Expanded Criteria Donor Organs Research Articles

Expanded Criteria Donor Heart Allograft Utilization: National Trends and Outcomes

BackgroundTo examine recent trends in the use of expanded criteria donor organs in heart transplantation, this study assessed center-level variation in acceptance of these allografts and analyzed their posttransplantation outcomes. MethodsAdult (aged ≥18 years) heart transplant recipients between 2011 and 2022 were identified in the Organ Procurement and Transplantation Network database. Expanded criteria allografts were defined using a previously validated risk score. After stratifying centers by cumulative transplantation volume, those centers in the top tertile (≥23/year) were considered high volume. Subsequently, the ratio of transplantations using expanded criteria allografts to total transplantations was calculated for each high-volume center. On the basis of tertiles, centers were then categorized as high-, medium-, and low-use centers. The primary outcome was death after transplantation. ResultsOf 23,290 transplantations performed, 5017 (22%) used expanded criteria donor allografts. High-volume heart transplantation centers performed 72% (3628) of these transplantations—1183 (75%) between 2011 and 2014, 1383 (73%) between 2015 and October 2018, and 1062 (68%) between November 2018 and June 2021. Compared with low-volume programs, undergoing expanded criteria heart transplantation at high-volume centers was associated with a significantly reduced hazard of mortality at 1 year (hazard ratio, 0.78; CI, 0.65-0.94; P = .01) and 5 years (hazard ratio, 0.85; CI, 0.75-0.98; P = .02). During the study period, survival rates 1 year after transplantation were similar across high-volume centers, regardless of their use of expanded criteria allografts. ConclusionsUndergoing heart transplantation with an expanded criteria donor allograft at a high-volume transplantation center provides a significant survival benefit. Further, the use of more expanded criteria criteria organs, in the right clinical settings, does not negatively affect overall patient outcomes at high-volume centers.

Comparison of Survival in Recipients of Marginal and Standard Cadaveric Donor Kidneys

Renal transplantation is the main treatment for end-stage renal disease and has rapidly increased in number over the past 3 decades, leading to an increasing need for organs. The disparity between organ access and the number of patients on the waiting list has led transplant surgeons to use marginal cadaveric donors. As a consequence, the concept of "marginal cadaveric kidney donor" has been developed. We retrospectively evaluated 120 patients who received kidneys from cadaveric donors between September 2009 and August 2021. The donors were divided into standard and marginal cadaveric donors, and their age, sex, cause of death, criteria of acceptance as marginal donors, and Kidney Donor Profile Index (KDPI) were recorded RESULTS: The donors included 69 men and 51 women, with a mean age of 52.9 ± 16.8 years. There were 52 standard donors and 68 marginal donors. Graft and donor survival were compared based on the KDPI values of the donors, and were respectively found to be higher in those with a KDPI of 0 to 60 than in those with a KDPI of 81 to 100 (P=.011 and .039, respectively). There was no significant difference between those with a KDPI of 61 to 80 and the other groups. Expanded criteria donor organs, which offer greater survival benefits than hemodialysis, can be used safely to meet the increasing need for donors. Expanded criteria donor organs should thus be considered a valuable alternative in this patient group.

MO985: Physical Function Trajectories Predict Patient Survival in Older Recipients of Deceased Donor Kidneys

