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Keywords:

  • expanded criteria donors;
  • legislation;
  • organ allocation;
  • organ donation;
  • organ preservation;
  • organ-exchange organizations;
  • professional education

Summary

  1. Top of page
  2. Summary
  3. Introduction
  4. Legislative measures
  5. Public campaigns to increase organ donation
  6. Optimizing the donation process: focus on Critical Care Units
  7. Expanded criteria donors, nonheart-beating donors
  8. Optimizing organ yield and quality by better clinical management and better organ preservation
  9. Transplantation techniques to maximize use of available organs
  10. Organ-allocation-related options to reduce organ discard rates and to improve transplant outcomes
  11. Summary
  12. Funding
  13. Acknowledgements
  14. References

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.


Introduction

  1. Top of page
  2. Summary
  3. Introduction
  4. Legislative measures
  5. Public campaigns to increase organ donation
  6. Optimizing the donation process: focus on Critical Care Units
  7. Expanded criteria donors, nonheart-beating donors
  8. Optimizing organ yield and quality by better clinical management and better organ preservation
  9. Transplantation techniques to maximize use of available organs
  10. Organ-allocation-related options to reduce organ discard rates and to improve transplant outcomes
  11. Summary
  12. Funding
  13. Acknowledgements
  14. References

Transplantation of organs from deceased or living donors has become the treatment of choice for many end-stage diseases thanks to continuously improving results. Data from the Council of Europe show that in 2008 a total of 27 809 transplants have been performed in the 27 countries of the EU (population: 493 million inhabitants) [1]. Unfortunately, transplantation has become the victim of its own successes as the number of available deceased or living donors seems to be insufficient to answer the growing demand for organs.

There are several possible approaches to address increasing gap between the number of patients in need for organ transplantation and the number of available donor organs:

  • 1
     Reduce the need for transplantation by either preventing the development of end-stage organ disease or at least slow down the progression of the underlying disease.
  • 2
     Make more donor organs available for transplantation either from deceased or living donors.
  • 3
     Prevent that reported suitable donor organs are not allocated and transplanted but discarded.
  • 4
     Apply special transplant techniques to make best use of available donor organs like split liver or domino transplantation.
  • 5
     Improve graft survival and reduce transplant loss to avoid the need for retransplantation.

There is a wide variety of donation and transplant rates between countries in Europe. We preferred to express countries' donation performance rates as organs retrieved and transplanted because from the point of view of a recipient waiting for a life-saving transplant, organs rather than donors seem to be relevant. Figure 1 depicts all deceased donor organs that were retrieved per country and subsequently transplanted either in the same country or abroad. In 2008, Belgium scored highest with nearly 90 organs per million population (PMP), closely followed by Spain, Portugal, Austria, and Norway with over 70 organs PMP [1,2]. Unfortunately, several countries were even unable to retrieve more than 20 organs PMP/year in 2008, which shows that there is definitely room for improvement and that it must be feasible to increase average donation rates in Europe substantially, based on best practice experience. But even in countries with currently already high organ-donation rates, there might be options to enhance organ transplantation further [3]. Therefore, this mini-review focuses on factors that have been demonstrated to impact on the availability of donor organs in Europe, such as legislative initiatives, optimization of the donation process, use of expanded criteria donors (ECD), innovative preservation, and surgical techniques as well as organizational efforts related to the allocation and transplantation process. It should be noted that this review does not cover the so-called “Spanish Model”, which is subject of a separate article in this issue. Prevention and treatment of end-stage organ disease and the wide variety of steps taken to improve the long-term outcome of transplantation are beyond the scope of this review and will also not be described in detail in this article.

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Figure 1.  Deceased donor organs retrieved and transplanted, PMP – 2008 – Council of Europe, Eurotransplant data 2008.

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Legislative measures

  1. Top of page
  2. Summary
  3. Introduction
  4. Legislative measures
  5. Public campaigns to increase organ donation
  6. Optimizing the donation process: focus on Critical Care Units
  7. Expanded criteria donors, nonheart-beating donors
  8. Optimizing organ yield and quality by better clinical management and better organ preservation
  9. Transplantation techniques to maximize use of available organs
  10. Organ-allocation-related options to reduce organ discard rates and to improve transplant outcomes
  11. Summary
  12. Funding
  13. Acknowledgements
  14. References

In this chapter, we will focus primarily on the governing legal frameworks for organ donation from deceased donors in EU member states and some recent initiatives of the European Commission with regard to organ donation and transplantation.

Basically, two types of consent to donation from deceased donors can be distinguished today in national legislations: the principle of presumed consent or “opting-out” (contracting-out) and explicit consent or “opting-in” (contracting-in). In a presumed consent system, no explicit consent is required to become a potential donor. The donation procedure can be initiated, unless the deceased person had objected during life. In an explicit consent system, the donor himself needs to consent to organ removal after death explicitly. In practice, and in the absence of such explicit consent, most laws require the deceased’s next-of-kin to consent to post-mortem organ removal. A majority of European countries have transplant laws today based on the presumed consent principle. Table 1 summarizes the current situation in 25 EU countries [4]. It should be noted that the practical application of national laws, particularly with regard to the role of next of kin in objecting or consenting to donation, varies substantially between countries, regions, hospitals, and even individual requestors and thus may impact on ultimate efficiency of national laws [4].

Table 1.   Legal systems regarding consent to organ donation in 25 EU Member States.
CountryLegal principleDaily practice*Date of Law
  1. *Authors’ survey, October 2010; ?, unknown.

AustriaOpting out?1982
BelgiumOpting out“Soft”1986 (amended in 2007)
BulgariaOpting out“Soft”1996
CroatiaOpting out“Soft”2000
Czech RepublicOpting out?2002
DenmarkOpting out“Soft”1990 (amended in 2001)
EstoniaOpting out“Soft”2002
FinlandOpting out“Soft”2001
FranceOpting out“Soft”1976 (amended several times)
GermanyOpting in1997
GreeceOpting out“Soft”1999
HungaryOpting out?1997
IrelandOpting inNo law directly regulating organ donation
ItalyOpting out“Soft”1999
LatviaOpting out?1995
LithuaniaOpting out?1999
LuxembourgOpting out“Soft”1982
PolandOpting out“Soft”1995 (amended in 2005)
PortugalOpting out“Soft”1993
SlovakiaOpting out?2004
SloveniaOpting out“Soft”2000
SpainOpting out“Soft”1979 (amended in 1999)
SwedenOpting out“Soft”1995
the NetherlandsOpting in1996
UKOpting in2006

Several countries with a presumed consent law, such as Belgium, Croatia, France, Poland, and Sweden, have developed a national nondonor registry to collect citizens’ objections during life. Interestingly, in almost all European countries with a presumed consent law, it is daily practice – especially in the absence of a registered will from the deceased – to approach donor families regardless of the legal situation. The families are, in this situation, not approached with a mostly confronting request to donate, but rather as an attempt to find out whether the deceased himself would have objected to donate. This subtle but fundamental difference in family-approach techniques between countries with an explicit consent law and those with a so-called “soft” presumed consent practice, by shifting the burden of a decision from the donor family to the donor himself, may be an important factor for explaining the significantly lower average refusal rates in the latter.

