Protocol for a multicentre prospective exploratory mixed-methods study investigating the modifiable psychosocial variables influencing access to and outcomes after kidney transplantation in children and young people in the UK.

INTRODUCTION: Kidney transplantation is the preferred therapy for children with stage 5 chronic kidney disease (CKD-5). However, there is a wide variation in access to kidney transplantation across the UK for children. This study aims to explore the psychosocial factors that influence access to and outcomes after kidney transplantation in children in the UK using a mixed-methods prospective longitudinal design. METHODS: Qualitative data will be collected through semistructured interviews with children affected by CKD-5, their carers and paediatric renal multidisciplinary team. Recruitment for interviews will continue till data saturation. These interviews will inform the choice of existing validated questionnaires, which will be distributed to a larger national cohort of children with pretransplant CKD-5 (n=180) and their carers. Follow-up questionnaires will be sent at protocolised time points regardless of whether they receive a kidney transplant or not. Coexisting health data from hospital, UK renal registry and National Health Service Blood and Transplant registry records will be mapped to each questionnaire time point. An integrative analysis of the mixed qualitative and quantitative data will define psychosocial aspects of care for potential intervention to improve transplant access. ANALYSIS: Qualitative data will be analysed using thematic analysis. Quantitative data will be analysed using appropriate statistical methods to understand how these factors influence access to transplantation, as well as the distribution of psychosocial factors pretransplantation and post-transplantation. ETHICS AND DISSEMINATION: This study protocol has been reviewed by the National Institute for Health Research Academy and approved by the Wales Research Ethics Committee 4 (IRAS number 270493/ref: 20/WA/0285) and the Scotland A Research Ethics Committee (ref: 21/SS/0038). Results from this study will be disseminated across media platforms accessed by affected families, presented at conferences and published in peer-reviewed journals.

"I am in favour of organ donation, but I feel you should opt-in"-qualitative analysis of the #options 2020 survey free-text responses from NHS staff toward opt-out organ donation legislation in England.

BACKGROUND: In May 2020, England moved to an opt-out organ donation system, meaning adults are presumed to be an organ donor unless within an excluded group or have opted-out. This change aims to improve organ donation rates following brain or circulatory death. Healthcare staff in the UK are supportive of organ donation, however, both healthcare staff and the public have raised concerns and ethical issues regarding the change. The #options survey was completed by NHS organisations with the aim of understanding awareness and support of the change. This paper analyses the free-text responses from the survey. METHODS: The #options survey was registered as a National Institute of Health Research (NIHR) portfolio trial [IRAS 275992] 14 February 2020, and was completed between July and December 2020 across NHS organisations in the North-East and North Cumbria, and North Thames. The survey contained 16 questions of which three were free-text, covering reasons against, additional information required and family discussions. The responses to these questions were thematically analysed. RESULTS: The #options survey received 5789 responses from NHS staff with 1404 individuals leaving 1657 free-text responses for analysis. The family discussion question elicited the largest number of responses (66%), followed by those against the legislation (19%), and those requiring more information (15%). Analysis revealed six main themes with 22 sub-themes. CONCLUSIONS: The overall #options survey indicated NHS staff are supportive of the legislative change. Analysis of the free-text responses indicates that the views of the NHS staff who are against the change reflect the reasons, misconceptions, and misunderstandings of the public. Additional concerns included the rationale for the change, informed decision making, easy access to information and information regarding organ donation processes. Educational materials and interventions need to be developed for NHS staff to address the concepts of autonomy and consent, organ donation processes, and promote family conversations. Wider public awareness campaigns should continue to promote the positives and refute the negatives thus reducing misconceptions and misunderstandings. TRIAL REGISTRATION: National Institute of Health Research (NIHR) [IRAS 275992].

Using oral bioaccessibility measurements to refine risk assessment of potentially toxic elements in topsoils across an urban area.

