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Background: Lung transplantation is the most effective treatment for end-stage respiratory diseases, but its application is limited by the shortage of organs. Ex vivo lung perfusion (EVLP) has emerged as a promising technique to evaluate and recondition donor lungs previously deemed unsuitable for transplantation. However, limitations such as lung contusions, air leaks, and perfusate extravasation, especially in portable EVLP systems, hinder the procedure. Despite prolonged perfusions that can result in blood pooling at the lung bases due to fixed lung positioning and diminished oncotic pressure, in some cases, extending perfusion time beyond the typical 5–6 h could benefit extended-criteria lungs, addressing factors such as edema or logistical complications. Methods: We present an innovative protocol involving prolonged EVLP, pronation of the graft, and the addition of anti-edematous drugs to the perfusate. Results: This novel approach, previously tested in animal models, enhances lung reconditioning and expands the donor pool. Conclusions: Our findings suggest that this strategy overcomes key limitations of standard EVLP, offering a valuable solution for improving the availability of transplantable lungs. [ABSTRACT FROM AUTHOR]

Thrombocytopenia is one of the common complications after liver transplantation, with pathophysiological mechanisms including insufficient platelet production and increased platelet consumption, which severely affects the prognosis of liver transplant recipients. Various factors such as preoperative hepatitis virus infection, intraoperative ischemic injury, and postoperative use of immunosuppressive drugs may lead to thrombocytopenia after liver transplantation. Early detection and effective treatment of thrombocytopenia after liver transplantation are currently hot topics of research. Based on the existing literature, this article reviews the definition, pathophysiological mechanisms, risk factors, treatment, and prevention of thrombocytopenia, and discusses the occurrence and development of thrombocytopenia after liver transplantation and related diagnosis and treatment strategies, aiming to optimize the existing treatment opinions, reduce the risk of thrombocytopenia after transplantation and improve the prognosis of liver transplant recipients. [ABSTRACT FROM AUTHOR]

Background: The number of marginal living kidney donors has increased. Medically complex donors who have hypertension, older age, or low estimated glomerular filtration rate (eGFR) have been more likely to be used. Methods: We conducted a retrospective cohort study of living kidney donors at a single center. We analyzed 309 living donors and divided them into three groups: group with older donors (aged ≥70 years) (n = 41), middle-aged (aged 46–69 years) (n = 239), and young donors (aged <46 years) (N = 29). Donor factors associated with chronic kidney disease (CKD) stage 3b or worse within 5 years post-donation were investigated. Results: Of the 309 live donors, 86 (27.8%) developed CKD stage3b or worse within 5 years post-donation. The incidence of CKD stage3b or worse within 5 years post-donation was significantly higher in older donor (p < 0.01). Cox regression models revealed that older donor ages and lower eGFR were significantly related to the development of CKD stage3b or worse, independent of comorbidities such as obesity and hypertension [hazard ratio (95% CI); 4.59 (1.02–20.6), p = 047, 0.95 (0.94–0.96), p ≤ 0.01, respectively]. However, recovery of eGFR 4–5 years after donation was noted in the middle-aged and older donor groups, whereas the level of eGFR remained unchanged in the young group. Conclusions: Older donors tend to develop CKD stage3b within 5 years post-donation but with the potential of recovery. Healthy older people (aged ≥70 years) could be candidates for living donors under careful monitoring of kidney function after donation. [ABSTRACT FROM AUTHOR]

Objective To evaluate the clinical outcome of kidney transplantation from donation after brain death (DBD) donors complicated with acute kidney injury (AKI). Methods Clinical data of 216 DBD donors were retrospectively analyzed, and they were divided into the AKI group (n=69) and control group (n=147) according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Donors in the AKI group were further divided into the KDIGO stage 1 and stage 2-3 subgroups. One hundred and thirty-five recipients were assigned into the AKI group and 288 recipients in the control group. Postoperative recovery of renal function and clinical outcomes of the recipients were recorded. The risk factors of delayed graft function (DGF) were identified. Results The highest serum creatinine (Scr) level, Scr level before procurement, the highest blood sodium level and blood sodium level before procurement in the AKI group were higher than those in the control group. The application duration of vasopressors in the AKI group was longer than that in the control group. In the AKI group, the amount of fluid resuscitation within 48 h was higher, the HCO3 − level at admission was lower, and the incidence of diabetes insipidus and hypotension was higher than those in the control group. The highest Scr level and the Scr level before procurement in KDIGO stage 2-3 donors were significantly higher than those in KDIGO stage 1 counterparts (all P<0.05). Compared with the control group, the incidence of DGF and acute rejection was higher, the proportion of continuous renal replacement therapy was higher, the Scr level within postoperative 90 d was higher, and the urine amount within postoperative 3 d was less than those of recipients in the AKI group. Compared with KDIGO stage 1 recipients, KDIGO stage 2-3 recipients had higher Scr levels at postoperative 3, 4, 5 and 15 d, and less urine amount at postoperative 2 d (all P<0.05). Univariate analysis showed that donor age, the highest Scr level, the highest blood sodium level and the amount of fluid resuscitation within 48 h were the risk factors for DGF in recipients after kidney transplantation. Multivariate analysis showed that donor age was the independent risk factor for DGF in recipients after kidney transplantation (all P<0.05). Conclusions For the application of DBD donors complicated with AKI, active organ maintenance should be performed to alleviate AKI. It exerts no effect upon graft function and survival rate at postoperative 6 months, which may achieve equivalent efficacy as non-AKI donors and may be used as a source of extended criteria donor kidneys. [ABSTRACT FROM AUTHOR]

Objective: This study aims to compare the post-transplant survival of untwinned single lung transplantation (SLT) to twinned SLT. In untwinned SLT, the contralateral lung is judged unsuitable for transplantation and might affect the lung graft within the donor body and recipient survival after SLT. Methods: A retrospective analysis was conducted on 84 SLT recipients at our center, divided into untwinned SLT and twinned SLT groups. The demographics of donors and recipients, surgical characteristics, complications, mortality, and survival rates were compared. Results: There were no significant differences in recipient and donor demographics between the two groups. Surgical characteristics showed no significant differences. Microbiological findings of the transplanted lungs indicated a low incidence of positive cultures in both groups. 3-month to 1-year mortality and overall survival rates were comparable between the two groups. Conclusion: At our institution, both untwinned and twinned SLT procedures exhibited excellent survival rates without significant differences between the two procedures. The favorable outcomes observed may be associated with the strategic advantages of Japan's MC system and the diligent management of marginal donor lungs although this requires further investigation to elucidate the specific contributory factors. [ABSTRACT FROM AUTHOR]

As a marginal organ donor, organs from hepatitis C donors have been applied in solid organ transplantation. While effectively alleviating the shortage of organs, it also faces certain challenges, such as the spread of hepatitis C virus (HCV). With the emergence and application of direct-acting antiviral agent, the cure of hepatitis C has gradually become a reality, laying the foundation for hepatitis C patients to become organ transplant donors. At present, with adjuvant treatment using antiviral drugs, certain efficacy has been achieved in solid organ transplantation from hepatitis C donors. In this article, research progress in kidney, heart, lung and liver transplantation from hepatitis C donors, the application of hepatitis C donors in solid organ transplantation and the safety and effectiveness of antiviral drugs were reviewed, and the feasibility of hepatitis C donors in solid organ transplantation was evaluated, aiming to provide reference for expanding the donor pool of organ transplantation and shortening the waiting time for organ transplantation in patients with end-stage diseases. [ABSTRACT FROM AUTHOR]

Since the first liver transplant was performed over six decades ago, the landscape of liver transplantation in the US has seen dramatic evolution. Numerous advancements in perioperative and operative techniques have resulted in major improvements in graft and patient survival rates. Despite the increase in transplants performed over the years, the waitlist mortality rate continues to remain high. The obesity epidemic and the resultant metabolic sequelae continue to result in more marginal donors and challenging recipients. In this review, we aim to highlight the changing characteristics of liver transplant recipients and liver allograft donors. We focus on issues relevant in successfully transplanting a high model for end stage liver disease recipient. We provide insights into the current use of terms and definitions utilized to discuss marginal allografts, discuss the need to look into more consistent ways to describe these organs and propose two new concepts we coin as “Liver Allograft Variables” (LAV) and “Liver Allograft Composite Score” (LACS) for this. We discuss the development of spectrum of risk indexes as a dynamic tool to characterize an allograft in real time. We believe that this concept has the potential to optimize the way we allocate, utilize and transplant livers across the US.