Some authors claim that given the multifactorial character of the donation process, national legislations alone are unlikely to explain variations in donation rates between countries [5,6]. Certainly, a combination of legislation, potential of medically suitable donors, investments in health care and infrastructure, underlying public attitudes, religion and, education may all play a role [3].

Donation figures within the Eurotransplant area, however, demonstrate a rather direct effect of legislative measures: organ donation rates in Belgium nearly doubled within 2 years after the implementation of a presumed consent law in 1987 [7]. When comparing four socio-economically comparable countries within the Eurotransplant area, donation rates PMP are nearly twice as high in Austria and Belgium (presumed consent) compared to those in Germany and the Netherlands [8]. One cannot ignore the correlation between donation rates PMP in the above mentioned countries and the consent system they adhere, as demonstrated in Fig. 2 and based on Eurotransplant Annual Reports [9].

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Figure 2.  Eurotransplant: deceased donors and available organs PMP – 2009.

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Two interesting studies based on a multi-variate analysis in 28 [10] and 22 [11] European countries have identified presumed consent laws as an independent factor that significantly impact on countries’ donation rates.

A study based on representative data from the Eurobarometer survey 58.2 undertaken in 2002 confirmed that presumed consent organ donation policy positively affects the willingness of individuals to donate their own organs and those of a relative [12].

Because of wide variations in quality and safety requirements between EU Member States (MS), the European Commission (EC) adopted in 2008 a proposal for a Directive on standards of quality and safety of human organs intended for transplantation [13]. This Directive also aims to facilitate the exchange of organs and expand the donor pool via several means:

  •  A competent authority in each MS will have to make sure that the quality and safety standards of the Directive are complied with;
  •  A system for the authorization of organ procurement and transplantation will be established;
  •  National quality programs will have to be introduced to ensure continuous monitoring of performance;
  •  MS will have to put in place organ traceability systems for the reporting of serious adverse events and reactions;
  •  Transplant teams in all MS will be assured to receive appropriate information required regardless of the country of origin of the organ.

After adoption by the EU Council and Parliament, and publication in the Official Journal in June 2010, member States now have 24 months to transpose the Directive into national law.

At the same time, the Commission launched an Action Plan designed to promote the availability of deceased and living donors across the European Union, increase the supply of organs, enhance transplantation systems and ensure the quality and safety of procedures. The Action Plan [14] includes a number of priorities, which are grouped under three challenges:

  •  Increasing organ availability
  •  Enhancing the efficiency and accessibility of transplantation systems
  •  Improving quality and safety

Public campaigns to increase organ donation

  1. Top of page
  2. Summary
  3. Introduction
  4. Legislative measures
  5. Public campaigns to increase organ donation
  6. Optimizing the donation process: focus on Critical Care Units
  7. Expanded criteria donors, nonheart-beating donors
  8. Optimizing organ yield and quality by better clinical management and better organ preservation
  9. Transplantation techniques to maximize use of available organs
  10. Organ-allocation-related options to reduce organ discard rates and to improve transplant outcomes
  11. Summary
  12. Funding
  13. Acknowledgements
  14. References

Refusal to donate represents an obstacle for deceased donation, especially in countries with informed consent, but to a certain extent also in countries with presumed consent, as in everyday practice even in the countries with presumed consent the families are approached to understand what the wishes of the deceased were on donation [15]. In several European countries, family refusal rates are well above 40% [1]. Achieving a higher consent rate would therefore have a substantial impact on the number of available donor organs. In an effort to reach this goal, nationwide public campaigns to increase organ donation have been carried out in almost all European countries nationwide or are currently under way. They typically aim at informing the public, creating a positive attitude toward transplantation and make people formally declare their decision. Only a few of these public campaigns, however, have been systematically evaluated [16]. Available data show a (transient) effect on knowledge about donation and transplantation. The impact on consent rates and especially on the number of transplantations on the other hand is limited if at all detectable [17–19]. This might in part be due to the difficulty to quantify the effect of such campaigns [20]. Another aspect of general public campaigns is that they often do not address the cultural microdiversity in the population and therefore are not likely to be effective and efficient [21].

Tailored educational efforts for specific targets have turned out to be more effective: Recent reports show that with educational intervention programs especially designed for secondary school or university students, the knowledge about the brain death concept, organ donation and transplantation can be increased substantially, resulting in improved opinions about deceased organ donation and a higher intention to donate organs [22–25]. Almost 80% of the students discussed organ donation with their families multiplying the effect of this approach [24]. Nevertheless, the actual effect on organ donation is difficult to estimate and might only become evident over time.

Education and training of intensive care nurses and doctors have achieved the highest and most immediate impact on organ donation of all initiatives described so far [26]. These courses aim both at improving knowledge about donor identification and transplantation as well as changing attitudes toward transplantation [27]. This approach has been picked up in the multinational European Training Program on Organ Donation (ETPOD) project supported by the European Union [28]. The central role of the critical care unit personnel in the donation process will be further addressed in following section.

Optimizing the donation process: focus on Critical Care Units

  1. Top of page
  2. Summary
  3. Introduction
  4. Legislative measures
  5. Public campaigns to increase organ donation
  6. Optimizing the donation process: focus on Critical Care Units
  7. Expanded criteria donors, nonheart-beating donors
  8. Optimizing organ yield and quality by better clinical management and better organ preservation
  9. Transplantation techniques to maximize use of available organs
  10. Organ-allocation-related options to reduce organ discard rates and to improve transplant outcomes
  11. Summary
  12. Funding
  13. Acknowledgements
  14. References

A variety of organizational initiatives to increase deceased donation have been developed at international, national or local hospital level. Experience in Europe and the U.S. indicates that a consistent hospital donation protocol built on multidisciplinary consensus and team building can lead to a significant increase in donation [29]. This approach was picked up during the third WHO Global Consultation on Organ Donation and Transplantation organized by the World Health Organization, The Transplantation Society (TTS), and the Organización Nacional de Trasplantes (ONT) in Madrid in March 2010. A “Critical Pathway for Organ Donation” has been developed presenting an algorithm of progression from a possible deceased donor to a utilized organ donor that will aid global harmonization of practice in this area. Such a protocol supports teamwork toward common goals: to identify all potential donors and provide optimal care for families. As an added value, it also cultivates a sense of institutional ownership of the donation process among hospitals and their Critical Care Units (CCUs). Although reports of activities on a local, regional or national scale show fragmentary successes in achieving these goals [30–32], two long-standing international European initiatives deserve some closer attention.