Abstract BACKGROUND AND AIMS Health-related quality of life (HRQOL) outcomes have been positively associated with patient survival after kidney transplantation (KT). In older recipients, poor HRQOL may indicate risk for clinical deterioration. We aimed to prospectively evaluate if, in older recipients of deceased brain-dead donor (DBD) kidneys, changes in HRQOL during the first year post-transplantation differed between survivor and non-survivors. METHOD KT candidates aged ≥65 years who were enlisted between January 2013 and November 2016 at the Norwegian national transplant center and received a deceased brain-dead donor (DBD) kidney were included. HRQOL was assessed using the Kidney Disease Quality of Life Short Form, version 1.3. HRQOL outcomes were collected prior to KT, at 10 weeks, 6 months and 12 months post-KT. A mixed-effect linear regression model was used to examine the development of HRQOL during the first year post-KT in survivors versus non-survivors. Longitudinal HRQOL trajectories were identified using a group-based trajectory modelling. A Cox proportional hazard regression was used to investigate the association of longitudinal HRQOL trajectories for each domain with patient survival. RESULTS We included 289 waitlisted candidates, of whom 192 received a DBD kidney. Mean age at KT was 72 (4.1) years, 133 (69%) were males, 47 (24%) were transplanted preemptively and 80% received an expanded criteria donor organ. During a median observation time of 4.6 (3.2, 6.3) years post-KT, 66 recipients died. In survivors, all the generic and kidney-specific HRQOL domains substantially improved during the first year post-KT, whereas HRQOL deteriorated in non-survivors (Figure 1). Three developmental trajectories, describing poor, fair and good outcomes were identified for most of the HRQOL domains. Recipients perceiving poor physical development during the first post-transplant year had a 2.5 higher mortality risk, while recipients with fair physical development had 1.4 increased mortality risk, compared with recipients with good physically development (Figure 2). CONCLUSION In elderly kidney transplant recipients, poor post-transplant physical function trajectory may indicate impaired survival. The systematic HRQOL monitoring following KT is warranted to identify high-risk patients and guide therapeutic decisions.

FC 111: A Comorbidity Index and Pretransplant Physical Status Predict Survival in Older Kidney Transplant Recipients

Abstract BACKGROUND AND AIMS Regardless of age, kidney transplantation (KT) is considered the optimal treatment for patients with end-stage kidney disease (ESKD). In the increasing elderly ESKD population, KT should be reserved for carefully selected candidates who are expected to experience favorable outcomes. We aimed to prospectively evaluate pre-transplant recipient factors that may predict post-transplant patient survival and can eventually guide therapeutic decisions in elderly with ESKD. METHOD Recipient factors were evaluated in KT candidates aged ≥65 years, who were enlisted for KT between January 2013 and November 2016 at the Norwegian national transplant centre. Pretransplant comorbidity was assessed at waitlisting, according to the Liu Comorbidity Index (LCI). Self-reported health-related quality of life was assessed using the Kidney Disease Quality of Life Short Form version 1.3 (KDQOL-SF). The Cox proportional hazard regression was used to evaluate predictors of patient survival. RESULTS We included 289 waitlisted candidates, of whom 192 received a deceased brain-dead donor kidney. Mean age at KT was 72 (4.1) years, 133 (69%) were male, 47 (24%) were transplanted preemptively and 80% received an expanded criteria donor organ. During a median observation time of 4.6 (3.2–6.3) years post-KT, 66 recipients died. LCI ≤ 3 was observed in 136 recipients (71%), between 4–6 in 39 recipients (20%) and 17 recipients (9%) had LCI ≥ 7. Elevated LCI ≥ 4 predicted poor patient survival, and was associated with a 2.2-times increase in mortality risk (Figure 1). In recipients with LCI ≥ 4, dialysis ≥2 years comprised a 2.5-fold higher mortality risk, compared with recipients on dialysis ≤2 years (Figure 2). Self-reported pretransplant physical function was also proven to be a significant positive predictor of survival, with scores ≤60 being associated with a 2-fold increase in mortality risk. CONCLUSION The implementation of LCI and a physical function score during the evaluation of older kidney transplant candidates may improve the selection and thereby optimize post-transplant outcomes.

Experimental long-term sub-normothermic machine perfusion for non-allocable human liver grafts: first data towards feasibility