Background: Delayed graft function (DGF) is common after kidney transplantation from deceased donors and may significantly affect post-transplant outcomes. This study aimed to evaluate whether an innovative approach, based on the administration of the intravenous prostaglandin analogue iloprost, could be beneficial in reducing the incidence of DGF occurring after kidney transplantation from deceased donors. Methods: This prospective, randomized (1:1), placebo-controlled study enrolled all consecutive patients who received a kidney transplant from a deceased donor from January 2000 to December 2012 and who were treated in the peri-transplant period with the prostaglandin analogue iloprost at 0.27 μg/min through an elastomeric pump (treatment group) or with a placebo (control group). Results: A total of 476 patients were included: DGF was reported in 172 (36.1%) patients in the entire cohort. The multivariate analysis showed that the donor's age > 70 years (OR 2.50, 95% confidence interval (CI): 1.40–3.05, p < 0.001), cold ischemia time > 24 h (OR 2.60, 95% CI: 1.50–4.51, p < 0.001), the donor's acute kidney injury (OR 2.71, 95% CI: 1.61–4.52, p = 0.021) and, above all, the recipient's arterial hypotension (OR 5.06, 95% CI: 2.52–10.1, p < 0.0001) were the strongest risk factors for developing post-transplant DGF. The incidence of DGF was 21.4% in the treatment group and 50.9% in the control group (p < 0.001). Interestingly, among patients who developed DGF, those who received iloprost had a shorter duration of post-transplant DGF (10.5 ± 8.3 vs. 13.4 ± 6.7, days, p = 0.016). Conclusions: This study showed that the use of a continuous infusion of iloprost could safely and effectively reduce the incidence of DGF in recipients of deceased-donor kidneys, allowing a better graft functionality as well as a better graft survival. [ABSTRACT FROM AUTHOR]

Background Heart transplantation is the gold standard therapy for end-stage heart failure; however, it is limited by a shortage of available donors. In recent years, heart transplantations have been performed using marginal donor hearts with valvular and/or congenital cardiac abnormalities. Case summary A 60-year-old woman with acromegalic cardiomyopathy underwent left ventricular assist device implantation and aortic valve (AV) closure 4 years prior. After 2 months, repeat AV closure and omental flap transposition were performed. During the outpatient follow-up, the patient developed recurrent severe AV regurgitation and bacteraemia-induced subarachnoid haemorrhage. She underwent urgent heart transplantation using a marginal donor heart with preserved cardiac function, mild pulmonary valve stenosis, and regurgitation after pulmonary valve-sparing tetralogy of Fallot (TOF) repair. An anatomical anastomosis was possible. She had no signs of infection, heart failure, arrhythmia, or immune rejection 15 months after the heart transplantation. Discussion In this case, the donor heart with repaired TOF did not require pulmonary valve replacement and was anatomically intact. Donor hearts with repaired TOF that are expected to have long-term durability in terms of cardiac function may be used for successful heart transplantations. The repair of marginal donor hearts creates an opportunity to increase the number of viable donors. [ABSTRACT FROM AUTHOR]

Several scores have been devised for providing a prognosis of outcomes after kidney transplantation. This study is a comprehensive test of these scores in a cohort of deceased donors with kidneys of lower-than-average quality and procurement biopsies. In total, 15 scores were tested on a retrospective cohort consisting of 221 donors, 223 procurement biopsies, and 223 recipient records for performance on delayed graft function, graft function, or death-censored graft loss. The best-performing score for DGF was the purely clinical Chapal score (AUC 0.709), followed by the Irish score (AUC 0.684); for graft function, the Nyberg score; and for transplant loss, the Snoeijs score (AUC 0.630) and the Leuven scores (AUCs 0.637 and 0.620). The only score with an acceptable performance was the Chapal score. Its disadvantage is that knowledge of the cold ischemia time is required, which is not known at allocation. None of the other scores performed acceptably. The scores fared better in discarded kidneys than in transplanted kidneys. Our study shows an unmet need for practical prognostic scores useful at the time of a decision about discarding or accepting deceased donor kidneys of lower-than-average quality in the Eurotransplant consortium. [ABSTRACT FROM AUTHOR]

Objective To construct a marginal donor model of porcine donation after cardiac death (DCD), and evaluate the pathological alteration of DCD donor kidneys. Methods Seven male mini pigs (4~6 months old, 13~17 kg) were divided into standard donor control group (C group, n=3) and DCD group (n=4). After intramuscular injection with phenobarbital sodium, their auricular vein channels were established, then propofol and sufentanil were injected to enhance the anesthetic induction while blood pressure, electrocardiogram and oxygen saturation (SaO2) were monitored at the same time. Group C received mechanical ventilation after endotracheal intubation, and maintained anesthesia with propofol, remifentanil and cisatracurium, and the kidneys were harvested under laparotomy. In the DCD group, 300 IU/kg heparin was injected intravenously for anticoagulation, followed by single bolus venous injection with 600 mg propofol and 10 mg cisatricurium to induce cardiac and respiratory arrest, and finally, the kidneys were harvested in 30 min after cardiac arrest. The kidneys in both groups were cut into small tissues, which were further fixed with 4% paraformaldehyde, embedded in paraffin wax and stained with HE for the pathological assessment and tissue damage scores under a optical microscope. Results The mean time for SaO2 to decline to 80% was 3.25±1.89 min and the mean time for cardiac arrest was 7.75±3.10 min in the 4 pigs of DCD group after injection with overdose of anesthetics. Compared with the C group, the renal tubular injury score of DCD marginal donor kidney after suffering from warm ischemia for 30 min, was higher (P < 0.05), and the mean score of glomerular injury was increased through no statistical difference. Conclusion Intravenous injection of excessive propofol and cisatracurium can effectively establish a porcine DCD marginal donor model.

Broader use of donation after circulatory death (DCD) and nonconventional grafts for liver transplant helps reduce disparities in organ availability. Limited data, however, exists on outcomes specific to nonconventional graft utilization in older patients. As such, this study aimed to investigate outcomes specific to conventional and nonconventional graft utilization in recipients > 70 y of age. 1-to-3 matching based on recipient sex, Model for End-Stage Liver Disease score, and donor type was performed on patients ≥70 and <70 y of age who underwent liver transplant alone at Mayo Clinic Arizona between 2015 and 2020. Primary outcomes were posttransplant patient and liver allograft survival for recipients greater than or less than 70 y of age. Secondary outcomes included grafts utilization patterns, hospital length of stay, need for reoperation, biliary complications and disposition at time of hospital discharge. In this cohort, 36.1% of grafts came from DCD donors, 17.4% were postcross clamp offers, and 20.8% were nationally allocated. Median recipient ages were 59 and 71 y (P < 0.01). Recipients had similar Intensive care unit (P = 0.82) and hospital (P = 0.14) lengths of stay, and there were no differences in patient (P = 0.68) or graft (P = 0.38) survival. When comparing donation after brain death and DCD grafts in those >70 y, there were no differences in patient (P = 0.89) or graft (P = 0.71) survival. Excellent outcomes can be achieved in older recipients, even with use of nonconventional grafts. Expanded use of nonconventional grafts can help facilitate transplant opportunities in older patients. [ABSTRACT FROM AUTHOR]