The European Donor Hospital Education Program (EDHEP), a Eurotransplant initiative launched in 1991, was designed to meet the training needs of medical and nursing Critical Care (CC) staff in breaking bad news, caring for the bereaved and requesting donation [33]. EDHEP aims at improving the communication with donor relatives regarding death and donation by providing insight in the grieving process and relatives’ emotional reactions related to the donation procedure [34]. The EDHEP Workshop “The grief response and donation request” has been organized hundreds of times and attended by several thousands of CC staff in Europe and beyond. It is available in over 15 languages and is part of post-graduation education today in over 35 countries all over the world [33].

Another initiative, and in fact a continuation of EDHEP but with a wider scope, is Donor Action® (DA), an international collaboration that brings together state-of-the-art expertise to help hospitals increase their donation performance through improved clinical practices [35,36]. Cornerstone of the DA program is its “Diagnostic Review” that takes a systematic approach toward achieving quality assurance in the whole donation process by helping CCUs to identify when, where, and why potential donors are missed along the donation pathway. DA’s “Diagnostic Review” has three components: a standardized Medical Record Review (MRR), a Hospital Attitude Survey (HAS), and a system database to analyze and report on collected findings. The program also provides improvement measures in modular format to fill gaps identified by the DA Diagnostic Review. A number of publications have reported on the feasibility of implementing this program locally and achieving donation increases between 70% and 160% in countries with sufficient follow-up [37–44]. A recent study from a French group reports an increase in donation rates from 13 to even 27.4 donors PMP (+95.8%), 2 years after implementing DA’s methodology [45] (Fig. 3).

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Figure 3.  Impact of implementing Donor Action in France’s EPACA/HC region.

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As mentioned already before, involving CC staff in the donation process is a key element to any successful program. Recent articles in this journal and elsewhere have identified a strong correlation between national donation rates and CC staff attitudes, confidence levels, and educational needs with regard to donation-related tasks [26,46].

Finally, and with regard to other educational initiatives on a European level, the European Society for Organ Transplantation (ESOT) has started offering a choice of courses and workshops aimed at enhancing professional skills of transplant coordinators and surgeons in the field of organ procurement:

  •  The annual Triple “C” course, which is an advanced course for deceased donor, living donor and recipient coordinators, aiming at providing insight and tools in addition to existing local, regional or national educational programs
  •  Regular hands-on TOP courses for young surgeons who are specializing in multiorgan procurement and transplant surgery

Expanded criteria donors, nonheart-beating donors

  1. Top of page
  2. Summary
  3. Introduction
  4. Legislative measures
  5. Public campaigns to increase organ donation
  6. Optimizing the donation process: focus on Critical Care Units
  7. Expanded criteria donors, nonheart-beating donors
  8. Optimizing organ yield and quality by better clinical management and better organ preservation
  9. Transplantation techniques to maximize use of available organs
  10. Organ-allocation-related options to reduce organ discard rates and to improve transplant outcomes
  11. Summary
  12. Funding
  13. Acknowledgements
  14. References

Kidneys

For reasons of a growing shortage of organs for kidney transplantation, the use of ECDs has increased significantly in recent years. The term “expanded criteria donor” (ECD) was introduced by Kauffman et al. in 1997 to describe transplantable organs that do not meet the standard criteria for organ donation (SCD), in preference to other descriptive terminologies in use, such as “marginal”, “suboptimal”, “compromised”, “inferior” or “nonstandard” donor kidneys [47]. In 2002, the US Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) established an ECD definition for kidneys based on donor age and three donor risk factors identified to be statistically significant in a previous Scientific Registry of Transplant Recipients (SRTR) analysis:

  •  History of arterial hypertension
  •  Terminal serum creatinine >1.5 mg/dl
  •  Cerebrovascular accident (CVA) as cause of death

Consequently, ECDs were defined as “any donor 60 years or older, or older than 50 years with at least 2 of the cited risk factors” [48].

Donor age in itself remains one of the most important risk factors impacting on renal transplant outcomes, as demonstrated in several multicenter studies. The number of patients, however, waiting for a kidney and aged 65 years and above is steadily increasing as well. Within the Eurotransplant area, there has been a significant increase in renal transplant recipients older than 65 years old from 3.6% in 1991 to 19.7% in 2007. During the same period, the proportion of deceased kidney donors in this age group increased from 2.3 to 18.1% [49]. These changing trends in donor and recipient profiles have encouraged Eurotransplant to launch in 1999 an old-for-old kidney allocation scheme named “European Senior Program (ESP)” with a twofold aim: to achieve a more efficient use of kidneys from older donors and to reduce the waiting time for elderly patients. The allocation scheme was solely based on the concept of matching between metabolic demand of the graft recipient and excretory capacity of the donor organ [50]. According to the ESP algorithm, kidneys from donors over 65 years were assigned with priority to registered ESP patients (inclusion criteria: recipient age >65 years, panel reactive antibodies <5%). Collaborating centers were required to keep the cold ischemia time as short as possible by circumventing HLA matching and transplanting kidneys into local recipients only [51]. Initial [51] and long-term [52,53] outcome evaluations have demonstrated that an old-for-old renal allocation algorithm can be successful provided that risk factors such as cold ischemia time are reduced. Three-year data showed that there was no difference between patients who received grafts from elderly donors via ESP and those who received similar kidneys via the usual HLA-driven allocation procedure.