Summary Background Patients with end-stage liver disease can only be cured by liver transplantation. Due to the gap between demand and supply, surgeons are forced to use expanded criteria donor (ECD) organs, which are more susceptible to ischemia–reperfusion injury (IRI). Therefore, enhanced storing techniques are required. Machine perfusion (MP) has moved into the spotlight of research because of its feasibility for investigating liver function prior to implantation. However, as the perfect MP protocol has not yet been found, we aimed to investigate the potential of sub-normothermic (SN)MP in this field. Methods Non-allocable human livers were subjected to 24 h of SNMP at 21 °C after delivery to the study team. Perfusion was performed with Custodiol® (Dr. Franz Köhler Chemie, Bensheim, Germany) or Belzer MPS® (Bridge to Life Europe, London, UK) and perfusate liver parameters were determined. For determination of biliary conditions, pH, glucose, and HCO3- levels were measured. Results Liver parameters were slightly increased irrespective of perfusate or reason for liver rejection during 24 h of perfusion. Six livers failed to produce bile completely, whereas the remaining 10 livers produced between 2.4 ml and 179 ml of bile. Biliary carbonate was increased in all but one liver. The bile-glucose-to-perfusate-glucose ratio was near 1 for most of the organs and bile pH was above 7 in all but one case. Conclusion This study provides promising data on the feasibility of long-term SNMP as a tool to gain time during MP to optimize ECD organs to decrease the gap between organ demand and supply. Long-term (24 h) sub-normothermic liver machine perfusion seems to be possible, although some adjustments to the protocol might be necessary to improve the general outcome. This has so far been shown for normothermic machine perfusion, bearing some drawbacks compared to the sub-normothermic variant.

Early experiments with hypothermic oxygenated machine perfusion of kidney grafts from extended criteria donors

Objective: to evaluate the safety and efficacy of hypothermic oxygenated machine perfusion (HOPE) for kidney grafts obtained from expanded criteria donors (ECD).Materials and methods. From June 2018 to June 2021, 200 surgeries involving kidney transplants from deceased donors were performed at Botkin City Clinical Hospital. Of these, 123 were men (61.5%) and 77 were women (38.5%). The mean age was 47.62 ± 11.69 (20–73) years. In 102 cases, kidney grafts were procured from ECD. In 92 recipients (90.2%) of kidney transplants from an expanded criteria donor, static cold storage done according to the standard technique was used to preserve the organ; these patients constituted observation group 1. In 10 recipients (9.8%), hypothermic oxygenated perfusion was used in addition to static cold preservation; these patients formed observation group 2.Results. No 30-day mortality was recorded in both observation groups. The mean static cold storage time in group 1 patients was 612.33 ± 178.88 (133–1180) minutes. Overall incidence of delayed graft function was 26.5% (53/200). Incidence of delayed graft function was 19.3% (19/98) for organs from standard donors using static cold storage and 35.8% (33/92) for ECD organs. Twenty-five patients (12.5%) had postoperative complications. Postoperative complications with delayed graft function were diagnosed in 12 patients, which was 22.6% (12/53), with immediate function in 13 patients, which was 8.8% (13/147). Mean cold storage time in group 2 patients was 319.11 ± 110.24 (311–525) minutes. Mean HOPE time was 202.34 ± 21.48 (150–210) minutes. Delayed graft function was recorded in 1 group 2 patient (10%). No complications, including perfusion-related one, were recorded in this group.Conclusion. The unique technique used at Botkin City Clinical Hospital for HOPE in kidney transplant is safe. It provides a low risk of delayed graft function for ECD kidneys.

Effects of expanded allocation programmes and organ and recipient quality metrics on transplant-related costs in kidney transplantation - an institutional analysis.

Expansions of donor pools have a controversial impact on healthcare expenditures. The aim of this study was to investigate the emerging costs of expanded criteria donor (ECD) kidney transplantations (KT) and to identify independent risk factors for increased transplant-related costs. We present a retrospective explorative analysis of hospital costs and reimbursements of KTs performed between 2012 and 2016 in a German university hospital. A total of 174 KTs were examined, including 92 (52.9%) ECD organ transplantations. The ECD group comprised 43 (24.7%) 'old-for-old' transplantations. Median healthcare costs were 19570€ (IQR 18735-27405€) in the standard criteria donor (SCD) group versus 25478€ (IQR 19957-29634€) in the ECD group (+30%; P=0.076). 'Old-for-old' transplantations showed the highest healthcare expenditures [26702€ (19570-33940€)]. Irrespective of the allocation group, transplant-related costs increased significantly in obese (+6221€; P=0.009) and elderly recipients (+6717€; P=0.019), in warm ischaemia time exceeding 30min (+3212€; P=0.009) and in kidneys with DGF or surgical complications (+8976€ and +10624€; both P<0.001). Transplantation of ECD organs is associated with incremental costs, especially in elderly and obese recipients. A critical patient selection, treatment of obesity before KT and keeping warm ischaemia times short seem to be crucial, in order to achieve a cost-effective KT regardless of the allocation group.