Introduction: Liver acceptance patterns vary significantly between transplant centers. Data pertaining to outcomes of livers declined by local and regional centers and allocated nationally remains limited. Project aim: The objective was to compare post-liver transplant outcomes between liver allografts transplanted as a result of national and local-regional allocation. Design: This was a retrospective evaluation of 109 nationally allocated liver allografts used for transplant by a single center. Outcomes of nationally allocated grafts were compared to standard allocation grafts (N = 505) during the same period. Results: Recipients of nationally allocated grafts had lower model for end stage liver disease scores (17 vs 22, P =.001). Nationally allocated grafts were more likely to be post-cross clamp offers (29.4% vs 13.4%, P =.001) and have longer cold ischemia times (median hours 7.8 vs 5.5, P =.001). Early allograft dysfunction was common (54.1% vs 52.5%, P =.75) and did not impact hospital length of stay (median 5 vs 6 days, P =.89). There were no differences in biliary complications (P =.11). There were no differences in patient (P =.88) or graft survival (P =.35). In a multivariate model, after accounting for differences in cold ischemia time and posttransplant biliary complications, nationally allocated grafts were not associated with increased risk for graft loss (HR 0.9, 95% CI 0.4-1.8). Abnormal liver biopsy findings (33.0%) followed by donor donation after circulatory death status (22.9%) were the most common reasons for decline by local-regional centers. Conclusion: Despite longer cold ischemia times, patient and graft survival outcomes remain excellent and comparable to those seen from standard allocation grafts. [ABSTRACT FROM AUTHOR]

Background: The use of donor hearts with valvular disease has been considered debatable in heart transplantation for many years. However, few reports indicate successful heart transplantation using donor hearts with mitral regurgitation that underwent mitral valve repair on the back bench. Case presentation: We report two cases of a 38-year-old and a 48-year-old woman with implantable left ventricular assist devices who underwent heart transplantation at our institution. Transthoracic echocardiography of donor hearts just before the explant revealed that each donor heart had preserved cardiac function and significant mitral regurgitation due to mitral posterior leaflet prolapse and annular dilatation, respectively. Bench mitral valve repair was accomplished using triangular resection for one patient and annuloplasty for the other. This was followed by confirmation of excellent mitral leaflet coaptation without residual mitral regurgitation. Transthoracic echocardiography and right heart catheterization performed 6 months after transplantation clarified the favorable cardiac function of each transplanted heart without mitral regurgitation recurrence. Conclusions: Efficient utilization of donor hearts with mitral regurgitation may be acceptable when the cardiac function of donor hearts with mitral regurgitation is preserved and heart transplantation, including bench mitral valve repair, is feasible within an acceptable ischemic time. [ABSTRACT FROM AUTHOR]

Background: We analysed the impact of perceived liver donor quality on transplant recipient outcomes. Methods: this prospective cohort study included all deceased liver donors during 2008–2018 in the Swiss Transplant Cohort Study. Perceived low‐quality liver donors were defined when refused for ≥5 top listed recipients or for all recipients in at least one centre before being transplanted. The effect of liver donor quality on relisting or recipient death at 1 week and 1 year after transplantation was analysed using Kaplan–Meier and Cox proportional hazard models. A 1:3 matching was also performed using a recipient score. Results: Of 973 liver donors, 187 (19.2%) had perceived poor‐quality. Males, obesity, donation after circulatory death and alanine aminotransferase values were significantly associated with perceived poor‐quality, with no significant effect of the perceived quality on re‐listing or death within the first week and first year post‐transplant [(aHR) = 1.45, 95% CI: (0.6, 3.5), P = 0.41 and aHR = 1.52 (95% CI 0.98–2.35), P = 0.06], adjusting by recipient age and gender, obesity, diabetes, prior liver transplantation and model for end‐stage liver disease (MELD) score. At 1 year, prior liver transplantation and higher MELD score associated with higher risk of re‐listing or death. Conclusion: Comparable post‐transplant outcomes with different perceived quality liver donors stresses the need to improve donor selection in liver transplantation. [ABSTRACT FROM AUTHOR]

Background: Delayed graft function (DGF) is common after kidney transplantation from deceased donors and may significantly affect post-transplant outcomes. This study aimed to evaluate whether an innovative approach, based on the administration of the intravenous prostaglandin analogue iloprost, could be beneficial in reducing the incidence of DGF occurring after kidney transplantation from deceased donors. Methods: This prospective, randomized (1:1), placebo-controlled study enrolled all consecutive patients who received a kidney transplant from a deceased donor from January 2000 to December 2012 and who were treated in the peri-transplant period with the prostaglandin analogue iloprost at 0.27 μg/min through an elastomeric pump (treatment group) or with a placebo (control group). Results: A total of 476 patients were included: DGF was reported in 172 (36.1%) patients in the entire cohort. The multivariate analysis showed that the donor’s age > 70 years (OR 2.50, 95% confidence interval (CI): 1.40–3.05, p < 0.001), cold ischemia time > 24 h (OR 2.60, 95% CI: 1.50–4.51, p < 0.001), the donor’s acute kidney injury (OR 2.71, 95% CI: 1.61–4.52, p = 0.021) and, above all, the recipient’s arterial hypotension (OR 5.06, 95% CI: 2.52–10.1, p < 0.0001) were the strongest risk factors for developing post-transplant DGF. The incidence of DGF was 21.4% in the treatment group and 50.9% in the control group (p < 0.001). Interestingly, among patients who developed DGF, those who received iloprost had a shorter duration of post-transplant DGF (10.5 ± 8.3 vs. 13.4 ± 6.7, days, p = 0.016). Conclusions: This study showed that the use of a continuous infusion of iloprost could safely and effectively reduce the incidence of DGF in recipients of deceased-donor kidneys, allowing a better graft functionality as well as a better graft survival.

Abstract Objectives To compare the donor outcomes of living donor kidney transplantation between standard donors (SDs) and marginal donors (MDs) including diabetic patients (MD + DM). Methods MDs were defined according to Japanese guideline criteria: (a) age >70‐years, (b) blood pressure ≤130/80 mmHg on hypertension medicine, (c) body mass index >25 to ≤32 kg/m2, (d) 24‐h creatinine clearance ≥70 to 6.2 or ≤6.5 with oral diabetic medicine. Fifty‐three of 114 donors were MDs. We compared donor kidney functions until 60 months postoperatively. Results No kidney function parameters were different between SDs and MDs. When comparing SD and MD + DM, MD + DM had a lower postoperative eGFR (48 vs. 41 (1 (month), p = .02), 49 vs. 40 (12, p

Abstract In Japan, 437 pancreas transplantations (PTx) were carried out between 2000 and 2019. Clinical data for all PTx cases are registered in the Japan Pancreas Transplant Registry of the Japan Society for Pancreas and Islet Transplantation. Here we analyzed the registry data to describe the current status of PTx in Japan. The 437 PTx included 410 from deceased donors (407 from brain‐dead and 3 from non‐heart‐beating donors) and 27 from living donors. We investigated the clinical characteristics of the 410 PTx from deceased donors. The rate of marginal donors using expanded donor criteria was higher in Japan than in other countries. At 1/5/10 years post‐PTx, the overall survival rates were 95.8%/94.2%/88.7%, and the graft survival rates were 85.9%/76.2%/67.4% for pancreas and 93.2%/90.8%/78.2% for kidney (non‐censored for death). These rates were comparable to those in other countries. When stratified by PTx category, survival was significantly better following simultaneous pancreas‐kidney transplantation (SPK) compared to pancreas‐after‐kidney transplantation (PAK) or PTx alone (PTA). Immunological rejection was more frequently the cause of graft loss in PAK/PTA cases than in SPK cases, potentially contributing to the poorer survival in PAK/PTA. These outcomes highlight two main concerns: substantial incidence of pancreas graft loss, and inferior outcomes after PAK/PTA. Overall, PTx outcome is favorable in Japan, despite the high rate of marginal donors. To improve outcomes, it is important to prevent and manage each cause of pancreas graft loss. Overcoming the poorer survival in PAK/PTA may require new immunosuppressive protocols or allogenic islet transplantation.

