Normothermic and hypothermic machine perfusion preservation versus static cold storage for deceased donor kidney transplantation.

BACKGROUND: Kidney transplantation is the optimal treatment for kidney failure. Donation, transport and transplant of kidney grafts leads to significant ischaemia reperfusion injury. Static cold storage (SCS), whereby the kidney is stored on ice after removal from the donor until the time of implantation, represents the simplest preservation method. However, technology is now available to perfuse or "pump" the kidney during the transport phase ("continuous") or at the recipient centre ("end-ischaemic"). This can be done at a variety of temperatures and using different perfusates. The effectiveness of these treatments manifests as improved kidney function post-transplant. OBJECTIVES: To compare machine perfusion (MP) technologies (hypothermic machine perfusion (HMP) and (sub) normothermic machine perfusion (NMP)) with each other and with standard SCS. SEARCH METHODS: We contacted the information specialist and searched the Cochrane Kidney and Transplant Register of Studies until 15 June 2024 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs comparing machine perfusion techniques with each other or versus SCS for deceased donor kidney transplantation were eligible for inclusion. All donor types were included (donor after circulatory death (DCD) and brainstem death (DBD), standard and extended/expanded criteria donors). Both paired and unpaired studies were eligible for inclusion. DATA COLLECTION AND ANALYSIS: The results of the literature search were screened, and a standard data extraction form was used to collect data. Both of these steps were performed by two independent authors. Dichotomous outcome results were expressed as risk ratios (RR) with 95% confidence intervals (CI). Survival analyses (time-to-event) were performed with the generic inverse variance meta-analysis of hazard ratios (HR). Continuous scales of measurement were expressed as a mean difference (MD). Random effects models were used for data analysis. The primary outcome was the incidence of delayed graft function (DGF). Secondary outcomes included graft survival, incidence of primary non-function (PNF), DGF duration, economic implications, graft function, patient survival and incidence of acute rejection. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Twenty-two studies (4007 participants) were included. The risk of bias was generally low across all studies and bias domains. The majority of the evidence compared non-oxygenated HMP with standard SCS (19 studies). The use of non-oxygenated HMP reduces the rate of DGF compared to SCS (16 studies, 3078 participants: RR 0.78, 95% CI 0.69 to 0.88; P < 0.0001; I2 = 31%; high certainty evidence). Subgroup analysis revealed that continuous (from donor hospital to implanting centre) HMP reduces DGF (high certainty evidence). In contrast, this benefit over SCS was not seen when non-oxygenated HMP was not performed continuously (low certainty evidence). Non-oxygenated HMP reduces DGF in both DCD and DBD settings in studies performed in the 'modern era' and when cold ischaemia times (CIT) were short. The number of perfusions required to prevent one episode of DGF was 7.69 and 12.5 in DCD and DBD grafts, respectively. Continuous non-oxygenated HMP versus SCS also improves one-year graft survival (3 studies, 1056 participants: HR 0.46, 0.29 to 0.75; P = 0.002; I2 = 0%; high certainty evidence). Assessing graft survival at maximal follow-up confirmed a benefit of continuous non-oxygenated HMP over SCS (4 studies, 1124 participants (follow-up 1 to 10 years): HR 0.55, 95% CI 0.40 to 0.77; P = 0.0005; I2 = 0%; high certainty evidence). This effect was not seen in studies where HMP was not continuous. The effect of non-oxygenated HMP on our other outcomes (PNF, incidence of acute rejection, patient survival, hospital stay, long-term graft function, duration of DGF) remains uncertain. Studies performing economic analyses suggest that HMP is either cost-saving (USA and European settings) or cost-effective (Brazil). One study investigated continuous oxygenated HMP versus non-oxygenated HMP (low risk of bias in all domains); the simple addition of oxygen during continuous HMP leads to additional benefits over non-oxygenated HMP in DCD donors (> 50 years), including further improvements in graft survival, improved one-year kidney function, and reduced acute rejection. One large, high-quality study investigated end-ischaemic oxygenated HMP versus SCS and found end-ischaemic oxygenated HMP (median machine perfusion time 4.6 hours) demonstrated no benefit compared to SCS. The impact of longer periods of end-ischaemic HMP is unknown. One study investigated NMP versus SCS (low risk of bias in all domains). One hour of end ischaemic NMP did not improve DGF compared with SCS alone. An indirect comparison revealed that continuous non-oxygenated HMP (the most studied intervention) was associated with improved graft survival compared with end-ischaemic NMP (indirect HR 0.31, 95% CI 0.11 to 0.92; P = 0.03). No studies investigated normothermic regional perfusion (NRP) or included any donors undergoing NRP. AUTHORS' CONCLUSIONS: Continuous non-oxygenated HMP is superior to SCS in deceased donor kidney transplantation, reducing DGF, improving graft survival and proving cost-effective. This is true for both DBD and DCD kidneys, both short and long CITs, and remains true in the modern era (studies performed after 2008). In DCD donors (> 50 years), the simple addition of oxygen to continuous HMP further improves graft survival, kidney function and acute rejection rate compared to non-oxygenated HMP. Timing of HMP is important, and benefits have not been demonstrated with short periods (median 4.6 hours) of end-ischaemic HMP. End-ischaemic NMP (one hour) does not confer meaningful benefits over SCS alone and is inferior to continuous HMP in an indirect comparison of graft survival. Further studies assessing NMP for viability assessment and therapeutic delivery are warranted and in progress.

