Metabolic Characterization of Deceased Donor Kidneys Undergoing Hypothermic Machine Perfusion Before Transplantation Using C-enriched Glucose.

Background: The provision of a metabolic substrate is one mechanism by which hypothermic machine perfusion (HMP) of kidneys provides clinical benefit. This study aimed to describe metabolism in ex vivo human kidneys undergoing HMP before transplantation using C-labeled glucose as a metabolic tracer.

Methods: Cadaveric human kidneys were perfused with modified clinical-grade perfusion fluid (kidney perfusion solution [KPS-1], Organ Recovery Systems), in which glucose was uniformly enriched with the stable isotope C ([U-C] glucose).

Current Evidence and Future Perspectives to Implement Continuous and End-Ischemic Use of Normothermic and Oxygenated Hypothermic Machine Perfusion in Clinical Practice.

The use of high-risk renal grafts for transplantation requires the optimization of pretransplant assessment and preservation reconditioning strategies to decrease the organ discard rate and to improve short- and long-term clinical outcomes. Active oxygenation is increasingly recognized to play a central role in dynamic preservation strategies, independent of preservation temperature, to recondition mitochondria and to restore the cellular energy profile. The oxygen-related decrease in mitochondrial succinate accumulation ameliorates the harmful effects of ischemia-reperfusion injury.

Kidney Transplantation From Deceased Donors With Vaccine-induced Immune Thrombocytopenia and Thrombosis: An Updated Analysis of the UK Experience.

Background: The emergence and attendant mortality of vaccine-induced immune thrombocytopenia and thrombosis (VITT) as a consequence of vaccination against severe acute respiratory syndrome coronavirus 2 have resulted in some patients with VITT being considered as deceased organ donors. Outcomes after kidney transplantation in this context are poorly described. Because the disease seems to be mediated by antiplatelet factor 4 antibodies, there is a theoretical risk of transmission via passenger leukocytes within the allograft.

Simply Adding Oxygen during Hypothermic Machine Perfusion to Combat the Negative Effects of Ischemia-Reperfusion Injury: Fundamentals and Current Evidence for Kidneys.

The use of high-risk renal grafts for transplantation requires optimization of pretransplant preservation and assessment strategies to improve clinical outcomes as well as to decrease organ discard rate. With oxygenation proposed as a resuscitative measure during hypothermic machine preservation, this review provides a critical overview of the fundamentals of active oxygenation during hypothermic machine perfusion, as well as the current preclinical and clinical evidence and suggests different strategies for clinical implementation.

Macroscopic assessment of the quality of cold perfusion after deceased-donor kidney procurement: A United Kingdom population-based cohort study.

Concern regarding the quality of cold perfusion (QOP) during macroscopic assessment of procured kidneys is a common reason for discard. In the UK, QOP is routinely graded by both retrieving and implanting teams during back-bench surgery as: 1 (good), 2 (fair), 3 (poor) or 4 (patchy). We evaluated the association of this grading with organ utilization, graft outcomes, and agreement between teams.

Recipient Sex Differences in Kidney Graft Survival Are Influenced by Donor Sex and Recipient Age.

Objectives: An age-dependent interaction has been described for the effect of donor-recipient sex mismatch on outcomes after kidney transplant in the United States. However, this has not been verified or tested in a different cohort from another country.

Materials And Methods: Data of 25 140 deceased donor kidney transplant recipients (2000-2016) were retro-spectively analyzed at a population-cohort level using the United Kingdom transplant registry.

Kidney transplantation outcomes for adult recipients of pediatric donor kidneys.

Despite a paucity of data assessing transplantation of deceased-donor pediatric donor kidneys into adult recipients, utilization of pediatric organs is declining in the UK, likely due to concerns that such organs may have inferior outcomes. However, we hypothesized that these concerns may be unfounded. As such, the aim of the study was to compare kidney transplant outcomes between adult recipients of pediatric and adult deceased-donor organs.

Brief O uploading during continuous hypothermic machine perfusion is simple yet effective oxygenation method to improve initial kidney function in a porcine autotransplant model.