BACKGROUND: The lack of donor heart resources is a worldwide problem in heart transplantation. Broadening the inclusion criteria of donor heart and rationally applying marginal donor heart are effective ways to alleviate the lack of donor heart resources, and they are also the development direction of heart transplantation. OBJECTIVE: To compare the effect of conventional donor and marginal donor heart transplantation in patients with end-stage heart disease. METHODS: Eighty patients with end-stage heart disease who underwent heart transplantation from April 2018 to March 2021 were divided into a conventional donor group (56 patients) and a marginal donor group (24 patients). All patients were given orthotopic heart transplantation. Then operative indicators, serum biochemical and prognostic were compared between the two groups. RESULTS AND CONCLUSION: Compared with the conventional donor group, the operation time [(465.35±62.45) min vs. (423.42±58.23) min, t=2.888, P < 0.05] was longer and intraoperative blood loss [(1 235.36±203.4) mL vs. (678.65±123.21) mL, t=15.075, P < 0.01)] was higher in the marginal donor group. During the follow-up of 12 months, there were no significant differences in serum creatine kinase MB isoenzyme, cardiac troponin I, total bilirubin, alanine aminotransferase and left ventricular ejection fraction between the two groups (t=0.693, 1.322, 1.514, 1.348, 1.285, P > 0.05). Compared with the conventional donor group (2%, 9%), incidence rates of infection and renal insufficiency were also significantly higher in the marginal donor group (17%, 29%; x2=6.349, 5.397, P < 0.05). On the premise of strict heart donor protection and perioperative management, marginal donor transplantation can achieve the surgical effect similar to conventional donor heart transplantation. However, complications such as postoperative infection and renal insufficiency should be prevented. [ABSTRACT FROM AUTHOR]

Dual kidney transplantation (DKT), utilizing two adult kidneys from the same donor for one recipient, has been used as a way to expand the available donor pool. These kidneys often come from high Kidney Donor Profile Index donors (KDPI > 85%). Data comparing outcomes between high KDPI DKT and single kidney transplants (SKT) remain limited. We assessed outcomes of 336 high KDPI kidney transplants performed at our center; 11.0% (n = 37) were DKT. Recipients of DKT were older (P =.02) and donors had a higher KDPI score (median 96% vs. 91%, P <.0001). DKT operative time was higher compared to SKT (+1.4 hours, P <.0001). There were no differences in delayed graft function (54.1% vs. 51.5%, P =.77) and hospital length of stay (median 4.0 vs. 3.0 days, P =.21) between DKT and SKT. Grade I Clavien‐Dindo complications occurred in 8.1% of DKT and 13.7% of SKT (P =.008). There were no grade IVa, IVb, or V complications in either group. DKT had more glomerulosclerosis (P =.04), interstitial fibrosis (P =.02), tubular atrophy (P =.01), and arterial thickening (P =.03) on 1‐year protocol biopsies. Estimated glomerular filtration was higher for DKT at 1‐ (P =.004) and 2‐years post‐transplant (P =.01). There were no differences in patient (HR 1.3, 95% CI.5‐3.3, P =.58) or graft (HR 1.1, 95% CI.5‐2.3, P =.83) survival. Good outcomes can be achieved with DKT using high KDPI kidneys with moderate chronic changes. DKT is a good option to help further utilize high KDPI kidneys and minimize discard. [ABSTRACT FROM AUTHOR]

Background and Objectives: Early allograft dysfunction (EAD) is considered a surrogate marker for adverse post-liver transplant (LT) outcomes. With the increasing use of nonconventional donors, EAD has become a more frequent occurrence. Given this background, we aimed to assess the prevalence and impact of EAD in an updated cohort inclusive of both conventional and nonconventional liver allografts. Materials and Methods: Perioperative and one-year outcomes were assessed for a total of 611 LT recipients with and without EAD from Mayo Clinic Arizona. EAD was defined as the presence of one or more of the following: bilirubin > 10 mg/dL on day 7, INR > 1.6 on day 7, or ALT and/or AST > 2000 IU/L within the first 7 days of LT. Results: Within this cohort, 31.8% of grafts (n = 194) came from donation after circulatory death (DCD) donors, 17.7% (n = 108) were nationally shared, 16.4% (n = 100) were allocated as post-cross clamp, and 8.7% contained moderate steatosis. EAD was observed in 52.2% (n = 321) of grafts in the study cohort (79% in DCD grafts and 40% in DBD grafts). EAD grafts had higher donor risk index (DRI) scores (1.9 vs. 1.6, p < 0.0001), were more likely to come from DCD donors (48% vs. 13.8%, p < 0.0001), were regionally allocated (p = 0.003), and had higher cold ischemia times (median 6.0 vs. 5.5 h, p = 0.001). Primary nonfunction events were rare in both groups (1.3% vs. 0.3%, p = 0.22). Post-LT acute kidney injury occurred at a similar frequency in recipients with and without EAD (43.6% vs. 30.3%, p = 0.41), and there were no differences in ICU (median 2 vs. 1 day, p = 0.60) or hospital (6 vs. 5 days, p = 0.24) length of stay. For DCD grafts, the rate of ischemic cholangiopathy was similar in the two groups (14.9% EAD vs. 17.5% no EAD, p = 0.69). One-year patient survival for grafts with and without EAD was 96.0% and 94.1% (HR 1.2, 95% CI 0.7–1.8; p = 0.54); one-year graft survival was 92.5% and 92.1% (HR 1.0, 95% CI 0.7–1.5; p = 0.88). Conclusions: In this cohort, EAD occurred in 52% of grafts. The occurrence of EAD, however, did not portend inferior outcomes. Compared to those without EAD, recipients with EAD had similar post-operative outcomes, as well as one-year patient and graft survival. EAD should be managed supportively and should not be viewed as a deterrent to utilization of non-ideal grafts. [ABSTRACT FROM AUTHOR]

Background This national multicentre retrospective cohort study aimed to assess the long-term outcomes of dual kidney transplantation (DKT) and compare them with those obtained from single kidney transplantation (SKT). Methods Our first analysis concerned all first transplants performed between May 2002 and December 2014, from marginal donors, defined as brain death donors older than 65 years, with an estimated glomerular filtration rate (eGFR) lower than 90 mL/min/1.73 m2. The second analysis was restricted to transplants adequately allocated according to the French DKT program based on donor eGFR: DKT for eGFR between 30 and 60, SKT for eGFR between 60 and 90 mL/min/1.73 m2. Recipients younger than 65 years or with a panel-reactive antibody percentage ≥25% were excluded. Results The first analysis included 461 DKT and 1131 SKT. DKT donors were significantly older (77.6 versus 74 years), had a more frequent history of hypertension and a lower eGFR (55.1 versus 63.6 mL/min/1.73 m2). While primary nonfunction and delayed graft function did not differ between SKT and DKT, 1-year eGFR was lower in SKT recipients (39 versus 49 mL/min/1.73 m2, P < 0.001). Graft survival was significantly better in DKT, even after adjustment for recipient and donor risk factors. Nevertheless, patient survival did not differ between these groups. The second analysis included 293 DKT and 687 SKT adequately allocated with donor eGFR and displayed similar results but with a smaller benefit in terms of graft survival. Conclusions In a context of organ shortage, DKT is a good option for optimizing the use of kidneys from very expanded criteria donors. [ABSTRACT FROM AUTHOR]

In search for novel biomarkers to assess graft quality, we investigated whether defined candidate genes are predictive for outcome after liver transplantation (LT).Zero-hour liver biopsies were obtained from 88 livers. Gene expression of selected candidate markers was analyzed and correlated with clinical parameters as well as short and long-term outcomes post LT. Whereas both, the calculated Eurotransplant Donor-Risk-Index and the donor body mass index, had either a poor or no predictive value concerning serum levels indicative for liver function (ALT, AST, GGT, bilirubin) after 6 months, chronological donor age was weakly predictive for serum bilirubin (AUC=0.67). In contrast, the major histcompatibility complex class I related chain A (MICA) mRNA expression demonstrated a high predictive value for serum liver function parameters revealing an inverse correlation (e.g. for ALT: 3 months p=0.0332; 6 months p=0.007, 12 months 0.0256, 24 months p=0.0098, 36 months, p=0.0153) and proved significant also in a multivariate regression model. Importantly, high expression of MICA mRNA revealed to be associated with prolonged graft survival (p=0.024; log rank test) after 10 years of observation, whereas low expression was associated with the occurrence of death in patients with transplant related mortality (p=0.031). Given the observed correlation with short and long-term graft function, we suggest MICA as a biomarker for pre-transplant graft evaluation.

