Background Although considered the best means of providing haemodialysis, arteriovenous fistulas (AVFs) may increase long-term cardiovascular morbidity and mortality because of the low peripheral resistance and high cardiac output that develops. We assessed whether a randomised controlled trial (RCT) examining the cardiovascular impact of AVF ligation in stable renal transplant patients was feasible. Methods A parallel two-arm, non-blinded, feasibility trial enrolled forty consenting adult kidney recipients with a patent AVF and with good transplant function (estimated Glomerular Filtration Rate > 35 mL/min/1.73m 2 ) from six UK centres. At baseline, each had maximal oxygen consumption (peak VO 2 ) quantified by cardiopulmonary exercise testing (CPET), and activity levels and other quality of life (QoL) domains assessed by wrist accelerometry and Short Form-36 questionnaire responses. Participants were randomised by a web response system in a 1:1 ratio to surgical disconnection of their AVF (intervention) or to continued conservative management (standard care), stratified according to AVF site (wrist or elbow) and AVF volume flow (low or high). The assessments were repeated six months later. The primary outcome measure was the proportion of approached patients who completed the study, with pre-determined red-amber-green criteria determining progression to the main study. Secondary non-blinded clinical outcome measures included: peak VO 2 ; physical functioning (SF-36 score); total activity levels (mg/day); N-terminal pro B-type natriuretic peptide (NT-proBNP – higher values indicating myocardial overstretch). Key findings The target 40 patients were recruited to the trial and randomised. However, only 27 (67.5%) received the allocated intervention and completed both CPETs, with 7 of 20 (35%) randomised to AVF disconnection not undergoing surgery, below the predetermined completion rate required for trial progression. Compliance to wearing the wrist accelerometers was generally much better. With regards secondary outcome measures, neither peak VO 2 (the proposed primary end-point for the main RCT) nor accelerometry activity levels were increased following AVF disconnection. There were, however, apparent improvements in 6-monthly NT-proBNP levels and physical functioning scores. Conclusions Although based on small numbers of participants, AVF ligation may be associated with improvements in physical functioning and NT-proBNP values. However, the much higher rates of participant drop-out than anticipated (particularly for the intervention group) would make successful delivery of the proposed RCT extremely challenging, with impractically large numbers of participants required. Alternative study designs should be considered. Trial registration number ISRCTN49033491. Trial Funding: National Institute for Health Research (NIHR) Research for Patient Benefit Funding grant (NIHR202255).

Textbook outcome is a composite measure reflecting an ideal perioperative course by integrating multiple care-quality indicators. While its use has been reported internationally for non-small cell lung cancer (NSCLC) resection, it has not previously been evaluated in the Australian setting. This study aimed to determine the proportion of patients achieving a textbook outcome after NSCLC resection, identify the components that most commonly prevented its attainment, and evaluate its association with long-term overall survival. A retrospective cohort study was conducted of adults undergoing lung resection for primary NSCLC at a tertiary Australian centre (2011–2023). Textbook outcome was defined according to the Dutch Lung Cancer Audit–Surgery criteria, requiring negative margins, complete lymph node dissection, absence of major complications, no 30-day mortality or reintervention, no prolonged ICU/high-dependency stay, no prolonged hospitalisation, and no readmission. Multivariable logistic regression identified predictors of textbook outcome, and Kaplan–Meier analysis was used to assess long-term survival. Of 731 patients, 163 (22.3

Complement activation during clinical kidney normothermic machine perfusion (NMP) is poorly defined. We examined whether perfusate complement biomarkers measured during prolonged NMP were associated with early graft recovery. Samples and outcome data were obtained from the NKP1 phase 1 trial of prolonged kidney NMP before transplantation (n=36). Perfusate C1s, collectin-11, C2, C3, C3d, factor B, Ba and soluble C5b-9 were measured at Hour 1 and end perfusion. Associations with functional delayed graft function (fDGF) and time to 50% fall in serum creatinine (TCr50) were assessed using nonparametric testing, Kaplan-Meier analysis and Cox models incorporating UK donor risk index (UKDRI). Paired pre-perfusion and post-reperfusion biopsies underwent multiplex immunofluorescence for C4d, C5b-9 and ICAM-1. C1s, collectin-11, C3d and soluble C5b-9 increased during NMP, whereas C2 and factor B decreased. Kidneys developing fDGF had higher end-perfusion soluble C5b-9 and Hour-1 C3, both significant after false discovery rate correction. Complement profiles stratified TCr50, including within UKDRI strata, and an Hour-1 grouping improved Cox model fit beyond UKDRI alone. Postreperfusion tissue C5b-9 and ICAM-1 increased, whereas C4d did not. Complement activation during prolonged NMP is associated with early graft outcomes and may support biomarker-guided assessment and future targeted intervention in clinical kidney transplantation practice.

