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Background. The hemodynamic effects of aortic arch vessel (AAV) clamping during normothermic regional perfusion (NRP) in donation after circulatory death is unknown. We investigated effects of AAV clamping during NRP compared with no clamping in a porcine model.Methods. In 16 pigs, hemodynamic parameters were recorded including biventricular pressure-volume measurements and invasive blood pressure. Additionally, blood gas parameters and inflammatory cytokines were used to assess the effect of AAV clamping. The animals were centrally cannulated for NRP, and baseline measurements were obtained before hypoxic circulatory arrest was induced by halting mechanical ventilation. During an 8-min asystole period, the animals were randomized to clamp (n = 8) or no-clamp (n = 8) of the AAV before commencement of NRP. During NRP, circulation was supported with norepinephrine (NE) and dobutamine. After 30 min of NRP, animals were weaned and observed for 180 min post-NRP.Results. All hearts were successfully reanimated and weaned from NRP. The nonclamp groups received significantly more NE to maintain a mean arterial pressure >60 mm Hg during and after NRP compared with the clamp group. There were no between group differences in blood pressure or cardiac output. Pressure-volume measurements demonstrated preserved cardiac function‚ including ejection fraction and diastolic and systolic function. No between group differences in inflammatory markers were observed.Conclusions. AAV clamping did not negatively affect donor cardiac function or inflammation after circulatory death and NRP. Significantly less NE was used to support in the clamp group than in the nonclamp group.

The gold-standard therapy for advanced-stage heart failure is cardiac transplantation. Since the first heart transplant in 1967, the majority of hearts transplanted came from brain death donors. Nevertheless, in recent years, the option of donation after circulatory death (DCD) is gaining importance to increase donor pool. Currently, heart-transplant programs using controlled donation after circulatory death (cDCD) have been implemented in the United Kingdom, Belgium, Australia, United States of America, and, recently, in Spain. In this article, we performed a concise review of the literature in heart cDCD; we summarize the pathophysiology involved in ischemia and reperfusion injury during this process, the different techniques of heart retrieval in cDCD donors, and the strategies that can be used to minimize the damage during retrieval and until transplantation. Heart transplant using DCD hearts is in continuous improvement and must be implemented in experienced cardiac transplant centers.

Background Normothermic ex situ liver perfusion (NEsLP) reduces reperfusion injury of donation after circulatory death (DCD) grafts and optimizes graft function. The goal of our study was to elucidate how NEsLP impacts global metabolism in DCD grafts using high-throughput metabolomics. Methods Pig livers were preserved by two different techniques: static cold storage (SCS) and normothermic ex-situ liver perfusion (NEsLP). Grafts obtained from heart-beating donors (HBD) were compared to donation after circulatory death (DCD) grafts with either 30 minutes (DCD30) or 60 minutes (DCD60) ischemia time. Liver tissues were collected at the end of preservation period (T0) with either cold storage or NEsLP (n=5 per group). Grafts were transplanted into recipient pigs and a second liver biopsy was collected 2 hours following liver transplantation (T1). Snap-frozen tissue was processed and analyzed by Sciex 6600 Q-TOF high resolution mass spectrometer. Data analysis was performed using MetaboAnalyst 4.0 software. Results Prolonged ischemia resulted in 38 out of 81 metabolites being differentially abundant over time. Mitochondrial metabolism was significantly affected, with disruption in oxidative phosphorylation capacity i.e the Warburg effect (p= 3.62E-03) and urea cycle (p=7.95E-0.4). NEsLP resulted in improved mitochondrial metabolism and glycolysis (4.20E-02) oxidation of branched chain fatty acids (p=4.07E-02). Conclusion This unbiased, high-throughput metabolomics study reveals that mitochondrial function is globally rescued with NEsLP, associated with improvement in DCD graft function. NEsLP is able to rescue DCD grafts, improving their metabolic function to that of livers not exposed to DCD procurement.

There is a severe shortage in the availability of donor organs for lung transplantation. Novel strategies are needed to optimize usage of available organs to address the growing global needs. Ex vivo lung perfusion has emerged as a powerful tool for the assessment, rehabilitation, and optimization of donor lungs before transplantation. In this review, we discuss the history of ex vivo lung perfusion, current evidence on its use for standard and extended criteria donors, and consider the exciting future opportunities that this technology provides for lung transplantation.

Background The detrimental role of platelets in sinusoidal endothelial cell (SEC) injury during liver transplantation (LT) has been previously addressed after static cold storage (SCS), however, it is currently unknown after normothermic ex vivo liver perfusion (NEVLP). Methods Pig LT was performed with livers from heart-beating donors or donation after circulatory death (DCD) donors subjected to SCS or NEVLP (n = 5/group). Results All pigs except for 1 (DCD-SCS-group) survived 4 days. The heart-beating donor- and DCD-NEVLP-groups showed significantly lower aspartate transaminase-levels compared with the SCS-groups 3 hours post-LT (P = 0.006), on postoperative day (POD) 2 (P = 0.005), POD3 (P = 0.007), and on POD4 (P = 0.012). Post-LT total platelet count recovered faster in the NEVLP than in the SCS-groups at 12 hours (P = 0.023) and 24 hours (P = 0.0038). Intrahepatic sequestration of platelets was significantly higher in the SCS-groups 3 hours postreperfusion and correlated with severity of SEC injury. In both SCS-groups, levels of tumor growth factor-β were higher 3 hours post-LT, on POD1 and on POD3. Moreover, platelet factor 4 levels and platelet-derived extracellular vesicles were increased in the SCS-groups. Hyaluronic acid levels were significantly higher in the SCS-groups, indicating a higher grade of endothelial cell dysfunction. Platelet inhibition achieved by pretreatment with clopidogrel (n = 3) partly reversed the detrimental effects on SEC injury and therefore provided further evidence of the important role of platelets in ischemia/reperfusion injury and SEC injury. Conclusions Normothermic perfusion of liver grafts before transplantation effectively reduced platelet aggregation and SEC injury, which translated into an improved posttransplant organ function.

