D. Talbot

The trouble with kidneys derived from the non heart-beating donor: a single center 10-year experience.

BACKGROUNDnThe demand for renal transplantation has increasingly outstripped the supply of donor organs especially over the past 10 years. Although related and unrelated live donation is being promoted as one option for increasing the donor pool, it is unlikely that this will in itself be able to bridge the gap. Non-heart beating donors (NHBD) can provide an alternative supply of organs, which should substantially increase the donor pool.nnnMETHODSnIn Newcastle, NHBD kidneys have been used for transplantation for a period of 10 years. In the early period (1988-1993) excellent results were obtained (90.5% success); however, these donors were controlled NHBD, Maastricht category III. In the second phase (1994-1998) increasing numbers of donors were obtained from the Accident and Emergency Department unit. These were failed resuscitation for cardiac arrest (category II). The rates of success in this period were poor (45.5% success) and the program was halted. The third phase of the program used machine perfusion of the kidneys and glutathione S transferase enzyme analysis to assess viability.nnnRESULTSnUsing such approaches renal transplants from largely category II donors produced a success rate of 92.3% which was significantly better than the phase II period of the program (P=0.023, Fisher two-tail test).nnnCONCLUSIONnMachine perfusion and viability assessment of NHB kidneys in phase III of the program has increased our donor pool as well as improved the graft survival. This is particularly relevant for the use of the category II NHB donor where the incidence of primary nonfunction was high, illustrated by phase II where machine perfusion/viability assessment was not used.

Co-administration of tacrolimus and mycophenolate mofetil in cadaveric renal transplant recipients

Co-administration of tacrolimus and mycophenolate mofetil in cadaveric renal transplant recipients.

Early results of a non-heartbeating donor (NHBD) programme with machine perfusion.

Abstract Freeman Hospital, Newcastle upon Tyne restarted their non‐heartbeating donor (NHBD) programme in September 1998 using machine perfusion, due to early poor results with conventional cold storage (45% graft survival, phase II). Since then, 15 NHBD kidneys have been transplanted. The retrieval protocol consisted of in situ perfusion with a double balloon triple lumen cannula in Maastricht category II male donors age range 13‐59 years. Mean primary warm ischaemic time was 24.8 min (range 10‐44). All kidneys were machine perfused through a locally developed perfusion system. The viability was assessed by serial measurements of total GST (maximum acceptable limit of 200 units/l) and intrarenal vascular resistance (IRVR) was recorded. Fifteen of the 22 kidneys (68.62%) were transplanted. Delayed graft function (DGF) was seen in ten recipients (66.6%), two kidneys had immediate function (IF), one organ was exported, two recipients died of unrelated causes and a further seven kidneys were discarded (two had high tGST, two were infected and three had poor flow characteristics). In phase III, a success rate of 91.7% was thus achieved, which was better than the phase II period (P = 0.027, Fisher 2‐tail test). Machine perfusion has been successfully introduced in phase III to the Newcastle NHBD programme and facilitates viability assessment of NHBD kidneys.

Evaluation of the ischemic protection efficacy of a laparoscopic renal cooling device using renal transplantation viability assessment criteria in a porcine model.

PURPOSEnWe assessed the efficacy of a prototype laparoscopic topical cooling device. The aim of regional renal hypothermia in laparoscopic surgery is to limit ischemic injury and extend safe operative time. A reliable model for assessing renal ischemic injury exists in the field of nonheart beating donor renal transplantation. Hypothermic machine perfusion allows calculation of the pressure flow index and measurement of glutathione S-transferase in the perfusate. These parameters allow accurate assessment of the extent of renal damage.nnnMATERIALS AND METHODSnThe device incorporates a 2-layer cooling bag and coolant circuit. The system achieves hypothermia by circulating coolant across the surface of the kidney. Using 10 pigs individual kidneys were subjected to periods of renal ischemia with or without device in situ cooling. Each kidney was then machine perfused and assessed using nonheart beating donor viability criteria.nnnRESULTSnThe best performance of the device achieved a renal parenchymal temperature of 15C in 11.2 minutes (mean +/- SD 21.4 +/- 8.42). In the warm ischemia groups significant deterioration of pressure flow index compared to controls occurred by 60 minutes (p = 0.0001). In cooled kidneys at 60 minutes the mean pressure flow index was not significantly different from that in controls. Greater mean glutathione S-transferase measurements were associated with the warm ischemia groups.nnnCONCLUSIONSnOur study reinforces the efficacy of topical renal cooling in the laparoscopic setting. We report the use of assessment techniques capable of accurate quantitative measurement of renal injury in an animal model. Our cooling device is currently undergoing further development to enhance its efficiency.

Randomized clinical trial of daclizumab induction and delayed introduction of tacrolimus for recipients of non‐heart‐beating kidney transplants

Kidneys from non‐heart‐beating donors (NHBDs) have high rates of delayed graft function (DGF). Use of calcineurin inhibitors is associated with a reduction in renal blood flow, which may delay graft recovery from ischaemic acute tubular necrosis.

