The living kidney donor profile index fails to discriminate allograft survival: implications for its use in kidney paired donation programs.

The inclusion of blood group- and human leukocyte antigen-compatible donor and recipient pairs (CPs) in kidney paired donation (KPD) programs is a novel strategy to increase living donor (LD) transplantation. Transplantation from a donor with a better Living Donor Kidney Profile Index (LKDPI) may encourage CP participation in KPD programs. We undertook parallel analyses using data from the Scientific Registry of Transplant Recipients and the Australia and New Zealand Dialysis and Transplant Registry to determine whether the LKDPI discriminates death-censored graft survival (DCGS) between LDs. Discrimination was assessed by the following: (1) the change in the Harrell C statistic with the sequential addition of variables in the LKDPI equation to reference models that included only recipient factors and (2) whether the LKDPI discriminated DCGS among pairs of prognosis-matched LD recipients. The addition of the LKDPI to reference models based on recipient variables increased the C statistic by only 0.02. Among prognosis-matched pairs, the C statistic in Cox models to determine the association of the LKDPI with DCGS was no better than chance alone (0.51 in the Scientific Registry of Transplant Recipient and 0.54 in the Australia and New Zealand Dialysis and Transplant Registry cohorts). We conclude that the LKDPI does not discriminate DCGS and should not be used to promote CP participation in KPD programs.

Cytoskeletal protein degradation in brain death donor kidneys associates with adverse posttransplant outcomes.

In brain death, cerebral injury contributes to systemic biological dysregulation, causing significant cellular stress in donor kidneys adversely impacting the quality of grafts. Here, we hypothesized that donation after brain death (DBD) kidneys undergo proteolytic processes that may deem grafts susceptible to posttransplant dysfunction. Using mass spectrometry and immunoblotting, we mapped degradation profiles of cytoskeletal proteins in deceased and living donor kidney biopsies. We found that key cytoskeletal proteins in DBD kidneys were proteolytically cleaved, generating peptide fragments, predominantly in grafts with suboptimal posttransplant function. Interestingly, α-actinin-4 and talin-1 proteolytic fragments were detected in brain death but not in circulatory death or living donor kidneys with similar donor characteristics. As talin-1 is a specific proteolytic target of calpain-1, we investigated a potential trigger of calpain activation and talin-1 degradation using human ex vivo precision-cut kidney slices and in vitro podocytes. Notably, we showed that activation of calpain-1 by transforming growth factor-ß generated proteolytic fragments of talin-1 that matched the degradation fragments detected in DBD preimplantation kidneys, also causing dysregulation of the actin cytoskeleton in human podocytes; events that were reversed by calpain-1 inhibition. Our data provide initial evidence that brain death donor kidneys are more susceptible to cytoskeletal protein degradation. Correlation to posttransplant outcomes may be established by future studies.

Development of ex situ normothermic reperfusion as an innovative method to assess pancreases after preservation.

Static cold storage (SCS) is the standard method for pancreas preservation prior to transplantation; however, it does not permit organ assessment. Normothermic reperfusion (NR) is utilized clinically for other organs to assess viability. Our aim was to develop NR using normothermic machine perfusion technique to simulate reperfusion at the time of transplantation, enabling evaluation of oxygenated hypothermic machine perfusion (HMPO2) as a newer strategy to optimize pancreas preservation. 13 porcine pancreases procured after circulatory death were divided into 3 groups: 4 pancreases preserved using SCS, and 2 groups preserved by HMPO2 (n = 4 and n = 5, differing by type of preservation solution). Duration of perfusion or cold storage was 6 hours before the 1-hour assessment using NR. Outcome measures were perfusion characteristics, biochemistry and change in tissue water mass as oedema assessment. During NR, the HMPO2 groups demonstrated better perfusion characteristics, normal macroscopic appearances, decreased water mass and one HMPO2 group demonstrated a response to glucose stimulation. Conversely, the SCS group showed an increased water mass and developed early macroscopic appearances of oedema, interstitial haemorrhage and minimal portal outflow. This study suggests that ex situ assessment of pancreases by NR is promising, and that HMPO2 may be better than SCS.

An analysis of the association between older recipient age and outcomes after whole-organ pancreas transplantation - a single-centre, retrospective study.