The innovative pure laparoscopic living donor right hepatectomy (LLDRH) procedure for liver transplantation has never been fully compared to open living donor right hepatectomy (OLDRH). We aimed to compare the donor safety and graft results of pure LLDRH to those of OLDRH.From May 2013 to July 2017, 288 consecutive donors underwent either OLDRH (n = 197) or pure LLDRH (n = 91). After propensity score matching, 72 donors were included in each group. The primary outcome was postoperative complications during a 90-day follow-up period. Comprehensive complication index, duration of hospital stay, need for additional pain control, readmission, and donor outcomes were also compared.The incidence of major complication during the 90-day follow-up was higher in the LLDRH group than the OLDRH group (6.6% vs 15.4%, P = 0.017) but was not statistically significant in propensity-matched analysis (11.1% vs 13.9%, odds ratio [OR], 1.29; 95% confidence interval [CI], 0.47-3.51; P = 0.62). A right hepatic duct1 cm was independently associated with complication in the pure LLDRH group (odds ratio, 4.01; 95% confidence interval, 1.08-14.99; P = 0.04).In the initial 91 pure LLDRH cases, incidence of major complication was higher than in the OLDRH group, but the difference was not significant in propensity-matched analysis. A right hepatic duct verified as1 cm may be related to increased frequency of complications in pure LLDRH donors. Further analysis is needed.

Because of the shortage of liver grafts available for transplantation, the restrictions on graft quality have been relaxed, and marginal grafts, such as steatotic livers, are now accepted. However, this policy change has not solved the problem, because steatotic liver grafts tolerate ischemia-reperfusion (I/R) injury poorly. Adipocytokines differentially modulate steatosis, inflammation, and fibrosis and are broadly present in hepatic resections and transplants. The potential use of adipocytokines as biomarkers of the severity of steatosis and liver damage to aid the identification of high-risk steatotic liver donors and to evaluate hepatic injury in the postoperative period are discussed. The hope of finding new therapeutic strategies aimed specifically at protecting steatotic livers undergoing surgery is a strong impetus for identifying the mechanisms responsible for hepatic failure after major surgical intervention. Hence, the most recently described roles of adipocytokines in steatotic livers subject to I/R injury are discussed, the conflicting results in the literature are summarized, and reasons are offered as to why strategic pharmacologic control of adipocytokines has yet to yield clinical benefits. After this, the next steps needed to transfer basic knowledge about adipocytokines into clinical practice to protect marginal livers subject to I/R injury are presented. Recent strategies based on adipocytokine regulation, which have shown efficacy in various pathologies, and hold promise for hepatic resection and transplantation are also outlined.

In parallel with the pandemic of obesity and diabetes, the prevalence of nonalcoholic fatty liver disease has progressively increased. Nonalcoholic steatohepatitis (NASH), a subtype of nonalcoholic fatty liver disease has also augmented considerably being currently cirrhosis due to NASH the second indication for liver transplantation in the United States. Innovative treatments for NASH have shown promising results in phase 2 studies and are being presently evaluated in phase 3 trials. On the other hand, the high mortality on the liver transplant waitlist and the organ shortage has obligated the transplant centers to consider suboptimal grafts, such as steatotic livers for transplantation. Fatty livers are vulnerable to preservation injury resulting in a higher rate of primary nonfunction, early allograft dysfunction and posttransplant vascular and biliary complications. Macrosteatosis of more than 30% in fact is an independent risk factor for graft loss. Therefore, it needs to be considered into the risk assessment scores. Growing evidence supports that moderate and severe macrosteatotic grafts can be successfully used for liver transplantation with careful recipient selection. Protective strategies, such as machine-based perfusion have been developed in experimental setting to minimize preservation-related injury and are now on the verge to move into the clinical implementation. This review focuses on the current and potential future treatment of NASH and the clinical practice in fatty liver transplantation, highlights its limitations and optimal allocation, and summarizes the advances of experimental protective strategies, and their potential for clinical application to increase the acceptance and improve the outcomes after liver transplantation with high-grade steatotic livers.

Donation after circulatory death (DCD) grafts are commonly used in liver transplantation. Attributable to the additional ischemic event during the donor warm ischemia time (DWIT), DCD grafts carry an increased risk for severe ischemia/reperfusion injury and postoperative complications, such as ischemic cholangiopathy. The actual ischemia during DWIT depends on the course of vital parameters after withdrawal of life support and varies widely between donors. The ischemic period (functional DWIT) starts when either Spo2 or blood pressure drop below a certain point and lasts until the start of cold perfusion during organ retrieval. Over the years, multiple definitions and thresholds of functional DWIT duration have been used. The International Liver Transplantation Society organized a Consensus Conference on DCD, Liver Preservation, and Machine Perfusion on January 31, 2020 in Venice, Italy. The aim of this conference was to reach consensus about various aspects of DCD liver transplantation in context of currently available evidence. Here we present the recommendations with regards to the definitions used for DWIT and functional DWIT, the importance of vital parameters after withdrawal of life support, and acceptable thresholds of duration of functional DWIT to proceed with liver transplantation. ispartof: TRANSPLANTATION vol:105 issue:6 pages:1156-1164 ispartof: location:United States status: published