Recipient outcomes in total laparoscopic live donor nephrectomy with multiple renal vessels.

INTRODUCTION: In kidney transplantation, total laparoscopic live donor nephrectomy (TLLDN) in the presence of multiple renal arteries (MRA) is technically challenging and has traditionally been associated with higher complication rates. We report our experience of using MRA grafts procured by TLLDN. MATERIALS AND METHODS: Patients undergoing TLLDN at our center (2004-2014) was identified from a prospectively maintained database and divided into single renal arteries (SRA) or MRA groups. Recipient perioperative parameters, postoperative complications, and long-term graft survival were analyzed. RESULTS: Of 465 patients, 106 had MRA and 359 had an SRA. There were six vascular complications in the SRA group and two in the MRA group (1.7% vs. 1.8%). There were eight ureteric complications requiring intervention in the SRA group compared to three in the MRA group (4% vs. 3%; P = 0.45). Acute rejection was observed in 12% of the SRA group compared to 9% in the MRA group (P = 0.23). One-, 5- and 10-year graft survivals were 98.2%, 91.3%, and 89.8% in the MRA group versus 98.0%, 90.4%, and 77.5% in the SRA group (log-rank P = 0.13). CONCLUSION: The use of MRA grafts procured by TLLDN has comparable complication rates to SRA grafts and should not preclude selection for renal transplantation.

Hypothermic machine perfusion is superior to static cold storage in deceased donor kidney transplantation: A meta-analysis.

BACKGROUND: There remains a lack of consensus on the optimal storage method for deceased donor kidneys. This meta-analysis compares storage with hypothermic machine perfusion (HMP) vs traditional static cold storage (SCS). METHODS: The Cochrane Kidney and Transplant Specialised Register was searched to identify (quasi-) randomized controlled trials (RCTs) to include in our meta-analysis. PRISMA guidelines were used to perform and write this review. RESULTS: There is high-certainty evidence that HMP reduces the risk of delayed graft function (DGF) when compared to SCS (2138 participants from 14 studies, RR = 0.77; 0.67-0.90, P = .0006). This benefit is significant in both donation following circulatory death (DCD; 772 patients from seven studies, RR = 0.75; 0.64-0.87, P = .0002) and donation following brainstem death (DBD) grafts (971 patients from four studies, RR = 0.78; 0.65-0.93, P = .006). The number of perfusions required to prevent one episode of DGF was 7.26 and 13.60 in DCD and DBD grafts, respectively. There is strong evidence that HMP also improves graft survival in both DBD and DCD grafts, at both 1 and 3 years. Economic analyses suggest HMP is cost-saving at 1 year compared with SCS. CONCLUSION: Hypothermic machine perfusion is superior to SCS in deceased donor renal transplantation. Direct comparisons with normothermic machine perfusion in RCTs are essential to identify optimal preservation methods in kidney transplantation.

