Optimizing Cadaveric Organ Procurement: the Catalan and Spanish Experience

Authors


*Corresponding author: J. M. Grinyó, grinyo@ibernet.com

Abstract

The need to face the increasing gap between the supply and the demand of transplants has led to the development of a permanent network of trained medical staff responsible for the organ donation and removal process in all centers accredited for that process. In Spain, this activity received a specific budget, like any other medical activity in hospitals, and the responsible staff became accountable for performance. This system dramatically increased the number of potential donors referred, not only young donors with trauma, but also elderly donors dying from stroke. The effect was that the donation rate increased by more than 100% in 10 years (from 14 to 34 donors per million population). Consequently, so did all the transplant figures. In some areas, such as Catalonia, it has been demonstrated that sustained kidney transplant activity of over 60 procedures per million population can maintain or slightly decrease the waiting list, despite increasing incidence and prevalence of end-stage renal failure. Quality monitoring of the donation and retrieval process shows that there are still opportunities for improvement if all potential donors are referred and all technical problems are overcome. Living donation and nonheart beating organ retrieval should also be promoted.

Introduction/Historical Background

The success of organ transplantation has led to an big increase in the number of patients admitted to the waiting lists in recent years. However, organ donor rates, and hence transplantation probabilities, have remained unchanged or slightly increased. Despite all the advantages of organ transplantation, many patients cannot benefit from such therapy. The improvement in the number of available organs for transplantation is a permanent challenge for health-care organizations all around the world (1–3). Indications for transplantation have risen much more than the number of grafts. This gap is much higher in the USA than in the European countries (Tables 1 and 2) (4,5).

Table 1.  Kidney transplants (annual absolute number) and waiting list patients (absolute number on the 31st December) (Tx/Wl)
 Million inhabitants*198919942001
  1. *Population is referred to 2002.

  2. (*)Eurotransplant: Germany, Austria, Belgium, Netherlands and Luxemburg

France 601.957/4.603 1.627/4.516 2.022/5.124
Eurotransplant (*)116.953.172/9.445 3.165/12.849 3.640/12.343
SkandiaTransplant 24.03  854/926  898/944  848/1.513
UK + Ireland 62.81.960/3.704 1.882/4.970 1.806/6.449
Spain 41.81.039/5.024 1.633/4.621 1.924/4.014
USA2688.988/16.29411.391/27.49814.152/52.216
Table 2.  Liver transplants (annual absolute number) and waiting list patients (absolute number on the 31st December) (Tx/Wl)
 Million inhabitants*198919942001
  1. *Population is referred to 2002.

  2. (*)Eurotransplant: Germany, Austria, Belgium, Netherlands and Luxemburg

  3. (**)SkandiaTransplant: Norway, Danmark, Sweden, Finland and Iceland.

France 60  585/183  621/359  803/457
Eurotransplant (*)116.95  499/180  916/2161.193/1.089
SkandiaTransplant (**) 24.03  65/21  183/26  209/45
UK + Ireland 62.8  298/51  644/115  700/180
Spain 41.8  170/90  614/218  972/522
USA2682.201/8273.652/4.0595.177/17.641

In Spain, kidney transplant activity was very low in the late seventies, with only 8 renal transplants per million population (pmp) per year. In 1979, transplant law was enacted to improve transplant activity. In addition to the new legal framework, in some areas the responsible health-care units designed a full approach to an integrated treatment for end-stage renal patients. This approach represented a very useful tool to regulate transplant activity, ensuring patients access to the waiting list. This was the case in Catalonia, when in 1982 the Chronic Renal Failure Care Program was created. This program worked with advisory groups, involving doctors and health care managers, formulating common criteria for the care of end-stage renal failure patients. The Kidney Patients' Catalan Registry, which is a mandatory registry for all renal units, was created. At the same time, a public education program in the field of organ donation and transplantation was promoted. Following all these measures, kidney transplant activity increased dramatically during the eighties, and liver and heart transplant programs were started.

During the late seventies, most European and North American countries developed organ exchange organizations, with the aim of creating a system for waiting list management, allocation of organs and data registry analysis. This approach was followed in some areas, such as Catalonia and the Basque Country, but not in other Spanish regions. After a maximum organ donation level of 16 donors pmp in 1986, donation and transplantation figures decreased by more than 20% during 1987 and were maintained at these low levels during 1988 and 1989. This led to exponential growth of the kidney waiting list. As a consequence, a complaint was lodged with the kidney patients' associations, and the Ombudsman intervened. This, together with the increasing complexity of heart and liver transplant procedures, waiting list management and other organizational problems, led the Health Ministry to set up the National Transplant Organization (ONT) at the end of 1989, with the main commitment to increase organ donation and transplantation rates.

