Rafael Matesanz

Current situation of donation after circulatory death in European countries

The aim of the present study was to describe the current situation of donation after circulatory death (DCD) in the Council of Europe, through a dedicated survey. Of 27 participating countries, only 10 confirmed any DCD activity, the highest one being described in Belgium, the Netherlands and the United Kingdom (mainly controlled) and France and Spain (mainly uncontrolled). During 2000–2009, as DCD increased, donation after brain death (DBD) decreased about 20% in the three countries with a predominant controlled DCD activity, while DBD had increased in the majority of European countries. The number of organs recovered and transplanted per DCD increased along time, although it remained substantially lower compared with DBD. During 2000–2008, 5004 organs were transplanted from DCD (4261 kidneys, 505 livers, 157 lungs and 81 pancreas). Short‐term outcomes of 2343 kidney recipients from controlled versus 649 from uncontrolled DCD were analyzed: primary non function occurred in 5% vs. 6.4% (P = NS) and delayed graft function in 50.2% vs. 75.7% (P < 0.001). In spite of this, 1 year graft survival was 85.9% vs. 88.9% (P = 0.04), respectively. DCD is increasingly accepted in Europe but still limited to a few countries. Controlled DCD might negatively impact DBD activity. The degree of utilization of DCD is lower compared with DBD. Short‐term results of DCD are promising with differences between kidney recipients transplanted from controlled versus uncontrolled DCD, an observation to be further analyzed.

Monocytic suppressive cells mediate cardiovascular transplantation tolerance in mice

One of the main unresolved questions in solid organ transplantation is how to establish indefinite graft survival that is free from long-term treatment with immunosuppressive drugs and chronic rejection (i.e., the establishment of tolerance). The failure to achieve this goal may be related to the difficulty in identifying the phenotype and function of the cell subsets that participate in the induction of tolerance. To address this issue, we investigated the suppressive roles of recipient myeloid cells that may be manipulated to induce tolerance to transplanted hearts in mice. Using depleting mAbs, clodronate-loaded liposomes, and transgenic mice specific for depletion of CD11c+, CD11b+, or CD115+ cells, we identified a tolerogenic role for CD11b+CD115+Gr1+ monocytes during the induction of tolerance by costimulatory blockade with CD40L-specific mAb. Early after transplantation, Gr1+ monocytes migrated from the bone marrow into the transplanted organ, where they prevented the initiation of adaptive immune responses that lead to allograft rejection and participated in the development of Tregs. Our results suggest that mobilization of bone marrow CD11b+CD115+Gr1+ monocytes under sterile inflammatory conditions mediates the induction of indefinite allograft survival. We propose that manipulating the common bone marrow monocyte progenitor could be a useful clinical therapeutic approach for inducing transplantation tolerance.

Spanish experience as a leading country: what kind of measures were taken?

A recent call for self‐sufficiency in transplantation issued by the WHO faces variable worldwide activity, in which Spain occupies a privileged position, with deceased donation rates of 33–35 per million population (pmp) and 85 transplants pmp. An evaluation of current challenges, including a decrease in deaths because of traffic accidents and cerebrovascular diseases, and a diversity of cultures in Spain, has been followed by a comprehensive strategy to increase organ availability. Actions include an earlier referral of possible donors to the transplant coordination teams, a benchmarking project to identify critical success factors in donation after brain death, new family approach and care methods, and the development of additional training courses aimed at specific groups of professionals, supported by their corresponding societies. Consensus documents to improve knowledge about safety limits for organ donation have been developed to minimize inappropriate discarding of organs. Use of organs from expanded criteria donors under an ‘old for old’ allocation policy has resulted from adaptation to the progressive decline of optimal organs. National strategic plans to deal better with organ shortage, while respecting solid ethical standards, are essential, as reflected in the WHO Guiding Principles and the Istanbul Declaration on Organ Trafficking and Transplant tourism.

A call for government accountability to achieve national self-sufficiency in organ donation and transplantation

Roughly 100,000 patients worldwide undergo organ transplantation annually, but many other patients remain on waiting lists. Transplantation rates vary substantially across countries. Affluent patients in nations with long waiting lists do not always wait for donations from within their own countries. Commercially driven transplantation, however, does not always ensure proper medical care of recipients or donors, and might lengthen waiting times for resident patients or increase the illegal and unethical purchase of organs from living donors. Governments should systematically address the needs of their countries according to a legal framework. Medical strategies to prevent end-stage organ failure must also be implemented. In view of the Madrid Resolution, the Declaration of Istanbul, and the 63rd World Health Assembly Resolution, a new paradigm of national self-sufficiency is needed. Each country or region should strive to provide a sufficient number of organs from within its own population, guided by WHO ethics principles.