Preemptive Appendicectomy at the Time of Pancreas Transplantation: Is It Necessary?

OBJECTIVES: Pancreas transplant is a major intraabdominal operation, and in most cases the graft is placed in the rightiliac fossa. At our center, preemptive appendicectomy is performed at the time of pancreas transplant to prevent any future risk in a complex transplant patient. The aim of this study was to review all histology reports from the removed appendices. MATERIALS AND METHODS: The histology reports from all incidental appendicectomies performed at pancreas transplant were reviewed. RESULTS: Between January 2001 and June 2016, 107 pancreas transplants were performed (86 simultaneous pancreas and kidney transplants, 11 pancreas after kidney transplants, and 10 pancreas transplants alone), and 65 appendix histology reports were available from this patient group. All were preemptive appendicectomies as none of the patients had symptoms to suggest acute appendicitis. Of the 65 appendix histologies, 43 (66.2%) were reported as normal. Twenty specimens (30.8%) showed fibrosis consistent with previous inflammation of the appendix, and 12 specimens (18.5%) showed fecal material in the lumen (1 due to an obstructing fecalith and another 2 showing luminal distension with feces). Three specimens (4.6%) showed lymphoid hyperplasia. There were 5 (7.7 %) unexpected findings upon histology. In review of histology reports, 1 patient had a 1.1-mm carcinoid tumor in an otherwise normal appendix, 1 had an Enterobius species worm infestation, 1 had focal endometriosis, 1 had crypt abscesses suggestive of inflammatory bowel disease, 1 had a metaplastic polyp, and 1 had melanosis coli of unknown clinical significance. There were no cases of overt acute appendicitis. No patients experienced a complication as a direct result of their appendicectomy. CONCLUSIONS: A policy ofroutine appendicectomy atthe time of pancreas transplant appears to be justified and safe.

Comparison of the Outcome of Kidney Transplant After Pulsatile or Continuous Ex Vivo Hypothermic Machine Perfusion of Kidneys Donated After Cardiac Death: Analysis of Kidney Pairs.

BACKGROUND: Hypothermic machine perfusion is used to improve renal perfusion and reduce the rate of early and late graft dysfunction. It has been used in our unit since 2001. It has 2 modes of flow: continuous or pulsatile. The aim of this study is to compare the modes of perfusion in terms of perfusion-related parameters, graft survival, and estimated glomerular filtration rate. METHODS: All donation after cardiac death kidneys between 2002 and 2014 were reviewed. A total of 64 pairs of kidneys were identified of which one kidney underwent pulsatile and the other continuous perfusion. Machine parameters including resistance and perfusion flow index levels at 0, 1, 2, 3, and 4 hours were recorded and glutathione S-transferase was measured in perfusate. Estimated glomerular filtration rate from the first week of transplant until the fifth year and graft survival rates were determined. RESULTS: Machine parameters were similar at all time points. Estimated glomerular filtration rates and graft survival were the same irrespective of perfusion mode. CONCLUSION: Pulsatile perfusion may be regarded as more physiological. However, we could not identify difference in outcome following transplant of kidneys from the same donor that had been perfused under pulsatile or continuous conditions.

Machine perfusion preservation versus static cold storage for deceased donor kidney transplantation.

