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).

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.

Anti-vimentin antibody detection in recipients of heart-beating and non-heart beating donor kidneys.

Alternative donor sources include non-heart-beating donors (NHBDs). There donors have been exposed to significant ischemia, so that it is common to utilize machine perfusion to either improve the organs or at least assess their viability. Both prolonged warm ischemia and machine perfusion can potentially damage the vascular endothelium, thereby exposing vimentin to antigenic recognition. The aim of this study was to determine whether anti-vimentin antibodies could be detected in the blood of renal transplant recipients at specific time points after transplant and whether they could be related to the donor source. Fifty-one recipients of NHBD kidneys were compared to 52 recipients of heart-beating donor (HBD) kidneys. All recipients had similar anti-vimentin levels pretransplant. However, at 1 month those kidneys from Maastricht category II NHB donors showed significantly higher levels. At 6 months both Maastricht category II and category III NHB donor recipients displayed significantly higher levels than recipients of HBD kidneys.

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.

Cardiovascular risk assessment scoring system for the determination of cardiovascular mortality in renal transplant patients.

It is well known that the greatest risk for mortality post-renal transplant is cardiovascular death. We compared a modified cardiac risk assessment system among renal transplant patients who subsequently died versus the group that survived. There was a good correlation between the low, medium, and high scores with survival. The deceased group had significantly greater cardiovascular scores than case controls.

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.

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.

Prospective randomised trial of the use of Daclizumab in renal transplantation using kidneys from non heart beating donors.

OBJECTIVES: Transplantation using non-heart beating donors (NHBD) is one way of reducing the global kidney shortage. Unfortunately the large warm ischaemic insult sustained by the graft leads to a high rate of delayed graft function (DGF). We have investigated the use of a regimen utilising an II-2r blocker (DZB) in place of Tacrolimus for the initial post-operative immunosupression with the aim of reducing the incidence of DGF. METHODS: Prospective randomised controlled trial based in two NHBD UK centres (Leicester and Newcastle). 51 patients were enrolled over two years and randomised into two treatment arms: 1. DZB/MMF/Steroids (Tacrolimus started when creatinine dropped below 350 micromol/l) 2. Tacro/MMF/Steroids. RESULTS: There was one death, during the study period, in a patient who had had a non-functioning graft removed. The overall incidence of immediate function (IF) was higher than expected (28%), no significant difference was found in the incidence of immediate graft function between the two groups (35% group 1 and 22% group 2). Sub-group analysis however has shown a significant advantage for the delayed introduction of Tacrolimus for machine perfused grafts (IF: 53% vs 13%, chi2 p=0.015). There was no difference in the rate of rejection. CONCLUSIONS: The delayed introduction of Tacrolimus reduces the incidence of DGF in machine-perfused NHBD kidney transplantation.

Weight increase during machine perfusion may be an indicator of organ and in particular, vascular damage.

OBJECTIVES: Hypothermic machine perfusion preservation has been shown to improve the outcome of renal grafts from non-heartbeating donors. We have noticed that organs gain a variable amount of weight during perfusion. METHODS: All grafts, whether used or discarded, were assessed with respect to their weight gain. Primary outcome measures were the results of viability testing. Secondary outcomes were early transplant variables including incidence and duration of delayed graft function and histological examination of protocol graft biopsies. RESULTS: Weight increase data was available on 97 grafts. There were no significant differences in weight gain between kidneys used and discarded (17% vs 20%). 14 patients received grafts which gained over 30% of their initial retrieval weight. There were no significant differences in secondary outcome measures between this group of recipients and patients who had received less "waterlogged" kidneys. Histological changes including endothelial inflammation and oedema were observed. CONCLUSIONS: Kidney grafts which have gained over 30% of weight on hypothermic machine perfusion preservation can be transplanted successfully. Complex interactions between the period of warm ischaemia, in situ flushing, perfusion pressures and perfusate probably lead to the phenomenon of excessive graft weight gain.

Reperfusion injury in renal transplantation: comparison of LD, HBD and NHBD renal transplants.

Comparison of reperfusion injury in kidneys transplanted from LD, HBD or NHBD donors is presented in the paper. Central venous blood samples (taken during perioperative period) was assessed for free radicals, total antioxidant activity and various markers of tissue injury. There was demonstrable ischemia reperfusion injury occurring at the time of revascularization, which was particularly notable in kidneys transplanted from NHBD donors.

Experiences learned in the successful establishment of a nonheart beating donor program for renal transplantation.

PURPOSE: With the continuing shortage of suitable donors increasing interest is being shown in nonheart beating donation. Such a resource is a new and, therefore, an underused source of donor organs. However because of the nature of such donors, the kidneys so derived have been damaged by primary warm ischemia, and so potentially they may never function. We introduced viability testing to identify such organs and, thus, avoid transplantation. We reviewed sentinel cases in our developing program from which we have learned. MATERIALS AND METHODS: Machine perfusion was developed locally and used to test the kidneys derived from such donors. Flow characteristics and enzyme analysis were used to define usable kidneys. The definitions of acceptable criteria evolved through the study during a 3-year period. RESULTS: As previously defined, acceptable criteria were initially adhered with decreasing resistance and a glutathione S-transferase of less than 200 IU/l/100 gm. After the series described acceptable limits were changed in favor of a high perfusion flow index, low temperature, low weight increase and low glutathione S-transferase. CONCLUSIONS: If such criteria are adhered to, graft survival becomes reliable from such donors.

Adverse and beneficial effects of plant extracts on skin and skin disorders.

Plants are of relevance to dermatology for both their adverse and beneficial effects on skin and skin disorders respectively. Virtually all cultures worldwide have relied historically, or continue to rely on medicinal plants for primary health care. Approximately one-third of all traditional medicines are for treatment of wounds or skin disorders, compared to only 1-3% of modern drugs. The use of such medicinal plant extracts for the treatment of skin disorders arguably has been based largely on historical/anecdotal evidence, since there has been relatively little data available in the scientific literature, particularly with regard to the efficacy of plant extracts in controlled clinical trials. In this article therefore, adverse and beneficial aspects of medicinal plants relating to skin and skin disorders have been reviewed, based on recently available information from the peer-reviewed scientific literature. Beneficial aspects of medicinal plants on skin include: healing of wounds and burn injuries (especially Aloe vera); antifungal, antiviral, antibacterial and acaricidal activity against skin infections such as acne, herpes and scabies (especially tea tree (Melaleuca alternifolia) oil); activity against inflammatory/immune disorders affecting skin (e.g. psoriasis); and anti-tumour promoting activity against skin cancer (identified using chemically-induced two-stage carcinogenesis in mice). Adverse effects of plants on skin reviewed include: irritant contact dermatitis caused mechanically (spines, irritant hairs) or by irritant chemicals in plant sap (especially members of the Ranunculaceae, Euphorbiaceae and Compositae plant families); phytophotodermatitis resulting from skin contamination by plants containing furocoumarins, and subsequent exposure to UV light (notably members of the Umbelliferae and Rutaceae plant families); and immediate (type I) or delayed hypersensitivity contact reactions mediated by the immune system in individuals sensitized to plants or plant products (e.g. peanut allergy, poison ivy (Toxicodendron) poisoning).