Hundreds of reports have been published meanwhile on the outcome of renal transplants from ECDs. A recent meta-analysis based on 1001 publications concludes that the use of ECDs for kidney transplantation increases the number of deceased donor kidneys available, results in shorter waiting times, and limits the morbidity and mortality associated with long-term dialysis therapy [54]. These kidneys are known to have worse long-term survival compared with SCD kidneys, and therefore adequate GFRs with acceptable histological characteristics remain to be required. Based on the available evidence, the authors conclude that patients under the age of 40 years or scheduled for kidney retransplantation should not receive an ECD kidney. Patients 40 years or older, especially with diabetic nephropathy or with longer waiting times, showed better survival receiving an ECD kidney than remaining on dialysis. An ECD kidney nephron-protecting strategy should be based on minimization of cold ischemia times, pulsatile perfusion preservation, and tailored immunosuppression.

Liver

Exemplary for the growing trend of using organs from older donors is the evolution of the median deceased-donor age for different organs in Eurotransplant between 1990 and 2009, as depicted in Fig. 4 [9]. It demonstrates that not only for kidneys, but also for other organs, donor age and other criteria are changing dramatically to meet the organ shortage: since 1990, the median donor age for livers doubled from 26 to 53 years in 2009. In contrast to other organs, the liver may be more immune to senescence, particularly in the otherwise healthy donor, possibly because of the liver’s large functional reserve, regenerative capacity, and dual blood supply, which exceeds its metabolic needs [55]. When controlling for other factors, older age may not adversely affect patient or graft survival, although recipients of older donor livers seem to experience more delayed function and a cholestatic pattern after transplantation [56]. Older donors have also an increased incidence of steatosis, which may potentiate preservation injury [57]. Therefore, and as grafts with more than 14 h of cold ischemia have been associated with a twofold increase in preservation damage [58,59], older donors need to be carefully selected, and each liver requires an assessment based on other risk factors, such as steatosis and cold ischemia time. In this context, two European review articles list following potential risk factors to be associated with liver graft dysfunction: donor age, gender, race weight, CVA as cause of death, lengthy stay in the ICU, high doses of inotropes, cold ischemia time >10–12 h, high serum sodium, elevated liver enzymes, and partial liver grafts [60,61]. Data analysis from the SRTR including 20 023 liver transplants from deceased donors identified several risk factors to have a significant impact on transplant outcomes: a donor age of >60 years, CVA as cause of death, nonheart-beating donor (NHBD) and split grafts, and cold ischemia time. Following analysis of this data, a donor risk index (DRI) was derived that correlated strongly with 1-year survival rates [62]. In March 2007, a Paris Consensus Meeting on Expanded Criteria Donors in Liver Transplantation was organized by the International Liver Transplantation Society (ILTS). Recommendations were formulated to define better which ECDs should be considered for transplantation, how they have to be managed, and in which candidates they should be transplanted to optimize scarce resource utilization [63].

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Figure 4.  Median age of deceased donors in Eurotransplant, 1990–2009.

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Heart

“Certainly it makes little sense to replace one diseased heart with another” is a well-known quote by DePasquale [64]. Forty years later, Wittwer et al. from the Cologne Heart Center (Germany) published an excellent review in this journal on the use of “marginal” heart donor grafts based on 25 years of experience [65]. The authors suggest a series of acceptance criteria for heart transplantation using marginal donors (Table 2), but emphasize that the decision making on whether a certain donor heart can be suitable for transplantation should be based on an individualized and recipient-oriented assessment, which is the responsibility of the transplanting physician, and which has to be based on a specific profile of risk factors and critical conditions of the particular recipient.

Table 2.   Acceptance criteria for heart transplantation using expanded donors, according to Wittwer et al. [65].
Age up to 65 years
Undersizing/oversizing by >20% body weight
Prolonged hospitalization
History of chest trauma
Open cardiac massage
Elevation of myocardial enzyme levels
Prolonged cardiopulmonary resuscitation (>5 min)
Transient hypotension (>30 min)
High-dose vasopressor requirement
Wall motion abnormalities by echocardiography
Long-distance procurement (>1000 miles)
Persistent conduction disturbances
Cold ischemia time up to 4–5 h
Bypassable one- or two-vessel disease
Correctable valvular dysfunction by echocardiography

Lung

Lung donor shortages, too, have resulted in the critical appraisal of deceased donor criteria in Europe and the gradual relaxation of once-strict guidelines. By necessity, most centers now routinely accept donors older than the original cut-off of 55 years, although concerns about reduced graft longevity have been raised. Recipients of lungs from older donors (up to 77 years of age), for example, show a higher incidence of the bronchiolitis obliterans syndrome (BOS) [66]. Nevertheless, an increasing number of centers will accept the lungs from donors in their seventies, as long as there are no other adverse features. In case of a younger donor, they will accept prolonged ischemia times and less optimal gas exchange, expecting the greater physiological reserve to allow recovery from ischemia–reperfusion injury [67]. In Europe, Belgium and Austria are currently taking the lead in offering deceased donor lungs for transplantation with respectively 14.0 and 13.9 lungs PMP, more than twice as high compared to US figures (see Fig. 1) [1]. The Leuven (Belgium) and Vienna (Austria) groups have published extensively on their experience with ECD lungs [68,69]. Meers et al. recently demonstrated in this journal that they could increase utilization rates of lung donors to 34.1% of all donors in their network of donor hospitals [68], which is significantly more than the average 25.3% in the Eurotransplant area or a 23% rate in North America [70]), and which resulted in doubling the number of transplants in their center. Successful techniques such as segmental resection, lobe transplantation, and pulmonary bipartitioning have been developed to transplant grafts from larger donors into smaller recipients [71]. The number of teams reporting successful transplantation of lungs from NHBDs, both controlled and uncontrolled, has increased over the past few years. Ex vivo perfusion for reconditioning of initially rejected donor lungs appears to be a promising development to increase the lung donor yield [69,72–74].

Nonheart-beating donation (NHBD), donation after euthanasia

Historically, Europe has been playing a pioneering role since the mid-1990s in elaborating the concept of “non-heart-beating donation (NHBD)” or “donation after cardiac death (DCD)” [75–77]. At the first international workshop on NHBD organized by Kootstra and his group in Maastricht in 1995, four NHBD types were categorized (Table 3) [78].