Renal Intra-Arterial Delivery of MSC to Ischemic Porcine Kidneys

MePEP consortium. Donor organ shortage is one of the main problems in kidney transplantation. The increase in the available donor kidney pool comes with the use of expanded criteria donor organs, leading to a poorer outcome for the grafts and the patients. Therefore, a number of techniques are arising to improve the organ quality, such as machine perfusion in combination with cell therapy. Mesenchymal stem cells (MSC) have tissue regenerative capacities exerted by paracrine secretion of different cytokines and physical interaction with surrounding cells. Porcine MSC from adipose tissue were isolated and grown to carry out the experiments. A model of unilateral ischemia-reperfusion injury by clamping the renal artery for 1 hour was established. 10 million MSC were fluorescently labelled with Qtracker beads and infused directly through the renal artery during 10 minutes. Fluorescent MSC were detected using flow cytometry Before, during and after the infusion, blood samples were taken from the renal vein to assess if MSC were leaving the kidney. After 30 minutes or 8 hours both kidneys were retrieved and biopsies were collected from multiple sites. These biopsies were mechanically disrupted and enzymatically digested to a single cell suspension and analyzed by flow cytometry. Slices from paraffin-embedded biopsies were stained by hematoxylin and eosin and analyzed by light and fluorescence microscopy to identify the exact localization of the administered MSC. Flow cytometric analyses of blood samples allowed us to observe MSC leaving the kidney (up to 2000 MSC/ml blood) during the infusion procedure, after which very low fluorescent cells were detected in renal venous blood (300 MSC/ml). Arterial blood was also analyzed but no MSC was identified. Flow cytometric analysis of dissociated renal cortex and medulla revealed that most MSC were present in renal cortex (8000-20000 MSC/gram of cortex) but a number of individual MSC were detected in the medulla (1000-3000 MSC/gram of medulla). From these MSC inside renal tissue, 80% were alive. Lung tissue was also analyzed and shown to contain a small population of MSC (200-400 MSC/ gram). Microscopy data validated these results. MSC were detected in the renal cortex, mainly inside the glomeruli but individual MSC were found also in tubuli, vessels and medulla.Delivery of MSC through the renal artery can successfully deliver MSC throughout the kidney. MSC were retained particularly in glomeruli for at least 8 hours. We were able to estimate the relative retainment and localization of MSC in the kidney. These studies will pave the way for survival studies in this large animal model aiming for future clinical studies with targeted delivery of MSC in renal disease, eg. in transplantation of high risk donor organs. Lundbeck Foundation under grant application no. R198-2015-184

The impact of diet-induced hepatic steatosis in a murine model of hepatic ischemia/reperfusion injury.

The prevalence of obesity-associated nonalcoholic fatty liver disease has significantly increased over the past decade, and end-stage liver disease secondary to nonalcoholic steatohepatitis has become 1 of the most common indications for liver transplantation. This both increases the demand for organs and decreases the availability of donor livers deemed suitable for transplantation. Although in the past many steatotic livers were discarded due to concerns over enhanced susceptibility to ischemia/reperfusion injury (IRI) and organ failure, the discrepancy between supply and demand has resulted in increasing use of expanded criteria donor organs including steatotic livers. However, it remains controversial whether steatotic livers can be safely used for transplantation and how best to improve the performance of steatotic grafts. We aimed to evaluate the impact of diet-induced hepatic steatosis in a murine model of IRI. Using a diet of high trans-fat, fructose, and cholesterol (HTF-C) and a diet high in saturated fats, sucrose, and cholesterol (Western diet), we were able to establish models of mixed macrovesicular and microvesicular steatosis (HTF-C) and microvesicular steatosis (Western). We found that the presence of hepatic steatosis, whether it is predominantly macrovesicular or microvesicular, significantly worsens IRI as measured by plasma alanine aminotransferase levels and inflammatory cytokine concentration, and histological evaluation for necrosis. Additionally, we report on a novel finding in which hepatic IRI in the setting of steatosis results in the induction of the necroptosis factors, receptor interacting protein kinase (RIPK) 3, RIPK1, and mixed-lineage kinase domain-like. These data lay the groundwork for additional experimentation to test potential therapeutic approaches to limit IRI in steatotic livers by using a genetically tractable system. Liver Transplantation 24 908-921 2018 AASLD.