Published Donor Risk Indices are often used to estimate the risk associated with transplanting a donor liver. Such indices have been constructed by considering only livers that are transplanted and estimating the risk of graft loss or patient death. Until now, there has been no index available that reflects the chance of an offered organ not being transplanted in the United Kingdom (UK). This paper presents a UK Donor Utilisation Index (UKDUI) which quantifies the impact of donor factors upon liver non-use. By comparing our developed UKDUI with a commonly used UK Donor Risk Index, we are able to see that there are differences between the factors that influence liver non-use and the factors that influence liver post-transplant outcomes. Importantly, this UKDUI can be used in future studies to characterise and identify offered livers that are either more or less likely to be transplanted. For example, the UKDUI can be used for study inclusion criteria or for risk adjustment/stratification.

Background:Pre-implantation biopsy may help select kidneys retrieved from elderly deceased donors for transplantation, but concerns persist that it may cause unnecessary discard of kidneys that would have provided acceptable transplant function. The PITHIA trial tested the hypothesis that introduction of a National Digital Pathology Service (NDPS) would increase the proportion of kidneys transplanted from elderly donors and/or improve their function. Methods:A stepped-wedge cluster randomised controlled registry trial delivered the NDPS to 22 UK kidney transplant centres (clusters) in 5 sequences at four-monthly intervals, using a restricted randomisation technique to ensure similar cluster sizes in the intervention and control status. Upon access to the intervention, centres could request urgent pre-implantation biopsy on kidneys from deceased donors aged 60 years or older. Co-primary outcome measures were the proportion of kidneys transplanted upon first offer according to whether the centre had access or not to the biopsy service, and the 1-year eGFR of the kidneys that were transplanted. Analysis adjusts for clustering and underlying secular trends, with 97.5% Confidence Intervals (CI) reported to reflect the two co-primary outcomes. The trial is complete (Trial Registration Number: ISRCTN 11708741). Findings:The trial commenced on 1st October 2018 and ended on 31st January 2022. Of the 2502 eligible kidneys offered, 1355 single and 67 dual transplants were performed. Regarding the first primary endpoint, a non-significantly lower proportion of those kidneys first offered to centres with access to the biopsy service were transplanted compared with those offered to centres without access (295 of 1241 (23.8%) vs. 377 of 1261 (29.9%): adjusted Odds Ratio (97.5% CI) 0.91 (0.60-1.39); p = 0.6083). For the second primary endpoint, the adjusted mean (SE) 1-year eGFR of the transplant kidneys was similar, irrespective of whether the implanting centre had access to the biopsy service or not (43.7 (1.3) ml/min/1.73 m2 vs. 42.2 (1.3) ml/min/1.73 m2; adjusted mean difference (97.5% CI) 1.53 (-2.33 to 5.40); p = 0.37). Secondary outcome analysis of how the biopsy service was adopted revealed that biopsies were performed on 287 of the 1493 (19.2%) kidneys offered to at least one centre with access to the biopsy service, with marked variation between transplant centres in requests for biopsy, and in implantation rates of biopsied kidneys. Nevertheless, 191 (66.6%) of biopsied kidneys were transplanted, compared with 643 of the 1009 (63.7%) kidneys only ever offered to centres without biopsy access, and 588 of the 1206 (48.8%) kidneys that were not biopsied, despite being offered to at least one centre with biopsy access. Interpretation:Implementation of the NDPS did not significantly increase transplantation rates of elderly deceased donor kidneys upon first offer, nor improve 1-year eGFR of the transplanted kidneys. This may reflect inter-centre variation in adoption and application of the biopsy service; such variations would need to be considered when designing future studies of pre-implantation biopsy analysis. Funding:NIHR Research for Patient Benefit programme (RfPB PB-PG-1215-20033).

