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.

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.

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.

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.

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.

Successful simultaneous liver-kidney transplant in an adult with atypical hemolytic uremic syndrome associated with a mutation in complement factor H.

Atypical hemolytic uremic syndrome was diagnosed in a 62-year-old man. Sequencing of the CFH gene, which encodes complement factor H, revealed a heterozygous adenine to guanine mutation at nucleotide 3550 of the complementary DNA, leading to a predicted substitution of alanine for threonine at amino acid position 1184 in the protein (c.3550A>G, p.Thr1184Ala). Three years later, he received a simultaneous liver-kidney transplant with plasmapheresis and intratransplant plasma infusion. The postoperative course was complicated by an anastomotic biliary stricture that was treated successfully using endoscopic stenting. One year later, he has excellent function of both transplants, emphasizing that simultaneous liver-kidney transplant is a valuable treatment option in the management of adult patients with atypical hemolytic uremic syndrome.

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.

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.

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.

Dual transplantation of marginal kidneys from nonheart beating donors selected using machine perfusion viability criteria.

PURPOSE: Viability testing can be used to avoid the transplantation of nonheart beating donor organs that are likely to have primary nonfunction. Such testing also identifies a second group of kidneys which, although unsuitable for solitary transplantation, may be considered for dual transplantation. In kidneys in this group solitary transplants would be unlikely to produce a sufficient glomerular filtration rate to support the recipient. However, if used together as a dual transplant, they have the potential to produce sufficient renal function in 1 patient. MATERIALS AND METHODS: The group at our unit has performed 23 dual nonheart beating donor renal transplants from 2003 to date. Using 3 and 12-month post-transplantation recipient glomerular filtration rates as primary end points we compared our dual transplant group with our series of 115 single nonheart beating donor transplants from 1998 to 2006. RESULTS: At 3 and 12 months mean glomerular filtration rates in the dual group were 46.2 and 45.5 ml per minute per 1.73 m(2), respectively. These values were not significantly different from the mean glomerular filtration rates of 40.7 and 43.0 ml per minute per 1.73 m(2), respectively, in the single transplant group. CONCLUSIONS: We have observed that a subset of nonheart beating donor kidneys that do not satisfy the viability criteria for single organ transplantation may become successful dual organ grafts, thus, avoiding unnecessary organ nonuse and maximizing organ resources.

Biliary cast syndrome: literature review and a single centre experience in liver transplant recipients.

BACKGROUND: Biliary cast syndrome (BCS) is an unusual complication of orthotopic liver transplantation (OLTx), and its management is difficult. Limited success using endoscopic retrograde cholangiopancreatography (ERCP) or open exploration to clear casts has been reported, but failure usually results in re-transplantation. We aimed to review our experience with BCS and highlight a novel combined percutaneous and endoscopic approach for duct clearance. A brief review of the literature is given. METHODS: We retrospectively reviewed our experience of managing BCS using case notes review. Details were also gathered from radiology, where interventional procedures were carried out. RESULTS: We had a total of three cases of BCS reported between 2002 and 2005. Multiple attempts were made to remove these casts. All three were treated in a variety of ways. Management is discussed along with highlighting a novel combined percutaneous and endoscopic approach for duct clearance. CONCLUSIONS: BCS is a potential complication of OLTx. Surgical and endoscopic methods of removing casts are used. However, in circumstances where these methods are technically difficult, a percutaneous endoscopic approach with serial dilatation of the cutaneous port and surgical removal of casts can be done.

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.

Thermography and colour duplex ultrasound assessments of arterio-venous fistula function in renal patients.

Vascular and clinical assessments of arterio-venous fistula (AVF) function and access are important in patients undergoing or preparing to undergo renal dialysis. Objective assessment techniques include colour duplex ultrasound and more recently medical infrared thermography. Ideally, these should help assess problems relating to fistula failure or to vascular steal from the hand which can result from excessive fistula blood flow. The clinical value of thermography, as yet, has not been assessed for this patient group. The aims of this study were therefore to investigate the relationships between thermography skin temperature measurement and (a) quantitative ultrasound measurement of AVF blood flow, and (b) qualitative clinical assessment of vascular steal from the hands. Fifteen adult patients underwent thermal imaging of the upper limbs, colour duplex ultrasound to derive AVF blood flow from brachial artery blood flow measurements, and a clinical evaluation for vascular steal. Temperature measurements were extracted from the thermograms, including bilateral arm and hand (Fistula -- Non-Fistula) differences, for comparison with derived AVF blood flow and steal grading. Derived AVF blood flow ranged from 30 to 1,950 ml min(-1), with a mean rate close to one litre per minute. Thermography detected the warmer superficial veins in proximity to the patent fistulas, with bilateral differences in fistula region skin temperature correlated with derived AVF blood flow (using maximum temperature measurements the correlation was +0.71 [p < 0.01]; and using mean temperature measurements the correlation was +0.56 [p < 0.05]). When thermography measurements were compared with the clinical assessment of steal the mean hand temperature differences separated steal from non-steal patients with an accuracy of greater than 90%. In summary, we have now demonstrated the potential clinical value of medical infrared thermography for assessing AVF function in renal patients.