Elevated concentrations of As, Cr, Cu, Ni, Pb, V and Zn in topsoils in Belfast, Northern Ireland have been found to exceed assessment criteria in the city and therefore may pose a risk to human health. Most generic assessment criteria (GAC) for potentially toxic elements (PTEs) in soils assume PTEs are 100% bioavailable to humans. Here we use in-vitro oral bioaccessibility testing using the Unified BARGE method (UBM) to measure what proportion of soil contamination dissolves in the digestive tract and therefore is available for absorption by the body. This study considers how PTE bioaccessibility in soils varies spatially across urban areas and refines human health risk assessment for these PTEs using site specific oral bioaccessibility results to present the first regional assessment of risk that incorporates bioaccessibility testing. A total of 103 urban soil samples were selected for UBM testing. Results showed low bioaccessible fraction (BAF) for the PTEs from geogenic sources: Cr (0.45-5.9%), Ni (1.1-46.3%) and V (2.2-23.9%). Higher BAF values were registered for PTEs from anthropogenic sources: As (8.0-86.9%), Cu (3.4-67.8%), Pb (9.1-106.2%) and Zn (2.4-77.5%). Graphs of bioaccessibility adjusted assessment criteria (BAAC) were derived for each urban land use type and PTE. These provide a visual representation of the significance of oral bioaccessibility when deriving BAAC and how this is affected by 1) dominant exposure pathways for each land use and 2) relative harm posed from exposure to PTEs via each pathway, allowing oral bioaccessibility research to be targeted to contaminants and pathways that most significantly impact risk assessment. Pb was the most widespread contaminant with 16.5% of sites exceeding the Pb GAC. Applying BAAC did not significantly change risk evaluation for these samples as many had Pb BAF>50%. In contrast, all samples that exceeded the As GAC were found to no longer exceed a minimal level of risk when oral bioaccessibility was considered. Oral bioaccessibility testing resulted in a 45% reduction in the number of sites identified as posing a potential risk to human health.

Predictable electronic tuning of FeII and RuII complexes via choice of azine: correlation of ligand pKa with Epa(MIII/II) of complex.

Five new mononuclear ruthenium(II) tris-ligated complexes have been synthesised, varying through the choice of azine in the family of 3-azinyl-4-(4-methylphenyl)-5-phenyl-4H-1,2,4-triazole ligands (Lazine): [Ru(Lpyridine)](PF6)2 (1), [Ru(Lpyridazine)](PF6)2 (2), [Ru(L4-pyrimidine)](PF6)2 (3), [Ru(Lpyrazine)](PF6)2 (4), [Ru(L2-pyrimidine)](PF6)2 (5). Three of them, 1·2MeCN·Et2O, 3·2MeCN·Et2O and 4·2MeCN, have been structurally characterised, confirming the presence of the meridional isomer, as was previously reported for the FeII analogues. Cyclic voltammetry studies, in dry CH3CN vs. Ag/0.01 M AgNO3, show that all five RuII complexes undergo a reversible RuIII/RuII process, with the midpoint potential (Em) increasing from 0.87 to 1.18 V as the azine is changed: pyridine < pyridazine < 2-pyrimidine < 4-pyrimidine < pyrazine. A strong inverse linear correlation (R2 = 0.98) is found between the RuIII/RuII redox potential and the calculated HOMO orbital energies, which is consistent with the expectation that it is easier to oxidise (lower Em) a metal ion with a higher HOMO orbital energy. The same trend was reported earlier for the family of analogous FeII complexes, albeit at lower values of Em in all cases. In addition, the ionisation potentials of the RuII complexes, as well as those of the other group 8 analogues (FeII and OsII), showed a linear relationship with Epa. As the MIII/II redox potentials of a family of complexes has been previously reported to correlate with ligand pKa values, a computational protocol to calculate, in silico, the pKa of the Lazine family of ligands was developed. A strong linear relationship was found between the readily calculated pKa of the Lazine ligand and the Epa of the MII complex, for all three families of complexes (R2 = 0.98).

Prognostic models: What the statistician wants the clinician to know.

Prognostic model building is a process that begins much earlier than data analysis and ends later than when a model is reached. It requires careful delineation of a clinical question, methodical planning of the approach and attentive exploration of the data before attempting model building. Once following these important initial steps, the researcher may postulate a model to describe the process of interest and build such model. Once built, the model will need to be checked, validated and the exercise may take the researcher back a few steps - for instance, to adapt the model to fit a variable that displays a 'curved' pattern - to then return to check and validate the model again. To interpret and report the results it is vital to relate the output to the original question, to be transparent in the methodology followed and to understand the limitations of the data and the approach.