Older people are increasingly being referred for consideration for pancreas transplantation (PT). We investigated the outcomes after PT in our older recipient cohort. A prospectively maintained database was interrogated. The cohort was analysed for associations between outcome and older recipient age. A total of 444 transplants were performed in patients aged 23-54 years and 83 transplants in patients aged 55-67 years. There was no difference in death-censored pancreas or kidney graft survival between the groups. Patient death was associated with older recipient age (HR 1.63 per 10-year increase). In multivariate Cox regression, risk of mortality was also associated with post-transplant myocardial infarction (HR 7.25, P = 0.006), pancreas failure (HR 1.91, P = 0.003) and kidney failure (HR 3.55, P < 0.001). About 40% of recipients who died in the first year post-transplant suffered early graft loss. Those alive at a year post-transplant had inferior survival if they had lost their kidney graft (P < 0.001). Mortality is higher in older patients and is strongly associated with pancreas and kidney graft failure. This suggests that pancreas transplantation is feasible in older recipients, and careful selection of donor organs is important to optimize survival.

Early postoperative continuous glucose monitoring in pancreas transplant recipients.

Continuous glucose monitoring (CGM) is used in people with type 1 diabetes to help with insulin treatment regimens. Its value in whole-organ pancreas transplantation (PT) is largely unknown. This study aimed to use CGM to assess the metabolic profile of pancreas transplant recipients in the early post-transplant period. We studied CGM data in 30 PT recipients and related findings to an early oral glucose tolerance test (OGTT). Complete data were available for 26 recipients. Seven days after a PT, normoglycaemia was present 77.9% of the time. Hypoglycaemic events (glucose <3.9 mmol/l) occurred in 10 of 26 (38.5%) of the cohort, but were infrequent (present 1.4% of the time). Hyperglycaemia (glucose >7.8 mmol/l) was present for 20.7% of the study period and correlated with a diagnosis of abnormal glucose tolerance. Whilst normoglycaemia is successfully achieved for the majority of the time after PT, hypoglycaemia can occur. Hyperglycaemia is more common and correlates well with the early postoperative OGTT, which is associated with graft failure. CGM is easier to perform and provides 24-h data that could inform clinical decision-making in patients in the postoperative period.

Validation of the Pancreas Donor Risk Index for use in a UK population.

Pancreas graft failure rates remain substantial. The PDRI can be used at the time of organ offering, to predict one-year graft survival. This study aimed to validate the PDRI for a UK population. Data for 1021 pancreas transplants were retrieved from a national database for all pancreas transplants. Cases were categorized by PDRI quartile and compared for death-censored graft survival. Significant differences were observed between the UK and US cohorts. The PDRI accurately discriminated graft survival for SPK and was associated with a hazard ratio of 1.52 (P = 0.009) in this group. However, in the PTA and PAK groups, no association between PDRI quartile and graft survival was observed. This is the largest study to validate the PDRI in a European cohort and has shown for the first time that the PDRI can be used as a tool to predict graft survival in SPK transplantation, but not PTA or PAK transplantation.

Postoperative impaired glucose tolerance is an early predictor of pancreas graft failure.

AIMS/HYPOTHESIS: The management of pancreatic transplantation is limited by a lack of clinically relevant early markers of graft dysfunction to enable intervention prior to irreversible damage. The aim of this study was to assess the OGTT as an early predictor of pancreatic graft failure. METHODS: Patients with graft failure (return to insulin dependence) were identified from a prospectively maintained clinical database. Data from OGTTs performed within 2 weeks of the transplant were retrospectively collected for 210 subjects, 42 with graft failure (21 after simultaneous pancreas-kidney transplant and 21 after isolated pancreas transplant) matched to 168 with functioning grafts. The groups were compared to assess the relationship between early OGTT result and pancreas graft failure. RESULTS: Mean 2 h glucose from the OGTT was significantly higher in the overall graft failure group compared with the control group (8.36 vs 6.81 mmol/l, p = 0.014). When interpreted in combination with fasting glucose, abnormal glucose tolerance was more common in the failed graft group (50% vs 22%, p = 0.001). In an adjusted model, abnormal glucose tolerance emerged as the most predictive independent factor for graft failure, HR 1.66 (95% CI 1.22, 2.24), p = 0.001. These findings were consistent between the different transplant procedures performed. CONCLUSIONS/INTERPRETATION: We conclude that early post-transplant abnormal glucose tolerance is associated with later whole organ pancreas graft failure. An OGTT performed within the first month postoperatively provides an easily measurable assessment of an independent early risk factor of pancreatic graft dysfunction.

Improving monitoring after pancreas transplantation alone: fine-tuning of an old technique.

