Kidney transplantation without prior dialysis in children: the Eurotransplant experience.

Kidney transplantation without prior dialysis may prevent dialysis-associated morbidity. We analyzed the outcome of 1113 first kidney transplants in children performed between 1990 and 2000 in the Eurotransplant community. Enlistment for a deceased donor kidney before start of dialysis (127/895, 14%) made dialysis redundant in 55% of cases. Mean residual creatinine clearance at transplantation of these patients was 8 mL/min/1.73 m(2). Pre-emptive transplantations of deceased donor kidneys showed less acute rejections (52% vs. 37% rejection-free at 3 years, p = 0.039), compared to transplantations following dialysis. The difference in graft survival between non-dialyzed and dialyzed patients (82% vs. 69% at 6 year) did not reach statistical significance (p = 0.055). No differences were noted after living donor transplantation. Multivariate analysis showed that the period of transplantation was the strongest predictor of graft survival (p < 0.001). Congenital structural abnormalities such as primary kidney disease predominated in nondialyzed patients as compared to dialyzed patients (p < 0.001); this factor did not influence graft survival. Based on our conclusion that pre-emptive transplantation is at least as good as post-dialysis transplantation, as well as on quality of life arguments, we recommend to consider pre-emptive transplantation in children with end-stage renal failure.

Allocation of organs, particularly kidneys, within Eurotransplant.

Allocation of scarce donor organs is an important discussion topic among ethical, medical, and legal experts, the public at large, and politicians. Since 1996, a new kidney allocation system based on primarily medical and patient-oriented criteria was introduced in Eurotransplant (ET). This point-scoring system takes the following factors into account: HLA-A,B,DR mismatch, mismatch probability, waiting period, i.e., time on dialysis, distance between donor/transplantation center, and balance between import/export of the six participating countries. Extra points are given to high urgency patients and to children. During the first 9 years of the new ET kidney allocation system (ETKAS) almost 30,000 deceased donor kidneys have been allocated of which 22.3% have been transplanted without HLA-A,B,DR mismatches. Twice as many long-waiting patients, i.e., >5 years, have been transplanted as compared with the pre-ETKAS period. Also substantially more children and highly sensitized patients received kidney transplants. Importantly, the balances between import and export of donor kidneys among the different ET countries remained among very well-accepted levels. Finally, overall kidney transplant survival was 78% after 3 years and a significant HLA-matching effect was noticed, i.e., 83% at 3 years for the HLA-A,B,DR mismatched combinations. In conclusion, the new ETKAS has reached its aims and goals. The main problem remains, however, the continuing shortage of deceased donor kidneys.

Acceptance criteria of pancreas grafts: how do surgeons decide in Europe?

OBJECTIVES: Some donor factors, such as age, cause of death, and obesity, affect the outcomes of pancreas transplantation. Donors with a high-risk profile are usually not declined for pancreas donation. The purpose of our study was to investigate differences between accepted and refused pancreata after being procured and offered. METHODS: In a retrospective study we analyzed all offered pancreata (n = 1360) in the "Eurotransplant Area" between May 25, 2002 and September 18, 2003. Included in this study were 525 pancreata transplanted (38.6%) and 608 pancreata refused for medical reasons (44.7%). A total of 227 pancreata (16.7%) refused for other than medical reasons were excluded from this analysis. RESULTS: The significant differences in the donor profiles between transplanted and refused pancreata were cause of death (P < .001), donor age (P < .001), body mass index (BMI, P < .001), serum lipase and amylase (P < .05) at the time of procurement, and a history of smoking (P = .001) or alcohol abuse (P < .001). No differences were found for serum sodium (P = .188), blood leukocytes (P = .349), serum glucose at the time of procurement (P = .155), amylase and lipase at the time of admission (P = .34; P = .758), and vasopressor use at the time of admission or at the procedure (P = .802; P = .982). CONCLUSION: Even after procuring and offering potentially good pancreata, nearly half the organs are refused for medical reasons. Acceptance criteria in the Eurotransplant region reveal a conservative attitude toward pancreas acceptance.

Predictors of lung transplant survival in eurotransplant.