NHS staff awareness, attitudes and actions towards the change in organ donation law in England-results of the #options survey 2020.

BACKGROUND: In Spring 2020 there was a change in organ donation legislation in England (UK). Much is known about public opinions to organ donation and the change in legislation, however, there is little evidence about the opinions of the NHS workforce. This study set out to understand the levels of awareness, support and action of NHS staff to this change and explore the impact of respondent demographics, place and type of work on awareness, support and action. METHODS: An online survey was offered to all NHS organisations in North Thames and the North East and North Cumbria through the NIHR Clinical Research Network between July and December 2020. Participating organisations were provided with an information package and promoted the survey via email and internal staff communications. Associations were compared univariately using chi-square tests and logistic regression was used for multivariable analysis to compare findings with NHS Blood and Transplant public Kantar survey data. RESULTS: A total of 5789 staff participated in the survey. They were more aware, more supportive, more likely to have discussed their organ donation choices with family and more likely to be on the organ donor register than the public. This increased awareness and support was found across minority ethnic and religious groups. Those working in a transplanting centre were most aware and supportive and those working in the ambulance service were most likely to 'opt-in' following the change in legislation. CONCLUSIONS: NHS staff in England were well informed about the change in organ donation legislation and levels of support were high. NHS staff were six times more likely than the public to have a conversation with their family about their organ donation choices. The size and ethnic diversity of the NHS workforce offers an opportunity to enable and support NHS staff to be advocates for organ donation and raise awareness of the change in legislation amongst their communities.

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.

Transplantation of Organs From DCD and DBD Donors Who Died After Ligature Asphyxiation.

BACKGROUND: The United Kingdom transplant registry data demonstrated similar transplant outcomes for recipients of kidneys from donors who died following ligature asphyxiation and those who received organs from donors dying from other causes. The impact that this donor cause of death has on the outcomes of other solid organ transplant recipients remains uncertain. METHODS: The United Kingdom transplant registry analysis was undertaken to determine transplant outcomes in recipients of lungs, hearts, livers' and pancreases from donors who died following ligature asphyxiation. RESULTS: Between January 01, 2003, and December 31, 2016, 2.7% (n = 521) of all potential United Kingdom donors died following ligature asphyxiation (mostly suicide by hanging). Of these, 416 (79.9%; 197 donation after brain stem death and 219 donation after circulatory death [DCD]) donated an organ for transplantation. These donors provided organs for 574 transplants (66 lung transplants, 75 heart transplants, 279 liver transplants, and 154 pancreas transplants). Patient and graft survival were similar for recipients of both donation after brain stem death and DCD hearts, livers, and pancreases from donors who died following ligature asphyxiation. Unadjusted graft and patient survival were significantly worse for recipients of lungs from DCD donors who died following ligature asphyxiation. This detrimental effect persisted after propensity score matching. CONCLUSIONS: Livers, hearts, and pancreases from donors who die following ligature asphyxiation suffer an additional warm ischemic insult, but this does not negatively impact transplant outcomes. Outcomes for recipients of DCD lungs appear to be significantly worse.

Utilization and clinical outcomes of kidney transplants from deceased donors with albuminuria in the UK: a national cohort study.

