants consider that the current system is effective. A minority of participants were concerned about the perceived lack of transparency of the general decision-making processes within the scheme. Most participants felt that people who are younger and those better matched to the donor kidney should be prioritised for kidney allocation, but in contrast to the current scheme, less priority was considered appropriate for longer waiting patients. Some non-medical themes were also discussed, such as whether parents of dependent children should be prioritised for allocation, and whether patients with substance abuse problems be deprioritised. CONCLUSIONS: Our participants held differing views about the most important factors for kidney allocation, some of which were in contrast to the current scheme. Patient participation in reviewing future allocation policies will provide insight as to what is considered acceptable to patients and inform healthcare staff of the kinds of information patients would find most useful.

Predicting patient survival after deceased donor kidney transplantation using flexible parametric modelling.

BACKGROUND: The influence of donor and recipient factors on outcomes following kidney transplantation is commonly analysed using Cox regression models, but this approach is not useful for predicting long-term survival beyond observed data. We demonstrate the application of a flexible parametric approach to fit a model that can be extrapolated for the purpose of predicting mean patient survival. The primary motivation for this analysis is to develop a predictive model to estimate post-transplant survival based on individual patient characteristics to inform the design of alternative approaches to allocating deceased donor kidneys to those on the transplant waiting list in the United Kingdom. METHODS: We analysed data from over 12,000 recipients of deceased donor kidney or combined kidney and pancreas transplants between 2003 and 2012. We fitted a flexible parametric model incorporating restricted cubic splines to characterise the baseline hazard function and explored a range of covariates including recipient, donor and transplant-related factors. RESULTS: Multivariable analysis showed the risk of death increased with recipient and donor age, diabetic nephropathy as the recipient's primary renal diagnosis and donor hypertension. The risk of death was lower in female recipients, patients with polycystic kidney disease and recipients of pre-emptive transplants. The final model was used to extrapolate survival curves in order to calculate mean survival times for patients with specific characteristics. CONCLUSION: The use of flexible parametric modelling techniques allowed us to address some of the limitations of both the Cox regression approach and of standard parametric models when the goal is to predict long-term survival.

Access to Transplantation and Transplant Outcome Measures (ATTOM): study protocol of a UK wide, in-depth, prospective cohort analysis.

INTRODUCTION: There is significant intercentre variability in access to renal transplantation in the UK due to poorly understood factors. The overarching aims of this study are to improve equity of access to kidney and kidney-pancreas transplantation across the UK and to optimise organ allocation to maximise the benefit and cost-effectiveness of transplantation. METHODS AND ANALYSIS: 6844 patients aged 18-75 years starting dialysis and/or receiving a transplant together with matched patients active on the transplant list from all 72 UK renal units were recruited between November 2011 and March 2013 and will be followed for at least 3 years. The outcomes of interest include patient survival, access to the transplant list, receipt of a transplant, patient-reported outcome measures (PROMs) including quality of life, treatment satisfaction, well-being and health status on different forms of renal replacement therapy. Sociodemographic and clinical data were prospectively collected from case notes and from interviews with patients and local clinical teams. Qualitative process exploration with clinical staff will help identify unit-specific factors that influence access to renal transplantation. A health economic analysis will explore costs and outcomes associated with alternative approaches to organ allocation. The study will deliver: (1) an understanding of patient and unit-specific factors influencing access to renal transplantation in the UK, informing potential changes to practices and policies to optimise outcomes and reduce intercentre variability; (2) a patient-survival probability model to standardise access to the renal transplant list and (3) an understanding of PROMs and health economic impact of kidney and kidney-pancreas transplantation to inform the development of a more sophisticated and fairer organ allocation algorithm. ETHICS AND DISSEMINATION: The protocol has been independently peer reviewed by National Institute for Health Research (NIHR) and approved by the East of England Research Ethics Committee. The results will be published in peer-reviewed journals and presented at conferences.

Logistical Factors Influencing Cold Ischemia Times in Deceased Donor Kidney Transplants.

BACKGROUND: Prolonged cold ischemia time (CIT) is associated with a significant risk of short- and long-term graft failure in deceased donor kidney transplants across the world. The aim of this prospective longitudinal study was to determine the importance of logistical factors on CIT. METHOD: Data on 1763 transplants were collected prospectively over 14 months from personnel in 16 transplant centers, 19 histocompatibility and immunogenetics laboratories, transport providers, and National Health Service Blood and Transplant. RESULTS: The overall mean CIT was 13.8 hours, with significant center variation (P < 0.0001). Factors that significantly reduced CIT were donation after circulatory death (P = 0.03), shorter transport time (P = 0.0002), use of virtual crossmatch (XM) (P < 0.0001), and use of donor blood for pretransplant XM (P < 0.0001). The CIT for transplants that went ahead with a virtual XM was 3 hours shorter than those requiring a pretransplant XM (P < 0.0001). There was a mean delay of 3 hours in starting transplants despite organ, recipient, and pretransplant XM result being ready, suggesting that theater access contributes significantly to increased CIT. DISCUSSION: This study identifies logistical factors relating to donor, transport, crossmatching, recipient, and theater that impact significantly on CIT in deceased donor renal transplantation, some of which are modifiable; attention should be focussed on addressing all of these.

Understanding cost of care for patients on renal replacement therapy: looking beyond fixed tariffs.

BACKGROUND: In a number of countries, reimbursement to hospitals providing renal dialysis services is set according to a fixed tariff. While the cost of maintenance dialysis and transplant surgery are amenable to a system of fixed tariffs, patients with established renal failure commonly present with comorbid conditions that can lead to variations in the need for hospitalization beyond the provision of renal replacement therapy. METHODS: Patient-level cost data for incident renal replacement therapy patients in England were obtained as a result of linkage of the Hospital Episodes Statistics dataset to UK Renal Registry data. Regression models were developed to explore variations in hospital costs in relation to treatment modality, number of years on treatment and factors such as age and comorbidities. The final models were then used to predict annual costs for patients with different sets of characteristics. RESULTS: Excluding the cost of renal replacement therapy itself, inpatient costs generally decreased with number of years on treatment for haemodialysis and transplant patients, whereas costs for patients receiving peritoneal dialysis remained constant. Diabetes was associated with higher mean annual costs for all patients irrespective of treatment modality and hospital setting. Age did not have a consistent effect on costs. CONCLUSIONS: Combining predicted hospital costs with the fixed costs of renal replacement therapy showed that the total cost differential for a patient continuing on dialysis rather than receiving a transplant is considerable following the first year of renal replacement therapy, thus reinforcing the longer-term economic advantage of transplantation over dialysis for the health service.