Normothermic machine perfusion versus static cold storage in donation after circulatory death kidney transplantation: a randomized controlled trial.

Kidney transplantation is the optimal treatment for end-stage renal disease, but it is still severely limited by a lack of suitable organ donors. Kidneys from donation after circulatory death (DCD) donors have been used to increase transplant rates, but these organs are susceptible to cold ischemic injury in the storage period before transplantation, the clinical consequence of which is high rates of delayed graft function (DGF). Normothermic machine perfusion (NMP) is an emerging technique that circulates a warmed, oxygenated red-cell-based perfusate through the kidney to maintain near-physiological conditions. We conducted a randomized controlled trial to compare the outcome of DCD kidney transplants after conventional static cold storage (SCS) alone or SCS plus 1-h NMP. A total of 338 kidneys were randomly allocated to SCS (n = 168) or NMP (n = 170), and 277 kidneys were included in the final intention-to-treat analysis. The primary endpoint was DGF, defined as the requirement for dialysis in the first 7 d after transplant. The rate of DGF was 82 of 135 (60.7%) in NMP kidneys versus 83 of 142 (58.5%) in SCS kidneys (adjusted odds ratio (95% confidence interval) 1.13 (0.69-1.84); P = 0.624). NMP was not associated with any increase in transplant thrombosis, infectious complications or any other adverse events. A 1-h period of NMP at the end of SCS did not reduce the rate of DGF in DCD kidneys. NMP was demonstrated to be feasible, safe and suitable for clinical application. Trial registration number: ISRCTN15821205 .

Risk of prolonged ischemic time linked to use of cardiopulmonary bypass during implantation for lung transplantation in the United Kingdom.

BACKGROUND: Some degree of ischemia is inevitable in organ transplantation, and for most, if not all organs, there is a relationship between ischemic time and transplant outcome. The contribution of ischemic time to lung injury is unclear, with conflicting recent data. In this study, we investigate the impact of ischemia time on survival after lung transplantation in a large national cohort. METHODS: We studied the outcomes for 1,565 UK adult lung transplants over a 12-year period, for whom donor, transplant, and recipient data were available from the UK Transplant Registry. We examined the effect of ischemia time (defined as donor cross-clamp to recipient reperfusion) and whether standard cardiopulmonary bypass was used using Cox proportional hazards models, adjusting for other risk factors. RESULTS: The total ischemic time increased from a median under 5 hours in 2003 to over 6.2 hours in 2013. Our findings show that, when the cardiopulmonary bypass was used, there was an increase in the hazard of death (of 13% [95% CI: 5%-21%] for 1-year patient survival) for each hour of total ischemic time. However, if the cardiopulmonary bypass was not used for implantation, this link disappeared-there was no statistically significant change in mortality with increasing ischemic time. CONCLUSIONS: We document that avoidance of bypass may remove ischemic time, within the limits of our observed range of ischemic times, as a risk factor for poor outcomes. Our data add to the evidence that bypass may be harmful to the donor lung.

Outcomes of Declined Deceased Donor Kidney Offers That Are Subsequently Implanted: A UK Registry Study.

BACKGROUND: Deceased donor kidneys are often declined for ≥1 patients but then implanted into another. Studies are needed to guide transplant clinicians and patients, especially given the increasing age and comorbidity of donors. This study compares outcomes of recipients of transplanted kidneys that were initially declined with outcomes of patients who remained on the waiting list. METHODS: This UK Transplant Registry study examined named-patient, adult donation after brain death donor single kidney-only offers that were declined for donor- or organ-related reasons (DORRs), in which the kidney was subsequently transplanted from January 1, 2010, to December 31, 2018. Outcomes included graft function and survival of kidneys transplanted following DORR decline, survival and transplant status of patients who had a kidney declined, and intercenter decline rates. RESULTS: A total of 4722 kidneys declined for DORRs, which eventually resulted in single kidney-only transplants, were examined. One year after the offer decline, 35% of patients for whom the organ was declined remained on the list, 55% received a deceased donor transplant at a median of 174 d after the initial offer decline, and 4% had been removed or died. For patients transplanted following offer decline, there was no significant difference in 5-y graft survival when comparing the outcomes to those recipients who received the declined kidney. There was significant variation in DORR decline rates between UK transplant units (17%-54%). CONCLUSIONS: This study shows reasonable outcomes of kidneys previously declined for DORRs and supports the utilization of those considered to be of higher risk for carefully selected recipients.

Improved Organ Utilization and Better Transplant Outcomes With In Situ Normothermic Regional Perfusion in Controlled Donation After Circulatory Death.