Objectives: To compare the donor outcomes of living donor kidney transplantation between standard donors (SDs) and marginal donors (MDs) including diabetic patients (MD + DM). Methods: MDs were defined according to Japanese guideline criteria: (a) age >70‐years, (b) blood pressure ≤130/80 mmHg on hypertension medicine, (c) body mass index >25 to ≤32 kg/m2, (d) 24‐h creatinine clearance ≥70 to <80 ml/min/1.73 m2, and (e) hemoglobin A1c > 6.2 or ≤6.5 with oral diabetic medicine. Fifty‐three of 114 donors were MDs. We compared donor kidney functions until 60 months postoperatively. Results: No kidney function parameters were different between SDs and MDs. When comparing SD and MD + DM, MD + DM had a lower postoperative eGFR (48 vs. 41 (1 (month), p =.02), 49 vs. 40 (12, p <.01), 48 vs. 42 (24, p =.04), 47 vs. 38 (36, p =.01)) and the percentage of residual eGFR (SD vs. MD + DM: 63 vs. 57 (1 (month), p <.01), 63 vs. 57 (2, p <.01), 64 vs. 56 (12, p <.01), 63 vs. 57 (24, p <.01), 63 vs. 52 (36, p =.02)). However, when MD with a single risk factor of DM was compared to SD, the difference disappeared. Nine out of 12 (75%) MD + DM had ≥2 risk factors. Conclusions: Although long‐term observation of donor kidney function is necessary, careful MD + DM selection had the potential to expand the donor pool. [ABSTRACT FROM AUTHOR]

Background: Pre‐emptive kidney transplantation for end‐stage kidney disease in children has many advantages and may lead to the consideration of marginal parent donors. Methods: Using the example of the transplant of a kidney with medullary sponge disease from a parent to the child, we review the ethical framework for working up such donors. Results: The four principles of health ethics include autonomy (the right of the patient to retain control over his/her own body); beneficence (healthcare providers must do all they can do to benefit the patient in each situation); non‐maleficence ("first do no harm"—providers must consider whether other people or society could be harmed by a decision made, even if it is made for the benefit of an individual patient) and justice (there should be an element of fairness in all medical decisions). Highly motivated donors may derive significant psychological benefit from their donation and may thus be willing to incur more risk. The transplantation team and, ideally, an independent donor advocate team must make a judgment about the acceptability of the risk‐benefit ratio for particular potential donors, who must also make their own assessment. The transplantation team and donor advocate team must be comfortable with the risk‐benefit ratio before proceeding. Conclusions: An independent donor advocacy team that focuses on the donor needs is needed with sufficient multidisciplinary ethical, social, and psychological expertise. The decision to accept or reject the donor should be within the authority of the independent donor advocacy team and not the providers or the donor. [ABSTRACT FROM AUTHOR]

In search for novel biomarkers to assess graft quality, we investigated whether defined candidate genes are predictive for outcome after liver transplantation (LT). Zero-hour liver biopsies were obtained from 88 livers. Gene expression of selected candidate markers was analyzed and correlated with clinical parameters as well as short and long-term outcomes post LT. Whereas both, the calculated Eurotransplant Donor-Risk-Index and the donor body mass index, had either a poor or no predictive value concerning serum levels indicative for liver function (ALT, AST, GGT, bilirubin) after 6 months, chronological donor age was weakly predictive for serum bilirubin (AUC=0.67). In contrast, the major histcompatibility complex class I related chain A (MICA) mRNA expression demonstrated a high predictive value for serum liver function parameters revealing an inverse correlation (e.g. for ALT: 3 months p=0.0332; 6 months p=0.007, 12 months 0.0256, 24 months p=0.0098, 36 months, p=0.0153) and proved significant also in a multivariate regression model. Importantly, high expression of MICA mRNA revealed to be associated with prolonged graft survival (p=0.024; log rank test) after 10 years of observation, whereas low expression was associated with the occurrence of death in patients with transplant related mortality (p=0.031). Given the observed correlation with short and long-term graft function, we suggest MICA as a biomarker for pre-transplant graft evaluation. [ABSTRACT FROM AUTHOR]

In Japan, 437 pancreas transplantations (PTx) were carried out between 2000 and 2019. Clinical data for all PTx cases are registered in the Japan Pancreas Transplant Registry of the Japan Society for Pancreas and Islet Transplantation. Here we analyzed the registry data to describe the current status of PTx in Japan. The 437 PTx included 410 from deceased donors (407 from brain‐dead and 3 from non‐heart‐beating donors) and 27 from living donors. We investigated the clinical characteristics of the 410 PTx from deceased donors. The rate of marginal donors using expanded donor criteria was higher in Japan than in other countries. At 1/5/10 years post‐PTx, the overall survival rates were 95.8%/94.2%/88.7%, and the graft survival rates were 85.9%/76.2%/67.4% for pancreas and 93.2%/90.8%/78.2% for kidney (non‐censored for death). These rates were comparable to those in other countries. When stratified by PTx category, survival was significantly better following simultaneous pancreas‐kidney transplantation (SPK) compared to pancreas‐after‐kidney transplantation (PAK) or PTx alone (PTA). Immunological rejection was more frequently the cause of graft loss in PAK/PTA cases than in SPK cases, potentially contributing to the poorer survival in PAK/PTA. These outcomes highlight two main concerns: substantial incidence of pancreas graft loss, and inferior outcomes after PAK/PTA. Overall, PTx outcome is favorable in Japan, despite the high rate of marginal donors. To improve outcomes, it is important to prevent and manage each cause of pancreas graft loss. Overcoming the poorer survival in PAK/PTA may require new immunosuppressive protocols or allogenic islet transplantation. [ABSTRACT FROM AUTHOR]

Purpose of review: With increasing survival of patients with stage D heart failure, the demand for heart transplantation has increased. The supply of donor hearts remains relatively limited. Strategies have been investigated and new technologies have been developed to expand the current donor pool. These new approaches will be discussed herein. Recent findings: Donor hearts are often considered "marginal" due to risk factors such as older age, size mismatch with the intended recipient, prolonged ischemic time, presence of left ventricular hypertrophy, and hepatitis B/C infection. We reviewed recent data regarding the use of donor hearts with these risk factors and suggest ways to safely liberalize current donor heart acceptance criteria. New technologies such as temperature-controlled transport systems and ex vivo cardiac perfusion methods have also demonstrated promising short-term and intermediate outcomes as compared with routine cold storage, by promoting heart preservation and enabling heart procurement from remote sites with shorter cold ischemic time. Recent use of hearts from donation after circulatory death donors has demonstrated comparable outcomes to conventional donation after brain death, which can further expand the current donor pool. Summary: Careful selection of "marginal" donor hearts, use of ex vivo cardiac perfusion, and acceptance of hearts after circulatory death may expand our current cardiac donor pool with comparable outcomes to conventional donor selection and preparation methods. [ABSTRACT FROM AUTHOR]

