L Roels

The European experience

This mini‐review on European experiences with tackling the problem of organ shortage for transplantation was based on a literature review of predominantly European publications dealing with the issue of organ donation from deceased donors. The authors tried to identify the most significant factors that have demonstrated to impact on donation rates from deceased donors and subsequent transplant successes. These factors include legislative measures (national laws and European Directives), optimization of the donation process, use of expanded criteria donors, innovative preservation and surgical techniques, organizational efforts, and improved allocation algorithms.

Inferior outcome of cadaveric kidneys preserved for more than 24 hr in histidine-tryptophan-ketoglutarate solution. Leuven Collaborative Group for Transplantation.

BACKGROUND During recent years, an increasing number of transplant centers within the Eurotransplant organization have used histidine-tryptophan-ketoglutarate (HTK) solution instead of University of Wisconsin (UW) solution as their preferred cold storage solution for abdominal organ preservation. We report on our single-center experience on the outcome of imported kidneys preserved with either HTK or UW solution in relation to the duration of cold ischemia time (CIT). METHODS Between July 1989 and July 1997, 323 cadaveric kidneys preserved with UW or HTK and imported as a result of an exchange within the Eurotransplant organization were transplanted at our institution. CIT was <24 hr in 216 kidneys (UW: n=174, HTK: n=42) and > or =24 hr in 107 kidneys (UW: n=67, HTK: n=40). Renal functional outcome was evaluated by comparing delayed graft function and initial non-function rates, daily urinary output, the evolution of serum creatinine, and creatinine clearance at 1, 3, 5, 7, and 14 days and at 1, 3, 6 and 12 months, and graft survival at 1 year after transplantation in relation to the type of cold storage solution and CIT < or > or =24 hr. RESULTS Whereas the incidence of delayed graft function did not differ significantly between kidneys preserved for less than 24 hr in UW (18.6%) or HTK (26.2%), this rate increased to 50% in HTK kidneys compared to 23.9% in UW kidneys when CIT exceeded 24 hr (P=0.006). Mean serum creatinine and creatinine clearance values were better at 1 and 5 days postoperatively in kidneys preserved <24 hr with UW as compared to HTK (P<0.05). After 24 hr of CIT, HTK-preserved kidneys showed an impaired renal function, not only in the immediate postoperative phase but also at 1, 3, 6, and 12 months after transplantation (P<0.05). Graft survival at 1 year was 92.9% in UW vs. 87.5% in HTK kidneys preserved for <24 hr (NS), and 91% vs. 77.4% when CIT exceeded 24 hr (P=0.059). CONCLUSIONS From these single-center findings, it can be concluded that UW is superior to HTK in kidney preservation, particularly when CIT exceeds 24 hr.

Critical Care staffs’ attitudes, confidence levels and educational needs correlate with countries’ donation rates: data from the Donor Action® database

To investigate on the impact of Critical Care (CC) staffs’ attitudes to donation, their acceptance of the brain death (BD) concept, their confidence with donation‐related tasks and educational needs on national donation rates. Donor Action (DA) Hospital Attitude Survey (HAS) data were collected from 19 537 CC staff in 11 countries, including personal attitudes to donation, self‐reported knowledge, involvement and comfort levels with donation‐related tasks and educational requirements. Countries’ donation performance was expressed as Procurement Efficiency Index (PEI) (organs procured and transplanted/deaths from eligible causes). National PEI rates correlated well with CC staffs’ average support to donation (R = 0.700, P = 0.014), acceptance of the BD concept (R = 0.742, P = 0.007), confidence levels (R = 0.796, P = 0.002) and average educational requirements with donation‐related tasks (R = −0.661, P = 0.025). Nurses reported significantly lower positive attitudes (P < 0.0001), acceptance of the BD concept (P < 0.0001), comfort levels (P < 0.0001) and requested more education (P = 0.0025) than medical staff members. DA’s HAS is a powerful, standardized tool to assess CC staffs’ attitudes and donation‐related skills in different environments. Measures to improve countries’ donation performance should focus on guidance and education of CC staff so as to ensure that all practitioners have sufficient knowledge and feel comfortable with donation‐related issues.