Having little evidence on the real extent of the minimally invasive donor hepatectomy (MIDH), a world survey was conducted aiming to picture the spread of MIDH and to identify geographical, institutional, and individual differences.A web-based survey was created with 5 sections (general, institutional, surgeon's experience, technical, and spread and dissemination), comprising up to a total of 47 questions. A thorough search was carried out to identify all possible centers and surgeons performing MIDH.A global MIDH experience of 2370 cases was collected: 1587 right hepatectomies (RHs; 48.9% pure laparoscopic), 471 left lateral sectionectomies (LLS; 81.1% pure laparoscopic), and 366 left hepatectomies (LHs; 77.6% laparoscopic-assisted). LLS and adult MIDH conversion rates were 5.4% and 3.9%, respectively. Median blood loss was 250 mL (100-600), 100 mL (50-250), and 150 mL (50-500) for RH, LLS, and LH, respectively. Intra- and postoperative transfusion rates were 0.5%, 0%, and 0.3%; and 1.3%, 1.6%, and 0% for RH, LLS, and LH, respectively. Geographically, Asia accounts up to 1730 cases (73% of the global experience, 49.6% pure lap), of which 1374 cases are RH; Europe and Middle East-395 cases-stands out for its experience in left lateral sectionectomy: 289 cases (93% pure lap). Finally, America accounts for 245 cases, using a laparoscopic-assisted technique in 72.6% of the cases (178).This world survey provides evidence and data on the global spread of MIDH and anticipates how in a near future a large-scale adoption of these techniques may be observed.

For 2 centuries, researchers have studied ex vivo perfusion intending to preserve the physiologic function of isolated organs. If it were indeed possible to maintain ex vivo organ viability for days, transplantation could become an elective operation with clinicians methodically surveilling and reconditioning allografts before surgery. To this day, experimental reports of successfully prolonged (≥24 hours) organ perfusion are rare and have not translated into clinical practice. To identify the crucial factors necessary for successful perfusion, this review summarizes the history of prolonged normothermic ex vivo organ perfusion. By examining successful techniques and protocols used, this review outlines the essential elements of successful perfusion, limitations of current perfusion systems, and areas where further research in preservation science is required.

Despite improvements in postliver transplant outcomes through refinements in perioperative management and surgical techniques, several changing trends in liver transplantation have presented challenges. Mortality on the waitlist remains high. In the United States, Europe, and the United Kingdom, there is an increasing need for liver transplantation, primarily as a result of increased incidence of nonalcoholic steatohepatitis-related cirrhosis and cancer indications. Meanwhile, donor suitability has decreased, as donors are often older and have more comorbidities. Despite a mismatch between organ need and availability, many organs are discarded. Notwithstanding this, many solutions have been developed to overcome these challenges. Innovative techniques in allograft preservation, viability assessment, and reconditioning have allowed the use of suboptimal organs with adequate results. Refinements in surgical procedures, including live donor liver transplantations, have increased the organ pool and are decreasing the time and mortality on the waitlist. Despite many challenges, a similar number of solutions and prospects are on the horizon. This review seeks to explore the changing trends and challenges in liver transplantation and highlight possible solutions and future directions.

BACKGROUND Recipients of kidneys from living donors who subsequently develop end-stage renal disease (ESRD) also have higher graft failure, suggesting the 2 donor kidneys share risk factors that could inform recipient outcomes. Given that donor ESRD is rare, an earlier and more common postdonation outcome could serve as a surrogate to individualize counseling and management for recipients. Hypertension is a frequent event before donor ESRD; thus, early postdonation hypertension might indicate higher risk of graft failure. METHODS We studied Scientific Registry of Transplant Recipients data to quantify the association between early postdonation hypertension and recipient graft failure using propensity score-weighted Cox proportional hazards regression. We also examined the association between postdonation systolic blood pressure and graft failure. RESULTS Of 37 901 recipients, 2.4% had a donor who developed hypertension within 2 years postdonation. Controlling for donor and recipient characteristics, recipients whose donors developed hypertension had no higher risk for graft failure (adjusted hazard ratio [aHR] 1.03, 95% confidence interval [CI] 0.85-1.25, P = 0.72). This was consistent among subgroups of recipients at higher risk for adverse outcomes due to hyperfiltration: African American recipients (aHR 1.10, 95% CI 0.70-1.73, P = 0.68) and those with ESRD caused by hypertension (aHR 1.10, 95% CI 0.65-1.85, P = 0.73) or diabetes (aHR 0.80, 95% CI 0.56-1.13, P = 0.20). However, graft failure was associated with postdonation systolic blood pressure (per 10 mm Hg, aHR 1.05, 95% CI 1.03-1.08, P < 0.001). CONCLUSIONS Although postdonation systolic blood pressure is associated with graft failure, the reported diagnosis of hypertension as determined by the requirement for blood pressure treatment early postdonation did not portend a higher risk of recipient graft failure in the same way as eventual postdonation ESRD.