This study was undertaken to assess the influence of patient/donor and center factors on lung transplantation outcome. Outcomes of all consecutive first cadaveric lung transplants performed at 21 Eurotransplant centers in 1997-99 were analyzed. The risk-adjusted center effect on mortality was estimated. A Cox model was built including donor and recipient age and gender, primary disease, HLA mismatches, patient's residence, cold ischemic time, donor's cause of death, serum creatinine, type of lung transplant, respiratory support status, clinical condition and percentage predicted FEV1. The center effect was calculated (expressed as the standardized difference between the observed and expected survival rates), and empirical and full Bayes methods were applied to evaluate between-center differences. A total of 590 adults underwent lung transplantation. The primary disease (p=0.01), HLA-mismatches (p = 0.02), clinical condition(p < 0.0001) and the patient's respiratory support status (p = 0.05) were significantly associated with survival. After adjusting for case-mix, no between-center differences could be found. An in-depth empirical Bayes analysis showed the between-center variation to be zero. Similar results were obtained from the full Bayes analysis. Based on these data, there is no scientific basis to support a hypothesis of possible association between center volume and lung survival rates.

Histocompatibility and corneal transplantation.

BACKGROUND: HLA typing and matching have been poorly implemented in corneal transplantation, mainly because of inconclusive or contradictory analytical results. Consequently, we studied the immune response of corneal transplant recipients to HLA histoincompatibilities in a large homogeneous study. METHODS: All corneal transplantations were performed by a single surgeon in a single center between 1976 and 1996. Population genetic and other statistical analyses were performed. Simulation studies assessed the effects of HLA-DR mistypings on analytical results. RESULTS: Mono- and multivariate analyses identified retransplantation, degree of vascularization, HLA-AB and -DR match grades, endothelial cell count, graft size, recipient gender, storage method and panel-reactive antibodies as significantly influencing the survival of corneal transplants. Simulation studies showed that the beneficial effect of HLA-DR matching is abrogated by HLA-DR mistypings. CONCLUSIONS: Corneal transplant recipients have a normal immune response to HLA incompatibilities. Demonstration of that fact requires accurate HLA typings.

Iso-risk curves as a tool for clinical decision-making: donor factors and medical urgency in cardiac transplantation.

UNLABELLED: BACKGROUND; No significant improvement of overall graft survival in cardiac transplantation has occurred during the past decade, notwithstanding the identification of several prognostic donor and recipient risk factors. By translating multivariate results into iso-risk curves plots, stratified for medical urgency, we attempt to present results in a more practical manner, to be used as guidelines at the time of donor heart offer and of allocation. METHODS: We analyzed all first heart-only transplants performed in adults and carried out between January 1, 1997, and June 30, 1998 (N = 1120). Before transplant, 687 patients were at home, 233 on hospital wards, and 200 on the intensive care unit. The overall Cox model yielded 5 independent factors associated with 1-year graft outcome: donor age, donor:recipient weight ratio, medical urgency, end-stage heart disease, and transplant country. We used the significant donor variables of donor age and donor:recipient weight ratio for the iso-risk curves; we calculated relative risks for all combinations of donor age and donor:recipient weight ratio. We obtained iso-risk curves by linking equal relative risks. RESULTS: All iso-risk curves showed that with older donor age, the donor:recipient weight ratio must be higher to obtain the same relative risk for all 3 medical urgency groups. The more urgent the heart transplant candidate, the higher the course of the iso-risk curve for all donor ages. CONCLUSIONS: Iso-risk curve is an elegant tool for presenting multivariate analyses in a more practical and patient-oriented manner. The more understandable prognostic factors become the more likely we are to achieve better results in cardiac transplantation and to use more optimally donor hearts. As an example, we have demonstrated the interaction between donor age, donor:recipient size ratio, and medical urgency.

Renal retransplantation of children: is a policy 'first cadaver donor, then live donor' an acceptable option?