Table 3.   Maastricht categories of nonheart-beating donors [78].
Maastricht categoryDescription
IDead on arrival (uncontrolled)
IIUnsuccessful resuscitation (uncontrolled)
IIIAwaiting cardiac arrest (controlled)
IVCardiac arrest while brain death (uncontrolled)

Liberal use of kidneys from NHB donors may increase the number of organ donors by 2.5 to 4 times, which could be sufficient to reduce or even eliminate the waiting list for kidney transplantation [77]. Compared with brain-dead donors, organs from NHB donors inevitably sustain a period of warm ischemia from circulatory arrest until start of preservation, resulting in ischemic injury and a subsequent incidence of primary nonfunction (PNF) and delayed graft function (DGF). A number of studies have described good medium-term graft survival rates for NHBD kidney transplants, despite poorer initial function [79]. In a review by Kootstra et al., the authors conclude that, despite a significantly higher incidence of DGF in NHBD kidneys (20–80%) compared to the 20–30% in HBD kidneys, medium-term survival rates are similar in both groups [80]. Barlow et al., in a report on long-term results of 112 NHBD renal transplants, mostly from uncontrolled donor cases, compared with a matched group of 162 HBD transplants, conclude that, despite increased DGF and creatinine levels, survival rates between the two groups remain comparable after 15 years [81].

Figure 5 shows the number of NHBD in Europe PMP and as a percentage of total deceased donors in 2008, demonstrating a leading position of the Netherlands and the UK. But every coin has two sides: optimism over NHBD might give the false impression that this process could compensate for the dwindling supply of HB donor organs. This, however, is not the case, at least not in the Netherlands and the UK. Published NHS statistics show that the huge rise of NHBDs, from 73 in 2004–2005 to 200 in 2008–2009, has coincided with a marked fall in HBD (from 697 to 609). Moreover, the average HB donor provides some 3.4 organs, whereas on average, only 2.1 organs are transplanted from a NHBD. As a consequence, NHBD is more resource intensive than HBD as more retrievals will be required to produce the same number of organs [82]. Figure 6 illustrates an even more dramatic evolution in the Netherlands, with a 58.7% decrease in HB donation after starting a NHBD program. Interestingly, at least one study reports on significantly lower family refusal rates among NHBD families (4%) compared to 24% (< 0.01) among HBD families [83].

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Figure 5.  Nonheart-beating donors in different European countries – 2008.

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Figure 6.  The Netherlands: evolution of heart-beating versus nonheart-beating donation.

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Finally, a new category of NHBDs was recently introduced in Belgium: “NHBD after euthanasia” [84]. Since 2005 till 2007, at least four patients expressed their will to donate their organs after euthanasia (legalized in Belgium since 2002). After clinical diagnosis of cardiac arrest by a separate medical team, organ procurement resulted in eight kidneys, four livers, two pairs of lungs, and one pancreas (islets) available for transplantation, or an organ/donor yield of 4.25, which is superior to the average yield of 3.44 organs in this country (Fig. 7).

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Figure 7.  Transplanted organs/deceased donor in different European countries – 2008.

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Optimizing organ yield and quality by better clinical management and better organ preservation

  1. Top of page
  2. Summary
  3. Introduction
  4. Legislative measures
  5. Public campaigns to increase organ donation
  6. Optimizing the donation process: focus on Critical Care Units
  7. Expanded criteria donors, nonheart-beating donors
  8. Optimizing organ yield and quality by better clinical management and better organ preservation
  9. Transplantation techniques to maximize use of available organs
  10. Organ-allocation-related options to reduce organ discard rates and to improve transplant outcomes
  11. Summary
  12. Funding
  13. Acknowledgements
  14. References

Donor management

Innovations in the field of donor management and organ preservation may offer a realistic hope to improve both the quality and size of the currently insufficient organ supply. As shown in Fig. 7, the average number of organs recovered and transplanted per deceased donor in 28 European countries, based on 2008 Eurotransplant and Council of Europe data, varies between 4.06 in Switzerland and only 1.8 in Latvia [1,2]. These data show that a substantial increase in overall transplant rates could be achieved by just retrieving and transplanting all suitable organs from available donors. One of the suggested strategies involves maximizing the number of organs from the available pool of deceased donors by using donor management protocols that treat the profound physiological disturbances associated with brain death.

Although the basic science dissecting the complex processes of brain death and subsequent ischemia/reperfusion injury is marked by exciting discoveries, the clinical science investigating donor management and organ preservation has been rather sparse [85].

Brain death can be considered a physiologic, cellular, and molecular catastrophe, associated with ischemia/reperfusion injury [86] and known to evoke an inflammatory response leading to endothelial dysfunction and release of cytokines in the circulation [87]. Biological modulation of renal ischemia/reperfusion injury holds the potential to reduce the incidence of early graft dysfunction and to expand safely the donor pool with kidneys that may have suffered prolonged ischemic injury before organ recovery [88].

A landmark article published already in 1995 by the Papworth, UK group proves that optimizing donor cardiovascular performance has a tremendous impact on the viability of all transplantable organs [89]. Clinical donor management today focuses on achieving and maintaining normal hemodynamics, cardiac output, volume status, oxygenation, ventilation, electrolyte balance, acid base status, coagulation parameters, and normothermia. Table 4 summarizes these goals [90].

Table 4.   Deceased donor management goals, according to Dictus et al. [90].
MAP ≥60 mmHg
CVP 6–10 mmHg
LVEF ≥45%
Urinary output 1.0 ml/kg/h
Core body temperature ≥35 °C
Blood glucose 80–150 mg/dl
Sodium <150 mm
Hemoglobin ≥10 g/dl
Platelet count 50 000/mm3
INR ≤1.5

Keeping a balance between an adequate fluid resuscitation for optimal organ perfusion versus minimizing the extravascular lung water from overzealous fluid resuscitation is challenging and requires vigilance with invasive monitoring. Because of a disparity between right- and left-sided filling pressures after brain death, central venous pressure monitoring alone to guide fluid loading may be misleading and the use of a pulmonary artery catheter may be helpful in selected cases to monitor pressures and cardiac performance correctly [74,91]. Vasopressors and inotropes may help stabilize fluctuations in blood pressure to optimize organ perfusion with the lowest myocardial oxygen demand. In a randomized, open-label, multicenter controlled trial, Schnüelle et al. could demonstrate that pretreatment of brain-dead donors with a low-dose regimen of dopamine (4 μg/kg/min) significantly improved early graft function in kidney transplant recipients [92]. Damage of the hypothalamus and the pituitary gland during brain death results in decreased circulating levels of adrenocorticotrophic hormone, vasopressin, triiodothyronine, and thyroxine in animal models and brain-dead donors [93]. Attempts to reverse these brain death sequels by hormonal substitution therapy have been reported to be successful, both in animal studies and humans [94,95]. Since these initial observations, several other groups, ours included, have confirmed the beneficial effect of hormonal resuscitation [96–98]. Hormonal substitution therapies are now widely used as an essential component of successful donor management strategies.

