Kidney and liver transplantation in the elderly.

BACKGROUND: Transplant surgery is facing a shortage of deceased donor organs. In response, the criteria for organ donation have been extended, and an increasing number of organs from older donors are being used. For recipients, the benefits of transplantation are great, and the growing ageing population has led to increasing numbers of elderly patients being accepted for transplantation. METHODS: The literature was reviewed to investigate the impact of age of donors and recipients in abdominal organ transplantation, and to highlight aspects of the fine balance in donor and recipient selection and screening, as well as allocation policies fair to young and old alike. RESULTS: Overall, kidney and liver transplantation from older deceased donors have good outcomes, but are not as good as those from younger donors. Careful donor selection based on risk indices, and potentially biomarkers, special allocation schemes to match elderly donors with elderly recipients, and vigorous recipient selection, allows good outcomes with increasing age of both donors and recipients. The results of live kidney donation have been excellent for donor and recipient, and there is a trend towards inclusion of older donors. Future strategies, including personalized immunosuppression for older recipients as well as machine preservation and reconditioning of donor organs, are promising ways to improve the outcome of transplantation between older donors and older recipients. CONCLUSION: Kidney and liver transplantation in the elderly is a clinical reality. Outcomes are good, but can be optimized by using strategies that modify donor risk factors and recipient co-morbidities, and personalized approaches to organ allocation and immunosuppression.

In situ normothermic regional perfusion for controlled donation after circulatory death--the United Kingdom experience.

Organs recovered from donors after circulatory death (DCD) suffer warm ischemia before cold storage which may prejudice graft survival and result in a greater risk of complications after transplant. A period of normothermic regional perfusion (NRP) in the donor may reverse these effects and improve organ function. Twenty-one NRP retrievals from Maastricht category III DCD donors were performed at three UK centers. NRP was established postasystole via aortic and caval cannulation and maintained for 2 h. Blood gases and biochemistry were monitored to assess organ function. Sixty-three organs were recovered. Forty-nine patients were transplanted. The median time from asystole to NRP was 16 min (range 10-23 min). Thirty-two patients received a kidney transplant. The median cold ischemia time was 12 h 30 min (range 5 h 25 min-18 h 22 min). The median creatinine at 3 and 12 months was 107 µmol/L (range 72-222) and 121 µmol/L (range 63-157), respectively. Thirteen (40%) recipients had delayed graft function and four lost the grafts. Eleven patients received a liver transplant. The first week median peak ALT was 389 IU/L (range 58-3043). One patient had primary nonfunction. Two combined pancreas-kidney transplants, one islet transplant and three double lung transplants were performed with primary function. NRP in DCD donation facilitates organ recovery and may improve short-term outcomes.

Impact of patient characteristics and comorbidity profile on activation of patients on the kidney transplantation waiting list.

BACKGROUND: The aim of this study was to examine which demographic and comorbidity factors affected the activation of patients with end-stage renal disease on the national kidney transplantation waiting list. METHODS: This was a prospective cohort study across 13 transplantation centers in the United Kingdom from October 1, 2006 to September 30, 2007. Data were collected for all new adult patients (n = 1530) referred to the renal transplantation assessment clinic. The proportion of patients who were activated to the waiting list after a minimum one year follow-up was estimated. Factors influencing activation of patients on the waiting list were examined. RESULTS: A total of 872 (58.9%) patients were activated to the transplantation waiting list. The likelihood of activation to the transplantation waiting list was lower in patients older than 65 years (P = .021), nonwhite ethnicity (P < .0001), smokers (P < .0001), and those in whom diabetes was the cause of renal failure (P = .004). Multivariate analysis showed that there was an adverse impact of comorbidity such as ischemic heart disease (P = .003), diabetes (P = .006), and peripheral vascular disease (P = .007) on the likelihood of activation to the waiting list. CONCLUSION: Patient characteristics and comorbidity are associated with the probability of activation of patients to the waiting list.

Uncovering a rare but critical complication following thyroid surgery: an audit across the UK and Ireland.