In liver transplantation, both cold and warm ischemia times are known to impact early graft function. The extraction time is a period during the initial phase of organ cooling which occurs during deceased donor procurement. During this time, the organ is at risk of suboptimal cooling. Whether donor extraction time, the time from donor aortic cross-clamp to removal of the donor organ from the body cavity has an effect on early graft function is not known.We investigated the effect of donor extraction time on early graft function in 292 recipients of liver grafts procured locally and transplanted at our center between June 2012 and December 2016. Early graft function was assessed using the model of early allograft function score in a multivariable regression model including donor extraction time, cold ischemia time, warm ischemia time, donor risk index, and terminal donor sodium.Donor extraction time had an independent effect on early graft function measured by the model of early allograft function score (coefficient, 0.021; 95% confidence interval, 0.007-0.035; P0.01; for each minute increase of donor extraction time). Besides donor extraction time, cold ischemia time, warm ischemia time, and donor risk index had a significant effect on early graft function.We demonstrate an independent effect of donor extraction time on graft function after liver transplantation. Efforts to minimize donor extraction time could improve early graft function in liver transplantation.

BACKGROUND The rate of measured glomerular filtration rate (GFR) change in kidney donor years after donation has not been adequately addressed. Whether this change is accelerated in the setting of 1 kidney is also understudied. METHODS Two hundred fourteen randomly selected donors underwent serial GFR measurements of nonradioactive iohexol. Estimated GFR at each visit was calculated using the Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease study equations. RESULTS Glomerular filtration rate visits were 4.8 ± 1.3 years apart and the second occurring 16.9 ± 9.1 years after donation. Most (97.7%) were white, 60.8% female, and 78.5% were related to their recipient. Most, 84.6%, had a GFR of 60 mL/min per 1.73 m or higher, 14.0% had a GFR between 45 and 60 mL/min per 1.73 m, and 1.4% had a GFR less than 45 mL/min per 1.73 m. Between visits 1 and 2, 56.5% had a GFR decline, 36.0% increase, and in 7.5%, there was no change. Overall, GFR declined at a rate of -0.42 mL/min per 1.73 m per year. Of GFR estimating models, only Chronic Kidney Disease Epidemiology Collaboration-Creatinine equation produced a slope that was steeper than measured GFR. CONCLUSIONS Nearly 2 decades postdonation GFR declined at a rate similar to that seen in the general population, and in one third, GFR continues to increase.

BACKGROUND Organ donation after circulatory death (DCD) is increasingly being used as a means of addressing the organ supply/demand mismatch in solid organ transplantation. There is reluctance to use DCD hearts, due to an inability to precisely identify hearts that have suffered irreversible injury. We investigated novel biomarkers and clinically relevant endpoints across a spectrum of warm ischemic times, before and during ex vivo heart perfusion (EVHP), to identify features associated with a nonviable cardiac phenotype. METHODS Donor rats sustained a hypoxic cardiac arrest, followed by variable acirculatory standoff periods (DCD groups). Left ventricular function, histochemical injury, and differences in left ventricular gene expression were studied before, and during, EVHP. RESULTS As warm ischemic time exposure increased in DCD groups, fewer hearts were functional during EVHP, and ventricular function was increasingly impaired. Histochemical assessment identified severely injured hearts during EVHP. A novel gene expression signature identified severely injured hearts during EVHP (upregulation of c-Jun, 3.19 (2.84-3.60); P = 0.0014; HMOX-1, 3.87 (2.72-5.50); P = 0.0037; and Hsp90, 7.66 (6.32-9.27); P < 0.0001 in DCD20), and may be useful in identifying high-risk hearts at the point of harvest (Hsp90). CONCLUSIONS We demonstrate that our preclinical model recapitulates the cardio-respiratory decompensation observed in humans, and that EVHP appears necessary to unmask distinguishing features of severely injured DCD hearts. Furthermore, we outline a clinically relevant multimodal approach to assessing candidate DCD hearts. Novel mRNA signatures correlated with elevations in cardiac Troponin-I in severely injured hearts during EVHP, and may also detect injury at the point of harvest.

Background Reduced-size liver transplantation (LT) was invented to overcome the shortage of donor livers; however, it has proven to be more susceptible to ischemia-reperfusion injury. Bone marrow-derived mesenchymal stem cell infusion has been shown to be protective following LT. Optimization of MSC infusion has been performed, among which hypoxia preconditioning and miRNA modulation have shown promise. MiR-199a inhibition was reported to induce angioneogenesis; however, whether mir-199a inhibition enhances the protective effect of Bone marrow-derived mesenchymal stem cells in LT remains unknown. In this study, we combined antagomiR-199a with hypoxia-preconditioned MSC (H-MSC) infusion to discuss their effect and mechanism in a rat model of reduced-size LT. Methods A reduced-size LT model was constructed and H-MSCs were intraportally injected during operation. AgomiR-199a and antagomir-199a were injected through the caudal vein once a day after LT. The level of apoptosis and proinflammatory cytokines were measured. An anti-vascular endothelial growth factor (VEGF) antibody was injected to further explore the underlying mechanism. Results AntagomiR-199a plus H-MSC not only significantly decreased ALT and AST 72 h after LT but also ameliorated the level of apoptosis and inhibited inflammatory reactions. On the contrary, agomir-199a reduced the protective effect of the H-MSC infusion. In terms of mechanism, the liver protective effect of miR-199a inhibition was abolished by treatment with a VEGF-neutralizing antibody. Conclusions AntagomiR-199a enhanced the protective effect of H-MSCs infusion via activation of the hypoxia induction factor 1α/VEGF axis.