Summary: Kidney transplantation from older and marginal donors is effective to confront organ shortage. However, limitations after transplantation of kidneys from very marginal kidney donors remain unclear. We compared patient and graft outcome, achieved allograft function and quality of life of renal transplantations from Very Senior Donors (VSD, defined as donors aged 70 years and older) with Senior Donors (SD, aged 60–70 years) and Regular Donors (RD, aged younger than 60 years) in Switzerland. We evaluated the outcome of 1554 adult recipients of deceased donor kidney transplantations from 05/2008 to 12/2019; median follow‐up was 4.7 years. Failure‐free survival (freedom from graft loss or death), glomerular filtration rate (eGFR), and quality of life at 12 months were analyzed for RD (reference group, n = 940), SD (n = 404), and VSD (n = 210). Failure‐free survival decreased with increasing donor age, mainly attributable to premature graft loss. Still, overall 5‐year failure‐free survival reached 83.1%, 81.0%, and 64.0% in the RD, SD, and VSD subgroups, respectively. eGFR 12 months post‐transplantation was significantly higher in RD compared with SD and VSD. The acceptance rate of donor candidates for kidney TPL was 78% for the entire cohort (87% for RD, 79% for SD, and 56% for VSD). Deceased donor kidney transplantation from donors aged 70 years or older is associated with an inferior, yet acceptable failure‐free outcome, with sustained quality of life. [ABSTRACT FROM AUTHOR]

In clinical kidney transplantation, the marginal kidney donors are known to develop chronic allograft rejection more frequently than living kidney donors. In our previous study, we have reported that the hydrogen gas-containing organ preservation solution prevented the development of acute injuries in the kidney of the donor after cardiac death by using preclinical miniature pig model. In the present study, we verified the impact of hydrogen gas treatment in transplantation with the optimal immunosuppressive protocol based on human clinical setting by using the miniature pig model. Marginal kidney processed by hydrogen gas-containing preservation solution has been engrafted for long-term (longer than 100 days). A few cases showed chronic rejection reaction; however, most were found to be free of chronic rejection such as graft tissue fibrosis or renal vasculitis. We concluded that marginal kidney graft from donor after cardiac death is an acceptable model for chronic rejection and that if the transplantation is carried out using a strict immunosuppressive protocol, chronic rejection may be alleviated even with the marginal kidney.

Background and Objectives: Early allograft dysfunction (EAD) is considered a surrogate marker for adverse post-liver transplant (LT) outcomes. With the increasing use of nonconventional donors, EAD has become a more frequent occurrence. Given this background, we aimed to assess the prevalence and impact of EAD in an updated cohort inclusive of both conventional and nonconventional liver allografts. Materials and Methods: Perioperative and one-year outcomes were assessed for a total of 611 LT recipients with and without EAD from Mayo Clinic Arizona. EAD was defined as the presence of one or more of the following: bilirubin > 10 mg/dL on day 7, INR > 1.6 on day 7, or ALT and/or AST > 2000 IU/L within the first 7 days of LT. Results: Within this cohort, 31.8% of grafts (n = 194) came from donation after circulatory death (DCD) donors, 17.7% (n = 108) were nationally shared, 16.4% (n = 100) were allocated as post-cross clamp, and 8.7% contained moderate steatosis. EAD was observed in 52.2% (n = 321) of grafts in the study cohort (79% in DCD grafts and 40% in DBD grafts). EAD grafts had higher donor risk index (DRI) scores (1.9 vs. 1.6, p < 0.0001), were more likely to come from DCD donors (48% vs. 13.8%, p < 0.0001), were regionally allocated (p = 0.003), and had higher cold ischemia times (median 6.0 vs. 5.5 h, p = 0.001). Primary nonfunction events were rare in both groups (1.3% vs. 0.3%, p = 0.22). Post-LT acute kidney injury occurred at a similar frequency in recipients with and without EAD (43.6% vs. 30.3%, p = 0.41), and there were no differences in ICU (median 2 vs. 1 day, p = 0.60) or hospital (6 vs. 5 days, p = 0.24) length of stay. For DCD grafts, the rate of ischemic cholangiopathy was similar in the two groups (14.9% EAD vs. 17.5% no EAD, p = 0.69). One-year patient survival for grafts with and without EAD was 96.0% and 94.1% (HR 1.2, 95% CI 0.7–1.8; p = 0.54); one-year graft survival was 92.5% and 92.1% (HR 1.0, 95% CI 0.7–1.5; p = 0.88). Conclusions: In this cohort, EAD occurred in 52% of grafts. The occurrence of EAD, however, did not portend inferior outcomes. Compared to those without EAD, recipients with EAD had similar post-operative outcomes, as well as one-year patient and graft survival. EAD should be managed supportively and should not be viewed as a deterrent to utilization of non-ideal grafts.

Full application of marginal donor organs is a critical method to expand donor pool and alleviate organ shortage. After accurate donor evaluation, allocation and recipient selection, adult donor dual kidney transplantation (DKT) can not only achieve equivalent clinical efficacy to single kidney transplantation (SKT), but also effectively reduce the discard rate of marginal donor kidney. In this article, the clinical application and progress on adult donor DKT were reviewed from the perspectives of the development situation, allocation standard, recipient selection, surgical methods and complications as well as clinical efficacy of DKT, aiming to provide reference and guidance for subsequent development of marginal donor DKT. [ABSTRACT FROM AUTHOR]

In clinical kidney transplantation, the marginal kidney donors are known to develop chronic allograft rejection more frequently than living kidney donors. In our previous study, we have reported that the hydrogen gas-containing organ preservation solution prevented the development of acute injuries in the kidney of the donor after cardiac death by using preclinical miniature pig model. In the present study, we verified the impact of hydrogen gas treatment in transplantation with the optimal immunosuppressive protocol based on human clinical setting by using the miniature pig model. Marginal kidney processed by hydrogen gas-containing preservation solution has been engrafted for long-term (longer than 100 days). A few cases showed chronic rejection reaction; however, most were found to be free of chronic rejection such as graft tissue fibrosis or renal vasculitis. We concluded that marginal kidney graft from donor after cardiac death is an acceptable model for chronic rejection and that if the transplantation is carried out using a strict immunosuppressive protocol, chronic rejection may be alleviated even with the marginal kidney. [ABSTRACT FROM AUTHOR]

Background: To evaluate the early and late outcome of heart transplantation (HT) using marginal (MDs) and optimal donors (ODs). Methods: Clinical records of recipients transplanted between July 2004 and December 2014 were retrospectively reviewed. MDs were defined as follows: age >55 years, high‐dose inotropic support, left ventricular ejection fraction <45%, left ventricular hypertrophy, donor to recipient predicted heart mass ratio <0.86, ischemic time >4 hours. Results: A total of 412 (55%) recipients received an organ from a MD; recipients who received an organ from an OD had less primary graft dysfunction (PGD) (25% vs 38%; P <.001), less acute renal failure (23% vs 34%; P <.001), and higher survival rates (90.2% vs 81.8% at 30 days, 79.5% vs 71.1% at 1 year, 51.8% vs 45.4% at 12 years; P =.01) than recipients who received an organ from a MD. There was no statistically significant difference in 30‐day conditional survival between the two groups (survival rates 57.4% vs 55.5% at 12 years; P =.43). PGD, perioperative hemodialysis, and sepsis were independent risk factors of mortality at multivariate analysis. Conclusions: Utilization of MDs for HT is associated with a higher incidence of PGD and acute renal failure, and a reduction of 30‐day survival. [ABSTRACT FROM AUTHOR]