International practices of organ donation

Organ donation and transplant rates vary widely across the globe, but there remains an almost universal shortage of deceased donors. The unmet need for transplants has resulted in many systematic approaches to increase donor rates, but there have also been practices that have crossed the boundaries of legal and ethical acceptability. Recent years have seen intense interest from international political organizations, led by the World Health Organization, and professional bodies, led by The Transplantation Society. Their efforts have focused on the development of a series of legal and ethical frameworks, designed to encourage all countries to eradicate unacceptable practices while introducing programmes that strive to achieve national or regional self-sufficiency in meeting the need for organ transplants. These programmes should seek to reduce both the need for transplantation and also develop deceased donation to its maximum potential. Living donation remains the mainstay of transplantation in many parts of the world, and many of the controversial--and unacceptable--areas of practice are found in the exploitation of living donors. However, until lessons are learnt, and applied, from countries with highly developed deceased donor programmes, these abuses of human rights will be difficult to eradicate. A clear international framework is now in place to achieve this.

The critical pathway for deceased donation: reportable uniformity in the approach to deceased donation

The critical pathway of deceased donation provides a systematic approach to the organ donation process, considering both donation after cardiac death than donation after brain death. The pathway provides a tool for assessing the potential of deceased donation and for the prospective identification and referral of possible deceased donors.

The 40 Donors Per Million Population Plan: An Action Plan for Improvement of Organ Donation and Transplantation in Spain

INTRODUCTION Spain has been showing the highest rate of deceased donor organ recovery in the world for a whole country, namely, 33-35 donors per million population (pmp) during the last years. This activity is attributed to the so-called Spanish Model of organ donation, an integrated approach to improve organ donation since the start of the Organización Nacional de Trasplantes (ONT) in 1989. However, in 2007 there were 7/17 regions with >40 donors pmp and a marked regional variability. Thus, ONT has set a large-scale, comprehensive strategy to achieve a substantial improvement in donation and transplantation in Spain in the coming years: The 40 Donors pmp Plan. PURPOSE AND SCOPE The overall objective is to increase the average rate of deceased donors to 40 pmp between 2008 and 2010. The areas of improvement, specific objectives, and actions have come from deep reflection on the data and the material generated from multidisciplinary discussions and open consultation with the donation and transplantation community. KEY AREAS SELECTED FOR ACTION Detection and management of brain-dead donors, with 4 specific subareas: access to intensive care units, new forms of hospital management, foreigners and ethnic minorities, and evaluation/maintenance of thoracic organ donors. Expanded criteria donors, with 3 subareas: aging, donors with positive tests to certain viral serologies, and donors with rare diseases. Special surgical techniques. Donation after cardiac death.

Veno-Occlusive Hepatic Disease of the Liver in Renal Transplantation: Is Azathioprine the Cause?

Five male patients with veno-occlusive disease of the liver (VOD) were observed in 200 consecutive renal transplants (RT) treated with azathioprine and prednisone. Mild liver enzymatic increases not justified by other reasons were detected between 2 and 9 months after RT. All 5 patients developed portal hypertension and died between 18 and 79 months following RT. Diagnosis of VOD was histological; in 3 cases diagnosis was made while the patients were still alive. In our patients, 9 previous viral hepatotropic infections (5 during hemodialysis and 4 after TR) were demonstrated. Due to the reported low incidence of VOD in RT patients, when many of them have been treated with azathioprine, the etiological role of this drug must be questioned. However, the possible association of a previous hepatotropic viral infection and the use of an immunosuppressive agent should be considered as a probable cause of VOD in kidney grafts.

Continuously Evaluating Performance in Deceased Donation: The Spanish Quality Assurance Program

The Spanish Quality Assurance Program applied to the process of donation after brain death entails an internal stage consisting of a continuous clinical chart review of deaths in critical care units (CCUs) performed by transplant coordinators and periodical external audits to selected centers. This paper describes the methodology and provides the most relevant results of this program, with information analyzed from 206,345 CCU deaths. According to the internal audit, 2.3% of hospital deaths and 12.4% of CCU deaths in Spain yield potential donors (clinical criteria consistent with brain death). Out of the potential donors, 54.6% become actual donors, 26% are lost due to medical unsuitability, 13.3% due to refusals to donation, 3.1% due to maintenance problems and 3% due to other reasons. Although the national pool of potential donors after brain death has progressively decreased from 65.2 per million population (pmp) in 2001 to 49 pmp in 2010, the number of actual donors after brain death has remained at about 30 pmp. External audits reveal that the number of actual donors could be 21.6% higher if all potential donors were identified and preventable losses avoided. We encourage other countries to develop similar comprehensive approaches to deceased donation performance.

Presumed consent: a distraction in the quest for increasing rates of organ donation

Spain has the highest rate of organ donation in the world and is often cited as a successful example of presumed consent legislation. However, the country does not have an opt-out register, nor is public awareness of the 1979 legislation promoted. John Fabre, Paul Murphy, and Rafael Matesanz argue that the presumed consent legislation is dormant, and that Spain in fact demonstrates it is possible to have the highest rates of organ donation without recourse to presumed consent