Retransplantation is often a necessity for children with end-stage renal disease (ESRD), as kidney graft survival is still not infinite. If a suitable live donor is present, the current policy is to use the live donor first, in order to obtain excellent long-term outcome and to prevent human leucocyte antigen (HLA) sensitization. Data from the Eurotransplant International Foundation were analyzed to determine whether the sequence, first a cadaveric donor then a live donor, is acceptable. Between January 1 1983 and December 31 1995, 1305 children received a first renal transplant; 269 of them had a second transplant during the same period. Follow-up of at least 1 yr was available. Categories were made according to the sequence of renal donor source: 217 patients were classified as first cadaver and second cadaver (1cad-2cad) transplant, 26 as first cadaver and second live (1cad-2liv) donor transplant, 23 as first live donor and second cadaver (1liv-2cad) transplant and three patients had two subsequent live donor transplants (1liv-2liv). When a live donor transplant was carried out, either first or second, the donor age was always higher, and the chance of a pre-emptive transplantation or short stay on dialysis was higher, compared with a cadaver transplant. The re-graft survival rate of the '1cad-2liv' was better than the '1cad-2cad' and '1liv-2cad' transplants. At 5 yr, the survival was 76%, 49%, and 61%, respectively. These data suggest that, when a suitable live donor is not available for a first transplantation owing to medical and/or familial reservations, a policy of 'first a cadaver donor then a live donor' transplantation is a viable option and should even be promoted. The pre-emptive stage of the second transplant, probably with a live donor, is additionally advantageous.

Listing for lung transplantation: life expectancy and transplant effect, stratified by type of end-stage lung disease, the Eurotransplant experience.

BACKGROUND: Increased referral for lung transplantation, persistent shortage of donor lungs, and moderate transplant outcome call not only for adequate listing criteria, but also for an optimal allocation scheme. We used global cohort survival after listing and survival benefit from transplantation to study the effect of a lung allocation scheme, primarily driven by waiting time, on the different types of end-stage lung disease. METHODS: We followed all adult patients consecutively listed for first, lung-only transplantation between 1990 and 1996 (n = 1,208) for at least 2 years, with an additional 2-year follow-up after transplantation (n = 744). We used the competing risk method, the Kaplan-Meier method, and a time-dependent non-proportional hazards model to analyze waiting-list outcome and global mortality after listing, post-transplant survival, and transplant effect, respectively. Each analysis was stratified for type of end-stage lung disease. RESULTS: At 2 years, 57% of the total cohort had received lung transplants, whereas 25% had died on the waiting list. The 2-year survival post-transplant was 55%. The global mortality of the cohort, since listing, amounted to 46% at 2 years. Compared with continued waiting, patients experienced benefit from transplantation by Day 100, which lasted until the end of the 2-year analysis period. We noticed the highest global mortality rates for patients with pulmonary fibrosis and pulmonary hypertension (54% and 52%); emphysema patients had the lowest (38%). Patients with pulmonary fibrosis and cystic fibrosis had much earlier benefit from transplantation, 55 and 90 days, respectively. Transplantation also benefited emphysema patients by Day 260. CONCLUSIONS: Lung transplantation conferred transplant benefit in a Western European cohort of adults, in particular for patients with pulmonary fibrosis and cystic fibrosis, but also for patients with emphysema. The global survival rate, reflecting the real life expectancy for a newly listed transplant candidate, is poor for patients with pulmonary fibrosis and pulmonary hypertension. Allocation algorithms that lessen the impact of waiting time and take into account the type of end-stage lung disease should be developed.

Protective and susceptible HLA polymorphisms in IgA nephropathy patients with end-stage renal failure.

Idiopathic immunoglobulin A (IgA) nephropathy is characterised by an extreme variability in clinical course, leading to end-stage renal failure in 15-20% of adults. This subgroup of patients with IgA nephropathy is usually included in the waiting lists of organ exchange organisations. The frequency of HLA-A,B,DR antigens of this subset of IgA nephropathy patients was calculated and compared to controls. The antigens HLA-B35 and DR5 were significantly increased in the patients with relative risk values of 1.385 and 1.487, respectively. The antigens HLA-B7, B8, DR2, and DR3 were found in a significantly lower frequency in the patients as compared to the controls. The relative risk (RR) values ranged between 0.695 and 0.727. Consequently, the haplotypes HLA-A1, B8, DR3, HLA-A3, B7, DR2, HLA-A2, B7, DR2 together with HLA-A1, B15, DR4, HLA-A9, B12, DR7, and HLA-A10, B18, DR2 were found to be protective with RR values ranging from 0.309 to 0.587. The only susceptible haplotype observed was HLA-A2-B5, DR5 (RR=2.990).