Summary: Livers from donation after circulatory death (DCD) donors are an increasingly more common source of organs for transplantation. While there are few high‐level studies in the field of DCD liver transplantation, clinical practice has undergone progressive changes during the past decade, in particular due to mounting use of postmortem normothermic regional perfusion (NRP). In Spain, uncontrolled DCD has been performed since the late 1980s/early 1990s, while controlled DCD was implemented nationally in 2012. Since 2012, the rise in DCD liver transplant activity in Spain has been considerable, and the great majority of DCD livers transplanted in Spain today are recovered with NRP. A panel of the Spanish Liver Transplantation Society was convened in 2018 to evaluate current evidence and accumulated experience in DCD liver transplantation, in particular addressing issues related to DCD liver evaluation, acceptance criteria, and recovery as well as recipient selection and postoperative management. This panel has created a series of consensus statements for the standard of practice in Spain and has published these statements with the hope they might help guide other groups interested in implementing new forms of DCD liver transplantation and/or introducing NRP into their clinical practices. [ABSTRACT FROM AUTHOR]

Background: Donor organ acceptance practices vary among pediatric heart transplant professionals. We sought to understand what is known about the interactions between the "high‐risk" recipient and the "marginal donor," and how donor risk scores can impact this discussion. Methods: A systematic review of published literature on pediatric HTx was undertaken with the assistance of a medical librarian. Two authors independently assessed search results, and papers were reviewed for inclusion. Results: We found that there are a large number of individual factors, and clusters of factors, that have been used to label individual recipients "high‐risk" and individual donors "marginal." The terms "high‐risk recipient" and "marginal donor" have been used broadly in the literature making it virtually impossible to make comparisons between publications. In general, the data support that patients who could be easily agreed to be "sicker recipients" are at more risk compared to those who are clearly "healthier," albeit still "sick enough" to need transplantation. Given this variability in the literature, we were unable to define how being a "high‐risk" recipient interplays with accepting a "marginal donor." Existing risk scores are described, but none were felt to adequately predict outcomes from factors available at the time of offer acceptance. Conclusions: We could not determine what makes a donor "marginal," a recipient "high‐risk," or how these factors interplay within the specific recipient‐donor pair to determine outcomes. Until there are better risk scores predicting outcomes at the time of organ acceptance, programs should continue to evaluate each organ and recipient individually. [ABSTRACT FROM AUTHOR]

Polycystic kidney disease is an otosomal dominant hereditary disorder which can progress to end stage kidney failure. In this disease, the cysts in distinct sizes and distinct number are seen in kidneys and in liver. Nowadays, there is a great diffence in the number of donors and the patients waiting for transplantation. Because of that, using marginal donors may be necessary. In this article, we aimed to discuss whether a 55 years old braindead polycystic kidney disease patient can be used for transplantation or not.

Abstract Background Lung transplantation (LTx) is limited by the shortage of suitable donors. To overcome this problem, many programs have begun to use donors with extended criteria (marginal donors). However, brain-dead patients with implanted mechanical circulatory support system have rarely been considered as potential lung donors. This case demonstrates the feasibility of lung transplantations from organ donors supported by a mechanical circulatory support system despite the possible difficulties of lung retrieval. Case presentation Our case presents a successful procurement and bilateral lung transplantation from a donor supported by a left ventricular assist device (LVAD) who experienced an intraoperatively haemodynamic complication. The use of portable normothermic perfusion device let us to reduce ischemic injury and assess these marginal donor lungs helping us to determine the clinical suitability for transplantation. Given our extensive experience with the device instrumentation and management, the EVLP process was uneventful with excellent post-transplant course. Conclusions This case report demonstrates the feasibility of lung transplantations from organ donors supported by a mechanical circulatory support system using the portable normothermic perfusion platform to assess and preserve these donor lungs.

The fate of transplanted kidneys is substantially influenced by graft quality, with transplantation of kidneys from elderly and expanded criteria donors (ECDs) associated with higher occurrence of delayed graft function, rejection, and inferior long-term outcomes. However, little is known about early molecular fingerprints of these events in different donor categories. Borderline changes represent the most frequent histological finding early after kidney transplantation. Therefore, we examined outcomes and transcriptomic profiles of early-case biopsies diagnosed as borderline changes in different donor categories. In this single-center, retrospective, observational study, we compared midterm outcomes of kidney transplant recipients with early borderline changes as a first pathology between ECD (n = 109), standard criteria donor (SCDs, n = 109), and living donor (LD, n = 51) cohorts. Intragraft gene expression profiling by microarray was performed in part of these ECD, SCD, and LD cohorts. Although 5 year graft survival in patients with borderline changes in early-case biopsies was not influenced by donor category (log-rank P = 0.293), impaired kidney graft function (estimated glomerular filtration rate by Chronic Kidney Disease Epidemiology Collaboration equation) at M3, 1, 2, and 3 years was observed in the ECD cohort (P < 0.001). Graft biopsies from ECD donors had higher vascular intimal fibrosis and arteriolar hyalinosis compared to SCD and LD (P < 0.001), suggesting chronic vascular changes. Increased transcripts typical for ECD, as compared to both LD and SCD, showed enrichment of the inflammatory, defense, and wounding responses and the ECM–receptor interaction pathway. Additionally, increased transcripts in ECD vs. LD showed activation of complement and coagulation and cytokine–cytokine receptor pathways along with platelet activation and cell cycle regulation. Comparative gene expression overlaps of ECD, SCD, and LD using Venn diagrams found 64 up- and 16 down-regulated genes in ECD compared to both LD and SCD. Shared increased transcripts in ECD vs. both SCD and LD included thrombospondin-2 (THBS2), angiopoietin-like 4 (ANGPTL4), collagens (COL6A3, COL1A1), chemokine CCL13, and interleukin IL11, and most significantly, down-regulated transcripts included proline-rich 35 (PRR35) and fibroblast growth factor 9. Early borderline changes in ECD kidney transplantation are characterized by increased regulation of inflammation, extracellular matrix remodeling, and acute kidney injury transcripts in comparison with both LD and SCD grafts.

There is a growing shortage of kidney donors leading to extended transplant waiting times associated with increased mortality. To expand the donor pool, clinicians nowadays regularly accept organs from elderly donors, including those aged ≥70 years. There is only limited and conflicting data whether kidneys from these elderly donors allow for satisfactory allograft outcome rates. To asses this question, the 5-year death censored graft survival of 116,870 adult first deceased donor kidney allograft recipients that were transplanted at European centers between 1997 and 2016 and reported to the “Collaborative Transplant Study” were analyzed using Kaplan–Meier analysis and country stratified Cox regression. The combinations of the two transplant periods 1997–2006 and 2007–2016 with the donor age categories 18–49, 50–59, 60–69, and ≥70 years were considered. From 1997–2006 to 2007–2016, the median donor age increased from 50 to 55 years and the proportion of kidneys from ≥60-year-old donors rose from 24.1 to 38.8%. At the same time, the proportion of kidneys from ≥70-year-old donors more than doubled (6.7 vs. 15.4%). Between 1997–2006 and 2007–2016, the 5-year graft survival improved in all donor age categories. During 2007–2016, the 5-year death censored graft survival of kidneys from ≥70-year-old donors was comparable to that of kidneys from 60 to 69-year-old donors during 1997–2006. This was true both for younger recipients (18–64 years) and older recipients (≥65 years). Among the younger recipients, 45–64-year-old recipients showed the best death censored graft survival rates for kidneys from old donors. In the country-stratified Cox regression analysis, compared to the reference of grafts from 18 to 49-year-old donors, the hazard ratio for grafts from ≥70-year-old donors during 2007–2016 was 1.92, exactly the same as the hazard ratio for grafts from 60 to 69-year-old donors during 1997–2006. Our analysis indicates that within only one further decade (1997–2006 vs. 2007–2016) the 5-year death censored graft survival of kidneys from ≥70-year old donors improved to the level of kidneys from 60 to 69-year-old donors in the previous decade.