Surgical trauma elicits a complex inflammatory stress response, contributing to postoperative morbidity and recovery variability. This response is influenced by patient-specific factors and surgical and anesthetic techniques. To isolate the impact of anesthesia on the acute phase response, we investigated plasma proteomic changes in a uniquely homogeneous cohort of healthy, living kidney donors (n = 36; propofol = 19; sevoflurane = 17) undergoing laparoscopic donor nephrectomy. Proteomic profiling of plasma samples collected preoperatively and at 2 and 24 h postoperatively revealed 633 quantifiable proteins, of which 22 showed significant perioperative expression changes. Eight proteins exhibited over two-fold increases, primarily related to the acute phase response (CRP, SAA1, SAA2, LBP), tissue repair (FGL1, A2GL), and anti-inflammatory regulation (AACT). These changes were largely independent of anesthetic type, though SAA2 and MAN1A1 showed anesthetic-specific expression. The upregulation of these proteins implicates the activation of immune pathways involved in host defense, tissue remodeling, and inflammation resolution. Our findings provide a molecular reference for the surgical stress response in healthy individuals and highlight candidate biomarkers for predicting and managing postoperative outcomes. Understanding these pathways may support the development of strategies to mitigate surgical stress and enhance recovery, particularly in vulnerable patient populations.

Normothermic machine perfusion of the kidney (NMP-K) is a technique for ex-situ preservation, assessment, and treatment of kidneys prior to transplantation. We have previously reported a phase 1 trial (NKP1) showing that up to 24 hours of NMP-K appears to be safe, feasible, and that ex-situ NRF-2 modulation may be of benefit. Nitric oxide (NO) is a potent inducer of NRF2 and has been shown to halve the rate of acute kidney injury after cardiopulmonary bypass. We therefore sought to develop and test a paradigm for NO treatment during NMP-K. Six pairs of porcine kidneys were retrieved and assigned at random to perfusion with NO administered at 40ppm via the oxygenator, or standard NMP-K. Five human kidneys deemed unsuitable for transplantation were perfused with a modified protocol involving treatment with NO, and co-administration of N-acetylcysteine and ascorbic acid. Comparisons were made to matched controls from NKP1. In the NKP1 cohort, IL-18 measured at hour 2 was associated with delayed graft function, and GST-Pi upregulation with good 12-month graft function. NO administration to porcine kidneys raised intracellular cGMP, enhanced GST-Pi, and suppressed IL-18. In discarded human kidneys, despite much longer cold ischaemia times than matched transplanted controls, GST-Pi appeared upregulated by NO treatment. Untargeted metabolomics (n=1) demonstrated replenishment of intracellular glutathione. However, IL-18 production was not suppressed. NO administration during NMP-K positively modulates ex-situ biomarkers. Pre-perfusion CIT has a profound effect on ex-situ assessment and treatment. NO delivery during NMP-K should be evaluated in a clinical trial.

Background Lung resection surgery is a common procedure in the treatment of lung cancer. It has been associated with a high cost burden, with complications considered a substantial contributor to associated expenses. This review sought to understand and describe the financial burden associated with complications of lung resection surgery. Methods Key databases (Ovid MEDLINE and Embase, Cochrane CENTRAL) were searched up to 14 October 2024. Studies reporting on costs of at least one complication of lung resection surgery, including lobectomy, wedge resection, segmentectomy, sleeve resection, pneumonectomy, or a combination of these, were included. Following identification of eligible articles, all relevant data were extracted. Quality assessment tools, including the Scottish Intercollegiate Guidelines Network Checklists for Economic Evaluations and Cohort Studies and the Risk Of Bias In Non-randomized Studies—of Interventions tool, were used to confirm articles for inclusion. Results In all, 31 articles were identified for inclusion: 2 prospective and 29 retrospective studies. All lung-specific complications and all but one non-pulmonary complication were associated with increased hospitalization costs. Hospital expenses also increased with increasing numbers and grades of complications. Conclusion Substantial variation in the definitions of costs and complications across studies has rendered a comparison of findings between studies challenging. Greater uniformity in definitions and classifications of costs and complications in future studies will facilitate further characterization of the cost burden of specific complications.