BACKGROUND: Kidney transplantation is the optimal treatment for end-stage kidney disease. Retrieval, transport and transplant of kidney grafts causes ischaemia reperfusion injury. The current accepted standard is static cold storage (SCS) whereby the kidney is stored on ice after removal from the donor and then removed from the ice box at the time of implantation. However, technology is now available to perfuse or "pump" the kidney during the transport phase or at the recipient centre. This can be done at a variety of temperatures and using different perfusates. The effectiveness of treatment is manifest clinically as delayed graft function (DGF), whereby the kidney fails to produce urine immediately after transplant. OBJECTIVES: To compare hypothermic machine perfusion (HMP) and (sub)normothermic machine perfusion (NMP) with standard SCS. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies to 18 October 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs comparing HMP/NMP versus SCS for deceased donor kidney transplantation were eligible for inclusion. All donor types were included (donor after circulatory (DCD) and brainstem death (DBD), standard and extended/expanded criteria donors). Both paired and unpaired studies were eligible for inclusion. DATA COLLECTION AND ANALYSIS: The results of the literature search were screened and a standard data extraction form was used to collect data. Both of these steps were performed by two independent authors. Dichotomous outcome results were expressed as risk ratio (RR) with 95% confidence intervals (CI). Continuous scales of measurement were expressed as a mean difference (MD). Random effects models were used for data analysis. The primary outcome was incidence of DGF. Secondary outcomes included: one-year graft survival, incidence of primary non-function (PNF), DGF duration, long term graft survival, economic implications, graft function, patient survival and incidence of acute rejection. MAIN RESULTS: No studies reported on NMP, however one ongoing study was identified.Sixteen studies (2266 participants) comparing HMP with SCS were included; 15 studies could be meta-analysed. Fourteen studies reported on requirement for dialysis in the first week post-transplant (DGF incidence); there is high-certainty evidence that HMP reduces the risk of DGF when compared to SCS (RR 0.77; 95% CI 0.67 to 0.90; P = 0.0006). HMP reduces the risk of DGF in kidneys from DCD donors (7 studies, 772 participants: RR 0.75; 95% CI 0.64 to 0.87; P = 0.0002; high certainty evidence), as well as kidneys from DBD donors (4 studies, 971 participants: RR 0.78, 95% CI 0.65 to 0.93; P = 0.006; high certainty evidence). The number of perfusions required to prevent one episode of DGF (number needed to treat, NNT) was 7.26 and 13.60 in DCD and DBD kidneys respectively. Studies performed in the last decade all used the LifePort machine and confirmed that HMP reduces the incidence of DGF in the modern era (5 studies, 1355 participants: RR 0.77, 95% CI 0.66 to 0.91; P = 0.002; high certainty evidence). Reports of economic analysis suggest that HMP can lead to cost savings in both the North American and European settings.Two studies reported HMP also improves graft survival however we were not able to meta-analyse these results. A reduction in incidence of PNF could not be demonstrated. The effect of HMP on our other outcomes (incidence of acute rejection, patient survival, hospital stay, long-term graft function, duration of DGF) remains uncertain. AUTHORS' CONCLUSIONS: HMP is superior to SCS in deceased donor kidney transplantation. This is true for both DBD and DCD kidneys, and remains true in the modern era (studies performed in the last decade). As kidneys from DCD donors have a higher overall DGF rate, fewer perfusions are needed to prevent one episode of DGF (7.26 versus 13.60 in DBD kidneys).Further studies looking solely at the impact of HMP on DGF incidence are not required. Follow-up reports detailing long-term graft survival from participants of the studies already included in this review would be an efficient way to generate further long-term graft survival data.Economic analysis, based on the results of this review, would help cement HMP as the standard preservation method in deceased donor kidney transplantation.RCTs investigating (sub)NMP are required.

Orthotopic Liver Transplantation for Hereditary Hemorrhagic Telangiectasia and MEN Type I Syndrome - Case Report and Review of Literature.