Worldwide variability in deceased organ donation registries

The variability in deceased organ donation registries worldwide has received little attention. We considered all operating registries, where individual wishes about organ donation were recorded in a computerized database. We included registries which recorded an individual’s decision to be a donor (donor registry), and registries which only recorded an individual’s objection (non‐donor registry). We collected information on 15 characteristics including history, design, use and number of registrants for 27 registries (68%). Most registries are nationally operated and government‐owned. Registrations in five nations expire and require renewal. Some registries provide the option to make specific organ selections in the donation decision. Just over half of donor registries provide legally binding authorization to donation. In all national donor registries, except one, the proportion of adults (15+) registered is modest (<40%). These proportions can be even lower when only affirmative decisions are considered. One nation provides priority status on the transplant waiting list as an incentive to affirmative registration, while another nation makes registering a donation decision mandatory to obtain a driver’s license. Registered objections in non‐donor registries are rare (<0.5%). The variation in organ donor registries worldwide necessitates public discourse and quality improvement initiatives, to identify and support leading practices in registry use.

Waiting for a thoracic transplant in Eurotransplant

The prospects of patients on the thoracic waiting list are governed by the chance of receiving an organ in time and by the outcome of the transplantation. The former probability is determined by a triad of disease severity, resource size and allocation rules. The aim of this study was to provide an objective description of the distributional effects of the thoracic allocation system in Eurotransplant. It appears that the interpretation of waiting‐list outflow indicators is not straightforward and that it is difficult to assess the fairness of an organ allocation system in the framework of changing donor–organ availability. The timing of listing for heart transplantation can substantially be improved; whether this is also true for lung transplantation cannot be determined from the available data. Allocation schemes cannot solve the problem of organ shortage; a shift of attention toward collaboration with procurement professionals is needed.

Donation Patterns in Four European Countries : Data From the Donor Action Database

Background. To analyze heart-beating organ donation patterns in four countries using the Donor Action (DA) Program nationally and to identify areas for improvement. Methods. Medical Record Review (MRR) of 18,118 critical care deaths between January 2006 and December 2007 in Belgium, Finland, France, and Switzerland. Data were entered to the DA System Database for analysis. Results. Of 6561 patients without contraindications to donation, 45.3% met preconditions for brain death (BD) diagnosis, 31.4% had signs of severe brain damage and 28.8% met criteria for formal BD diagnosis. Belgium had the highest number of patients with formal BD diagnosis (75.7%) and Switzerland (57.4%, P<0.0001) the lowest. Although donor identification rates were uppermost in France (93.6%) and lowest in Finland (47.7%, P<0.0001); Finland excelled in donor referral (93.9% of identified cases) versus only 63.8% in Switzerland (P<0.0001), and excelled in family approach rates (92.7%) versus only 70.2% in France (P<0.0001). Consent rates were superior in Belgium and Finland and lowest in France (P<0.0001). Conversion rates (percent of potential donors vs. actual donors) were higher in France and Belgium and significantly lower in Finland and Switzerland (P=0.0187). Only Belgium had a non–heart-beating donation policy during the study period, resulting in 11.2% more donors added to the country’s donor pool. Conclusions. The DA MRR proved to be an excellent tool to identify areas of improvement within certain steps of the donation process. Moreover, DA’s MRR has shown to be applicable in different countries and environments and should be considered as a unique tool for comparing countries’ donation performance.

A prospective, randomized trial of pretransplant blood transfusions in cadaver kidney transplant candidates

Abstract To assess the effect of pretransplant blood transfusions on the outcome of cadaveric kidney transplantation, a single‐centre analysis was performed of 171 patients randomly assigned to receive no pretransplant transfusion (n= 85) or to receive at least three random blood transfusions (n= 86). After transfusion 18 of the latter patients developed circulating lymphocytotoxic T‐cell antibodies, but the sensitization was only transient. At the time of transplantation, none was still sensitized. In both groups 60 patients have been transplanted. Patient and graft survival rates were significantly higher in the transfused group than in the non‐transfused group. In the non‐transfused patients the higher mortality was due to complications related to repeated anti‐rejection therapy. Non‐transfused patients had more repeated acute rejection episodes than the transfused patients. The present study indicates that pretransplant blood transfusions still facilitate graft acceptance even in the setting of good HLA matching and with cyclosporine as the basic immunosuppressant. The risk of sensitization is very low.