BACKGROUND:Up to 50% of kidney transplant patients are diagnosed with delayed graft function (DGF) following transplantation-the majority being linked to ischaemia reperfusion injury (IRI). DGF is traditionally defined as the requirement for dialysis during the first week after transplantation and is associated with inferior graft and patient outcomes. Local synthesis of complement components, largely by the renal tubule, plays a critical role in IRI. We have developed Mirococept, a membrane-targeted complement inhibitor, that can be administered to the donor kidney ex vivo prior to transplantation. After administration, Mirococept is retained in the donor organ, thereby minimising the risk of systemic side effects. We previously launched the EMPIRIKAL study aiming to evaluate the efficacy of Mirococept in reducing DGF in deceased-donor kidney transplantation (KT). The funding body recommended termination of the study to allow a dose-saturating study before the next stage of clinical evaluation. This was carried out in a porcine kidney model and led to a revised dosing regimen for EMPIRIKAL-2 (60-180 mg compared with 5-25 mg in the initial trial). The EMPIRIKAL-2 trial (REC 24/NE/0071) aims to identify the most safe and efficacious dose of Mirococept to reduce DGF rate in deceased-donor KT. METHODS AND ANALYSIS:EMPIRIKAL-2 is a Phase IIa multicentre double-blind randomised controlled trial (RCT) with an initial safety run. Participants will be recruited from renal departments at National Health Service tertiary hospital sites in the UK. The purpose of the safety run is to assess the tolerance of each of the three proposed Mirococept doses (60, 120 or 180 mg), before the RCT begins. Three patients will be assigned to each treatment dose, starting from the lower dose. The safety run will be considered successful if at least one dose can be taken forward to the RCT for comparison to placebo.If safety is met, 144 participants (36 per arm excluding drop-outs) will be randomised to all doses meeting the safety criteria or placebo on a 1:1:1:1 basis. The primary endpoint is DGF, defined as the requirement for dialysis during the first week after transplantation. Safety evaluation will include the monitoring of laboratory data and the recording of all adverse events. Immunosuppression therapy, antibiotic and antiviral prophylaxis will be administered as per local centre protocols. Enrolment in the RCT is anticipated to take approximately 12 months, and patients will be followed-up for 12 months. ETHICS AND DISSEMINATION:The study has been approved by the Northeast - Newcastle and North Tyneside 2 Research Ethics Service Committee, REC reference 24/NE/0071. The results of the study will be reported and disseminated at international conferences and in peer-reviewed scientific journals. Once published, a lay summary of the results will be made available to participants who request this information. TRIAL REGISTRATION NUMBER:ISRCTN14279222. Registered on 4 July 2024. PROTOCOL VERSION:2.0 dated 9 May 2024.

To keep the transplantation community informed about recently published level 1 evidence in organ transplantation ESOT and the Centre for Evidence in Transplantation have developed the Transplant Trial Watch. The Transplant Trial Watch is a monthly overview of 10 new randomised controlled trials (RCTs) and systematic reviews. This page of Transplant International offers commentaries on methodological issues and clinical implications on 2 articles article of particular interest from the CET Transplant Trial Watch monthly selection. For all high quality evidence in solid organ transplantation, visit the Transplant Library: www.transplantlibrary.com.

Kidney transplantation is the preferred treatment for end-stage renal disease and is limited by donor organ availability. Normothermic Machine Perfusion (NMP) might facilitate safe transplantation of marginal organs. NKP1 is a single centre, phase 1, 36-patient, three-stage cohort study investigating the safety and feasibility of up to 24 hours of renal NMP prior to transplantation. 30-day graft survival (primary endpoint) was 100%. Secondary objectives were assessment of the effect of NMP on post-transplant clinical outcomes and ischaemia-reperfusion injury, identification of predictive biomarkers, and characterisation of the performance of the preservation system. Clinical outcomes were comparable to a matched control cohort with 12-month estimated glomerular filtration rate (eGFR) 46.3 vs 49.5 mL/min/1.73m2 (p = 0.44) despite much longer total preservation times (15.7 vs 8.9 hours controls, p < 0.0001). We saw strong correlations between biomarkers measured ex-situ and post-transplant outcomes, including graft function at one year (correlation between GST-Pi delta and 12-month eGFR, R = 0.54, p = 0.001). Renal NMP is useful for optimising logistics and as an organ assessment technique, and has potential to expand the donor pool. Trial registration number: ISRCTN13292277.