BACKGROUND: Association between the apolipoprotein L1 gene (APOL1) and nephropathy has altered the epidemiology of chronic kidney disease (CKD). In addition, donor APOL1 genotypes play important roles in the time to allograft failure in kidneys transplanted from deceased donors and the safety of living kidney donation. METHODS: This manuscript reviews genetic testing for inherited kidney disease in living kidney donors to improve donor safety. APOL1 genotyping in donors with recent African ancestry is considered. RESULTS: Based on current data, transplant physicians should discuss APOL1 genotyping with potential living kidney donors self-reporting recent African ancestry. Until results from APOL1 Long-term Kidney Transplant Outcomes Network (APOLLO) ancillary studies are available, we present practical approaches from our experience for considering APOL1 genotyping in the living donor evaluation. CONCLUSIONS: Transplant physicians should inform potential living kidney donors at-risk for APOL1-associated nephropathy about the gene and possibility of genetic testing early in the donor evaluation, well before scheduling the donor nephrectomy. Transplant programs must weigh risks of performing a donor nephrectomy in those with two APOL1 renal-risk variants (high-risk genotypes), particularly younger individuals. Our program counsels kidney donors with APOL1 high-risk genotypes in the same fashion as with risk genotypes in other nephropathy genes. Because most African American kidney donor candidates lacking hypertension, proteinuria and reduced kidney function after workup will not possess APOL1 high-risk genotypes, genetic testing is unlikely to markedly increase donor declines and may reassure donors with regard to their long-term kidney outcomes, potentially increasing the number of African American donors.

As the gap between organ donors and patients on the recipient waiting list grows, residents of the United States who are in need of kidney transplantation occasionally contract with living donors from outside the United States. Those donors then travel to the United States to undergo living donor kidney donation at US transplant centers. This practice is not limited to the United States and occurs with some regularity around the world. However, there is very little written about this practice from the perspective of the US transplant system, and there is little in the way of guidance (either legal or ethical) to assist centers that accommodate it in distinguishing between ethically permissible travel for transplant and what could potentially be human trafficking for organ removal. This article will present an ethical analysis of travel for organ donation with particular attention to lessons that can be drawn from living donor donation in other countries. This inquiry is particularly germane because Organ Procurement and Transplantation Network has promulgated guidelines with respect to obligations owed to living donors, but those guidelines appear to assume that the donor is a US resident. The critical question then is whether or to what extent those guidelines are applicable to the instant scenario in which the living donor is a nonresident. In addition, this article addresses several critical ethical concerns implicated by the often vulnerable populations from which donors are drawn. Finally, this article proposes that focused inquiry by transplant centers is necessary when donors are nonresidents.

BACKGROUND For patients with a solitary kidney, such as living kidney donors, the surgical treatment of renal tumors may result in loss of function of the remaining kidney. METHODS We conducted a retrospective, matched cohort study to determine the long-term risk of partial or total nephrectomy in previous living kidney donors compared to healthy nondonors. We reviewed the predonation charts for all living kidney donors in Ontario, Canada between 1992 and 2010 and linked this information to provincial healthcare databases. RESULTS We matched 2119 donors to 21190 nondonors from the general population with similar baseline health. The median length of follow-up was 9.5 years (maximum 21.7 years). The rate of nephrectomy in follow-up was lower in donors versus nondonors (0 vs. 1.78 per 10000 person years; P = 0.037). In a subset of 1773 donors matched to 1773 healthy nondonors with renal imaging (median follow-up 7.6 years, maximum 21.0 years), the rate of nephrectomy was not statistically different in donors versus nondonors (0 vs. ≤5 per 10000 person years; P > 0.08). CONCLUSION No living kidney donor in our cohort received a partial or total nephrectomy of their remaining kidney during our follow-up period. Although we will continue to follow people in this study, these interim results are reassuring for the safety of kidney donation.

The development of minimally invasive surgical approaches to donor nephrectomy (DN) has been driven by the potential advantages for the donor, with questions remaining about long-term outcomes.All living DN performed from June 1963 through December 2014 at the University of Minnesota were reviewed. Outcomes were compared among 4 DN techniques.We performed 4286 DNs: 2759 open DN (ODNs), 1190 hand-assisted (HA) laparoscopic DNs (LDNs), 203 pure LDN (P-LDNs), and 97 robot-assisted-LDN. Laparoscopic DN was associated with an older (P0.001) and heavier (P0.001) donor population. Laparoscopic DN was associated with a higher probability of left kidney procurement (P0.001). All 3 LDN modalities required a longer operative time (P0.001); robot-assisted-LDN took significantly longer than HA-LDN or P-LDN. Laparoscopic DN decreased the need for intraoperative blood transfusion (P0.001) and reduced the incidence of intraoperative complications (P0.001) and hospital length of stay (P0.001). However, LDN led to a significantly higher rate of readmissions, both short-term (30 day, P0.001) and long-term (30 day, P0.001). Undergoing HA-LDN was associated with a higher rate of an incisional hernia compared with all other modalities (P0.001). For recipients, LDN seemed to be associated with lower rates of graft failure at 1 year compared with ODN (P = 0.002). The odds of delayed graft function increased for kidneys with multiple arteries procured via P-LDN compared with HA-LDN (OR 3 [1,10]) and ODN (OR 5 [2, 15]).In our experience, LDN was associated with decreased donor intraoperative complications and hospital length of stay but higher rates of readmission and long-term complications.