Biliary reconstruction with or without an internal biliary stent in orthotopic liver transplantation: a prospective randomised trial

Abstract Choledochocholedochostomy (CCD) with a 7 fr/8 fr Cotton Leung internal biliary stent removed at endoscopic retrograde cholangiography (ERC) 3 months following orthotopic liver transplantation (OLT) was the technique used on our unit for biliary reconstruction. From June 1995 to July 1996, we randomised 37 OLT patients with CCDs to receive either an internal stent (group I, nd = 18) or no stent (group II, n= 19). Patients in group I had an ERC at 3 months for stent removal whereas patients in group II had an ERC if indicated. The mean follow up was 19 (13–26) months. Biliary complications occurred in 9 out of 18 patients in group I compared to 1 out of 19 patients in group II (P= 0.007). In group I, ERC was required for complications in 8 patients and early surgery in 2, compared to 1 ERC for abnormal liver function tests in group II. Five of the early complications in group I were stent related. Late biliary stenosis occurred in 1 patient at 9 months. There was one stent‐related death. The use of stents contributes to biliary complications and CCD without stenting is safe after OLT.

Donation after Cardiac Death Kidneys with Low Severity Pre‐Arrest Acute Renal Failure

The widening gap between supply and demand for renal transplantation has prompted many centers to use donors after cardiac death. Some of these donors exhibit signs of acute renal failure (ARF) prior to cardiac arrest. Concern has been expressed about poor quality of graft function from such donors. In response to this perception, we reviewed 49 single renal transplant recipients from category III donors after cardiac death between 1998 and 2005, at out center. All kidneys but one had hypothermic machine perfusion and viability testing prior to transplantation. According to the RIFLE criteria, nine recipients had kidneys from donors with “low severity pre‐arrest ARF”. The remainder of the recipients were used as control group. There was no statistical significant difference in delayed graft function and rejection rates between these two groups. Recipients GFR at 12 months was 44.4 ± 17.1 and 45.2 ± 14.7 (mL/min/1.73m2) from donors with ARF and without ARF, respectively (p = 0.96). In conclusion, low severity ARF in kidneys from controlled after cardiac death donors can be a reversible condition after transplantation. Short‐term results are comparable to the kidneys from same category donors without renal failure, providing that some form of viability assessment is implemented prior to transplantation.

Ischemia-Reperfusion Injury in Cadaveric Nonheart Beating, Cadaveric Heart Beating and Live Donor Renal Transplants

PURPOSEnIschemia-reperfusion injury is gaining importance in transplantation as being responsible for allograft dysfunction. Ischemia occurs during kidney procurement, which is shortest in LDs, and prolonged in cadaveric HBDs and NHBDs.nnnMATERIALS AND METHODSnRenal transplants from 17 LDs, 15 HBDs and 19 NHBDs were assessed during reperfusion for biochemical markers of ischemia-reperfusion injury and assessed clinically. Central venous blood sampling was assayed for free radicals using electron spin resonance and tissue injury biomarkers, namely lactate dehydrogenase, fatty acid binding protein, alanine aminopeptidase, lactate and total antioxidants.nnnRESULTSnThe return to stable renal function was more rapid in LD renal transplants, while recovery continued from 3 months after hospital discharge in NHBD renal transplants. Injury markers, such as lactate dehydrogenase, fatty acid binding protein, alanine aminopeptidase and lactate, were raised at the time of reperfusion, especially in NHBD renal transplants. Free radical release measured by electron spin resonance showed 2 phase release, that is early (0 to 10-minute) and late (20 to 40-minute) release. In NHBD, HBD and LD renal transplants the index of free radical release in the early phase was 1.43, 1.36 and 1.20, and in the late phase it was 1.43, 1.38 and 0.97, respectively (each ANOVA p <0.05).nnnCONCLUSIONSnNHBD renal transplants were accompanied by a greater release of free radicals at reperfusion (NHBD > HBD > LD), which was associated with an increase in tissue injury markers at reperfusion. This was reflected in a slower return to stable renal function in NHBD compared to HBD and LD renal transplants.

Dynamic EBV gene loads in renal, hepatic, and cardiothoracic transplant recipients as determined by real-time PCR light cycler.

Abstract: Background: Epstein–Barr virus (EBV) is recognised as one of the causative agents for most cases of post‐transplant lymphoproliferative disease (PTLD). Elevated levels of EBV DNA are known to be associated with the onset of PTLD, but little information is available regarding how EBV loads change with time in asymptomatic transplant recipients following transplantation. Our aims were to study the trend of EBV loads in renal (RTx), hepatic, and cardiothoracic transplant recipients and to compare their EBV loads with other healthy and patient controls.

Conversion of renal transplant recipients from cyclosporin to low‐dose tacrolimus for refractory rejection

Abstract Twenty‐five patients with refractory rejection following renal transplantation were converted from cyclosporin to tacrolimus in an attempt to salvage the allografts. All patients had received two or three pulses of methylprednisolone, 6 had OKT3, 14 had antithymocyte globulin (ATG) and 2 had both OKT3 and ATG prior to conversion. The median time from transplantation to conversion to tacrolimus was 32 days (range 12–322). Patients underwent a simple switch from cyclosporin‐ to tacrolimusbased therapy with tacrolimus administered at a median dose of 0.15 mg/kg per day. Doses were adjusted according to clinical response and trough blood levels. Twenty‐one of the 25 patients (84 %) with refractory rejection showed evidence of reversal of rejection as indicated by a significant reduction in serum creatinine (Students paired t‐test, P < 0.05) following conversion to tacrolimus. None of these patients had further episodes of rejection. Three patients had ongoing rejection and returned to dialysis, and 1 patient showed deteriorating renal function associated with a cytomegalovirus infection. Of 18 patients currently on tacrolimus, 15 have improved renal function and 3 have shown no further deterioration. We conclude that low‐dose tacrolimus appears to be effective in salvaging renal allografts with resistant rejection.