The Welsh Transplant Incident

Abstract Hughes and Stuart’s shocking and unexpected deaths from the transplant treatments they received at Cardiff’s University Hospital of Wales could, in Lord Denning’s terminology, be described as ‘a most extraordinary chapter of accidents’. As Hughes and Stuart’s transplant treatments were based on expanded criteria donor kidneys, their deaths underscore not only the perennial problem of organ shortage in England and Wales which necessitates the clinical use of ‘high risk’ organs; but also, their deaths invite a re-examination of some of the ethical and legal issues involved in transplantation with expanded criteria donor organs. Being incomparable in calamity and rarity, the Welsh transplant incident is bound to raise novel issues of first impression in negligence, issues that this essay attempts to identify and analyse.

Mesenchymal Stromal Cells as Anti-Inflammatory and Regenerative Mediators for Donor Kidneys During Normothermic Machine Perfusion.

There is great demand for transplant kidneys for the treatment of end-stage kidney disease patients. To expand the donor pool, organs from older and comorbid brain death donors, so-called expanded criteria donors (ECD), as well as donation after circulatory death donors, are considered for transplantation. However, the quality of these organs may be inferior to standard donor organs. A major issue affecting graft function and survival is ischemia/reperfusion injury, which particularly affects kidneys from deceased donors. The development of hypothermic machine perfusion has been introduced in kidney transplantation as a preservation technique and has improved outcomes in ECD and marginal organs compared to static cold storage. Normothermic machine perfusion (NMP) is the most recent evolution of perfusion technology and allows assessment of the donor organ before transplantation. The possibility to control the content of the perfusion fluid offers opportunities for damage control and reparative therapies during machine perfusion. Mesenchymal stromal cells (MSC) have been demonstrated to possess potent regenerative properties via the release of paracrine effectors. The combination of NMP and MSC administration at the same time is a promising procedure in the field of transplantation. Therefore, the MePEP consortium has been created to study this novel modality of treatment in preparation for human trials. MePEP aims to assess the therapeutic effects of MSC administered ex vivo by NMP in the mechanisms of injury and repair in a porcine kidney autotransplantation model.

Organ Donor Recovery Performed at an Organ Procurement Organization-Based Facility Is an Effective Way to Minimize Organ Recovery Costs and Increase Organ Yield

A new era in organ donation with national redistricting is being proposed. With these proposals, costs of organ acquisition are estimated to more than double. Traditionally, organ recoveries occur in the donor hospital setting, incurring premium hospital expenses. The aim of the study was to determine organ recovery costs and organ yield for donor recoveries performed at an organ procurement organization (OPO) facility. In 2001, we established an OPO facility and in 2008 began transferring the donor expeditiously when brain death was declared. The OPO donor and hospital costs on a per donor basis were calculated. Donation after cardiac death donors cannot be transferred and were included in the hospital cost analysis. From January 2009 to December 2014, nine hundred and sixty-three donors originating in our OPO had organs recovered and transplanted. Seven hundred and sixty-six (79.5%) donors were transferred to the OPO facility 8.6 hours (range 0.6 to 23.6 hours) after declaration of brain death. Donor recovery cost was 51% less when donors were transferred to the OPO facility ($16,153 OPO recovery vs $33,161 hospital recovery; p < 0.0001). Organ yield was 27.5% better (3.43 organs) from OPO-recovered donors vs an organ yield of 2.69 from hospital-recovered donors (p < 0.0001). Standard criteria donor organ yield from our OPO was 6% higher than the national average (3.92 vs 3.7 nationally; p= 0.012) and expanded criteria donor organ yield was 18% higher (2.2 vs 1.87 nationally; p= 0.03). An OPO facility for donor organ recovery increases efficiency and organ yield, reduces costs, and minimizes organ acquisition charge. As we face new considerations with broader sharing, increased efficiencies, cost. and organ use should be considered.