Introduction: Hereditary haemorrhagic telangiectasia (HHT) is a rare autosomal dominant genetic disorder characterized by arteriovenous malformations (AVMs) mainly affecting the lungs and the liver. In this case AVM's resulted in liver cirrhosis and an indication for orthotopic liver transplantation (OLT). Case Report: A 59 year-old male patient with HHT who had been previously diagnosed with Multiple Endocrine Neoplasia type 1 Syndrome (MEN 1) was listed for OLT for end-stage liver disease due to hepatic AVMs. During the procedure, a novel type of arterial anastomosis (end-toside) was chosen because of the mismatch in diameter between the hepatic artery (HA) of the donor and the recipient, respectively. Graft function was normal and repeat Doppler ultrasound studies showed a normally functioning arterial anastomosis. However, the patient died on POD 34 due to an un-related cause (cardiac arrest resulting from myocardial infarction). Conclusion: To the best of our knowledge this is the first report of an association of HHT and MEN 1. Moreover, this is also the first reported end-to-side arterial anastomosis in an HHT patient during OLT. Our paper shows that the surgical technique we applied is both feasible and safe.

The UK National Registry of ABO and HLA Antibody Incompatible Renal Transplantation: Pretransplant Factors Associated With Outcome in 879 Transplants.

BACKGROUND: ABO and HLA antibody incompatible (HLAi) renal transplants (AIT) now comprise around 10% of living donor kidney transplants. However, the relationship between pretransplant factors and medium-term outcomes are not fully understood, especially in relation to factors that may vary between centers. METHODS: The comprehensive national registry of AIT in the United Kingdom was investigated to describe the donor, recipient and transplant characteristics of AIT. Kaplan-Meier analysis was used to compare survival of AIT to all other compatible kidney transplants performed in the United Kingdom. Cox proportional hazards regression modeling was used to determine which pretransplant factors were associated with transplant survival in HLAi and ABOi separately. The primary outcome was transplant survival, taking account of death and graft failure. RESULTS: For 522 HLAi and 357 ABO incompatible (ABOi) transplants, 5-year transplant survival rates were 71% (95% confidence interval [CI], 66-75%) for HLAi and 83% (95% CI, 78-87%) for ABOi, compared with 88% (95% CI, 87-89%) for 7290 standard living donor transplants, and 78% (95% CI, 77-79%) for 15 322 standard deceased donor transplants (P < 0.0001). Increased chance of transplant loss in HLAi was associated with increasing number of donor specific HLA antibodies, center performing the transplant, antibody level at the time of transplant, and an interaction between donor age and dialysis status. In ABOi, transplant loss was associated with no use of IVIg, cytomegalovirus seronegative recipient, 000 HLA donor-recipient mismatch; and increasing recipient age. CONCLUSIONS: Results of AIT were acceptable, certainly in the context of a choice between living donor AIT and an antibody compatible deceased donor transplant. Several factors were associated with increased chance of transplant loss, and these can lead to testable hypotheses for further improving therapy.

Recommendations for donation after circulatory death kidney transplantation in Europe.

Donation after circulatory death (DCD) donors provides an invaluable source for kidneys for transplantation. Over the last decade, we have observed a substantial increase in the number of DCD kidneys, particularly within Europe. We provide an overview of risk factors associated with DCD kidney function and survival and formulate recommendations from the sixth international conference on organ donation in Paris, for best-practice guidelines. A systematic review of the literature was performed using Ovid Medline, Embase and Cochrane databases. Topics are discussed, including donor selection, organ procurement, organ preservation, recipient selection and transplant management.

Behaviour of transplanted tumours and role of matching in rejection.