Graft survival after pancreas transplantation alone (PTA) is significantly poorer than graft survival after simultaneous pancreas kidney (SPK) and is particularly affected by difficulty in monitoring rejection. Exocrine bladder drainage allows assessment of pancreas graft function as urinary amylase (UA). However, standards for UA collection and interpretation are not well defined. In this study, 21 bladder-drained PTA recipients were monitored with daily values for UA and urine creatinine (Creat) concentration from post-transplant 10-mL samples and 24-h collections. Clinical events were documented and correlated to UA measurements. UA values were found to increase post-transplant until day 15, and large interpatient variability was noted (median 12 676 IU/L, range 668-60 369 IU/L). A strong correlation was found total 24-h UA production and spot UA/Creat ratio (r = 0.80, p < 0.001). UA/Creat ratio showed less variation during episodes of impaired renal function; therefore, urinary amylase baseline was defined as the median UA/Creat ratio after day 15. A > 25% decrease of UA predicted 9/13 (69%) events. We conclude that individual baselines should be set once the values have stabilized after 15 d post-transplant and that spot UA/Creat measures are reliable, patient friendly and indicate potential events after PTA.

Vessel rejection secondary to human leucocyte antigen antibodies directed against the arterial conduit following pancreas transplantation from a separate donor.

Whole-organ pancreas transplantation is typically carried out using a Y-graft derived from the donor iliac vessels. We describe a case in which a 31-year-old male underwent a simultaneous pancreas-kidney transplant, but in which vessels from a different donor were used for the arterial anastomosis of the pancreas graft. Although initially there was good function, 18 months post-transplant the patient was admitted with diabetic ketoacidosis secondary to pancreas graft failure. Radiological investigations revealed complete occlusion of the vascular Y-graft, and laboratory investigations demonstrated donor-specific human leucocyte antigen (HLA) antibodies directed against HLA mismatches of the vessel donor. This case highlights the risks of using allogeneic vascular material for surgical anastomoses.

Kidney Tissue Proteome Profiles in Short Versus Long Duration of Delayed Graft Function - A Pilot Study in Donation After Circulatory Death Donors.

Introduction: Delayed graft function (DGF) is often defined as the need for dialysis treatment in the first week after a kidney transplantation. This definition, though readily applicable, is generic and unable to distinguish between "types" of DGF or time needed to recover function that may also significantly affect longer-term outcomes. We aimed to profile biological pathways in donation after circulatory death (DCD) kidney donors that correlate with DGF and different DGF durations. Methods: A total of N = 30 DCD kidney biopsies were selected from the UK Quality in Organ Donation (QUOD) biobank and stratified according to DGF duration (immediate function, IF n = 10; "short-DGF" (1-6 days), SDGF n = 10; "long-DGF" (7-22 days), LDGF n = 10). Samples were matched for donor and recipient demographics and analyzed by label-free quantitative (LFQ) proteomics, yielding identification of N = 3378 proteins. Results: Ingenuity pathway analysis (IPA) on differentially abundant proteins showed that SDGF kidneys presented upregulation of stress response pathways, whereas LDGF presented impaired response to stress, compared to IF. LDGF showed extensive metabolic deficits compared to IF and SDGF. Conclusion: DCD kidneys requiring dialysis only in the first week posttransplant present acute cellular injury at donation, alongside repair pathways upregulation. In contrast, DCD kidneys requiring prolonged dialysis beyond 7 days present minimal metabolic and antioxidant responses, suggesting that current DGF definitions might not be adequate in distinguishing different patterns of injury in donor kidneys contributing to DGF.

App to reality: snapshot validation of the US Pancreas Donor Risk Index in a UK center.

BACKGROUND: A pancreas donor risk index (PDRI) has been derived by Axelrod et al. to inform organ acceptance and developed into a smartphone app by Marc Melcher. This paper aims to validate the app for use in a single UK transplant center through a snapshot of donors and outcomes during one calendar year. METHODS: Donor details for all pancreas transplants performed in 2011 were collected from a prospectively maintained clinical database to calculate a PDRI using the Pancreas Transplant Donor Risk Index smartphone app. RESULTS: Ninety pancreas transplants were included in the analysis (72 simultaneous pancreas kidney [SPK], 18 pancreas transplant alone [PTA]). PDRI scores were found to be positively skewed compared with donors described in the US literature. The PDRI was predictive of poorer 1-y graft outcome in the SPK group but not in the PTA group. PDRI was not predictive of time to failure or failure cause. CONCLUSION: Validation of the PDRI app against data from our center shows that it can be used as a tool to predict poorer graft outcome in the SPK group. However, it was not predictive in the PTA group, and differences in US and UK donor characteristics were evident. Development of a UK-specific PDRI may overcome these limitations.