Organ preservation

Maintaining organ viability after donation and until transplantation is key to optimal graft function and survival after transplantation. To date, static cold (ice) storage (CS) is the most widely used technique of preservation in daily clinical practice. The principle of CS preservation is based on suppression of cell metabolism and catabolic enzymes by hypothermia (4 °C). Cell metabolic rates are halved with each 10 °C drop in temperature [99]. In an excellent overview of principles, pathophysiological mechanisms and current techniques in abdominal organ preservation, Maathuis et al. question whether this method is able to prevent deterioration of organ quality in the present era of organ retrieval from older, more marginal and even NHBDs [100]. To improve organ viability further, a more dynamic preservation method is needed therefore the possibilities of machine perfusion (MP) are currently revisited. Since its clinical application by Belzer et al. in the late 1960s, retrospective studies have suggested that MP may result in better short-term outcome, with lower rates of DGF after transplantation of kidneys from standard and ECDs [101]. In an excellent state-of-the art overview, Taylor et al. list several benefits of MP over CS (Table 5) [102].

Table 5.   Anticipated/emerging benefits of hypothermic machine perfusion, according to Taylor et al. [102].
  1. DGF, delayed graft function; ECD, expanded criteria donor; NHBD, nonheart-beating donor; PNF, primary nonfunction.

1. Maintaining the patency of the vascular bed
2. Providing nutrients and low-demand oxygen to support reduced energy demands
3. Removal of metabolic by-products and toxins
4. Provision of access for administration of cytoprotective agents and/or immunomodulatory drugs
5. Better access for viability assessment and tissue matching
6. Facilitation of a change from emergency to elective scheduled surgery with reduced costs and improved outcomes
7. Improved clinical outcomes as demonstrated by reduced PNF and DGF parameters
8. Improved stabilization or rescue of ECD kidneys or organs from NHBD that increase the size of the donor pool
9. Significant economic benefit for transplant centers and reduced health care expenditures

Only recently, an international, randomized, controlled trial was organized by Eurotransplant to compare CS with MP in 672 kidneys from 336 consecutive donors [103]. This Machine Perfusion Trial (MPT) demonstrated that MP reduced the incidence and duration of DGF and that machine-perfused renal allografts had an improved 1-year graft survival as compared with CS kidneys. Groen et al. could demonstrate that MP results in more life-years and quality adjusted life-years, reduced costs, and more favorable cost-effectiveness and cost-utility compared with CS [104]. Outcome data from this same MPT have been used also to conduct a comparative cost-effectiveness analysis based on preservation method for both standard criteria and ECD kidney transplants in the United States [105]. At 1-year post-transplant, machine perfusion was a more cost-effective option than cold storage for organ preservation in transplants involving either standard or ECD kidneys. Moreover, the cost-effectiveness ratios for transplants involving MP ECD kidneys were similar to those for transplants using CS standard criteria kidneys.

Since the mid-1990s, the Maastricht group and others have suggested intravascular resistance measurement and glutathione s-transferase release in the MP perfusate as kidney-viability testing tools [77,106], yet their use is limited, and their role in predicting kidney in vivo function and transplant outcome remains controversial.

True resuscitation, viability testing, and active biological modulation of an ischemically compromised graft may require not just oxygen and substrates offered by MP but also normothermia. Several European teams are actively exploring this technically challenging but potentially more effective new approach for kidney [107], liver [108,109], and lung [72,110,111] preservation. Normothermic MP is definitely much more than an alternative preservation method. It may be the storage method of choice in the future, not only because it is a superior method of preservation, but also because of its potential of resuscitation and prediction of post-transplant function.

Transplantation techniques to maximize use of available organs

  1. Top of page
  2. Summary
  3. Introduction
  4. Legislative measures
  5. Public campaigns to increase organ donation
  6. Optimizing the donation process: focus on Critical Care Units
  7. Expanded criteria donors, nonheart-beating donors
  8. Optimizing organ yield and quality by better clinical management and better organ preservation
  9. Transplantation techniques to maximize use of available organs
  10. Organ-allocation-related options to reduce organ discard rates and to improve transplant outcomes
  11. Summary
  12. Funding
  13. Acknowledgements
  14. References

Split liver transplantation

To expand the donor pool, the surgical technique of reduced liver transplantation first performed in 1984 [112] was modified to allow the transplantation of two recipients with one donor organ. For this purpose, the liver was divided into a left lateral lobe graft (segment II, III) typically for a pediatric and a remnant extended right lobe graft (segment I, IV–VIII) suitable for the transplantation of an adult recipient [113,114]. Besides this classical asymmetric split in later years, techniques for separating the liver into a full left lobe [segment (II–IV or I–IV)] and a full right lobe (segment I, VI–VIII or IV–VIII) were developed to serve two adult recipients with one donor liver (symmetric, true or full split technique) [115,116].

Two approaches are available to generate split-liver allografts: the ex vivo technique, in which the organ is removed from the donor and divided on the back table after the organ has been flushed and cooled, and the in situ technique, in which the dissection and parenchymal division is performed in the donor while the organs are still being perfused. In situ splitting has the advantage of avoiding prolonged cold ischemia time and rewarming during the bench procedure typical for ex vivo splitting [117].

Complications after split-liver transplantation (SLT) are in general similar to those of whole-organ liver transplantation with a slightly elevated rate of bile leaks [117,118]. Another typical complication that occurs more frequently with split grafts is the small-for-size syndrome (SFSS) [119].

In the early reports, results of split liver transplantation were poor [120], but meanwhile several reports of larger series of classical split liver transplants [121–124] including matched pair analyses [125] show comparable results of classical split and whole liver transplantation. Prerequisite for achieving these good results is careful donor and recipient selection and sufficient experience in split liver transplantation. Data on the short- and long-term results of true split transplants are sparse, but show that with highly selected donors acceptable short- and long-term results can be achieved [126].

Although split liver transplantation remains infrequent in the adult population, with only about 7.2% of all deceased donor liver transplants in 2009 in the Eurotransplant countries [9], it has become an increasingly frequent procedure in the young pediatric population, accounting for almost a third of all transplants in this recipient group [123]. If all suitable donor organs were split, waiting time for pediatric patients would substantially decrease [127] and thereby the need for performing living related liver transplants would be reduced significantly.