OBJECTIVE: Serious wound infection after thyroidectomy is uncommon, but actual incidence is not well documented in the literature. In the past a patient in our unit died secondary to fulminant streptococcal sepsis after thyroidectomy for benign disease. This prompted us to audit experience of serious wound infection among British Association of Endocrine Surgery (BAES) members. DESIGN: A questionnaire was posted to BAES members inquiring about experience of major wound infection following cervicotomy, incidence of minor wound infection, and prophylactic and therapeutic antibiotic usage. MAIN OUTCOME: Eight respondents experienced a case of fulminant wound infection after cervicotomy (8% total respondents). Five patients died and, in 6 patients, cases of streptococci were cultured. Then, 9% of respondents used prophylactic antibiotics routinely, 16% sometimes and 75% never. The most commonly used antibiotic was augmentin, and the most common reasons for use among those with a selective policy were re-operative cases (38%) and immunocompromised patients (38%). Also, 40% of respondents experienced major wound infection requiring intravenous antibiotics or surgical drainage. The most common choices of antibiotic used before sensitivities were obtained were augmentin (43%) and flucloxacillin (35%). CONCLUSIONS: Although rare, fulminant streptococcal wound infection after cervicotomy does occasionally occur and carries a high mortality.

Graft function and other risk factors as predictors of cardiovascular disease outcome.

The high incidence of cardiovascular disease after renal transplantation is related to a high prevalence and accumulation of risk factors before and after transplantation. Hypertension, posttransplantation diabetes, and hyperlipidemia are well-recognized risk factors for the development of cardiovascular events after renal transplantation and are strongly associated with immunosuppressive therapy. Hyperhomocysteinemia is a potential risk factor for cardiovascular disease in renal transplant recipients, but although a growing matter of study, a direct association with immunosuppressive agents is not yet proven. In addition to treatment intervention, risk management should also involve tailoring the immunosuppressive regimen to minimize the more indirect cardiovascular risk factors such as renal dysfunction and acute rejection.

Dose optimization of mycophenolate mofetil when administered with a low dose of tacrolimus in cadaveric renal transplant recipients.

BACKGROUND: Supplementation of immunosuppressive therapy with mycophenolate mofetil (MMF) has been found to reduce the rate of acute rejection in renal transplantation. We report a dose-finding study for MMF when administered in combination with low-dose tacrolimus and corticosteroid prophylaxis in cadaveric renal transplant recipients. METHODS: Two hundred thirty-two patients at 16 centers were enrolled in this randomized, parallel-group study. The three treatment groups were tacrolimus and corticosteroids (MMF-0 group, n=82); tacrolimus, corticosteroids, and 1 g of MMF daily (MMF-1 g group, n=79); and tacrolimus, corticosteroids, and 2 g of MMF daily (MMF-2 g group, n=71). Study duration was 6 months, and patients were followed up for patient and graft survival for 12 months. RESULTS: At 6 months posttransplantation, daily doses of 1 g and 2 g of MMF were associated with significantly lower rates of acute rejection compared with tacrolimus alone. The Kaplan-Meier rates were 48.5%, 24.9%, and 22.9%, respectively, for the three treatment groups when acute rejection was determined by clinical criteria (P=0.007). At month 12, patient survival rates were 100%, 97.5%, and 97.2% and graft survival rates were 90.2%, 92.4%, and 93.0% for the MMF-0 group, MMF-1 g group, and the MMF-2 g group, respectively. Gastrointestinal adverse events and leukopenia were higher in the MMF groups, especially in the MMF-2 g group (P<0.05). CONCLUSIONS: Low-dose tacrolimus combined with a MMF dose of 1 g daily and corticosteroids provided an optimized efficacy and safety profile. A higher dose of MMF (2 g) was associated with greater toxicity without a significant improvement in efficacy.

Training opportunities in liver transplantation surgery.

BACKGROUND: Liver transplantation surgery is carried out in only a few selected centres in the UK. This study was performed with a view to identifying potential training opportunities available for the general and specialist higher surgical trainee, and also to assess the outcome following liver transplant surgery according to the grade of the surgeon performing the procedure. METHODS: Data on 111 liver transplants with caval preservation undertaken consecutively in a single unit during a 32-month period were collected and analysed. The transplant procedures were grouped into those performed by consultants and those performed by supervised trainees. Survival was estimated by the Kaplan-Meier method. The Cox regression model was used to examine the influence of grade of the surgeon on survival. chi2 and independent sample t tests were used to identify significant preoperative, intraoperative and postoperative variables. RESULTS: Trainees carried out 34 recipient hepatectomies (31 per cent), 47 implant procedures (42 per cent) and all 143 retrieval operations. The mean time taken by a supervised trainee to carry out a recipient hepatectomy and implantation was 183 and 44 min compared with 165 and 46 min for a consultant (P = 0. 22 and P = 0.44 respectively). The mean intraoperative red cell requirement was 8 units for both consultants and trainees (P = 0.85). The overall patient survival rate was 88 per cent at 3 years and the grade of the surgeon made no difference to survival or the occurrence of complications (P > 0.05). CONCLUSION: The outcome following liver transplantation with caval preservation did not differ according to the grade of the surgeon performing the procedure. Extensive training opportunities are available to learn hepatobiliary and vascular surgical techniques in liver transplantation surgery.