With oxygenation proposed as a resuscitative measure during hypothermic models of preservation, the aim of this study was to evaluate the optimal start time of oxygenation during continuous hypothermic machine perfusion (HMP). In this porcine ischemia-reperfusion autotransplant model, the left kidney of a ±40 kg pig was exposed to 30 minutes of warm ischemia prior to 22 hours of HMP and autotransplantation. Kidneys were randomized to receive 2 hours of oxygenation during HMP either at the start (n = 6), or end of the perfusion (n = 5) and outcomes were compared to standard, nonoxygenated HMP (n = 6) and continuous oxygenated HMP (n = 8).

Influence of Different Partial Pressures of Oxygen During Continuous Hypothermic Machine Perfusion in a Pig Kidney Ischemia-reperfusion Autotransplant Model.

Background: The optimal perfusate partial pressure of oxygen (PO2) during hypothermic machine perfusion (HMP) is unknown. The aims of the study were to determine the functional, metabolic, structural, and flow dynamic effects of low and high perfusate PO2 during continuous HMP in a pig kidney ischemia-reperfusion autotransplant model.

Methods: The left kidneys of a ±40 kg pigs were exposed to 30 minutes of warm ischemia and randomized to receive 22-hour HMP with either low perfusate PO2 (30% oxygen, low oxygenated HMP [HMPO2]) (n = 8) or high perfusate PO2 (90% oxygen, HMPO2high) (n = 8), before autotransplantation.

Donor-recipient Sex Differences Do Not Affect Survival Outcomes After Kidney Transplantation: A Population Cohort Study.

Background: Donor factors can influence decision making for organ utilization for potential kidney transplant candidates. Prior studies exploring the effect of donor-recipient sex matching on kidney transplant outcomes have reported heterogenous and conflicting results. The aim of this contemporary population-cohort analysis was to explore the effect of donor-recipient sex matching on kidney transplant outcomes in the United Kingdom.

Recipient Outcomes From Nondirected Live Kidney Donors: A UK-based Cohort Study.

Background: Increasing numbers of patients with end-stage renal failure are receiving kidneys from nondirected kidney donors (NKDs), also known as altruistic donors. Transplant outcomes for recipients of such kidneys are largely inferred from studies on specified kidney donors (SKDs), which may be inaccurate due to differences in donor, recipient and transplant specific factors. We report the outcomes for recipients of NKD in the United Kingdom.

Repatriation of Patients to Referral Centers and Outcomes After Kidney Transplantation: A Single-center Analysis From the United Kingdom.

Background: The aim of this study was to compare posttransplant outcomes of kidney allograft recipients between those followed up at transplant centers and those that were repatriated back to referral renal units.

Methods: We analyzed data for 1375 consecutive patients transplanted in a single center in the United Kingdom. Patients were stratified into 3 groups: (1) externally referred patients with repatriation back for external follow-up (repatriated, n = 463), (2) externally referred patients not repatriated and followed-up internally at transplant center (nonrepatriated, n = 365), and (3) internally referred patients within transplant center with continued internal transplant center follow-up (internal, n = 547).

The Influence of Donor to Recipient Size Matching on Kidney Transplant Outcomes.

Background: Nephron endowment in renal transplantation is infrequently considered, but may have important implications for post kidney transplantation outcomes. In this population-cohort study, we analyzed the deceased-donor kidney transplant outcomes stratified by donor-to-recipient size ratios.

Methods: Data for all deceased-donor adult kidney transplantation recipients between 2003 and 2015 were extracted from the UK Transplant Registry.

The Effects of Oxygenation on Ex Vivo Kidneys Undergoing Hypothermic Machine Perfusion.

Background: Supplemental oxygenation of the standard hypothermic machine perfusion (HMP) circuit has the potential to invoke favorable changes in metabolism, optimizing cadaveric organs before transplantation.

Methods: Eight pairs of porcine kidneys underwent 18 hours of either oxygenated (HMP/O2) or aerated (HMP/Air) HMP in a paired donation after circulatory death model of transplantation. Circulating perfusion fluid was supplemented with the metabolic tracer universally labeled glucose.

Black Ethnicity is Not a Risk Factor for Mortality or Graft Loss After Kidney Transplant in the United Kingdom.

Objectives: There are conflicting reports in the literature regarding outcomes after kidney transplant for patients of black ethnicity. To investigate further, we compared outcomes for black versus white kidney transplant recipients in a single UK transplant center.

Materials And Methods: We analyzed 1066 kidney transplant recipients (80 black patients, 986 white patients) within a single-center cohort (2007-2017) in the United Kingdom, with cumulative 4446 patient-year follow-up.