Single lung versus bilateral lung transplantation

Since the late 1980s, single lung transplantations (SLT) were successfully performed as an alternative procedure to bilateral lung transplantation (BLT) [128]. Typically, SLT is performed in patients with a diagnosis of either chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF). An argument in favor of single-lung transplantation are some reports showing perioperative and early postoperative survival advantage of single versus double lung transplantation [129,130]. More recent data indicate that with increased experience in the management of recipient in the early phase after lung transplantation, the perioperative risk is similar for SLT and BLT. Today, long-term survival is substantially better in double lung transplant recipients and BOS develops less frequently in these patients [131–133]. This has resulted in an ethical dilemma of either using one donor for a BLT transplanting only one patient or performing two SLT helping two patients with on the other hand reduced long-term outcome. In view of the current donor shortage, some authors still advocate SLT, especially for patients with IPF [134], others are more reserved and either rather recommend BLT (especially for patients with COPD) [131] or suggest to conduct a randomized trial to identify the optimal treatment strategy for these patient groups [133]. In clinical reality a continuous shift toward BLT has already taken place over the last years [135]. Nevertheless, SLT can still be considered a valuable option for selected recipients and in situations where only one lung of a donor is suitable for transplantation.

Domino transplantation

The use of explanted livers for transplantation from patients who themselves underwent liver transplantation was first performed in Portugal in 1995 [136]. This technique has been named “domino liver transplantation (DLT)” and can be considered in patients with selected genetic or biochemical disorders. The liver must be fully functional and the genetic defect should recur in the recipient with a sufficient latency period [137]. The classical indication fulfilling these criteria is familial amyloidotic polyneuropathy (FAP) [138].

Domino liver transplantation is justified for patients who have a live expectancy that is shorter than the time needed to develop disease symptoms, either due to their age or the underlying disease. Therefore, the procedure is typically performed in recipients older than 60 years or with malignancies such as hepatocellular carcinoma [139]. The Familial Amyloidotic World Transplant Register (FAPWTR) and the Domino Liver World Transplant Register (DLTR) are two registers containing data on transplanted FAP patients and on domino liver transplant recipients. As of 31.12.2009, a total of 790 DLT have been registered, the largest number (371) of this type of transplants has been performed in Portugal. DLTR data on survival and cause of death of domino liver transplant recipients show results comparable with other deceased donor liver transplants, especially when taking into account the recipient age and the underlying diseases of the recipients [139]. The procedure does not add any additional risk to the donor as compared with the risk of a conventionally performed transplantation.

In summary, the domino liver procedure has become a useful tool to increase the supply of livers available for transplantation especially in areas where FAP is endemic like Portugal.

Organ-allocation-related options to reduce organ discard rates and to improve transplant outcomes

  1. Top of page
  2. Summary
  3. Introduction
  4. Legislative measures
  5. Public campaigns to increase organ donation
  6. Optimizing the donation process: focus on Critical Care Units
  7. Expanded criteria donors, nonheart-beating donors
  8. Optimizing organ yield and quality by better clinical management and better organ preservation
  9. Transplantation techniques to maximize use of available organs
  10. Organ-allocation-related options to reduce organ discard rates and to improve transplant outcomes
  11. Summary
  12. Funding
  13. Acknowledgements
  14. References

As described in chapter 4, the disparity between organ availability and the growing demand for transplantation has motivated most organ procurement organizations to broaden the strict criteria for organ reporting to the transplant programs. Older donors and other extended criteria donors are therefore offered more often to the transplant centers now. In fact, the most rapid numerical increase in donation during the last decade has been in ECD, both in the Eurotransplant countries and in the US [140]. This worsening of the donor profile raises the pressure on organ allocation organizations to minimize the organ discard rates. Unfortunately, reliable data on the organ discard rates in the different European countries are not available. Figure 8 depicts the transplant realization rate for all organs reported to Eurotransplant in 2006, showing the fraction of all reported organs that were offered and accepted as well as those that were finally transplanted. Discard rates vary substantially from organ to organ and are the highest for pancreas. Experiences in the US suggest that with the increased reporting of organs form ECD, discard rates tend to increase [141]. Several modified allocation protocols established by the different European organ exchange organizations (EOEO) aim at reducing this discard rate:

image

Figure 8.  Organ transplant realization rate: Organs offered, accepted and transplanted as fraction of all reported deceased donor organs – Eurotransplant 2006.

Download figure to PowerPoint

By introducing and documenting detailed donor-specific recipient profiles, it is possible to offer donor organs from ECD only to those recipients who are suitable for these donor organs and have previously indicated to be willing to accept these organs. This approach will be the more successful, the larger the potential recipient pool. Therefore, structured regional and national organ sharing has been established that aims at allocating organs that would otherwise be discarded, because no suitable recipient could be found in the donor center or region. The SITF Project (Innovative strategies to expand cadaveric donor pool for liver transplantation), a network between Italian transplantation centers to improve the use of split livers is an example of such cooperation [142]. In fact, the previously described Eurotransplant Senior Program for the allocation of kidneys of donors older than 65 years to recipients older than 65 years can be regarded as a large-scale approach to match ECD organs to suitable recipients better.

Another option to prevent discarding suitable donor organs is the establishment of a rescue allocation policy. In the Eurotransplant countries, allocation can be switched from the classical patient-oriented scheme to rescue allocation in case of impending organ loss due to either donor instability or difficulty to allocate the donor organ based on medical reasons related to the donor. In practice, rescue allocation is started if an organ offer has been turned down three times (five times for kidneys) from different transplant centers for donor or organ quality reasons. The major feature of this rescue allocation policy is that the offers are no longer made to individual patients but to the transplant center, where any listed recipient can be selected from the local waiting list [143,144]. Obviously, such a rescue allocation policy is of special relevance for organizations with otherwise patient-oriented organ allocation. This rescue allocation policy turned out to be quite effective, more than 50% of the ECD organs that had been turned down several times by different transplant centers could ultimately be allocated successfully and were used for transplantation [144].

The exchange of organs is often not limited to organs that would otherwise be discarded. In most countries, rules for mandatory exchange between centers or regions are established to help special vulnerable patients groups like children, highly urgent or highly immunized patients. In addition, mandatory exchange targets at achieving optimal donor and recipient matching to improve long-term outcome of organ transplantation. HLA-matching, has a significant influence on kidney graft survival [145–150], therefore the achievement of an optimal HLA-compatibility between donor and recipient has traditionally been an aim of organ exchange organizations.

These benefits of cooperation (Table 6) within a country can be further enhanced if the exchange of organs is extended beyond country borders. The most prevalent type of international cooperation between the different countries and their organ exchange organizations is based on the principles of the above described rescue allocation policy. Most EOEOs have agreed upon a loose form of cooperation to facilitate exchange of otherwise lost organs even across borders. In case an organ can not be allocated within the area of an EOEO, the donor organ is offered to other neighboring organizations. Allocation follows the first come first serve principle, the OEO transplant center that accepts the donor organ first, receives first the organ for transplantation.