Expanded criteria donor and donation after circulatory death renal allografts in the West of Scotland: Their place in the kidney allocation process

IntroductionDue to the rising disparity between demand and availability, organs from expanded criteria donors (ECD) and donors after determination of circulatory death (DCD) are increasingly used. The purpose of this study was to report outcomes in recipients of ECD and DCD renal allografts from a single centre. MethodsA retrospective analysis from a single centre for all renal transplants performed between 2001 and 2010 inclusive was undertaken. SCD (standard criteria donor) and ECD organs were compared, as were DCD and DBD (donation after determination of brain stem death) organs. Baseline data and predefined standard transplant outcomes were collected and compared using appropriate statistical tests. P < 0.05 was defined as significant. Results729 renal transplants were performed. Comparing ECD to SCD organs, there was a significant difference in graft survival between groups (logrank for trend, p = 0.032) with ECD organs doing worse than SCD organs. Short-term outcomes showed a similar disparity with a higher 1-year post-transplant creatinine and delayed graft function (DGF) rate in ECD grafts. Nevertheless, outcomes were still clinically acceptable. When comparing DCD to DBD organs, no such differences were apparent, with DCD organs appearing to perform at least as well as DBD organs. In our cohort, unlike some previous studies, DGF rates were similar in both DCD and DBD groups. ConclusionsAlthough ECD organs perform less well than SCD organs, outcomes are still acceptable and our results support their continuing use. When considering DCD organs, our data support the view that they should no longer be necessarily regarded as marginal grafts. Our low DGF rates are perhaps explained by local factors contributing to a short CIT.

Live donor kidney transplantation in India: effects of donor and recipient age on graft survival

Introduction: The increasing gap between demand and supply of human kidneys has resulted in the use of more expanded criteria donor organs are used. The influence of age on short- and long-term survival of renal allograft has not been well studied in Indian population. Materials and methods: Two hundred and seventy-eight patients were evaluated retrospectively who underwent kidney transplantation from Jan 2008 to June 2011. Patients were divided into 6 groups: group A (donor age 20–40 years, recipient age <50 years), group B (donor age 20–40 years, recipient age >50 years), group C (donor age 40–60 years, recipient age <50 years), group D (donor age 40–60 years, recipient age >50 years), group E (donor age >60 years, recipient age <50 years) and group F (donor age >60 years, recipient age >50 years). Uni-variate analysis was used to assess the effect of donor and recipient age as predictive factors for graft outcome, using the Kaplan–Meier method (log-rank) with p < 0.05 considered significant. Results: Graft survival was found to be lowest in elderly recipients and in patients with donor age >60 years. Renal function was superior using younger donors both in short and long term. The incidence of acute rejection was found to be lower in elderly donor group than in younger, although the difference was not statistically significant. Conclusion: Donor’s higher age did not show significant impact on allograft survival although, kidney allografts demonstrated decreased short and long term renal function.