Live donor liver transplantation is the predominant form of liver transplantation in India and in most Asian countries. Donor outcome reports are an important source of information to be shared with prospective donors at the time of informed consent. This is the first donor outcome series from India.Analysis of donor characteristics and morbidity of 275 live donors from a single large volume center is documented.Two hundred seventy-five patients donated from November 2009 to October 2014, 144 were women and 131 were men, 180 donated to adults and 95 donated to children. Right lobe donors were majority at 62.2% followed by left lateral segment 28%. Two thirds of the live donors did not have any morbidity; 114 complications were encountered in 85 patients. The complications were graded as per Clavien 5 tier grading and major morbidity (grade III b, grade IV grade V) was 4.36%. Postoperative biliary complication was seen in 3 donors.This large single-center study is the first donor outcome report from India, and the results are comparable to other published donor series. Documentation and regular audit of donor outcomes is important to help improve the safety of donor hepatectomy and to provide a database for informed consent of prospective donors.

Introduction Obese donors are increasingly accepted for living kidney donation. Obese individuals benefit the most from minimal access surgery; however, laparoscopic donor nephrectomy may be technically challenging in these individuals. Retroperitoneal laparoscopic donor nephrectomy (RLDN) in particular may be hampered by excessive perinephric fat. We performed a prospective nonrandomized controlled study comparing outcomes of RLDN in obese and nonobese kidney donors. Aim To compare operative parameters, donor complications, and recipient outcomes in RLDN performed in obese and nonobese donors. Materials and Methods From June 2014 to April 2016, 200 donors underwent RLDN. Of these, 160 were nonobese (group I), and 40 were obese (group II). Preoperative parameters including body mass index, age, and sex, and operative parameters including total operative time, warm ischemia time, and estimated blood loss were recorded. Complications were compared using the Clavien-Dindo classification. Recipients’ serum creatinine at day 7, 15, and 30 was compared between recipients who received grafts from obese and nonobese donors. Results There were 17.5% right-sided donors in group I and 15% in group II. Operative time, warm ischemia time, blood loss, length of hospital stay, and complications were similar in the 2 groups, and there were no statistically significant differences. Serum creatinine in the recipients was similar on follow-up. Conclusions RLDN is safe and efficacious in obese donors. It gives all the benefits of minimal-access surgery without compromising on recipient outcomes.

Background Cold ischemia-reperfusion injury is unavoidable during organ transplantation, and prolonged preservation is associated with poorer function recovery. Cardiotrophin-1 (CT-1) is an IL-6 family cytokine with cytoprotective properties. This preclinical study in rats tested whether CT-1 mitigates cold renal ischemia-reperfusion injury in the context of the transplantation of long-time preserved kidneys. Methods Kidneys were flushed with cold (4°C) University of Wisconsin solution containing 0.2 μg/mL CT-1 and stored for several periods of time at 4°C in the same solution. In a second approach, kidneys were first cold-preserved for 6 hours and then were perfused with University of Wisconsin solution containing CT-1 (0, 16, 32, or 64 μg/mL) and further cold-preserved. Organ damage markers were measured in the kidneys at the end of the storage period. For renal transplantation, recipient consanguineous Fischer rats underwent bilateral nephrectomy and received a previously cold-preserved (24 hours) kidney as described above. Survival and creatinine clearance were monitored over 30 days. Results Cardiotrophin-1 in perfusion and preservation fluids reduced oxidative stress markers (superoxide anion and inducible nitric oxide synthase), inflammation markers (NF-κB and tumor necrosis factor-α), and vascular damage (vascular cell adhesion molecule-1) and activated leukemia inhibitory factor receptor and STAT-3 survival signaling. Transplantation of kidneys cold-preserved with CT-1 increased rat survival and renal function (ie, lower plasma creatinine and higher creatinine clearance) and improved kidney damage markers after transplantation (ie, lower superoxide anion, tumor necrosis factor-α, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 and higher NF-κB). Conclusions Cardiotrophin-1 represents a novel therapeutic strategy to reduce ischemia-reperfusion and cold preservation injury to rescue suboptimal kidneys and, consequently, to improve the clinical outcomes of renal transplantation.

Kidney transplantation holds much promise as a treatment of choice for patients with end-stage kidney disease. The impact of cold ischemia time (CIT) on acute renal transplant rejection (ARTR) remains to be fully studied in a large cohort of renal transplant patients.From the Organ Procurement and Transplantation Network database, we analyzed 63 798 deceased donor renal transplants performed between 2000 and 2010. We assessed the association between CIT and ARTR. We also evaluated the association between recipient age and ARTR.Six thousand eight hundred two (11%) patients were clinically diagnosed with ARTR. Longer CIT was associated with an increased risk of ARTR. After multivariable adjustment, compared with recipients with CIT12 hours, the relative risk of ARTR was 1.13 (95% confidence interval, 1.04-1.23) in recipients with CIT ≥ 24 hours. The association of CIT and ARTR was more pronounced in patients undergoing retransplantation: compared with recipients with CIT less than 12 hours, the relative risk of ARTR was 1.66 (95% confidence interval, 1.01-2.73) in recipients with CIT of 24 hours or longer. Additionally, older age was associated with a decreased risk of ARTR. Compared with recipients aged 18 to 29 years, the relative risk of ARTR was 0.50 (95% confidence interval, 0.45-0.57) in recipients 60 years or older. Longer CIT was also associated with increased risk of death-censored graft loss. Compared with recipients with CIT less than 12 hours, the hazard ratio of death-censored graft loss was 1.22 (95% confidence interval, 1.14-1.30) in recipients with CIT of 24 hours or longer.Prolonged CIT is associated with an increased risk of ARTR and death-censored graft loss. Older age was associated with a lower risk of ARTR.

