Depopulated bovine ureteric xenograft for complex haemodialysis vascular access.
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Animals↗
Biomedical subjects
D Talbot
Publications and source records attributed to D Talbot.
Agonal period in potential non-heart-beating donors.
The shortage of donor kidneys for renal transplantation is becoming more severe as the gap between the number of patients waiting for renal transplantation and the number of cadaveric organs available continues to widen. Therefore, many centres have started using non-heart-beating (NHB) donors. There was no clear plan for maximal duration of agonal period in Maastricht category NHB donors after withdrawal of treatment in Newcastle. This withdrawal has been audited in retrospect. Our current wait time is now a maximum of 5 hours; however, previously there have been some considerably longer periods. Concern has always been expressed about poor quality with protracted periods. Nonuse in this review of 58 kidneys can be expressed against time: 0 to 2 hours 13%, 2 to 5 hours 33%, and >5 hours 45%. Therefore, though the nonuse rate was significantly different between 0 to 2 hours and >5 hours (P < .05, chi-square), there were 16 transplants performed with kidneys >2 hours and 12 transplanted >5 hours. In conclusion, although good usable kidneys can still be used with protracted withdrawal, there are considerable logistical difficulties with our 5-hour cut-off, which means that one third of potential kidneys will not be utilized.
Heart Arrest↗
Dual renal transplantation for kidneys from marginal non-heart-beating donors.
Kidneys transplanted from non-heart-beating donors (NHBD) are generally regarded as marginal or extended criteria grafts due to the associated period of warm ischemia. The most prolonged periods occurring in the category II (uncontrolled) donor. This potential for injury can adversely affect the glomular filtration rate (GFR), which in severe cases results in primary nonfunction. Viability testing can identify a group of kidneys that, although unsuitable for solitary transplantation, may be considered for dual transplant. This retrospective study examined a series of 11 dual renal transplants, comparing 3- and 12-month GFR outcome data with 81 single NHBD transplants. The mean GFR at 3 months in the dual group was 47.6 and at 12 months was 48.6. In the single group the GFR at 3 months was 40.6 and at 12 months was 41.9. Thus using viability testing to identify NHBD kidneys suitable for dual transplant appears reliable and predictable.
Follow-Up Studies↗
Renal transplants from category III non-heart-beating donors with evidence of pre-arrest acute renal failure.
Kidneys transplanted from non-heart-beating donors (NHBDs) have been exposed to varying degrees of ischemic damage after death. Category III donors have invariably been managed, treated, and investigated in a hospital setting prior to arrest and death. Some therefore exhibit evidence of renal dysfunction and even acute renal failure (ARF) before death. Many surgeons would regard a NHBD with pre-arrest evidence of ARF as too marginal for renal transplantation. This retrospective study examines five Maastricht category III NHBD donors with evidence of pre-arrest ARF. We compare 3- and 12-month GFR outcome data from the nine resulting transplants with 40 category III NHBD transplants with normal pre-arrest renal function. The mean GFR at 3 months was 45.4 and 43.8 for the ARF and normal group, respectively. At 12 months the GFR was 42.2 and 44.7 in the ARF and normal groups, respectively. Thus evidence of ARF pre-arrest does not preclude successful category III NHBD renal transplantation.
Acute Kidney Injury↗
Predisposing factors for biliary complications following liver transplantation.
INTRODUCTION: Biliary complications remain a major cause of morbidity and mortality in patients following liver transplantation. We sought to identify possible risk factors predisposing to biliary complications after OLT using duct-to-duct biliary reconstruction. MATERIALS AND METHODS: We retrospectively reviewed 5 years of prospectively collected donor and recipient data between April 1999 and April 2004. We evaluated the presence of biliary complications, donor and recipient age, cold ischemia time, hepatic artery thrombosis, non-heart-beating donor (NHBD), and graft steatosis (>30%). The results were compared with a control group of OLT patients without biliary complications. RESULTS: Among 173 OLT recipients, biliary complications occurred in 28 patients (16.2%), of whom 12 were leaks, 15 strictures, and 1 a nonanastomotic intrahepatic stricture. The mortality following biliary complications was 11%, compared to 6% in the control group. CONCLUSION: Biliary complications remain a persistent problem in OLT. Analysis of risk factors identified hepatic artery thrombosis and steatosis as predisposing factors. With greater experience, NHBD livers may also prove to be at greater risk of biliary complications.