21. Supplemented oxygenation during hypothermic storage: Friend or foe

There is a shortage of donated organs for clinical allo-transplantation with potential recipients dying while on the waiting list. Despite that only a fraction of the donated organs are currently utilized. For example certain organs with prolonged cold ischemia times and organs from expanded criteria donors (ECD) are not routinely utilized. ECD organs may be more sensitive to stressful conditions during preservation and maintenance of the health of these organs during preservation is even more critical and challenging and may require more sophisticated preservation techniques. This has led to substantial interest and investment in improved methods for organ preservation. The lack of oxygen during hypothermic preservation is believed to be detrimental to cellular viability and maybe responsible for priming the organ for damage during normothermic reperfusion (ischemia reperfusion injury). As a consequence, oxygen supply is a major research focus in the field of organ preservation. It has been demonstrated that the simplest and most widely used technique for hypothermic organ preservation, static cold storage can only oxygenate to a maximum depth of a millimeter from the surface of an organ even if the organ preservation solution around the organ is fully saturated with 100% oxygen. In this case, even though the oxygen demand is substantially reduced by hypothermia, it still exceeds the supply by diffusion. Even hypothermic machine perfusion, which has been designed to deliver cold preservation solution into the organ via the circulation, may be incapable of delivering adequate oxygen to an organ during preservation, particularly when the perfusate does not have substantially higher oxygen carrying capacity than water and it is not saturated with a gas containing higher oxygen fraction than air. New and improved methods for oxygen delivery to organs during hypothermic preservation are clearly still needed. A major consideration in the development of such methods is that even though lack of oxygen can be detrimental, high levels of oxygen (hyperoxia) could be equally or more damaging. Emerging literature suggests that negative effects of hyperoxia may be more pronounced under hypothermia because the cellular antioxidant mechanisms in place may not be as effective at lower temperatures. The effects of high or low oxygen may be temperature as well as organ dependent and are currently not well defined. Further research is needed to define the fine balance between oxygen demand and delivery for the organ or tissue of interest at relevant temperatures. In this paper we will present data on the effects of high and low oxygen on pancreas and islet (beta-cell) health at various temperatures ranging from 4C to 37C. Islets are known to be particularly sensitive to oxidative damage as they express lower levels of antioxidant enzymes typically found in other cell types under physiological conditions. Islets are also particularly sensitive to hypoxia because they express very low levels of LDH-alpha and they cannot effectively generate energy anaerobically, which makes them an interesting and challenging model system in the context of oxygen delivery optimization to avoid hypoxia induced damage without resulting to high oxygen toxicity.

Prediction of Three-Year Outcome of Renal Transplantation from Optimal Donors versus Expanded Criteria Donors

Background/Aims: The shortage in organ supply has required the use of expanded criteria donors (ECD) for kidney transplantation. Current pre-transplant evaluations of ECD organs are based on histological, clinical or mixed criteria. This monocentric study investigates the predictivity of Karpinski’s histological score on 3-year graft function in renal transplant. Ex-post classification using Nyberg’s score was carried out to assess the reliability of a purely clinical score and its applicability for organ allocation. Methods: We evaluated 407 deceased donors (251 optimal and 156 ECD) for renal transplants performed between 2001 and 2006. The differences in creatinine levels and MDRD-GFR at transplant and 1, 2 and 3 years post-transplant between optimal donors and ECD were recorded. Amongst ECD organs, the effect of different Karpinski score classes (0–1, 2, 3, 4, double transplants) on 3-year graft outcomes was analyzed. We then compared renal function over time across the Nyberg grades (A, B, C, and D). Results: Karpinski scores 0–1 and 2 and double transplants were associated with improved graft function compared to scores 3 and 4. Nyberg’s clinical score shows a good fit with medium-term outcome and Karpinski’s score, but among the donors with a high Nyberg grade (C and D), it fails to differentiate between allocable or non-allocable organs (due to Karpinski’s score ≥7). Conclusions: Our data demonstrate a correlation of histological damage at the time of transplant with 3-year graft function, but at present we are unable to provide any supposition on the possible outcome of the discarded kidneys.

Analysis of 80 Dual-Kidney Transplantations: A Multicenter Experience

Introduction The use of kidneys from expanded criteria donors (ECD) is an attractive strategy to enlarge the pool of organs available for transplantation. Considering the fact that ECD organs have a reduced nephron mass, they are preferentially allocated for dual-kidney transplantation (DKT). Authors have reported excellent results of DKT when pretransplant ECD organs are evaluated for histological scores. The aim of this study was to evaluate DKT donor and recipient characteristics for comparison with DKT posttransplant outcomes versus those of recipients of single-kidney transplantations from expanded criteria (edSKT) and ideal donors (idSKT). We analyzed the potential prognostic factors involved in DKT among a population derived from three transplant centers. Materials and methods Between 2001 and 2007, DKT ( n = 80) were performed based upon the ECD kidney allocation assessed by biopsy. Results The average donor ages for the DKT, edSKT, and idSKT groups were 68.8 ± 7.8, 65.3 ± 7.2, and 40.1 ± 13.8 years, respectively ( P < .001). The number of human leukocyte antigen mismatches was greater in the DKT group (3.1 ± 1.2, P < .05). Patient and graft 5-year survival rates were similar among DKT, edSKT, and idSKT recipients, namely, 97.5% versus 95.8% versus 96.9% and 93.7% versus 87.4% versus 86.9%, respectively. Mean serum creatinine values at discharge were lower in the DKT and idSKT recipients (1.5 ± 0.9 and 1.6 ± 0.7 mg/dL; P < .05) compared with the edSKT group (1.9 ± 0.7 mg/dL). Correlations between supposed prognostic factors and survival among the DKT group noted worse outcomes in reoperation cases ( P < .05). Conclusion We confirmed that DKT produced successful outcomes. An accurate surgical procedure is particularly important to try to avoid reoperations. In our experience, the use of a biopsy as an absolute criterion to allocate ECD kidneys may be too protective.