We previously reported that short oxygenated warm perfusion before cold storage (CS) had improved the graft viability of rat livers from donors after circulatory death (DCD). In this study, we investigated the effectiveness of short-term oxygenated subnormothermic perfusion for different durations after CS in a rat DCD model.We used an isolated perfused rat liver system. In study 1: the grafts were retrieved from Wistar rats 30 minutes after cardiac arrest (thoracotomy), preserved in CS for 6 hours, and perfused with oxygenated subnormothermic (20-25°C) Krebs-Henseleit buffer for different durations (0, 15, 30, 60, and 90 minutes groups; n = 5 in each). In study 2: in addition to subnormothermic ex vivo liver perfusion (SELP), after 15-minute incubation at room temperature, the grafts were reperfused under normothermic condition for 60 minutes as a model of liver transplantation (0, 30, 60, and 90 minutes groups; n = 5 in each).In study 1, portal flow, bile production and tissue adenosine triphosphate increased with perfusion duration. In study 2, SELP significantly improved portal flow volume (P0.05), and bile production (P0.05), decreased liver enzymes (P0.05) and cytokines (P0.0001), and increased tissue adenosine triphosphate (P0.01). Histological examinations showed that additional SELP ameliorated tissue deterioration, preserved the parenchymal structure, and decreased apoptosis (P0.01). Furthermore, scanning electron microscopy revealed that additional SELP alleviated sinusoidal endothelial cells and hepatic microvasculature.Even 30 minutes of SELP after CS rescued DCD livers from ischemia-reperfusion injury, which may help the viability of the grafts.

BACKGROUND Islet isolation currently requires collagenase, neutral protease and other components. Thermolysin (TL) from Bacillus thermoproteolyticus is the gold standard neutral protease. However, we speculated that neutral protease derived from Clostridium histolyticum (Ch; ChNP) would be biologically superior for islet isolation. Tryptic-like activity has also been reported to be important. Therefore, we focused on clostripain (CP), since it is one of the main proteases in Clostridium histolyticum which possesses tryptic-like activity. We then examined the synergistic effects of highly purified ChNP and CP on rat islet isolation. METHODS The same amount of collagenase was used in all four groups (TL, ChNP, TL+CP and ChNP+CP; n = 12/group). The efficiency was evaluated by the islet yield and function. An immunohistochemical analysis, in vitro digestion assay for each enzyme component and evaluation of the activation of endogenous exocrine proteases during islet isolation were also performed. RESULTS The islet yield of the TL group was significantly higher than that of the ChNP group (P < 0.01). The islet yield was dose dependently increased in the ChNP+CP group, but was decreased in the TL + CP group. The islet yield in the ChNP + CP group was significantly higher than that in the TL group, but their islet function was similar. Different specificities for laminin, especially laminin-511, were observed in the TL, ChNP, and CP groups. CONCLUSIONS Clostripain had a strong synergistic effect with ChNP, but not with TL. Therefore, ChNP and CP, in combination with collagenase derived from the same bacteria, may effectively increase the isolation efficiency without affecting the quality of islets.

BACKGROUND Little is known about living kidney donors' satisfaction with life (SWL) after donation. We compared donors' SWL to previously reported general population samples and investigated predictors of donors' SWL. METHODS Three transplant centers mailed questionnaires to assess SWL, physical health, optimism, retrospective evaluation of the donation experience, and demographic characteristics to living kidney donors' homes between 2010 and 2012. Two thousand four hundred fifty-five donors who were between 5 and 48 years from the time of their donor surgery completed the questionnaire. RESULTS Eighty-four percent of donors were satisfied with their lives (scores ≥ 20 on the Satisfaction With Life Scale). Donors were at least as satisfied with their lives as previously reported general population samples. After adjusting for physical health, optimism, and demographics, donors' SWL was significantly associated with donors' recalled experience of donation. Social support and positive effects of the donation on relationships predicted greater SWL. Financial difficulties associated with donation and longer recovery times predicted lower SWL. Recipient outcomes were not significantly related to donor SWL. DISCUSSION Limitations include the lack of predonation SWL data, potential bias in postdonation SWL because of the situational context of the questionnaire, and a sample that is not representative of all U.S. living kidney donors. Nonetheless, strategies focused on improving the donation experience, particularly related to recovery time, financial issues, and social support, may result in greater SWL after donation.

BACKGROUND Outcomes of retroperitoneoscopic procurement of living kidneys with multiple renal arteries (MRA) in the recipients are largely unknown. Our aim is to access the effect of kidney allografts with MRA on donor and recipient outcomes after pure retroperitoneoscopic live donor nephrectomy (RPLDN). METHODS From July 2001 to August 2010, 533 patients underwent live donor kidney transplants with allografts procured by RPLDN at our center. Of these 533 transplants, 406, 105, and 22 patients had one, two, and three renal arteries, respectively. We compared the retrospectively collected clinical data of each donor with MRA and the recipient using those with single renal artery as controls. RESULTS Significant differences were found among the one-renal artery and three-renal artery groups regarding operative time, estimated blood loss, warm and cold ischemic time, and incidence of slow graft function (SGF). However, there was no significant difference regarding patient and graft survival among the three groups. Major complications, such as open conversion, bleeding, and blood transfusion, were not found in patients with MRA. Five ureteral complications occurred. Of these, there was one patient with MRA. In univariate analysis, MRA patients had a risk factor of developing SGF (P=0.005) but not ureteral complications following RPLDN. CONCLUSION Kidneys with MRA after RPLDN increase the risk of SGF in recipients. However, they provide similar outcomes as to long-term graft survival and complications compared with those of single renal artery. Renal artery multiplicity should not be a contraindication for live kidney donation and may not increase the risk of ureteral complications.