Adult↗
Diabetic donors as a source of non-heart-beating renal transplants.
Due to the organ shortage, many renal transplantation centers attempt to increase the donor pool by using non-heart-beating donors (NHBDs). These kidneys are generally regarded as "marginal" grafts. Many centers do not consider transplantation from an NHBD with a history of diabetes as it is a more suboptimal donor. We began our NHBD program in 1998 and have performed 5 renal transplants from diabetic NHBDs. Viability testing identified kidneys suitable for single or dual transplantation. Although kidneys from brain stem dead donors with diabetes have been used successfully, our data suggested that kidneys from diabetic NHBDs can also be used although we still need long-term results.
Cadaver↗
Renal graft function after prolonged agonal time in non-heart-beating donors.
To deal with the increasing gap between organ demand and supply for kidney transplantation, many centers have started to use non-heart-beating (NHB) donors. When we initiated our program to utilize kidneys from such donors in 1998, we had no protocol for the maximal agonal period. This however was audited in retrospect. Our current wait time is now a maximum of 5 hours. Concern has been expressed in the past about possible deterioration in the quality of the organs with a protracted agonal time. We aimed in this study to examine the effect of prolonging agonal period on the quality of kidneys retrieved from Maastricht category III donors: A total of 40 kidneys were transplanted from 29 category III donors between 1998 and 2004. Eleven kidneys had donor agonal times of >5 hours; the remainder, agonal times <5 hours. Both groups were matched for donor and recipient factors. The mean glomerular filtration rates at 12 months for <5 hours versus >5 hours agonal time were 43.8 +/- 4.4 versus 49.8 +/- 5.8, respectively (P = .24) and at 24 months, 46.83 +/- 8.99 versus 37.67 +/- 3.85, respectively (P = .24). In conclusion, intermediate graft function is comparable to ones with shorter agonal time, although we await long-term results.
Adult↗
Non-heart-beating kidney transplantation: 6-year outcomes.
Non-heart-beating donor kidneys (NHBD) are being used to increase the donor pool due to the scarcity of cadaveric heart beating donors (HBD). We evaluated the long-term outcomes of renal transplantation using NHBD kidneys, comparing the first 100 NHBD kidneys transplanted at our facility to the next consecutive cadaveric HBD kidneys for graft survival, recipient survival, and quality of graft function. Recipient survival (P = .22) and graft survival (P = .19) at 6 years did not differ between recipients of NHBD (83%, 80%) and HBD (89%, 87%) kidneys. Quality of graft function using the mean glomular filtration rates were significantly lower in the NHBD group up to 3 months following discharge (41 +/- 2 vs 47 +/- 2, P = .007) but were then comparable up to 6 years following transplantation (43 +/- 5 vs 46 +/- 4, P = .55).
Adolescent↗
Ischemia-reperfusion injury in cadaveric nonheart beating, cadaveric heart beating and live donor renal transplants.
PURPOSE: Ischemia-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. MATERIALS AND METHODS: Renal 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. RESULTS: The 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). CONCLUSIONS: NHBD 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.
Adult↗
Soya isoflavone-enriched cereal bars affect markers of endothelial function in postmenopausal women.
Soya isoflavones are thought to be cardioprotective due to their structural similarity to oestrogen. In order to investigate the effect of soya isoflavones on markers of endothelial function we conducted a randomised, double-blind, placebo-controlled, cross-over study with thirty healthy postmenopausal women. The women consumed cereal bars, with or without soya isoflavones (50 mg/d), for 8 weeks, separated by an 8-week washout period. Systemic arterial compliance (SAC), isobaric arterial compliance (IAC), flow-mediated endothelium-dependent vasodilation (FMD) and nitroglycerine-mediated endothelium-independent vasodilation (NMD) were measured at the beginning of the study and after each intervention period. Blood pressure (BP) and plasma concentrations of nitrite and nitrate (NOx) and endothelin-1 (ET-1) were measured at the beginning and end of each intervention period. NMD was 13.4 (SEM 2.0)% at baseline and 15.5 (SEM 1.1) % after isoflavone treatment compared with 12.4 (SEM 1.0)% after placebo treatment (P=0.03). NOx increased from 27.7 (SEM 2.7) to 31.1 (SEM 3.2) microM after isoflavones treatment compared with 25.4 (SEM 1.5) to 20.4 (SEM 1.1) microM after placebo treatment (P=0.003) and a significant increase in the NOx:ET-1 ratio (P=0.005) was observed after the isoflavone treatment compared with placebo. A significant difference in SAC after the isoflavone and placebo treatment was observed (P=0.04). No significant difference was found in FMD, IAC, BP and ET-1. In conclusion, 8 weeks' consumption of cereals bars enriched with 50 mg soya isoflavones/d increased plasma NOx concentrations and improved endothelium-independent vasodilation in healthy postmenopausal women.