The fate of transplanted kidneys is substantially influenced by graft quality, with transplantation of kidneys from elderly and expanded criteria donors (ECDs) associated with higher occurrence of delayed graft function, rejection, and inferior long-term outcomes. However, little is known about early molecular fingerprints of these events in different donor categories. Borderline changes represent the most frequent histological finding early after kidney transplantation. Therefore, we examined outcomes and transcriptomic profiles of early-case biopsies diagnosed as borderline changes in different donor categories. In this single-center, retrospective, observational study, we compared midterm outcomes of kidney transplant recipients with early borderline changes as a first pathology between ECD (n = 109), standard criteria donor (SCDs, n = 109), and living donor (LD, n = 51) cohorts. Intragraft gene expression profiling by microarray was performed in part of these ECD, SCD, and LD cohorts. Although 5 year graft survival in patients with borderline changes in early-case biopsies was not influenced by donor category (log-rank P = 0.293), impaired kidney graft function (estimated glomerular filtration rate by Chronic Kidney Disease Epidemiology Collaboration equation) at M3, 1, 2, and 3 years was observed in the ECD cohort (P < 0.001). Graft biopsies from ECD donors had higher vascular intimal fibrosis and arteriolar hyalinosis compared to SCD and LD (P < 0.001), suggesting chronic vascular changes. Increased transcripts typical for ECD, as compared to both LD and SCD, showed enrichment of the inflammatory, defense, and wounding responses and the ECM–receptor interaction pathway. Additionally, increased transcripts in ECD vs. LD showed activation of complement and coagulation and cytokine–cytokine receptor pathways along with platelet activation and cell cycle regulation. Comparative gene expression overlaps of ECD, SCD, and LD using Venn diagrams found 64 up- and 16 down-regulated genes in ECD compared to both LD and SCD. Shared increased transcripts in ECD vs. both SCD and LD included thrombospondin-2 (THBS2), angiopoietin-like 4 (ANGPTL4), collagens (COL6A3, COL1A1), chemokine CCL13 , and interleukin IL11 , and most significantly, down-regulated transcripts included proline-rich 35 (PRR35) and fibroblast growth factor 9. Early borderline changes in ECD kidney transplantation are characterized by increased regulation of inflammation, extracellular matrix remodeling, and acute kidney injury transcripts in comparison with both LD and SCD grafts. [ABSTRACT FROM AUTHOR]

There is a growing shortage of kidney donors leading to extended transplant waiting times associated with increased mortality. To expand the donor pool, clinicians nowadays regularly accept organs from elderly donors, including those aged ≥70 years. There is only limited and conflicting data whether kidneys from these elderly donors allow for satisfactory allograft outcome rates. To asses this question, the 5-year death censored graft survival of 116,870 adult first deceased donor kidney allograft recipients that were transplanted at European centers between 1997 and 2016 and reported to the "Collaborative Transplant Study" were analyzed using Kaplan–Meier analysis and country stratified Cox regression. The combinations of the two transplant periods 1997–2006 and 2007–2016 with the donor age categories 18–49, 50–59, 60–69, and ≥70 years were considered. From 1997–2006 to 2007–2016, the median donor age increased from 50 to 55 years and the proportion of kidneys from ≥60-year-old donors rose from 24.1 to 38.8%. At the same time, the proportion of kidneys from ≥70-year-old donors more than doubled (6.7 vs. 15.4%). Between 1997–2006 and 2007–2016, the 5-year graft survival improved in all donor age categories. During 2007–2016, the 5-year death censored graft survival of kidneys from ≥70-year-old donors was comparable to that of kidneys from 60 to 69-year-old donors during 1997–2006. This was true both for younger recipients (18–64 years) and older recipients (≥65 years). Among the younger recipients, 45–64-year-old recipients showed the best death censored graft survival rates for kidneys from old donors. In the country-stratified Cox regression analysis, compared to the reference of grafts from 18 to 49-year-old donors, the hazard ratio for grafts from ≥70-year-old donors during 2007–2016 was 1.92, exactly the same as the hazard ratio for grafts from 60 to 69-year-old donors during 1997–2006. Our analysis indicates that within only one further decade (1997–2006 vs. 2007–2016) the 5-year death censored graft survival of kidneys from ≥70-year old donors improved to the level of kidneys from 60 to 69-year-old donors in the previous decade. [ABSTRACT FROM AUTHOR]

Background: Recently, living-donor kidney transplantation from marginal donors has been increasing. However, a simple prediction model for graft function including preoperative marginal factors is limited. Here, we developed and validated a new prediction model for graft function using preoperative marginal factors in living-donor kidney transplantation. Methods: We retrospectively investigated 343 patients who underwent living-donor kidney transplantation at Kyushu University Hospital (derivation cohort). Low graft function was defined as an estimated glomerular filtration rate of < 45 mL/min/1.73 m2 at 1 year. A prediction model was developed using a multivariable logistic regression model, and verified using data from 232 patients who underwent living-donor kidney transplantation at Tokyo Women's Medical University Hospital (validation cohort). Results: In the derivation cohort, 89 patients (25.9%) had low graft function at 1 year. Donor age, donor-estimated glomerular filtration rate, donor hypertension, and donor/recipient body weight ratio were selected as predictive factors. This model demonstrated modest discrimination (c-statistic = 0.77) and calibration (Hosmer–Lemeshow test, P = 0.83). Furthermore, this model demonstrated good discrimination (c-statistic = 0.76) and calibration (Hosmer–Lemeshow test, P = 0.54) in the validation cohort. Furthermore, donor age, donor-estimated glomerular filtration rate, and donor hypertension were strongly associated with glomerulosclerosis and atherosclerotic vascular changes in the "zero-time" biopsy. Conclusions: This model using four pre-operative variables will be a simple, but useful guide to estimate graft function at 1 year after kidney transplantation, especially in marginal donors, in the clinical setting. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • In cDCD livers, postmortem NRP reduces biliary complications, in particular ITBL. • Postmortem NRP helps improve cDCD liver graft survival. • Use of postmortem NRP facilitates successful transplantation of older cDCD livers. Background & Aims Although there is increasing interest in its use, definitive evidence demonstrating a benefit for postmortem normothermic regional perfusion (NRP) in controlled donation after circulatory death (cDCD) liver transplantation is lacking. The aim of this study was to compare results of cDCD liver transplants performed with postmortem NRP vs. super-rapid recovery (SRR), the current standard for cDCD. Methods This was an observational cohort study including all cDCD liver transplants performed in Spain between June 2012 and December 2016, with follow-up ending in December 2017. Each donor hospital determined whether organ recovery was performed using NRP or SRR. The propensity scores technique based on the inverse probability of treatment weighting (IPTW) was used to balance covariates across study groups; logistic and Cox regression models were used for binary and time-to-event outcomes. Results During the study period, there were 95 cDCD liver transplants performed with postmortem NRP and 117 with SRR. The median donor age was 56 years (interquartile range 45–65 years). After IPTW analysis, baseline covariates were balanced, with all absolute standardised differences <0.15. IPTW-adjusted risks were significantly improved among NRP livers for overall biliary complications (odds ratio 0.14; 95% CI 0.06–0.35, p <0.001), ischaemic type biliary lesions (odds ratio 0.11; 95% CI 0.02–0.57; p = 0.008), and graft loss (hazard ratio 0.39; 95% CI 0.20–0.78; p = 0.008). Conclusions The use of postmortem NRP in cDCD liver transplantation appears to reduce postoperative biliary complications, ischaemic type biliary lesions and graft loss, and allows for the transplantation of livers even from cDCD donors of advanced age. Lay summary This is a propensity-matched nationwide observational cohort study performed using livers recovered from donors undergoing cardiac arrest provoked by the intentional withdrawal of life support (controlled donation after circulatory death, cDCD). Approximately half of the livers were recovered after a period of postmortem in situ normothermic regional perfusion, which restored warm oxygenated blood to the abdominal organs, whereas the remainder were recovered after rapid preservation with a cold solution. The study results suggest that the use of postmortem normothermic regional perfusion helps reduce rates of post-transplant biliary complications and graft loss and allows for the successful transplantation of livers from older cDCD donors. [ABSTRACT FROM AUTHOR]