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The use of University of Wisconsin (UW) solution in liver transplantation (LTX) has significantly prolonged preservation times and facilitated semielective transplant procedures. Despite this advantage potential risk factors related to the donor, recipient, or cold storage method will persist in the UW era and detrimental effects will be reflected by primary dysfunction (PDF) after LTX. Concern has been voiced about the maximum period of UW preservation in LTX and various cold ischemia times (CIT) are mentioned. To evaluate the effect of UW solution in LTX, a prospective European multicenter study was initiated in 1988 and short-term results have been reported previously. This report focuses on the long-term effects and survival of prolonged preservation with UW solution and primary function after LTX. Three hundred and fifteen LTXs were performed in 288 patients in participating European centers. Complete follow up of at least 6 years was available for 296 grafts in 277 patients. Effects of donor, preservation, and recipient risk factors on PDF including primary non-function (PNF) and initial poor function (IPF) were evaluated. Next, the effect of risk factors on graft survival (GS) was analyzed including the long-term impact of PNF and IPF using multivariate analyses and the Kaplan-Meyer method. PDF occurred in 15.2% (45/296) with PNF in 7.8% and IPF in 7.4%. Patients with IPF had a 34% lower GS at 3 months those with immediate function (IF; 58% vs 91%; P < 0.001). This difference persisted up to 6 years for patients with IPF with a 39% GS vs 72% after IF (P < 0.001). Median CIT was significantly longer in grafts with PNF compared to IPF or IF (P = 0.03). Long-term GS, however, was significantly influenced at a lower CIT threshold with a 6-year GS for CIT < or = 16 h of 67%, compared to a CIT > 16 h of 51% (P = 0.02). Other independent risk factors for the 6-year survival rate were re-LTX, ABO incompatibility, and recipient diagnosis of acute hepatic failure. In conclusion, liver patients with PNF, but not with IPF, have a significantly lower CIT. IPF is associated with a significantly lower 3 month GS compared to IF, but this difference of 34% does not further increase during a 6-year follow up. Although a short term follow up (3 months) shows that with UW solution CIT up to 18 h has no adverse effect on GS, the 6-year data clearyl suggest that CIT should be kept to less than < 16 h to avoid tetrimental effects on lang-term GS after LTX.

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BACKGROUND: During the past few years the number of organ donors in the UK has declined after a slow but steady increase during the 1980s. Concern about the decline led to a survey by the British Transplantation Society. The report of this survey highlighted a number of reasons for the decline and this manuscript presents and discuss the main items in the report. METHODS: Comprehensive information relating to organ donation was obtained by a combination of structured interviews during visits to intensive care units (ICUs) and neurosurgical units, the use of detailed questionnaires sent to all UK ICUs, and from the register held by the United Kingdom Transplant Support Service Authority. RESULTS: The information obtained highlighted a number of reasons for the decline in organ donor numbers and these are presented and discussed. The pool of potential donors is shrinking as death rates from road traffic accidents and intracranial haemorrhage decrease. Also the increasing use of modern imaging techniques has improved predictive ability in patients with severe brain damage with the result that more patients whose prognosis is assessed as hopeless are not treated by ventilation. Inadequacies both in intensive care unit bed provision and the resourcing of the transplant co-ordinator service were also thought to be important. CONCLUSIONS: Eight recommendations have been made, covering ICU bed provision, neurosurgical provision, transplant surgical staffing, the transplant co-ordinator network, reimbursement to donor units, asystolic donation, live donor transplantation, and interventional ventilation.

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An important contribution of HLA-A antigen matching in renal transplantation was reported initially, hut later publications showed a minor or absent role. We analyzed the contribution of HLA-A locus matching to graft survival in 17,672 first renal transplants from unrelated, nonliving donors. We show that an independent HLA-A matching effect still exists. Due to its relative weakness and late appearance, large numbers and longer follow-up periods are required. The HLA-A matching effect is a significant factor in first renal allograft survival up to 6 years after transplantation, with an increasing effect over time. This is in contrast to the strong, short-lived, effects of HLA-DR and -B matching, which can only be detected up to 6 months and 2 years after transplantation, respectively. A clear additive beneficial effect of HLA-A matching is shown in the group without B and DR mismatches. Therefore, prospective matching for the HLA-A antigens remains important for renal allograft survival.