Immunological and clinical observations in diabetic kidney graft recipients pretreated with total-lymphoid irradiation

In a feasibility study, twenty patients with end-stage diabetic nephropathy were treated with fractionated total-lymphoid irradiation (TLI, mean dose 25 Gy), before transplantation of a first cadaveric kidney. During radiotherapy, only one patient had a serious side effect (bone marrow depression). After transplantation four patients died (one of a myocardial infarction, one of ketoacidosis, and two of infections occurring during treatment of rejection crises). One graft was lost because of chronic rejection. The other 15 patients have a functioning graft (mean follow-up 24 months) and receive low-dose prednisone alone (<10 mg/day, n=ll) or in conjunction with cyclosporine (n=4) as maintenance immunosuppressive therapy. A favorable clinical outcome after TLI (no, or only one, steroid-sensitive rejection crisis) was significantly correlated with (1) a high pre-TLI helper/suppressor lymphocyte ratio, (2) a short interval between TLI and the time of transplantation, and (3) the occurrence of functional suppressor cells early after TLI. The most striking immunological changes provoked by TLI consisted of a long-term depression of the mixed lymphocyte reaction and of the phytohemagglutinin, and Concanavalin A or pokeweed-mitogen-induced blastogenesis. A rapid and complete recovery of the natural killer cell activity was observed after TLI. A permanent inversion of the OKT4+ (T helper/inducer) over OKT8+ (T suppressor/cytotoxic) lymphocyte ratio was provoked by a decrease of the OTK4+ subpopulation, together with a supranormal recovery of the OKT8+ lymphocytes. A majority of the latter lymphocytes did also express the Leu 7 and the Leu 15 phenotype.

Potential for deceased donation not optimally exploited: donor action data from six countries.

Background Most countries today promote living donation as an alternative to challenge the organ shortage from deceased donors. This seems justifiable provided the potential for deceased donation is optimally exploited. Methods We used the Donor Action (DA) Medical Record Review (MRR) methodology in six countries, to measure whether the potential for heart-beating (HB) deceased donors was adequately converted to donation. Medical record review data were collected from 52,383 patients who died in 605 critical care units in 227 hospitals between January 2007 and December 2009. Results On a total of 17,903 ventilated patients aged younger than 76 years and without contraindications to HB donation, 4,855 cases met criteria for brain death (BD) diagnosis and were considered potential HB donors. On average, 24.8±15.9% was not identified as potential donor, 21.9% of identified cases was not referred as such to a procurement team, and in 11.3% of identified cases, no approached was offered with the option to donate. Average consent rates/family approaches or registry consultation was 69.1±14.5%, and average conversion of potential into actual donors was 42.1±7.3%. Conclusions Over 57% of deceased potential donors in the study cohort were missed along the donation pathway because of nonidentification, no referral, no approach of relatives, or objections to donate. In countries with lower donation rates, expectedly more potential donors are missed proportionally. Efforts to increase the organ pool should therefore focus on optimizing clinical practices in deceased organ donation in addition to promoting living organ donation.

Importance of HLA-DR matching in polytransfused cadaveric kidney transplant recipients. A prospective one-center study

Since August 1978 prospective HLA-DR typing has been performed in 157 donor-recipient pairs. All recipients received pretransplant blood transfusions. This study shows that HLA-DR matching can significantly improve the survival of cadaveric kidney allografts, even in polytransfused recipients. Patients receiving kidneys with no HLA-DR incompatibilities have a one-year graft survival of 97%, versus 86% for recipients with 1 HLA-DR incompatibility and 73% for recipients with 2 HLA-DR incompatibilities. The cumulative dose of corticosteroids during the first year after transplantation is significantly lower in patients with no DR-incompatibilities. HLA-A and B matching have no additional effect on graft survival.