BACKGROUND: . We evaluated whether the use of normothermic regional perfusion (NRP) was associated with increased organ recovery and improved transplant outcomes from controlled donation after circulatory death (cDCD). METHODS: . This is a retrospective analysis of UK adult cDCD donors' where at least 1 abdominal organ was accepted for transplantation between January 1, 2011, and December 31, 2019. RESULTS: . A mean of 3.3 organs was transplanted when NRP was used compared with 2.6 organs per donor when NRP was not used. When adjusting for organ-specific donor risk profiles, the use of NRP increased the odds of all abdominal organs being transplanted by 3-fold for liver ( P < 0.0001; 95% confidence interval [CI], 2.20-4.29), 1.5-fold for kidney ( P = 0.12; 95% CI, 0.87-2.58), and 1.6-fold for pancreas ( P = 0.0611; 95% CI, 0.98-2.64). Twelve-mo liver transplant survival was superior for recipients of a cDCD NRP graft with a 51% lower risk-adjusted hazard of transplant failure (HR = 0.494). In risk-adjusted analyses, NRP kidneys had a 35% lower chance of developing delayed graft function than non-NRP kidneys (odds ratio, 0.65; 95% CI, 0.465-0.901)' and the expected 12-mo estimated glomerular filtration rate was 6.3 mL/min/1.73 m 2 better if abdominal NRP was used ( P < 0.0001). CONCLUSIONS: . The use of NRP during DCD organ recovery leads to increased organ utilization and improved transplant outcomes compared with conventional organ recovery.

Convalescent plasma for COVID-19: Donor demographic factors associated high neutralising antibody titres.

BACKGROUND: Convalescent plasma containing high levels of SARS-CoV-2 antibodies has been studied as a possible treatment for COVID-19. Better understanding of predictors of high antibody levels is needed for improving supply of high-quality therapeutic plasma. AIMS: We have evaluated demographic and clinical factors associated with the probability of a convalescent plasma donor having high SARS-CoV-2 IgG antibody levels. METHODS: A total of 29,585 convalescent plasma donors employed during the first and second waves of the COVID-19 pandemic in England were included in this study. All had been tested for SARS-CoV-2 IgG antibodies by EUROimmun ELISA. A multivariable logistic regression model was used to quantify the association of the demographic and clinical factors with high (EUROimmun S/Co>6.0) SARS-CoV-2 IgG antibody level. RESULTS: Most of the donors were male (23,024; 78%), with white ethnic background (24,598;83%) and had not been tested for SARS-CoV-2 (15,266; 52%).Overall, less than 20% of convalescent plasma donors with confirmed or suspected SARS-CoV-2 infection harboured high SARS-CoV-2 antibody levels (n = 4,978). We found that older male donors who had been hospitalised with COVID-19 were most likely to harbour high levels of antibodies. White donors were less likely to have high SARS-CoV-2 antibody levels than donors with Asian orblack ethnic backgrounds residing in affluent areas likely reflecting ethnic inequality previously associated with SARS-CoV-2 infection. DISCUSSION: In a time of great uncertainty, and predicted new waves associated with newly emerging SARS-CoV-2 variants, these results will help us to target future convalescent plasma collections.

Convalescent plasma for COVID-19: male gender, older age and hospitalisation associated with high neutralising antibody levels, England, 22 April to 12 May 2020.

We analysed factors associated with neutralising antibody levels in 330 convalescent plasma donors. Women and younger donors were more likely not to have measurable neutralising antibodies, while higher antibody levels were observed in men, in older donors and in those who had been hospitalised. These data will be of value in the timely recruitment of convalescent plasma donors most likely to have high levels of neutralising antibodies for ongoing studies investigating its effectiveness.

Convalescent plasma treatment for SARS-CoV-2 infection: analysis of the first 436 donors in England, 22 April to 12 May 2020.

Serological reactivity was analysed in plasma from 436 individuals with a history of disease compatible with COVID-19, including 256 who had been laboratory-confirmed with SARS-CoV-2 infection. Over 99% of laboratory-confirmed cases developed a measurable antibody response (254/256) and 88% harboured neutralising antibodies (226/256). Antibody levels declined over 3 months following diagnosis, emphasising the importance of the timing of convalescent plasma collections. Binding antibody measurements can inform selection of convalescent plasma donors with high neutralising antibody levels.

Prioritising transplantation for adult congenital heart disease, UK national data.

OBJECTIVE: There are no multi-centre data on the outcomes of transplant for adult congenital heart disease (ACHD) outside of North America. The literature has identified a number of concerns for this population such as increased wait-list and early post-operative mortality. We investigated outcomes in a national cohort to see if these problems are replicated outside of America. METHODS: Adults (aged ≥16 years) undergoing primary heart transplantation 1995-2014 were identified in the UK Registry and registration, operative and post-transplantation related clinical factors were compared to non ACHD recipients. RESULTS: Of 3026 adults who underwent primary heart transplantation, 134 (4.4%) had ACHD (median age 30 years; 40.3% female). For the ACHD patients listed as urgent status, the time to transplant was not significantly different to non ACHD patients and ACHD were not more likely to die or be removed from the wait list. Despite ACHD recipients having longer hospital stays (27 vs. 22 days; p = 0.003) and worse 90-day survival (79.5% vs. 86.6%; p = 0.02), long-term post-transplantation survival was not significantly different. Creatinine clearance was significantly better in ACHD patients at follow-up. In the last 10 years of our study period, all single ventricle transplants have been restricted to experienced ACHD teams, one year survival for Fontan patients was 89.5%. CONCLUSIONS: The use of urgent listing appears to have benefited the ACHD group by allowing equal access to transplantation, and recent concentration of expertise for single ventricle transplants has been associated with excellent early survival.