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A study of film reject and repeat rates was undertaken in the Department of Dental Radiology of King's College School of Medicine and Dentistry over a 6 month period. The aim of the study was to assess the effects of changes implemented after a previous audit, and to carry out a more detailed analysis of the factors influencing the reject and repeat rates using a larger volume of data. The information recorded included the equipment and projection used, and the age of the patient if under 16 years. The overall reject rate was 3.06%, 1.84% less than recorded in the earlier study, and the repeat rate was 0.93%. Positioning errors were the most frequent cause for rejection. Significant differences in reject rates were noted between different projections, and also between qualified staff and those in training. The rejection rate for patients under 16 years was not significantly higher than for patients over 16 years, the most frequent cause of rejection was still positioning faults, but patient movement accounted for a larger proportion of the rejects than was the case in adult patients. The results demonstrate the role of audit in isolating factors leading to additional exposures. The effectiveness of changes implemented following a reject film analysis is also shown.

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The construction, validation and updating of a prognostic model for kidney graft survival is reported using data from the Eurotransplant database. First, a model is constructed for data from transplantations in the period 1984 to 1987. The model is later updated for the 1988 1990 data. The first data set was randomly split into a training set (two-thirds of the data) and a validation set (one-third). To prevent overfitting empirical Bayes estimation of the transplantation centre effect was employed. After that, the validation set was used for fine-tuning by shrinkage. For updating with the 1988 1990 data parametric models were used after suitable transformation of the time axis; it appeared that survival had slightly improved. This necessitated a correction of the parameters in the exponential model. Correctness of the model was checked by extension to a Weibull model. The lack of fit was statistically significant, but practically ignorable. Recommendations are made to place less emphasis on the selection of variables and cut-off points, and more emphasis on the fine-tuning of the prognostic model by means of low-dimensional parametric models in independent data sets.

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Chronic rejection of renal allografts is a major cause of late graft loss. However, time of onset, relation with acute early rejection episodes, and risk factors are largely unknown. We undertook a cohort study of 482 consecutive patients from a single center who received a cadaveric renal allograft between January 1983 and April 1991. During the first 3 months after transplantation, 76 (15.8%) patients developed vascular rejection and 115 (23.9%) developed interstitial rejection. One-year graft survival of patients without rejection, with interstitial rejection, and with vascular rejection was 87.8%, 87%, and 48.7%, respectively. Five-year graft survival was 73.5% for the group without rejection, 71.4% for patients with interstitial rejection, and 34.3% for patients with vascular rejection. The adjusted relative risk of graft loss was 4.92 (95% CI 3.25-7.43) for patients with vascular rejection and 1.27 (95% CI 0.80-2.02) for patients with interstitial rejection compared with patients without early rejection, taking the time dependency of the rejection events and prognostic factors into account. The incidence of vascular rejection was increased in patients with primary nonfunction (RR 1.69, 95% CI 1.01-2.84), with 1 HLA-DR mismatch (RR 2.38, 95% CI 1.44-3.93), with 2 HLA-DR mismatches (RR 3.24, 95% CI 1.25-8.42), with a prolonged cold ischemia time (RR 1.03, 95% CI 1.00-1.06 per hr), and with 1 or more previous transplantations (RR 1.76, 95% CI 1.01-3.07). Risk of developing vascular rejection was decreased in patients using CsA as compared with azathioprine (RR 0.41, 95% CI 0.24-0.67). Early vascular rejection, occurring within 3 months after transplantation, is the most important predicting variable of both early and late graft loss. Use of CsA, less HLA-DR mismatching, and a cold ischemia time of short duration possibly prevent the development of vascular rejection.

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Pancreas graft survival is influenced by various donor and recipient factors. Factors that have posed serious problems to pancreas transplantation have included the limited cold ischemia time, early graft thrombosis, and rejection. A limited cold ischemia time not only causes problems in terms of logistics but also implies limitations with regard to HLA matching and organ exchange. Between August 1988 and August 1989 we performed a prospective, nonrandomized European multicenter study to evaluate the effect of University of Wisconsin (UW) solution on pancreas graft survival. In addition, donor and recipient factors were collected and their influence on graft survival analyzed. Overall pancreas graft survival at 1 and 4 years was 67% and 59%, respectively (n = 62). When only simultaneous pancreas and kidney transplants were included, the graft survival was 70% and 63% at 1 and 4 years, respectively. The incidence of pancreas graft thrombosis was 8%. Cold ischemia time was not found to significantly influence pancreas graft survival even when it exceeded 12 h. Factors that did were HLA-DR matching, simultaneous pancreas and kidney transplantation versus pancreas transplantation alone, and ABO blood group matching. We feel that the use of UW solution for pancreas preservation has contributed to improved pancreas graft survival and has reduced early graft thrombosis despite much longer cold ischemia times of over 12 h. Given this and the significant effect of HLA and blood group matching, we conclude that more attention should be paid to preoperative matching and organ exchange in order to further improve pancreas graft survival.