Risk analysis for deterioration of renal function after pancreas alone transplant.

The risk of progression to renal replacement after pancreas transplant alone (PTA) is a concern in patients with pre-transplant estimated glomerular filtration rate (eGFR) < 70 mL/min/1.73 m(2). This is a retrospective, single-center risk analysis of potential factors affecting renal function after PTA. Twenty-four patients, transplanted over a three-yr period, with functioning pancreatic grafts at the study's end point were included. High tacrolimus levels (> 12 mg/dL) at six months post-transplant was the only independent risk factor identifying a substantial decline in native renal function by Cox regression analysis (HR = 14.300, CI = 1.271-160.907, p = 0.031). The presence of severe pre-transplant proteinuria (urine Pr/Cr ≥ 100 mg/mmol) marginally failed to reach significance (p = 0.056). Low eGFR levels alone (≤ 45 and ≤ 40 mL/min/1.73 m(2)) at the time of transplant did not correlate with substantial decline in renal function. Our data suggest that PTA is a justifiable therapy for patients with hypoglycemia unawareness or other life-threatening diabetic complications, even in those with borderline renal function, provided that they do not suffer from severe proteinuria and appropriate monitoring and tailoring of immunosuppression is ensured.

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.

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.

Renal function in type 1 diabetics one year after successful pancreas transplantation.

The effect of pancreas transplantation on renal function remains a matter of debate. The purpose of this retrospective, single-unit study is a preliminary analysis of renal function one yr after pancreas transplant (pancreas alone [PTA] or pancreas after kidney [PAK]). Fifty-nine patients were included. Serum creatinine and estimated glomerular filtration rate (eGFR) levels were compared three, six, and 12 months post-transplantation for the whole sample and separately for PTA and PAK and high (>45 mL/min/1.73 m(2)) and low (≤45 mL/min/1.73 m(2)) pre-transplant eGFR subgroups. Overall, eGFR did not change significantly (p = 0.228) at the end of the first year post-transplant, with patients of low initial eGFR presenting a more prominent trend toward stable or improved levels. In the PAK subgroup, eGFR was significantly improved (p = 0.035). High eGFR subgroup demonstrated no significant deterioration in renal function, while patients with low initial eGFR had significantly higher levels 3 (p = 0.012) and six months (p = 0.009) post-transplant. Our study shows that renal function did not deteriorate significantly one yr after pancreas transplant (PTA or PAK), even in patients with substantial pre-existing renal dysfunction. Evaluation at a wider scale and identification of risk factors for potential deterioration are challenges for future research.

Bench to bedside: A role for erythropoietin in sepsis.

Sepsis is the systemic inflammatory response to infection and can result in multiple organ dysfunction syndrome with associated high mortality, morbidity and health costs. Erythropoietin is a well-established treatment for the anaemia of renal failure due to its anti-apoptotic effects on red blood cells and their precursors. The extra-haemopoietic actions of erythropoietin include vasopressor, anti-apoptotic, cytoprotective and immunomodulating actions, all of which could prove beneficial in sepsis. Attenuation of organ dysfunction has been shown in several animal models and its vasopressor effects have been well characterised in laboratory and clinical settings. Clinical trials of erythropoietin in single organ disorders have suggested promising cytoprotective effects, and while no randomised trials have been performed in patients with sepsis, good quality data exist from studies on anaemia in critically ill patients, giving useful information of its pharmacokinetics and potential for harm. An observational cohort study examining the microvascular effects of erythropoietin is underway and the evidence would support further phase II and III clinical trials examining this molecule as an adjunctive treatment in sepsis.

Pancreatic Islet Changes in Human Whole Organ Pancreas Explants: What Can Be Learned From Explanted Samples?