BACKGROUND: Tumour transfer/development is one of the more serious risks associated with transplantation. The behaviour of a tumour can be unpredictable in immunosuppressed recipients. We report a highly sensitive method to monitor tumour behaviour in real time in a rodent tumour transplant model. This paper also explores the effect of MHC matching on tumour growth among control and immunosuppressed hosts. METHODS: Luciferase expressing Wistar rat kidney tumour cells were transplanted into either Wistar or Lewis recipients which mimic a well and poorly matched combination to assess the effects of MHC matching on transplanted tumour cells. Experimental groups included controls with no immunosuppression and animals immunosuppressed with cyclosporine. The latter group was further divided into a continuous treatment group which received four weeks of immunosuppression and a treatment withdrawal group where immunosuppression was stopped after two weeks to assess the effects of rejection on tumour growth. RESULTS: All the tumour cells were rejected in the control animals that received no immunosuppression, within 2 weeks among well-matched combination and within one week in the poorly matched combination (p 0.001). The transplanted tumour cells continued to grow in both well-matched and poorly matched groups who were treated with cyclosporine, but growth was significantly faster in the well-matched combination (p 0.033). After treatment withdrawal the tumour cells were rejected in all the animals of the poorly matched group compared to 50% in well matched animals within the four-week study period (p 0.039). CONCLUSION: In the absence of immunosuppression the hosts reject the transplanted tumour cells, and the anti-tumour response is stronger when there is a greater mismatch in MHC with the recipient. In the presence of cyclosporine immunosuppression the tumour continues to grow, however, after withdrawal of the immunosuppression, tumour clearance is quicker in the poorly matched background. This data supports the idea of expansion of the donor pool by using kidneys after ex vivo resection of small renal tumours and that these organs should be transplanted into a less well-matched HLA recipient. We hypothesise that should a tumour recurrence occur a poorly matched recipient could clear the tumour through withdrawal of immunosuppression.

Development of an ex vivo technique to achieve reanimation of hearts sourced from a porcine donation after circulatory death model.

BACKGROUND: This study reports on the development of a novel method for achieving ex vivo reanimation of hearts from a porcine donation after circulatory death (DCD) model without the use of donor pretreatment. METHODS: Porcine hearts (n = 23) were procured 10-29 min after confirmation of asystole. All hearts underwent initial flush with AQIX RS-I solution (London, UK). A 2-h preservation period followed: group 1 hearts (n1-n11) were preserved using static cold storage, group 2 hearts (n12-n17) were preserved using oxygenated, hypothermic machine perfusion (MP), and group 3 hearts (n18-n23) were subjected to retrograde oxygen persufflation. Reperfusion was performed on a Langendorff modification of a Model 33 Functional Circulation circuit. In hearts n16-n23, a dialysis circuit was incorporated into the circuit to facilitate removal of metabolites. The experimental protocol was allowed to follow an evolutionary course, with the aim of achieving greater success with reanimation. RESULTS: In group 1 (static cold storage), 7 of the 11 hearts (63.6%) achieved reanimation on the ex vivo circuit. Two of the six hearts (33.3%) in group 2 (MP) were successfully reanimated. All the six hearts (100%) in group 3 (persufflation) were successfully reanimated. The period of sustained reanimation increased when dialysis was incorporated into the circuit with a maximum of 300 min. CONCLUSIONS: Porcine DCD hearts after 29 min of warm ischemia can be reanimated using the method described. A mechanism of reoxygenation (oxygenated MP or coronary sinus oxygen persufflation) during preservation appears mandatory for hearts from DCDs. Persufflation was associated with a higher probability of successful reanimation. Dialysis in the warm phase was useful in removing metabolites that could interfere with reanimation. The results demonstrate the potential of DCDs to counter the decline affecting heart transplantation.

Portal Venous Oxygen Persufflation of the Donation after Cardiac Death pancreas in a rat model is superior to static cold storage and hypothermic machine perfusion.

Success of clinical pancreatic islet transplantation depends on the mass of viable islets transplanted and the proportion of transplanted islets that survive early ischaemia reperfusion injury. Novel pancreas preservation techniques to improve islet preservation and viability can increase the utilization of donation after cardiac death donor pancreases for islet transplantation. Rat pancreases were retrieved after 30 min of warm ischaemia and preserved by static cold storage, hypothermic machine perfusion or retrograde portal venous oxygen persufflation for 6 h. They underwent collagenase digestion and density gradient separation to isolate islets. The yield, viability, morphology were compared. In vitro function of isolated islets was compared using glucose stimulated insulin secretion test. Portal venous oxygen persufflation improved the islet yield, viability and morphology as compared to static cold storage. The percentage of pancreases with good in vitro function (stimulation index > 1.0) was also higher after oxygen persufflation as compared to static cold storage. Retrograde portal venous oxygen persufflation of donation after cardiac death donor rat pancreases has the potential to improve islet yield.