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This paper concerns the survival analysis of liver transplant patients when patients with a potentially fatal rejection of the transplanted organ may receive a retransplant. A multistate model, analysing the states 'alive with first graft' and 'alive with second graft' separately, is suggested. Proportional hazards models and logistic regression models are used to evaluate which risk factors related to donor, preservation and recipient, influence the transition intensities. The complete model is used to predict overall survival of a patient and to study the influence of the risk factors on total survival.

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Serum samples of 64 consecutive patients who underwent renal transplantation in our institution were examined for the presence of antibody-dependent cellular cytotoxicity (ADCC) activity against endothelial cells (EC). From each patient serum samples were obtained immediately before transplantation and 1 week, 1 month and 1 year thereafter. The results were evaluated in the context of tests to measure donor-specific humoral immunity against lymphocytes and monocytes, and related to parameters of presensitization, graft survival, and histology. Sera from 10 patients were positive for ADCC on a panel of HLA-typed endothelial cells. In 8 patients sera were already positive before transplantation and remained positive thereafter. In 4 patients a positive crossmatch with donor T and B cells and monocytes could be observed after transplantation. In only one patient were these crossmatches positive before transplantation. A significant correlation was found between ADCC positivity and vascular rejection (P = 0.015); in addition graft survival was significantly better in the ADCC negative group vs. the positive group (P = 0.0004). These data demonstrate the significance of allospecific anti EC antibodies for the occurrence of vascular rejection and graft loss after renal transplantation.

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We examined the graft survival of 12,883 first unrelated kidney grafts from nonliving donors, transplanted between 1 January 1971 and 31 December 1987 within 52 renal transplantation centers participating in the Eurotransplant organization. The 5-year graft survival increased from 38.8% for the period 1971-1975 to 66.0% for the period 1981-1987 for patients treated with cyclosporine, whereas the half-life increased by only 2 years, from 9.7 years to 11.6 years over the same period, based on grafts functioning at 1 year posttransplantation. Results per HLA locus showed considerable improvements within mismatch groups over the entire period. Large differences between mismatch groups for the early years were observed, but within the cyclosporine era only HLA-B showed a statistically significant difference in half-lives (13.2 versus 9.0 years, for 0 and 2 mismatches respectively, P = 0.013). When other prognostic factors were taken into account, it was revealed by means of an exponential model that number of HLA-B mismatches, donor and recipient age and sex, and recipient diagnosis of diabetes had significant effects on the long-term outcome of the grafts. Depending on the combination of these parameters, estimates of half-life varied from 4.9 to 14.5 years. These results show that matching for HLA-B is still of benefit in the longer term and that other prognostic factors play an important role in predicting the late outcome of renal allografts.

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University of Wisconsin (UW) preservation solution has been reported to be beneficial for canine organ transplants and for human liver and pancreas transplants. To examine whether it affects renal graft survival, a randomised multicentre trial was conducted to compare its effect with that of EuroCollins solution on delayed graft function, renal function, and patient and graft survival in 695 recipients of cadaveric renal transplants. 352 kidneys were preserved with UW and 343 with EuroCollins solution. Delayed graft function occurred in 23% of the UW group and in 33% of the EuroCollins group (p = 0.003). Three factors other than type of preservation fluid were associated with a higher incidence of delayed graft function: older donor age, intracerebral haemorrhage in the donor, and oliguria in the donor. Renal function as indicated by serum creatinine concentration was better in the UW than in the EuroCollins group. Patient survival in the UW and EuroCollins groups after 1 year was 95% and 94%, respectively. In both groups, delayed graft function reduced 1-year graft survival by 15% (p = 0.0001). 1-year graft survival of UW-preserved kidneys was 6% higher than that of controls (88.2% vs 82.5%, p = 0.04). Delayed graft function is significantly associated with a reduction in 1-year graft survival. The preservation solution is the most important factor influencing development of delayed graft function, and UW solution is superior to EuroCollins solution in reducing occurrence of delayed graft function, improving graft function, extending graft survival.

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The aims of the study were threefold: (1) to analyse the long-term overall kidney graft survival within Eurotransplant for the period 1971-1987; (2) to examine the effect of matching for HLA over the years, with the aid of half-lives after the first post-transplant year; and (3) to take prognostic factors into account for the period 1981-1987, comparing their influence on the long-term outcome of the graft and to predict half-lives for various combinations of factors.

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