BACKGROUND: Whole pancreas transplantation (Tx) is a successful treatment for type 1 diabetes resulting in independence from antidiabetic therapies. Transplant-related factors contributing to pancreatic islet failure are largely unknown; both recurring insulitis and pancreatitis have been implicated. The aim was to determine if cellular changes in islets and exocrine tissue are evident early in Tx, which could contribute to eventual graft failure using well-preserved tissue of grafts explanted from largely normoglycemic recipients. METHODS: Histological specimens of explants (n = 31), Tx duration 1 day-8 years (median 29 d), cold ischemia time 7.2-17.3 hours (median 11.1 h), donor age 13-54 years (median 38 y) were examined; sections were labeled for inflammation, islet amyloidosis, and tissue fibrosis, and morphometry performed on immunolabeled insulin and glucagon positive islet cells. Data were related to clinical details of donor, recipient, and features of Tx. RESULTS: Islet inflammation consistent with recurrent insulitis was not seen in any sample. Insulin-labeled islet cell proportion decreased with donor age (P < 0.05) and cold ischemia (P < 0.01) in explants from 26 normoglycemic patients; glucagon-labeled area proportion increased with cold ischemia (P < 0.05). Clinical pancreatitis was the explant reason in 12 of 28 normoglycemic cases. Exocrine fibrotic area/pancreas was variable (0.7%-55%) and unrelated to clinical/pathological features. Islet amyloid was present in 3 normoglycemic cases (donor ages 58, 42, and 31 y; Tx duration 8 y, 31 and 33 d, respectively). In 1 patient receiving antidiabetic therapy, the insulin-labeled area was reduced but with no evidence of islet inflammation. CONCLUSIONS: Explant histological changes after short-term Tx are similar to those seen in type 2 diabetes and occur in the absence of immunologic rejection without causing hyperglycemia. This suggests that factors associated with Tx affect islet stability; persistent deterioration of islet integrity and exocrine tissue fibrosis could impact on sustainability of islet function.

A retrospective analysis of the utility and safety of kidney transplant biopsies by nephrology trainees and consultants.

BACKGROUND AND AIMS: Dysfunction of a kidney transplant often requires histological sampling by percutaneous ultrasound-guided core needle biopsy. Transplant biopsy is more specialized than native kidney biopsy, the indications and complications are less well defined and in England are performed mainly by nephrologists. The aims of the study were to evaluate the adequacy and complication rate in living and deceased donor recipients according to training status of the nephrologist, assess the accuracy of physicians in predicting rejection, the threshold creatinine rise for biopsy, and the change in drug management post-biopsy. MATERIALS AND METHODS: We performed a retrospective analysis of all adult patients undergoing a kidney transplant biopsy in 2015 at a major teaching hospital in the UK as part of a service evaluation program. The primary outcome measure was the rate of major complications and secondary measures included sample adequacy, seniority of operator, clinician-predicted diagnosis, biopsy diagnosis and change in drug management. RESULTS: One hundred and seven (n = 107) transplant biopsies were performed across 27 living donor (LD) recipients and 57 deceased donor (DD) recipients. LDs were statistically less likely to have diabetes, more likely to take azathioprine. Biopsies were performed by trainees rather than consultants at a ratio of 3:1. The complication rate was low with no major bleeding complications. Visible haematuria occurred in 4.7% and 2.8% of patients developed transplant pyelonephritis. 3.7% of biopsies contained no glomeruli. There was no effect attributed to training status. The pre-biopsy rise in creatinine was significantly less for LD compared to DD recipients (45% vs 70%). A clinician-suspected diagnosis of rejection was confirmed on biopsy in 42.9% of cases and overall about 47.9% of biopsies led to a change in drug management. CONCLUSIONS: Kidney transplant biopsies were safe, performed adequately by trainee nephrologists and were often associated with a change in drug management.

Preserving and perfusing the allograft pancreas: Past, present, and future.

The concept of organ preservation by perfusion dates back to the mid-19th century. Innovations since then have included temperature regulation, perfusion fluid composition and various pumping systems. Advances made in liver, heart and kidney machine preservation are now contributing to increased graft utilisation, assessment of graft viability and potentially improved graft survival. Pancreas transplantation has not benefitted to the same extent from the application of perfusion technology, although the need is just as great. This overview reviews current pancreas specific preservation techniques. We explore concepts, which include static cold storage, use of preservation solutions, the 'two-layer method', and machine perfusion. We also discuss ideas for future development. Narrative review of literature from inception to December 2017 using OVID interfaces searching EMBASE, Google Scholar, and MEDLINE databases. All studies relevant to pancreas perfusion and preservation were examined for clinical relevance with no exclusion criteria. Conference papers and presentations were also reviewed and included where appropriate. The application of recent advances in understanding in ischaemia-reperfusion as well as technical developments in machine preservation Ischaemia-reperfusion have the potential to improve organ utilisation, viability and outcome.