Use of liver grafts from donation after cardiac death donors for recipients with hepatitis C virus

Hepatitis C virus (HCV) infection is the most common indication for orthotopic liver transplantation in the United States. Although studies have addressed the use of expanded criteria donor organs in HCV(+) patients, to date the use of liver grafts from donation after cardiac death (DCD) donors in HCV(+) patients has been addressed by only a limited number of studies. This retrospective analysis was undertaken to study the outcomes of DCD liver grafts used in HCV(+) recipients. Seventy-seven HCV(+) patients who received DCD liver grafts were compared to 77 matched HCV(+) patients who received donation after brain death (DBD) liver grafts and 77 unmatched non-HCV patients who received DCD liver grafts. There were no differences in 1-, 3-, and 5-year patient or graft survival among the groups. Multivariate analysis showed that the Model for End-Stage Liver Disease score [hazard ratio (HR) = 1.037, 95% confidence interval (CI) = 1.006-1.069, P = 0.018] and posttransplant cytomegalovirus infection (HR = 3.367, 95% CI = 1.493-7.593, P = 0.003) were significant factors for graft loss. A comparison of the HCV(+) groups for fibrosis progression based on protocol biopsy samples up to 5 years post-transplant did not show any difference; in multivariate analysis, HCV genotype 1 was the only factor that affected progression to stage 2 fibrosis (genotype 1 versus non-1 genotypes: HR = 2.739, 95% CI = 1.047-7.143, P = 0.040). In conclusion, this match-controlled, retrospective analysis demonstrates that DCD liver graft utilization does not cause untoward effects on disease progression or patient and graft survival in comparison with DBD liver grafts in HCV(+) patients.

The D&amp;T Report

The D&amp;T Report

Kidney transplant Medicare payments and length of stay: associations with comorbidities and organ quality

IntroductionWe investigated associations between pre-transplant comorbidities, length of stay (LOS) and Medicare payments for transplant hospitalization.Material and methodsWe examined United States Renal Data System for 24,963 recipients of first deceased-donor kidney transplants in 1995-2002 for whom Medicare was the primary payer for at least a year pre-transplant. Pre-transplant ICD-9-CM codes from claims were classified with the Charlson and Elixhauser algorithms. Regression models for payments and LOS included: 1) baseline recipient, donor and transplant factors from the Organ Procurement and Transplant Network (OPTN), 2) OPTN variables and individual comorbidities and 3) OPTN variables and counts of Charlson or Elixhauser comorbidities.ResultsFactors most strongly associated with LOS were type I diabetes, cold ischemia time > 36 h, expanded criteria donor (ECD) and donation after cardiac death (DCD). Except for ECD, each was associated with increased payments. Upper respiratory disease, liver disease, peptic ulcer disease, diabetes, cancer and other diseases were also associated with increased LOS and payments. Each additional Charlson comorbidity increased LOS by 2.94% and payments by $471 (Elixhauser results: 1.71% for LOS, $277 for payments). Use of ECD or DCD organs were associated with 10-15% higher LOS and 5% increased Medicare payments for DCD.ConclusionsThis methodology could be used to explore if Medicare reimbursement for transplantation of higher-risk recipients and using non-standard organs is financially adequate and to analyze related questions in other healthcare systems.