BACKGROUND: Urinalysis is a standard component of potential deceased kidney donor assessment in the UK. The value of albuminuria as a biomarker for organ quality is uncertain. We examined the relationship between deceased donor albuminuria and kidney utilization, survival and function. METHODS: We performed a national cohort study on adult deceased donors and kidney transplant recipients between 2016 and 2020, using data from the UK Transplant Registry. We examined the influence of donor albuminuria, defined as ≥2+ on dipstick testing, on kidney utilization, early graft function, graft failure and estimated glomerular filtration rate (eGFR). RESULTS: Eighteen percent (1681/9309) of consented donors had albuminuria. After adjustment for confounders, kidneys from donors with albuminuria were less likely to be accepted for transplantation (74% versus 82%; odds ratio 0.70, 95% confidence interval 0.61 to 0.81). Of 9834 kidney transplants included in our study, 1550 (16%) came from donors with albuminuria. After a median follow-up of 2 years, 8% (118/1550) and 9% (706/8284) of transplants from donors with and without albuminuria failed, respectively. There was no association between donor albuminuria and graft failure (hazard ratio 0.91, 95% confidence interval 0.74 to 1.11). There was also no association with delayed graft function, patient survival or eGFR at 1 or 3 years. CONCLUSIONS: Our study suggests reluctance in the UK to utilize kidneys from deceased donors with dipstick albuminuria but no evidence of an association with graft survival or function. This may represent a potential to expand organ utilization without negatively impacting transplant outcomes.

Donor characteristics and their impact on kidney transplantation outcomes: Results from two nationwide instrumental variable analyses based on outcomes of donor kidney pairs accepted for transplantation.

Background: Donor-characteristics and donor characteristics-based decision algorithms are being progressively used in the decision process whether or not to accept an available donor kidney graft for transplantation. While this may improve outcomes, the performance characteristics of the algorithms remains moderate. To estimate the impact of donor factors of grafts accepted for transplantation on transplant outcomes, and to test whether implementation of donor-characteristics-based algorithms in clinical decision-making is justified, we applied an instrumental variable analysis to outcomes for kidney donor pairs transplanted in different individuals. Methods: This analysis used (dis)congruent outcomes of kidney donor pairs as an instrument and was based on national transplantation registry data for all donor kidney pairs transplanted in separate individuals in the Netherlands (1990-2018, 2,845 donor pairs), and the United Kingdom (UK, 2000-2018, 11,450 pairs). Incident early graft loss (EGL) was used as the primary discriminatory factor. It was reasoned that a scenario with a dominant impact of donor variables on transplantation outcomes would result in high concordance of EGL in both recipients, whilst dominance of asymmetrical outcomes could indicate a more complex scenario, involving an interaction of donor, procedural and recipient factors. Findings: Incidences of congruent EGL (Netherlands: 1·2%, UK: 0·7%) were slightly lower than the arithmetical (stochastic) incidences, suggesting that once a graft has been accepted for transplantation, donor factors minimally contribute to incident EGL. A long-term impact of donor factors was explored by comparing outcomes for functional grafts from donor pairs with asymmetrical vs. symmetrical outcomes. Recipient survival was similar for both groups, but a slightly compromised graft survival was observed for grafts with asymmetrical outcomes in the UK cohort: (10-years Hazard Ratio for graft loss: 1·18 [1·03-1·35] p<0·018); and 5 years eGFR (48·6 [48·3-49·0] vs. 46·0 [44·5-47·6] ml/min in the symmetrical outcome group, p<0·001). Interpretation: Our results suggest that donor factors for kidney grafts deemed acceptable for transplantation impact minimally on transplantation outcomes. A strong reliance on donor factors and/or donor-characteristics-based decision algorithms could result in unjustified rejection of grafts. Future efforts to optimize transplant outcomes should focus on a better understanding of the recipient factors underlying transplant outcomes. Funding: None.

Transplant and Recipient Factors in Prediction of Kidney Transplant Outcomes: A UK-Wide Paired Analysis.

BACKGROUND: In kidney transplantation, the relative contribution of various donor, procedure and recipient-related factors on clinical outcomes is unknown. Previous paired studies have largely focused on examining factors predicting early outcomes, where the effect of donor factors is thought to be most important. Here, we sought to examine the relationship between early and long-term outcomes in a UK-wide paired kidney analysis. METHODS: UK Transplant Registry data covering 24,090 kidney transplants performed between 2001-2018, where both kidneys from each donor were transplanted, were analysed. Case-control studies were constructed using matched pairs of kidneys from the same donor discordant for outcome, to delineate the impact of transplant and recipient factors on longer-term outcomes. RESULTS: Multivariable conditional logistic regression identified HLA mismatch as an important predictor of prolonged delayed graft function (DGF), in the context of a paired study controlling for the influence of donor factors, even when adjusting for early acute rejection. Prolonged DGF, but not human leucocyte antigen (HLA) mismatch, strongly predicted 12-month graft function, and impaired 12-month graft function was associated with an increased risk of graft failure. CONCLUSIONS: This study indicates prolonged DGF is associated with adverse long-term outcomes and suggests that alloimmunity may contribute to prolonged DGF by a mechanism distinct from typical early acute rejection.