Horseshoe kidney transplantation within the eurotransplant region: a case control study.

BACKGROUND: The horseshoe kidney is the most common anatomic renal variation, with an incidence of 1 in 600 to 800. It represents a fusion anomaly, usually of the lower poles. Horseshoe kidneys can be transplanted en bloc or after division of the renal isthmus. However, the great variation in origin, number, and size of renal arteries and veins leads to some reluctance to use horseshoe kidneys for transplantation. The aim of this study is to assess the results of horseshoe kidney transplantation. METHODS: All data concerning horseshoe kidney transplantations within the Eurotransplant region were collected and were divided into en bloc and split transplantations. A matched control group was defined, and the three groups were analyzed with respect to the occurrence of primary nonfunction, graft survival, patient survival, and finally posttransplant serum creatinine values. RESULTS: From 1983 to 2000, 8 horseshoe kidneys were transplanted en bloc and 26 were split and transplanted into 47 recipients. The results of these transplantations were compared with 110 transplantations in the control group. No significant differences among the three groups could be found, either in the short- or long-term posttransplant results. CONCLUSIONS: The results of horseshoe kidney transplantation, either en bloc or split, are equal to the posttransplant results of kidneys with a normal anatomy. Bearing in mind the shortage of donors, horseshoe kidneys should certainly be used for transplantation.

Beneficial effect of HLA-DR matching on the survival of corneal allografts.

BACKGROUND: Although HLA typing and matching have been used for 3 decades, that practice has been poorly implemented in corneal transplantation, mainly because of inconclusive or contradictory analytical results. Consequently, we studied the immune response of corneal transplant recipients to HLA histoincompatibilities in a large homogeneous study. METHODS: All corneal transplantations performed by a single surgeon between 1976 and 1996 were studied. HLA-AB matching was used for recipient selection. All HLA typings were performed by a single experienced laboratory. Population genetic techniques were used to assess the validity of the HLA typings. Mono- and multivariate analyses were performed to identify the factors which significantly influence the survival of corneal allografts. Simulation studies were carried out to demonstrate the effects of mis-typed donor and recipient HLA-DR typings on analytical results. RESULTS: Retransplantation, degree of vascularization, HLA-AB and DR matching, endothelial cell count, graft size, recipient gender, and storage method were identified as significant factors by our monovariate analyses. A Cox proportional hazards survival analysis model identified degree of vascularization and HLA-AB and DR matching as significant prognostic factors when all immunological rejection episodes were used, P=0.000001. When only irreversible immunological rejection episodes were used, panel reactive antibodies, retransplantation, and number of rejection events were also identified, P=0.000001. Simulation studies showed that the effects of HLA-DR matching are abrogated by poor HLA-DR typings. CONCLUSIONS: Corneal allograft recipients have a normal alloimmune response to histoincompatibilities. Demonstration of that fact requires accurate HLA typings.

Permanent detrimental effect of nonimmunological factors on long-term renal graft survival: a parsimonious model of time-dependency.

PURPOSE: We attempted to model and test the pattern of effects of prognostic factors on renal graft survival during the posttransplantation time course. PATIENTS AND METHODS: Patients who received a cadaveric kidney-only transplant between January 1990 and December 1995 in Eurotransplant, who received cyclosporine as induction therapy, and who had a complete follow-up at the time of analysis were included in the study (n= 10614). An index summarizing all covariate information was calculated and used for modeling the time-dependent effects with relation to graft failure. RESULTS: The immunological factors (HLA mismatch and % panel-reactive antibody) were seen to have a slowly decreasing negative effect on renal graft survival. The cold ischemic trauma (>24 hr) exerted a permanent detrimental effect on the grafts. The use of organs obtained from old donors was associated with a constant higher risk of graft loss. CONCLUSIONS: An analysis of determinants of human allograft dysfunction should also study the interaction between the effects and time. Nonimmunological factors had a constant detrimental effect on graft failure, whereas the impact of the immunological factors--although remaining important for late graft loss--very slowly decreased. In the context of marginal transplants, clustering of unfavorable factors should be avoided to prevent late graft losses.