Biomarkers↗
Preservation solutions for solid organ transplantation.
Solid organ transplantation was one of the greatest medical advances of the 20th century. Current preservation technology falls short of maintaining organs ex vivo in perpetuity. This review examines the biochemical basis of organ degradation in response to ischaemia, preservation solution composition and potential future organ preservation technology.
Calcium↗
Randomized clinical trial of daclizumab induction and delayed introduction of tacrolimus for recipients of non-heart-beating kidney transplants.
BACKGROUND: 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. METHODS: To assess whether daclizumab (DZB) could safely replace tacrolimus in the immediate postoperative period, patients were randomized to receive DZB induction and daily mycophenolate mofetil with steroids (DZB group) or standard tacrolimus-based triple therapy (control group). Tacrolimus was given to patients in the DZB group when the serum creatinine level dropped below 350 micromol/l. RESULTS: Fifty-one patients were recruited at two centres over a 2-year interval between 2000 and 2003. The overall rate of immediate function was 28 per cent (13 of 46 grafts), with the highest rate in recipients of machine-perfused kidneys treated with DZB (eight of 15 patients). CONCLUSION: Induction with DZB and delayed introduction of tacrolimus reduced the incidence of DGF in recipients of machine-perfused NHBD kidneys.
Adult↗
Vimentin antibodies: a non-HLA antibody as a potential risk factor in renal transplantation.
Chronic allograft rejection is the major problem encountered in solid organ transplantation and is the end point of several complex processes. A number of recent studies show both alloimmune and autoimmune responses may have roles to play. The importance of HLA antibodies in transplantation is well documented, but despite the introduction of very sensitive HLA screening assays, antibody-mediated allograft rejection still occurs without detectable HLA antibodies. The target for antibody-mediated allograft rejection in these circumstances remains elusive, perhaps due to the variety of potential targets presented on endothelial cells. Recent studies identifying C4d and immunoglobulin deposits in patients undergoing late allograft loss provide evidence that chronic rejection involves humoral as well as cellular components. Several endothelial cell antigens that might be important in chronic rejection have been suggested, including MHC class I chain-related genes; Lewis; and the intermediate filament protein, vimentin. Vimentin is an ideal candidate antigen for antibody-mediated rejection as it is found in endothelial cells and is exposed to the immune system following surgery or by chronic allograft rejection due to endothelial cell breakdown, where the development of antibodies may cause further damage. We have developed a flow cytometric assay for the detection of antibodies to vimentin and have investigated whether HLA or vimentin antibodies are present in renal transplant recipients undergoing chronic rejection.
Graft Rejection↗
A simple cardiovascular risk score can predict poor outcome in non-heart-beating donor renal transplantation.
A simple cardiovascular risk score used in our centre to plan cardiovascular work-up for renal transplantation can predict outcome in non-heart-beating donor (NHBD) renal transplantation. Patients in the higher-risk group, with a score of >12 of a maximum of 36 are likely to have a longer duration of delayed graft function, poorer glomerular filtration rate at 6 months, and inferior graft and patient survival, together with a relative rate of graft loss within 60 days of 4.514 (P = .019) and within 1 year of 3.511 (P = .036). Although a high cardiovascular risk score should not be regarded as a contraindication to NHBD transplantation, the score can be used to facilitate recipient selection.
Adult↗
Evaluation of daclizumab to reduce delayed graft function in non-heart-beating renal transplantation: a prospective, randomized trial.