Background Ensuring donor wellbeing warrants ongoing monitoring after living kidney donation. However, there is considerable variability in donor follow-up processes, including information provided to donors regarding self-care. Loss to follow-up is common, suggesting that the aims and benefits of monitoring and follow-up may not be apparent. We aimed to describe the experiences and expectations of living kidney donors regarding follow-up and self-care after donation. Methods Participants from 3 transplant centers in Australia and Canada participated in 14 focus groups (n = 123). Transcripts were analyzed thematically. Results We identified 4 themes: lacking identification as a patient (invincibility and confidence in health, immediate return to normality, avoid burdening specialty services, redundancy of specialist attention, unnecessary travel), empowerment for health (self-preservation for devastating consequences, self-advocacy and education, needing lifestyle advice, tracking own results), safety net and reassurance (availability of psychosocial support, confidence in kidney-focused care, continuity and rapport, and access to waitlist priority), and neglect and inattention (unrecognized ongoing debilitations, primary focus on recipient, hospital abandonment, overlooking individual priorities, disconnected from system, coping with dual roles, and lacking support for financial consequences). Conclusions Living kidney donors who felt well and confident about their health regarded specialist follow-up as largely unnecessary. However, some felt they did not receive adequate medical attention, were prematurely detached from the health system, or held unresolved anxieties about the consequences of their decision to donate. Ongoing access to healthcare, psychosocial support, and education may reassure donors that any risks to their health are minimized.

BACKGROUND Hormonal therapy to the brain-dead potential organ donor can include thyroid hormone (triiodothyronine [T3] or levothyroxine [T4]), corticosteroids, antidiuretic hormone, and insulin. METHODS Data on 66,629 donors (2000-2009) were retrospectively reviewed. Documentation on T3/T4 was available in 63,593 (study 1), but 23,469 had incomplete documentation of other hormones. In 40,124, details of all four hormones were recorded (study 2). In this cohort, group A (received T3/T4) consisted of 23,022, and group B (no T3/T4) consisted of 17,102 donors. A multivariate analysis was performed to determine whether age, sex, ethnicity, cause of death, body mass index, Organ Procurement Organization region, or other hormonal therapy influenced procurement. Posttransplantation organ graft survival at 1 and 12 months was compared. RESULTS In study 1, 30,962 (48.69%) received T3/T4, providing a mean of 3.35 organs per donor, and 32,631 (51.31%) did not receive T3/T4, providing a mean of 2.97 organs per donor, an increase of 12.8% of organs from T3/T4-treated donors (P

BACKGROUND Given the stable number of potential organ donors after brain death, donors after circulatory death have been an increasing source of organs procured for transplant. Among the most important considerations for donation after circulatory death (DCD) is the prediction that death will occur within a reasonable period of time after the withdrawal of cardiorespiratory support (WCRS). Accurate prediction of time to death is necessary for the procurement process. We aimed to develop simple predictive rules for death in less than 60 min and test the accuracy of these rules in a pool of potential DCD donors. METHODS A multicenter prospective longitudinal cohort design of DCD eligible patients (n=318), with the primary binary outcome being death in less than 60 min after withdrawal of cardiorespiratory support conducted in 28 accredited intensive care units (ICUs) in Australia. We used a random split-half method to produce two samples, first to develop the predictive classification rules and then to estimate accuracy in an independent sample. RESULTS The best classification model used only three simple classification rules to produce an overall efficiency of 0.79 (0.72-0.85), sensitivity of 0.82 (0.73-0.90), and a positive predictive value of 0.80 (0.70-0.87) in the independent sample. Using only intensive care unit specialist prediction (a single classification rule) produced comparable efficiency 0.80 (0.73-0.86), sensitivity 0.87 (0.78-0.93), and positive predictive value 0.78 (0.68-0.86). CONCLUSION This best predictive model missed only 18% of all potential donors. A positive prediction would be incorrect on only 20% of occasions, meaning there is an acceptable level of lost opportunity costs involved in the unnecessary assembly of transplantation teams and theatres.

Background Over 40% of deceased donors in the UK donate after circulatory death (DCD). Normothermic regional perfusion has been reported to improve outcomes in such donors in Europe and the United States. Unlike the United States, legal and professional requirements in the UK prevent cannulation and heparinization before verification of death, which must be a minimum of 5 min after circulatory arrest. We developed a novel protocol for in situ normothermic regional perfusion (NRP) which complied with these requirements. Methods NRP was achieved by cannulating the aorta and vena cava after death. Donor blood was then warmed and oxygenated using a bespoke extracorporeal membrane oxygenator circuit before return to the donor. A shunt was incorporated into the extracorporeal circuit to permit heparin mixing before oxygenation and warming was commenced to prevent thrombosis of the oxygenator. Normothermic perfusion was continued for 2 hr before in situ cold perfusion with preservation fluid. All organs were subject to static cold storage after recovery. Results Eight controlled DCD donors underwent NRP from which 3 livers, 2 pancreases, and 14 kidneys were transplanted. Four livers were not used because of biochemical evidence of hepatocellular damage and one because of cirrhosis. Two kidneys were lost from venous thrombosis before function returned and two developed delayed graft function; all transplanted livers and pancreases had primary function. Conclusions Cannulation and heparinization after circulatory arrest does not prevent successful normothermic regional perfusion. The technique permits evaluation of donor organs before implantation and may improve short-term outcomes.