Mono-copper far more active than analogous di-copper complex for electrocatalytic hydrogen evolution.

The di-copper(II) analogue, [CuII2(bis-LEt)](BF4)2 (2), of the previously reported mono-copper(II) complex [CuIILEt]BF4 (1) which resulted in long lived electrocatalytic hydrogen evolution reaction (HER), has been prepared, characterised and tested for HER. The new bis-macrocycle, bis-HLEt, was formed from two HLEt Schiff base macrocycles (prepared by 1 + 1 condensation of 2,2'-iminobisbenzaldehyde and diethylenetriamine) being connected by selective alkylation of the less sterically hindered secondary alkyl amine group (NH) of each, using α,α'-dibromo-para-xylene to form a linker between them. The desired dicopper(II) complex, [Cu2II(bis-LEt)](BF4)2·4H2O (2·4H2O), was readily prepared, as a yellowish brown solid in 82% yield. SCXRD on yellow-brown crystals of [CuII2(bis-LEt)](BF4)2·2MeCN (2·2MeCN) revealed both copper(II) centres are square planar with a very similar copper(II) coordination environment to that of square planar 1. Although dicopper(II) complex 2 is easier to reduce than the analogous monocopper(II) complex 1 in MeCN (E1/2(ΔE): 2 -1.20(0.12) V, 1 -1.39(0.09) V, vs. 0.01 M AgNO3/Ag), electrocatalytic HER testing of dicopper complex 2·4H2O, in MeCN with 80 equivalents of acetic acid, revealed it was inactive, in stark contrast to the high and ongoing activity of 1 under the same conditions. So two is definitely not better than one metal ion in this case. Rather, it may be that the presence of an NH group in the macrocycle of 1, but absent in the bis-macrocycle of 2 (due to alkylating that NH to link the two macrocycles), may be key to the HER activity seen for 1.

Solid Organ Transplantation From Deceased Donors With Infective Endocarditis: The UK Experience.

BACKGROUND: There is little evidence regarding the use of organs from deceased donors with infective endocarditis. We performed a retrospective analysis of the utilization, safety, and long-term survival of transplants from donors with infective endocarditis in the United Kingdom. METHODS: We studied deceased donor transplants over an 18-y period (2001-2018) using data from the UK Transplant Registry. We estimated the risk of infection transmission, defined as a microbiological isolate in the recipient matching the causative organism in the donor in the first 30 days posttransplant. We examined all-cause allograft failure up to 5 years in kidney and liver recipients, comparing transplants from donors with endocarditis with randomly selected matched control transplants. RESULTS: We studied 88 transplants from 42 donors with infective endocarditis. We found no cases of infection transmission. There was no difference in allograft failure between transplants from donors with infective endocarditis and matched control transplants, among either kidney (hazard ratio, 1.48; 95% CI, 0.66-3.34) or liver (hazard ratio, 1.14; 95% CI, 0.54-2.41) recipients. Compared with matched controls, donors with infective endocarditis donated fewer organs (2.3 versus 3.2 organs per donor; P < 0.001) and were less likely to become kidney donors (odds ratio, 0.29; 95% CI, 0.16-0.55). CONCLUSIONS: We found acceptable safety and long-term allograft survival in transplants from selected donors with infective endocarditis in the United Kingdom. This may have implications for donor selection and organ utilization.

The Impact of Cold Ischaemia Time on Outcomes of Living Donor Kidney Transplantation in the UK Living Kidney Sharing Scheme.