Kidney damage during organ retrieval: data from UK National Transplant Database. Kidney Advisory Group.

BACKGROUND: Kidney damage at organ retrieval is believed to be an increasing problem that is under reported. We aimed to identify the true rate of such damage and assess the effects on transplant survival. METHODS: Data from the UK National Transplant Database were analysed on all cadaveric kidneys donated over a 5-year period in the UK. Records indicated whether kidneys had been retrieved by a liver or renal surgical team and whether damage was noted at the time of retrieval or at the transplant procedure. Multivariate Cox's regression models were fitted to 1-year and 3-year transplant-survival data in those kidneys that were transplanted between 1992 and 1994. FINDINGS: Of 9014 kidneys retrieved, 96 could not be transplanted because of damage sustained at retrieval. Damage was reported in 1726 (19%) kidneys although by both donor and recipient centres in only 270 (3%). 1070 (62%) of the damaged organs were from donors aged 40 years or older. Reported kidney damage was more likely for retrievals of kidney only by a renal team (503 [26%]) than for multiorgan retrieval (454 [21%]), the proportion was lower when a liver team retrieved both liver and kidneys (415 [17%]). 794 (14%) kidneys retrieved and retained locally were reported as damaged, compared with 932 (29%) kidneys which had been exported. Donors' age had a significant effect on both 1-year and 3-year transplant survival (p<0.01 for both) but kidney damage did not (1 year p=0.40; 3 year p=0.81). INTERPRETATION: Despite the high rate of damage to kidneys at retrieval, most of the organs can be transplanted with no adverse effect on transplant survival. Kidney damage is least likely to occur with kidneys from young donors, and when liver teams or centres undertaking more than 50 retrievals per year do the retrieval.

Live kidney donor assessment in the UK and Ireland.

BACKGROUND: The criteria and methods for assessing live kidney donors are not clear. This study was undertaken to establish whether there is a consensus regarding the organization and methods of assessment of living kidney donors by renal transplant centres in the UK and the Republic of Ireland. METHODS: All transplant centres in the UK and Ireland involved in living donor kidney transplantation were contacted by telephone survey followed by postal questionnaire. RESULTS: Considerable variation was observed in the organization of living kidney donor evaluation and the methods of assessment used. The upper and lower age limits considered acceptable for kidney donation were variable, with six of 29 centres setting no lower age limit and 11 setting no upper age limit. Four centres do not currently offer living donor kidney transplantation. Of the 29 centres involved with living donor transplantation ten had no protocol for donor assessment. A dedicated transplant coordinator/nurse practitioner was employed by 20 centres and ten routinely used an independent medical assessor to evaluate living related donors. The frequency and duration of donor follow-up after kidney donation also varied widely, with 18 centres providing life-time, seven limited and three no follow-up after initial postoperative assessment. CONCLUSION: The wide variation in organizational structure and method of assessment of living kidney donors in the UK and Ireland supports the need for establishment of guidelines for this practice.

The effect of a positive T-lymphocytotoxic crossmatch on hepatic allograft survival and rejection.

The influence of crossmatching in liver transplantation is still controversial, and at present, our unit does not alter management according to the result of standard lymphocytotoxicity testing. This study retrospectively assessed outcome of grafts transplanted in the presence of preformed antidonor cytotoxic antibody. One hundred twelve patients undergoing their first orthotopic liver transplantation had results available (mean follow-up: 18 months). Twelve patients had a positive crossmatch and 100 negative. The 1-year graft survival was 58% in the positive crossmatch group, compared with 81% in the negative crossmatch group (P = .02). The 1-year patient survival was 83% in the positive crossmatch group compared with 90% in the negative group (P = .41). Acute cellular rejection occurred in 6 of 7 (86%) grafts surviving more than 7 days in the positive crossmatch group compared with 46 of 88 (52%) grafts in the negative group (P = .09). However, episodes of further acute cellular rejection requiring treatment occurred in 4 of the 6 grafts in the positive crossmatch group but in only 4 of the 46 grafts with a negative crossmatch (P = .0006). The authors conclude that evidence exists in our population that preformed antidonor antibodies adversely affect the outcome of hepatic allografts but not patient survival.

Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group.

BACKGROUND: To confirm the results of a number of studies conducted in Europe, the United States, and Japan, this multicenter, randomized trial compared the 12-month efficacy and safety of tacrolimus- and cyclosporine-based immunosuppressive regimens in the prevention of renal allograft rejection. METHODS: A total of 448 renal transplant recipients were recruited from 15 centers and assigned to receive triple-drug therapy consisting of tacrolimus (n=303) or cyclosporine (n=145) in conjunction with azathioprine and low-dose corticosteroids. RESULTS: At 12 months after transplantation, tacrolimus therapy was associated with a significant reduction in the frequency of both acute (tacrolimus 25.9% vs. cyclosporine 45.7%; P<0.001 [absolute difference: 19.8%, 95% confidence interval: 10.0-29.6%]) and corticosteroid-resistant rejection (11.3% vs. 21.6%; P=0.001 [absolute difference: 10.3%, 95% confidence interval: 2.5-18.2%]). Actuarial 1-year patient (tacrolimus 93.0% vs. cyclosporine 96.5%; P=0.140) and graft survival rates (82.5% vs. 86.2%; P=0.380) did not differ significantly between the two treatment groups. Overall, the safety profiles of the tacrolimus- and cyclosporine-based regimens were quite comparable. Infections, renal impairment, neurological complications, and gastrointestinal complaints were frequently reported but were mostly reversible in both groups. Higher incidences of elevated serum creatinine, tremor, diarrhea, hyperglycemia, diabetes mellitus, and angina pectoris were reported in the tacrolimus treatment group, whereas acne, arrhythmia, gingival hyperplasia, and hirsutism were more frequent with cyclosporine treatment. CONCLUSIONS: The significant reduction in the incidence of episodes of allograft rejection observed with tacrolimus therapy may have important long-term implications given the prognostic influence of rejection on graft survival.

Flow cytometric crossmatching in renal transplantation--the long-term outcome.

The association of a positive flow cytometric crossmatch between recipient IgG directed against donor T lymphocytes and poor outcome is well described in renal transplantation. Until now no long-term follow-up on such patients has been available. In this study, 117 renal transplant patients were followed up for a period of 5 years. Of these 21 were known to have donor T cell directed IgG and five had B lymphocyte directed IgG. Both groups of patients with these antibodies had a significantly poorer outcome at 5 years than did the group of patients without IgG (p < 0.0001, Handel Maenzel test). Patients with antibody detected preoperatively were tested again either at the time of graft failure or at 5 years post-transplantation. The sera were tested against stored donor cells and the intensity of surface IgG compared with the preoperative levels. In those recipients who lost their grafts the levels increased in 60% of cases, but those who retained their grafts also had an increase in levels of donor directed antibody in 50% of cases. The changing levels of antibody therefore appeared to have little relevance to outcome. However when IgG isotypes were considered, in those who experienced graft failure and also had a gamma 3 isotype, a rise in IgG was demonstrated in all cases. Conversely, successful grafts with gamma 3 had a decline in levels between preoperative and 5-year samples in three of the four cases (not significant).

The value of posttransplant monitoring of interleukin (IL)-2, IL-3, IL-4, IL-6, IL-8, and soluble CD23 in the plasma of renal allograft recipients.

Over the past few years, the central role of cytokines in the amplification of the immune response has been reported and several studies have examined the relationship between the plasma level of individual lymphokines during renal allograft rejection. The aim of the present investigation was to study simultaneously IL-2, IL-3, IL-4, IL-6, IL-8, and soluble CD23. Analysis of results has allowed both the prognostic value and any possible interrelationships between the measured cytokines to be determined. We studied 16 renal transplant recipients for the first 14 days after transplantation. Seven patients showed clinical evidence of acute allograft rejection and 5 showed excellent stable graft function with no signs of rejection. Primary nonfunction was seen in 4 patients. The plasma levels of each cytokine were measured by commercially available ELISA and immunoradiometric assay kits. As reported in previous studies, plasma IL-2 levels, whenever found at detectable levels, were predictive of impending graft rejection. Serial monitoring of IL-4 and IL-6 was more reliable for the differential diagnosis of rejection, particularly toward the end of the first week after transplantation. IL-3, IL-8, and soluble CD23 were not diagnostic or predictive of rejection, due to the occurrence of significantly high levels in transplant patients who showed no evidence of clinical rejection. While the value of cytokine monitoring has been shown in this study, it should be remembered that infection, although not seen in these studies, may have a profound affect on the results obtained.