A Prospective Randomised Paired Trial of Sirolimus versus Tacrolimus as Primary Immunosuppression following Non-Heart Beating Donor Kidney Transplantation.

INTRODUCTION: With calcineurin inhibitors potentiating damage from ischaemia-reperfusion injury in kidneys from donors after cardiac death we wanted to investigate the role of substituting sirolimus for tacrolimus in the delayed introduction of calcineurin inhibitor regime used in our centre. METHOD: A prospective randomised paired open-label study was performed taking pairs of kidneys from each donor and randomising one to a tacrolimus-based regime and the other to a similar regime based on sirolimus. Graft function at one year was the primary endpoint. RESULTS: Total 31 pairs of kidneys were randomised to each group, with 19 pairs of recipients available for analysis after post-randomisation study exclusions. Despite a higher incidence of biopsy proven acute rejection in the sirolimus group, renal allograft function was similar in both groups at three-monthly intervals up to one year post-transplant. All episodes of acute rejection in the sirolimus group occurred in the first three months. Graft and patient survival at one year was 100% in the tacrolimus group, with one death with functioning graft in the sirolimus group (95% survival). Unfortunately, 10 of the 19 patients in the sirolimus arm required switch of medication to tacrolimus due to acute rejection or intolerable drug side effects. CONCLUSIONS: Graft survival and function were very similar in the two groups despite the higher rate of acute rejection in the sirolimus arm, raising the possibility that the damage done by acute rejection was adequately offset by the nephron-sparing effect of sirolimus compared to tacrolimus. Sirolimus may have a role as a longer-term maintenance immunosuppressant after initial treatment with a different agent such as tacrolimus or belatacept.

Successful endovascular salvage of a pancreatic graft after a venous thrombosis: case report and literature review.

Simultaneous kidney and pancreatic transplant is the criterion standard for treatment of end-stage renal failure because of diabetic nephropathy. Venous thrombosis occurs in approximately 5% of pancreatic transplants, and it is notoriously difficult to treat, forming the most common nonimmunologic cause of graft loss. We report a case of early detection of pancreatic graft venous thrombosis by measuring urinary amylase, resulting in the successful endovascular salvage of the pancreatic graft.

Extracorporeal membrane oxygenation for resuscitation of deceased cardiac donor livers for hepatocyte isolation.

BACKGROUND: Deceased cardiac donors (DCDs) have become a useful source of organs for liver transplantation; nevertheless, there are concerns about the longevity of these grafts. The aim of this study was to evaluate the use of extracorporeal membrane oxygenation (ECMO) to resuscitate DCD porcine livers as a preclinical model using hepatocyte isolation and viability as a marker to assess whole-graft preservation. MATERIALS AND METHODS: We randomized Landrace pigs into three groups after cardiac death and 30 min of warm ischemia: group 1, peritoneal cooling with intravascular cooling for 2 h; group 2, ECMO for 2 h; and group 3, control (conventional intravascular cooling and retrieval). We then reperfused group 1 and 2 livers for 2 h on an ex vivo reperfusion circuit and isolated hepatocytes. RESULTS: After reperfusion, hepatocyte viability was significantly improved in the ECMO group compared to the cooling groups, as measured by trypan blue, methylthiazolyldiphenyl-tetrazolium bromide, and seeding efficiency. Glycogen and reduced glutathione content were significantly used in the ECMO group both before and after reperfusion compared with group 2. The adenosine diphosphate:adenosine triphosphate ratio showed an improved trend (lower) in the ECMO group compared with the cooling group but did not reach statistical significance either before or after reperfusion. CONCLUSIONS: This preclinical study suggests that ECMO is a viable technique for liver preservation that gives an improved yield of hepatocytes when isolated from a DCD liver, suggesting improved liver preservation.

Liver transplantation using Donation after Cardiac Death donors.