OBJECTIVE: To assess the impact of CIT on living donor kidney transplantation (LDKT) outcomes in the UKLKSS versus outside the scheme. BACKGROUND: LDKT provides the best treatment option for end-stage kidney disease patients. end-stage kidney disease patients with an incompatible living donor still have an opportunity to be transplanted through Kidney Exchange Programmes (KEP). In KEPs where kidneys travel rather than donors, cold ischaemia time (CIT) can be prolonged. METHODS: Data from all UK adult LDKT between 2007 and 2018 were analysed. RESULTS: 9969 LDKT were performed during this period, of which 1396 (14%) were transplanted through the UKLKSS, which we refer to as KEP. Median CIT was significantly different for KEP versus non-KEP (339 versus 182 minutes, P < 0.001). KEP LDKT had a higher incidence of delayed graft function (DGF) (2.91% versus 5.73%, P < 0.0001), lower 1-year (estimated Glomerular Filtration Rate (eGFR) 57.90 versus 55.25 ml/min, P = 0.04) and 5-year graft function (eGFR 55.62 versus 53.09 ml/min, P = 0.01) compared to the non-KEP group, but 1- and 5-year graft survival were similar. Within KEP, a prolonged CIT was associated with more DGF (3.47% versus 1.95%, P = 0.03), and lower graft function at 1 and 5-years (eGFR = 55 vs 50 ml/min, P = 0.02), but had no impact on graft survival. CONCLUSION: Whilst CIT was longer in KEP, associated with more DGF and lower graft function, excellent 5-year graft survival similar to non-KEP was found.

Data and optimisation requirements for Kidney Exchange Programs.

Kidney Exchange Programs (KEP) are valuable tools to increase the options of living donor kidney transplantation for patients with end-stage kidney disease with an immunologically incompatible live donor. Maximising the benefits of a KEP requires an information system to manage data and to optimise transplants. The data input specifications of the systems that relate to key information on blood group and Human Leukocyte Antigen (HLA) types and HLA antibodies are crucial in order to maximise the number of identified matched pairs while minimising the risk of match failures due to unanticipated positive crossmatches. Based on a survey of eight national and one transnational kidney exchange program, we discuss data requirements for running a KEP. We note large variations in the data recorded by different KEPs, reflecting varying medical practices. Furthermore, we describe how the information system supports decision making throughout these kidney exchange programs.

Changing patterns of clinical decision making: are falling numbers of antibody incompatible transplants related to the increasing success of the UK Living Kidney Sharing Scheme? A national cohort study.

Antibody incompatibility is a barrier to living kidney transplantation; antibody incompatible transplantation (AIT) is an accepted treatment modality, albeit higher risk. This study aims to determine changes to clinical decision making and access to AIT in the UK. An electronic survey was sent to all UK renal transplant centres (n = 24), in 2014, and again in 2018. Questions focused on entry & duration in the UKLKSS for HLA and ABO-incompatible pairs, Can and provision of direct AIT transplantation within those centres. Between 2014 & 2018, the duration recommended for patients in the UKLKSS increased. In 2014, 34.8% of centres reported leaving HLA-i pairs in the UKLKSS indefinitely, or reviewing on a case by case basis, by 2018 this increased to 61%. Centres offering direct HLA-i transplantation reduced from 58% to 37%. For low titre (1:8) ABO-i recipients, 66% of centres recommended at least 9 months (3 matching runs) in the UKLKSS scheme in 2018, compared to 47% in 2014, 50% fewer units consider direct ABO-i transplantation for unsuccessful pairs with high ABO titres (>1:512). Over time, clinicians appear to be facilitating more conservative management of AIT patients, potentially limiting access to living donor transplantation.

Convalescent plasma therapy for the treatment of patients with COVID-19: Assessment of methods available for antibody detection and their correlation with neutralising antibody levels.