Deceased donor kidney transplantation is often the only treatment for patients in end-stage renal disease and other life-threatening conditions. Kidney transplant processes can be fraught with uncertainty for both clinicians making critical decisions about whether to transplant an organ and the kidney recipients. There is potential for AI-informed software-based systems to support the activities of information-giving, decision-making, and waiting. This study analyses qualitative interviews to explore the user perspectives including those of both clinicians and transplant patients regarding this kind of decision making aid. Fourteen kidney transplant recipients and ten clinicians were recruited in a U.K transplant centre clinic. Data was collected via face-to-face and video-recorded semi-structured interviews and was analysed using a modified grounded-theory approach. Two patient themes were generated: 'The murky waters of AI' and 'AI-driven tools could help transplant patients.' The clinician themes included: 'Understanding AI and the general perception around this technology,' and 'AI can be a friend to call on.' The results highlight the possibility of an AI software programme to explain complex ideas to patients, by providing visual and graphical representations of AI-powered, individualised survival calculations or organ wait list times. The design and implementation of such tools must centre around trust in AI technology for clinicians and patients. The balance of staying on the waiting list or accepting an organ involves many complex factors but using AI-informed technology would be welcomed by patients and clinicians.

Survival analysis, which estimates the probability of event occurrence over time from censored data, is fundamental in numerous real-world applications, particularly in high-stakes domains such as healthcare and risk assessment. Despite advances in numerous survival models, quantifying the uncertainty of predictions from these models remains underexplored and challenging. The lack of reliable uncertainty quantification limits the interpretability and trustworthiness of survival models, hindering their adoption in clinical decision-making and other sensitive applications. To bridge this gap, in this work, we introduce SurvUnc, a novel meta-model based framework for post-hoc uncertainty quantification for survival models. SurvUnc introduces an anchor-based learning strategy that integrates concordance knowledge into meta-model optimization, leveraging pairwise ranking performance to estimate uncertainty effectively. Notably, our framework is model-agnostic, ensuring compatibility with any survival model without requiring modifications to its architecture or access to its internal parameters. Especially, we design a comprehensive evaluation pipeline tailored to this critical yet overlooked problem. Through extensive experiments on four publicly available benchmarking datasets and five representative survival models, we demonstrate the superiority of SurvUnc across multiple evaluation scenarios, including selective prediction, misprediction detection, and out-of-domain detection. Our results highlight the effectiveness of SurvUnc in enhancing model interpretability and reliability, paving the way for more trustworthy survival predictions in real-world applications.

The decision to accept a deceased donor organ offer for transplant, or wait for something potentially better in the future, can be challenging. Clinical decision support tools predicting transplant outcomes are lacking. This project uses interpretable methods to predict both graft failure and patient death using data from previously accepted kidney transplant offers. Using more than 25 years of transplant outcome data, we train and compare several survival analysis models in single risk settings. In addition, we use post hoc interpretability techniques to clinically validate these models. Neural networks show comparable performance to the Cox proportional hazard model, with concordance of 0.63 and 0.79 for prediction of graft failure and patient death, respectively. Donor and recipient ages, the number of mismatches at DR locus, dialysis type, and primary renal disease appear to be important features for transplant outcome prediction. Owing to their good predictive performance and the clinical relevance of their post hoc interpretation, neural networks represent a promising core component in the construction of future decision support systems for transplant offering.

Introduction Extrapleural pneumonectomy (EPP) and extended pleurectomy/decortication (ePD) are surgical cytoreductive techniques aimed at achieving macroscopic resection in malignant pleural tumours such as pleural mesothelioma, non-mesothelioma pleural malignancies such as thymoma and sarcoma, and rarely for pleural tuberculosis, in a more limited fashion. Despite extensive studies on both surgical techniques and consequences, a significant knowledge gap remains regarding how best to approach the perioperative anaesthesia challenges for EPP and ePD.It is unknown if the risk stratification processes for such surgeries are standardised or what types of functional and dynamic cardiac and pulmonary tests are employed preoperatively to assist in the perioperative risk stratification. Further, it is unknown whether the types of anaesthesia and analgesia techniques employed, and the types of haemodynamic monitoring tools used, impact on outcomes. It is also unknown whether individualised haemodynamic protocols are used to guide the rational use of fluids, vasoactive drugs and inotropes.Finally, there is a dearth of evidence regarding how best to monitor these patients postoperatively or what the most effective enhanced recovery protocols are to best mitigate postoperative complications and accelerate hospital discharge. To increase our knowledge of the perioperative and anaesthetic treatment for patients undergoing EPP/ePD, this scoping review attempts to synthesise the literature and identify these knowledge gaps.Methods and analysis This scoping review will be conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Extension for Scoping Review Protocols methodology. Electronic databases, OVID Medline, EMBASE and the Cochrane Library, will be systematically searched for relevant literature corresponding to EPP or ePD and perioperative or anaesthetic management. Data will be analysed and summarised descriptively and organised according to the three perioperative stages: preoperative, intraoperative and postoperative factors in clinical care.Ethics and dissemination Ethics approval was not required. The findings will be disseminated through professional networks, conference presentations and publications in scientific journals.