Daclizumab (DZB), an interleukin-2 receptor blocker, has been shown to reduce the rate of acute rejection, while non-heart-beating kidney recipients have high rates of delayed graft function that may be prolonged by high levels of calcineurin inhibitors. This study assessed whether DZB could safely replace calcineurin inhibitors in the immediate postoperative period and promote recovery from ischemic acute tubular necrosis. Patients were randomized into one of two groups: DZB induction and daily mycophenolate mofetil (MMF; 2 g) with steroids (20 mg prednisone) or standard triple therapy with tacrolimus, MMF, and prednisone. Patients in the DZB arm were converted to the control arm when either the serum creatinine dropped to <350 micromol/L or there was biopsy evidence of acute rejection. Over 2 years, Leicester and Newcastle non-heart-beating donor (NHBD) centers recruited 51 patients. There was one patient death in the DZB arm, during the study period, after a nonfunctioning graft was removed. A total of two (8%) grafts in the DZB arm and three (11.5%) grafts in the control arm failed to function. The overall rate of immediate function improved from around 5% (pre-2001) to 28%. There were no significant differences in the incidence of acute rejection or graft function (GFR) at 3 months. Machine-perfused kidneys in DZB-treated recipients had the highest rates of immediate function (53%, P = .015). We found that a calcineurin-sparing regime is safe and may be beneficial for recipients of machine-perfused grafts damaged by warm ischemia.
Antibodies, Monoclonal↗
Does donor cardiopulmonary resuscitation time affect outcome in uncontrolled non-heart-beating donor renal transplants?
Uncontrolled non-heart-beating donors offer the opportunity to significantly expand the potential pool of kidney donors but are associated with a variable duration of cardiopulmonary resuscitation (CPR), where cardiac output is only 30% to 40% of normal. We were concerned that prolonged CPR would adversely affect the function of transplanted kidneys. In our series of 46 uncontrolled donors the mean duration of CPR was 60 minutes, which also represents a realistic cutoff point for CPR duration. Taking a cutoff point of 60 minutes, we found no differences in kidney discard rates following viability assessment, primary nonfunction rate, or duration of delayed graft function. We therefore conclude that if formal viability assessment is performed, kidneys may be retrieved from uncontrolled non-heart-beating donors irrespective of duration of CPR.
Cardiac Output↗
Audit of diabetes in a renal transplant population.
AIMS: To determine the prevalence of diabetes and its glycemic control in the renal transplant population of northeast England (Newcastle, Sunderland, Middlesborough, and Carlisle). METHODS: All renal transplant notes in northeast England were reviewed. Data on patient details, type of diabetes, time of onset of diabetes, diabetes medications, time of insulin commencement, date of renal transplant, immunosuppressive medications, and HbA(1C) were recorded. RESULTS: Living renal transplant patients (n = 1073) transplanted between March 1982 and November 5, 2003 were identified. One hundred and nine (10.2%) patients had diabetes, of whom 39 were type 1 and 70 were type 2. Median HBA(1C) in patients with type 1 diabetes on tacrolimus was 10.1% +/- 1.94% (SD) versus 7.8% +/- 1.98% (SD) for patients not on tacrolimus. Among patients with type 2 diabetes, 25 had diabetes prior to transplant and 45 (4.5%) developed posttransplant diabetes (PTDM). Those who developed PTDM and were taking tacrolimus were more likely to require insulin for blood glucose control (0.39 U/kg/24 hours vs 0 U/kg/24 hours; P = .05) compared to those not on tacrolimus. Both type 1 and type 2 diabetics on tacrolimus showed better preservation of renal function as measured by mean serum creatinine (type 1: 145 +/- 53 vs 196 +/- 74, P = .02; type 2 pretransplant: 159 +/- 73 vs 172 +/- 59, P = .35; type 2 posttransplant: 123 +/- 35 vs 167 +/- 63, P = .01). CONCLUSIONS: Tacrolimus use in renal transplant patients with diabetes appeared to be associated with more problematic blood glucose control; however, it seemed to be better at preserving renal function. Intensive blood glucose monitoring is recommended for this group.
Blood Glucose↗
Do recipients of kidneys from donors treated with streptokinase develop anti-streptokinase antibodies?
Streptokinase is used for preflush for non-heart-beating donors (NHBDs) in our center. The aim of this study was to evaluate whether the use of thrombolytic streptokinase results in the production of anti-streptokinase antibodies in the recipients after renal transplantation. Recipient sera taken prior to and at 1 and 6 months posttransplant were tested for the presence of antibodies to streptokinase using an enzyme-linked immunosorbent assay assay. No differences were detected between a group of 18 recipients who had kidneys from thrombolytic-treated NHBDs and a further group of 18 who received NHBD kidneys without such treatment.
Antibodies↗