INTRODUCTION: The lack of approved specific therapeutic agents to treat coronavirus disease (COVID-19) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has led to the rapid implementation of convalescent plasma therapy (CPT) trials in many countries, including the United Kingdom. Effective CPT is likely to require high titres of neutralising antibody (nAb) in convalescent donations. Understanding the relationship between functional neutralising antibodies and antibody levels to specific SARS-CoV-2 proteins in scalable assays will be crucial for the success of a large-scale collection. We assessed whether neutralising antibody titres correlated with reactivity in a range of enzyme-linked immunosorbent assays (ELISA) targeting the spike (S) protein, the main target for human immune response. METHODS: Blood samples were collected from 52 individuals with a previous laboratory-confirmed SARS-CoV-2 infection. These were assayed for SARS-CoV-2 nAbs by microneutralisation and pseudo-type assays and for antibodies by four different ELISAs. Receiver operating characteristic (ROC) analysis was used to further identify sensitivity and specificity of selected assays to identify samples containing high nAb levels. RESULTS: All samples contained SARS-CoV-2 antibodies, whereas neutralising antibody titres of greater than 1:20 were detected in 43 samples (83% of those tested) and >1:100 in 22 samples (42%). The best correlations were observed with EUROimmun immunoglobulin G (IgG) reactivity (Spearman Rho correlation coefficient 0.88; p < 0.001). Based on ROC analysis, EUROimmun would detect 60% of samples with titres of >1:100 with 100% specificity using a reactivity index of 9.1 (13/22). DISCUSSION: Robust associations between nAb titres and reactivity in several ELISA-based antibody tests demonstrate their possible utility for scaled-up production of convalescent plasma containing potentially therapeutic levels of anti-SARS-CoV-2 nAbs.

A propensity score-matched analysis indicates screening for asymptomatic coronary artery disease does not predict cardiac events in kidney transplant recipients.

Screening for asymptomatic coronary artery disease prior to kidney transplantation aims to reduce peri- and post-operative cardiac events. It is uncertain if this is achieved. Here, we investigated whether pre-transplant screening with a stress test or coronary angiogram associated with any difference in major adverse cardiac events (MACE) up to five years post-transplantation. We examined a national prospective cohort recruited to the Access to Transplant and Transplant Outcome Measures study who received a kidney transplant between 2011-2017, and linked patient demographics and details of cardiac screening investigations to outcome data extracted from the Hospital Episode Statistics dataset and United Kingdom Renal Registry. Propensity score matched groups were analyzed using Kaplan-Meier and Cox survival analyses. Overall, 2572 individuals were transplanted in 18 centers; 51% underwent screening and the proportion undergoing screening by center ranged from 5-100%. The incidence of MACE at 90 days, one and five years was 0.9%, 2.1% and 9.4% respectively. After propensity score matching based on the presence or absence of screening, 1760 individuals were examined (880 each in screened and unscreened groups). There was no statistically significant association between screening and MACE at 90 days (hazard ratio 0.80, 95% Confidence Interval 0.31-2.05), one year (1.12, 0.51-2.47) or five years (1.31, 0.86-1.99). Age, male sex and history of ischemic heart disease were associated with MACE. Thus, there is no association between screening for asymptomatic coronary artery disease and MACE up to five years post-transplant. Practices involving unselected screening of transplant recipients should be reviewed.

Outcomes of Patients Suspended From the National Kidney Transplant Waiting List in the United Kingdom Between 2000 and 2010.

BACKGROUND: In the United Kingdom, 1 in 3 patients on the National Kidney Transplant Waiting List (NKTWL) is suspended from the list at least once during their wait. The mortality of this large cohort of patients remains underreported and poorly described. METHODS: We linked patient records from the UK transplant registry to mortality data from the Office of National Statistics and evaluated the impact of a clinically induced suspension event by estimating hazard ratios (HRs) that compared mortality and graft survival between those who had experienced a suspension event and those who had not. RESULTS: Between January 1, 2000, and December 31, 2010, 16.7% (2221/13 322) of all patients registered on the NKTWL were suspended. Forty-eight percent (588/1225) of those who were suspended and who were never transplanted died, most often from cardiothoracic causes. A suspension event was associated with increased mortality from the time of listing (adjusted HR [aHR], 1.79; 1.64-1.95) and from the time of transplantation (aHR, 1.20; 1.06-1.37; P = 0.005). Graft survival was also poorer in those who had been suspended (aHR, 1.13; 1.01-1.28; P = 0.04). CONCLUSIONS: Patients suspended on the NKTWL have a significantly higher rate of mortality both on the waiting list and following transplantation. Earlier prioritization of patients at risk of experiencing a suspension event may improve their outcomes.