The success of solid organ transplantation has brought about burgeoning waiting lists with insufficient donation rates and substantial waiting list mortality. All countries have strived to expand donor numbers beyond the standard Donation after Brain Death (DBD). This has lead to the utilization of Donation after Cardiac Death (DCD) donors, also frequently referred to as Non-Heart Beating Donors (NHBD). Organs from these donors inevitably sustain warm ischaemic damage which varies in its extent and affects early graft function as well as graft survival. As a consequence, 'non-vital' organs such as renal transplants have increased rapidly from DCD donors but more 'vital' organ transplants such as the liver have lagged behind. However, an increasing proportion of liver transplants are now derived from DCD donors. This article covers this expansion, current results, pitfalls, and steps taken to minimize complications and to improve outcome, and future developments that are likely to occur.

The modified Barry technique to prevent vesicoureteric reflux in paediatric renal transplant recipients: initial recipient outcomes.

OBJECTIVE: We present the initial clinical results of the 'modified Barry technique' for the prevention of VUR in paediatric renal transplant grafts. Ours is the only centre in the UK using this technique, as confirmed in a questionnaire developed in our department. PATIENTS AND METHODS: We retrospectively analysed data of 15 paediatric renal transplant patients (operated June 2006-November 2009) who had their vesicoureteric anastomosis performed using the modified Barry technique with a 2-cm submucosal anti-reflux tunnel. The original Barry technique involved the creation of a 4-cm tunnel; this was modified by us to reduce the risk of ureteric stenosis. RESULTS: At a median follow up of 23.7 months (6.3-39.4), the incidence of VUR was 7% (1/15). There was no evidence of postoperative urological complications, such as urinary leak, primary ureteric obstruction including anastomotic stricture/stenosis, transplant graft renal calculi and chronic rejection. At current follow up, graft and patient survival are 100%. CONCLUSION: With the introduction of the modified Barry technique, the incidence of VUR in our series fell 10-fold to 7%, compared with our earlier study (P<0.0001), without any urological complications. Although the initial results are encouraging, larger patient numbers and longer follow up are required to validate this technique further.

The influence of perfusion solution on renal graft viability assessment.

BACKGROUND: Kidneys from donors after cardiac or circulatory death are exposed to extended periods of both warm ischemia and intra-arterial cooling before organ recovery. Marshall's hypertonic citrate (HOC) and Bretschneider's histidine-tryptophan-ketoglutarate (HTK) preservation solutions are cheap, low viscosity preservation solutions used clinically for organ flushing. The aim of the present study was to evaluate the effects of these two solutions both on parameters used in clinical practice to assess organ viability prior to transplantation and histological evidence of ischemic injury after reperfusion. METHODS: Rodent kidneys were exposed to post-mortem warm ischemia, extended intra-arterial cooling (IAC) (up to 2 h) with preservation solution and reperfusion with either Krebs-Hensleit or whole blood in a transplant model. Control kidneys were either reperfused directly after retrieval or stored in 0.9% saline. Biochemical, immunological and histological parameters were assessed using glutathione-S-transferase (GST) enzymatic assays, polymerase chain reaction and mitochondrial electron microscopy respectively. Vascular function was assessed by supplementing the Krebs-Hensleit perfusion solution with phenylephrine to stimulate smooth muscle contraction followed by acetylcholine to trigger endothelial dependent relaxation. RESULTS: When compared with kidneys reperfused directly post mortem, 2 h of IAC significantly reduced smooth muscle contractile function, endothelial function and upregulated vascular cellular adhesion molecule type 1 (VCAM-1) independent of the preservation solution. However, GST release, vascular resistance, weight gain and histological mitochondrial injury were dependent on the preservation solution used. CONCLUSIONS: We conclude that initial machine perfusion viability tests, including ischemic vascular resistance and GST, are dependent on the perfusion solution used during in situ cooling. HTK-perfused kidneys will be heavier, have higher GST readings and yet reduced mitochondrial ischemic injury when compared with HOC-perfused kidneys. Clinicians should be aware of this when deciding which kidneys to transplant or discard.