Table 6.   Benefits of international cooperation in organ transplantation.
Preventing organ loss
Addressing the needs of special patient groups
Improving the outcome of organ transplantation
International harmonization of activities in organ donation and transplantation
Scientific cooperation in the area of transplantation

In some European areas, a more structured international cooperation has been developed with the establishment of multinational EOEOs: England, Scotland, Wales, and Northern Ireland cooperate in what was formally known as “UK-Transplant” [now part of National Health Service Blood and Transplant (NHSBT)]. Denmark, Finland, Iceland, Norway, and Sweden participate in Scandiatransplant [151], an organization established in 1969, and Austria, Belgium, Croatia, Germany, Luxemburg, the Netherlands, and Slovenia are linked together via Eurotransplant, an organization founded in 1967. Within each of these different multinational EOEOs, rules for mandatory organ exchange have been developed to address the needs of special patient groups and to improve transplant outcome [152]. The Eurotransplant kidney allocation system (ETKAS) goes even a step further with the establishment of a common multinational waiting list for patients from all participating countries [153]. Due to this international cooperation, the median waiting time of highly urgent liver transplant recipients can be kept as low as 2 days in the Eurotransplant area and full HLA-A,B,DR-matching can be achieved in more than 20% of the kidney recipients receiving their organ via standard allocation. To prevent an unacceptable mismatch in organ exchange between the countries of such a multinational organ exchange organization that could easily result in case of different organ donation rates per country, specific balancing rules between the countries are typically established.

With the implementation of the EU Directive on standards of quality and safety of human organs intended for transplantation, it is expected that the different forms of international organ exchange (Table 7) will be further facilitated with increasing donor quality and safety resulting from clearly defined standards for organ characterization on the one hand and an international cooperation for organ vigilance on the other hand.

Table 7.   Levels of international cooperation in organ transplantation.
No cooperation – isolation
Exchange of organs in case there is no suitable recipient in the donor country
Cooperation for special patient groups
 Optional organ exchange
 Mandatory organ exchange
Common waiting list with harmonized allocation rules
 With national balancing rules
 Without national balancing rules

Summary

  1. Top of page
  2. Summary
  3. Introduction
  4. Legislative measures
  5. Public campaigns to increase organ donation
  6. Optimizing the donation process: focus on Critical Care Units
  7. Expanded criteria donors, nonheart-beating donors
  8. Optimizing organ yield and quality by better clinical management and better organ preservation
  9. Transplantation techniques to maximize use of available organs
  10. Organ-allocation-related options to reduce organ discard rates and to improve transplant outcomes
  11. Summary
  12. Funding
  13. Acknowledgements
  14. References

Professionalization of donor identification and management including the establishment of in-house transplant coordinators is currently considered in most European countries the most promising approach for further fostering organ donation and transplantation. The careful evaluation and broader use of extended criteria donors like older donors and nonheart beating donors together with tailored allocation mechanisms including international cooperation have in the past years resulted in a substantial increase in the donor pool and will contribute also in the future to address the organ need. The most controversial and emotionally discussed approach at least for countries with an informed consent system is a change in legislation with the move towards a presumed consent system. Available evidence shows that such a change has a positive albeit limited effect on organ availability. Perhaps the biggest risk associated with this approach is that it could distract discussion and efforts from the other well defined measures to improve organ donation. Therefore, it is important to keep in mind that any legal environment – whether based on presumed, informed or explicit consent – that shifts the burden of a decision on donation from grieving relatives to the deceased himself will most probably be an efficient one.

Funding

  1. Top of page
  2. Summary
  3. Introduction
  4. Legislative measures
  5. Public campaigns to increase organ donation
  6. Optimizing the donation process: focus on Critical Care Units
  7. Expanded criteria donors, nonheart-beating donors
  8. Optimizing organ yield and quality by better clinical management and better organ preservation
  9. Transplantation techniques to maximize use of available organs
  10. Organ-allocation-related options to reduce organ discard rates and to improve transplant outcomes
  11. Summary
  12. Funding
  13. Acknowledgements
  14. References

The authors have declared no personal funding. The Donor Action Foundation is currently co-funded by the European Commission (contract nr. 2009 11 10, SOHOV&S Project), Astellas Pharma Europe Ltd, (UK), Novartis Pharma AG (Basel, Switzerland), Bristol-Myers Squibb (Braine-l’Alleud, Belgium), Genzyme Europe BV (Naarden, The Netherlands), Dr Franz Koehler Chemie GmbH (Germany), Institut Georges Lopez (St.-Didier-au-Mont-d’Or, France) and Organ Recovery Systems (Zaventem, Belgium).

Acknowledgements

  1. Top of page
  2. Summary
  3. Introduction
  4. Legislative measures
  5. Public campaigns to increase organ donation
  6. Optimizing the donation process: focus on Critical Care Units
  7. Expanded criteria donors, nonheart-beating donors
  8. Optimizing organ yield and quality by better clinical management and better organ preservation
  9. Transplantation techniques to maximize use of available organs
  10. Organ-allocation-related options to reduce organ discard rates and to improve transplant outcomes
  11. Summary
  12. Funding
  13. Acknowledgements
  14. References

We thank following colleagues for their invaluable comments and/or providing us with us with information on their country’s application of presumed consent laws: Danica Avsec-Letonja (Slovenia), Mirela Busic (Croatia), Leen Coene (Belgium), Bernard Cohen (The Netherlands), Jonathan Cohen (Israel), Peter Desatnik (Sweden), Beatriz Dominguez-Gil (Spain), Claudia Ferraro (Italy), Krister Hoeckerstedt (Finland), Karim Laouabdia (France), Dariusz Patrzalek (Poland), Lorenza Ridolfi (Italy).

References

  1. Top of page
  2. Summary
  3. Introduction
  4. Legislative measures
  5. Public campaigns to increase organ donation
  6. Optimizing the donation process: focus on Critical Care Units
  7. Expanded criteria donors, nonheart-beating donors
  8. Optimizing organ yield and quality by better clinical management and better organ preservation
  9. Transplantation techniques to maximize use of available organs
  10. Organ-allocation-related options to reduce organ discard rates and to improve transplant outcomes
  11. Summary
  12. Funding
  13. Acknowledgements
  14. References