BACKGROUND:Liver disease is the third leading cause of premature death in the UK. Transplantation is the only successful treatment for end-stage liver disease but is limited by a shortage of suitable donor organs. As a result, up to 20% of patients on liver transplant waiting lists die before receiving a transplant. A third of donated livers are not suitable for transplant, often due to steatosis. Hepatic steatosis, which affects 33% of the UK population, is strongly associated with obesity, an increasing problem in the potential donor pool. We have recently tested defatting interventions during normothermic machine perfusion (NMP) in discarded steatotic human livers that were not transplanted. A combination of therapies including forskolin (NKH477) and L-carnitine to defat liver cells and lipoprotein apheresis filtration were investigated. These interventions resulted in functional improvement during perfusion and reduced the intrahepatocellular triglyceride (IHTG) content. We hypothesise that defatting during NMP will allow more steatotic livers to be transplanted with improved outcomes. METHODS:In the proposed multi-centre clinical trial, we will randomly assign 60 livers from donors with a high-risk of hepatic steatosis to either NMP alone or NMP with defatting interventions. We aim to test the safety and feasibility of the defatting intervention and will explore efficacy by comparing ex-situ and post-reperfusion liver function between the groups. The primary endpoint will be the proportion of livers that achieve predefined functional criteria during perfusion which indicate potential suitability for transplantation. These criteria reflect hepatic metabolism and injury and include lactate clearance, perfusate pH, glucose metabolism, bile composition, vascular flows and transaminase levels. Clinical secondary endpoints will include proportion of livers transplanted in the two arms, graft function; cell-free DNA (cfDNA) at follow-up visits; patient and graft survival; hospital and ITU stay; evidence of ischemia-reperfusion injury (IRI); non-anastomotic biliary strictures and recurrence of steatosis (determined on MRI at 6 months). DISCUSSION:This study explores ex-situ pharmacological optimisation of steatotic donor livers during NMP. If the intervention proves effective, it will allow the safe transplantation of livers that are currently very likely to be discarded, thereby reducing waiting list deaths. TRIAL REGISTRATION:ISRCTN ISRCTN14957538. Registered in October 2022.

Abstract Background The storage lesion is a multifactorial degradation effect seen in units of banked blood, and results in an increase in the time-constant of oxygen-unloading from red cells (tau). We have previously shown the relevance of this effect in observational data from a recent clinical trial of prolonged normothermic kidney perfusion as a preservation technique ahead of transplantation. We sought direct confirmatory evidence for diffusion-limited oxygen release by stored red cells (RBCs) during normothermic kidney perfusion in a precisely controlled experimental setting. Methods A novel twinned-circuit kidney perfusion system using common, recirculated dialysis was developed, achieving physical separation of RBCs of two conditions whilst allowing non-cellular components of the perfusate to equilibrate throughout. Using human kidneys unsuitable for transplantation, perfusion was alternated between stored and rejuvenated RBCs (treated with PIPA solution) originating from the same donation, to manipulate oxygen-unloading whilst holding all non-RBC parameters constant, without interrupting blood flow. Results Tau improved with PIPA treatment (1.6 to 1.1s). Rejuvenated oxygen-unloading kinetics reversibly and significantly improved the kidney’s oxygen diffusion capacity and increased cortical oxygen tension by 60%. This supported observations from our clinical trial, where increased tau was strongly associated with restricted renal oxygen consumption. Conclusions We have confirmed that oxygen delivery to tissues can become diffusion-limited during normothermic perfusion with stored blood. This effect is reversible by treatment with PIPA solution. This has important implications for ex-vivo normothermic organ perfusion, and potentially for other scenarios such as major hemorrhage, elective surgery with high blood product utilisation, and paediatric transfusion.