Hypoalbuminaemia at time of surgery is associated with an increased risk for overall graft loss after kidney transplantation.

Aim: The aim of this retrospective cohort study was to investigate whether pre-operative hypoalbuminaemia (<35 g/L) is associated with adverse outcomes post-kidney transplantation.

Methods: Our retrospective, single-centre analysis included all patients who received their kidney transplant between 2007 and 2017, with documented admission albumin levels prior to surgery. Survival analyses were undertaken to explore the relationship of pre-transplant hypoalbuminaemia versus other baseline variables upon post-transplant outcomes.

Deceased-Donor Smoking History Is Associated With Increased Recipient Mortality After Kidney Transplant: A Population-Cohort Study.

Objectives: Historical data have suggested that donor smoking is associated with detrimental clinical outcomes for recipients of kidneys from deceased donors. However, the effects of smoking status of a kidney donor on the outcomes of the recipient in a contemporary setting of immunosuppression and transplant practice have not yet been ascertained.

Materials And Methods: This retrospective, population-cohort study analyzed data of all deceased-donor kidney-alone transplant procedures performed in the United Kingdom between April 2001 and April 2013.

The impact of donor body mass index on outcomes after deceased kidney transplantation - a national population-cohort study.

The aim of this study was to determine the effect of donor body mass index (BMI) on deceased donor kidney transplant outcomes. Data were collected from the UK Transplant Registry for all deceased donor kidney transplant recipients between January 2003 and January 2015. Univariable and multivariable analyses were undertaken to assess the impact of donor BMI on a range of outcomes.

Ethnicity matching and outcomes after kidney transplantation in the United Kingdom.

Background: Kidneys from non-white donors have inferior outcomes, but it is unclear if ethnicity matching between donors and recipients achieves better post kidney transplant outcomes.

Methods: We undertook a retrospective, population cohort study utilising UK Transplant Registry data. The cohort comprised adult, kidney-alone, transplant recipients receiving their first kidney transplant between 2003-2015, with data censored at 1st October 2016.

Mortality risk after cancer diagnosis in kidney transplant recipients: the limitations of analyzing hospital administration data alone.

Administrative data are frequently used for epidemiological studies but its usefulness to analyze cancer epidemiology after kidney transplantation is unclear. In this retrospective population-based cohort study, we identified every adult kidney-alone transplant performed in England (2003-2014) using administrative data from Hospital Episode Statistics. Results were compared to the hospitalized adult general population in England to calculate standardized incidence and mortality ratios.

Outcomes of donation after circulatory death kidneys undergoing hypothermic machine perfusion following static cold storage: A UK population-based cohort study.

Evidence is currently lacking regarding the outcomes of kidneys undergoing hypothermic machine perfusion (HMP) in patients in the United Kingdom. Using the National Health Service Blood and Transplant database, the authors compared outcomes for recipients of single-organ donation after circulatory death (DCD) kidneys preserved with HMP with those preserved using only static cold storage (SCS). Between 2007 and 2015, HMP was used in 19.

Smoking History Is Associated With Adverse Outcomes for Kidney Allograft Recipients.

Objectives: Donor kidney measurements may affect outcomes of transplanted allografts. We tested allograft and recipient measurements on kidney allograft outcomes. In this study, we compared the effects of kidney allograft volumes, which were measured using computed tomographic angiography before transplant, and allograft weight, which was measured during surgery, in relation to the recipient's body weight and body mass index on kidney function at 6 and 12 months after transplant.

Do outcomes after kidney transplantation differ for black patients in England versus New York State? A comparative, population-cohort analysis.

Objectives: Inferior outcomes for black kidney transplant recipients in the USA may not be generalisable elsewhere. In this population cohort analysis, we compared outcomes for black kidney transplant patients in England versus New York State.

Design: Retrospective, comparative, population cohort study utilising administrative data registries.

Cancer-related outcomes in kidney allograft recipients in England versus New York State: a comparative population-cohort analysis between 2003 and 2013.

It is unclear whether cancer-related epidemiology after kidney transplantation is translatable between countries. In this population-cohort study, we compared cancer incidence and all-cause mortality after extracting data for every kidney-alone transplant procedure performed in England and New York State (NYS) between 2003 and 2013. Data were analyzed for 18,493 and 11,602 adult recipients from England and NYS respectively, with median follow up 6.