The Organizational System

Spain is a European Union country with 41.8 million inhabitants living in 17 autonomous regions. The National Health System comprises all facilities and public services devoted to health, and is organized into 17 Health Services. Today, public health care is available for 99.5% of the population, with the health budget being 6.4% of gross domestic product (GDP). Health counselors from each autonomous region, together with the State Minister for Health, comprise the Interregional Council for the National Health System. This council has several permanent working groups, one of those being the Transplant Working Group. This group is in charge of the coordination, design and implementation of transplant policies in the whole country.

Spanish transplant law is very similar to the corresponding laws in other Western countries. Although the law on transplant presumes consent, according to a subsequent decree relatives of a potential donor must be approached to determine the deceased's wishes regarding organ donation. In the absence of this knowledge, close relatives can sign the authorization, after internal discussion if required. At present, the annual refusal rate for organ donation is around 20–23% of all donation interviews. Death is defined as the total and irreversible cessation of brain or cardio-respiratory functions. Clinical evaluation and complimentary tests required are detailed within the legal text allowing organ retrieval either from brain-stem death donors or from non-heart-beating donors (6).

Like other coordinating systems worldwide, the Spanish system has to monitor the management of waiting lists, organ allocation, and statistical analysis. Nevertheless, it was considered that a continuous monitoring system over the entire organ donation process was essential. A network of health-care professionals responsible for the organ donation process as a whole has been set up at all levels (national, regional and hospital). This implies the need for training, organization and coordination of activities (7,8).

It was considered that these professionals working at the grass roots level must feel involved and that they must be accountable for performance. Most of them are physicians, mainly intensive care unit (ICU) specialists, and they belong to the staff of the hospital. They generally continue in their medical role, but as transplant coordinators their main objective is to improve the organ donation rate. Currently, 143 hospitals are officially authorized to take care of organ donor programs. A quality control system has been developed for the organ donor process – the ICU mortality registry and the brain death registry – a common practice in most of them (9). By law (RD 2070, 30 December 1999), transplant coordinators are the professionals responsible for the whole donation and retrieval process.

National and regional offices are service agencies supporting the organ donation and transplantation programs. They deal with organ sharing and waiting list management. They arrange organ or team shifts. They are responsible for the official statistics and reports on organ donation and transplantation. They promote legal statements and binding consensus guidelines. They also promote public education and address any doubt or question about organ donation and transplantation. A 24-h hot line and E-mail system have been put in place to keep all interested groups or individuals informed. They are also concerned with and involved in training and research programs. Any activity that could improve donation or facilitate the transplant team activities can be promoted through this network.

Organ transplantation has been considered to be a hospital medical activity for which a specific budget and personnel are allocated. This kind of activity can never be an economic overload for the hospital. The annual general budget for transplantation procedures in Spain is around 180 million Euros. The annual budget for the organ procurement network is around 15 million Euros (less than 10% of the budget covering organ procurement activities). This donation budget covers all extra-salary and extra-time activities of both coordinators and surgical retrieval teams, as well as any donor evaluation tests, the ICU bed daily costs, etc. This economic figure also covers coordinating offices, training courses and some of the educational programs. The payment model for the extra work of coordinating and organ retrieval for the professionals on call differs depending on the region. It can be a fixed amount, based on the registered activity, or a mixed system (it does not usually exceed 30% of the total salary).

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Organ Donation and Transplantation Evolution in Spain (10)

Since this basic network of transplant coordination was started in Spain, the number of solid organ donors has increased steadily. The average current organ donor annual rate is nearly 34 donors pmp (Figure 1), almost double the rate in the average European country. However, the number of organs retrieved and transplanted per donor did not increase. It was increasing during the nineties up to 2.8 organs grafted per donor, but has decreased today to 2.6 organs grafted per donor. This is a result of the change in the donor profile (Figures 2 and 3) (10). Mean donor age has increased by more than 10 years since 1992. Currently, more than 34% of our donors are over 60 years of age and more than 11% over 70 years of age. Ten years ago, most of our donors died due to cranial trauma, and today only 17% of our organ donors die in motor vehicle accidents. During the same period in the USA, the percentage of cadaver donors over 65 years of age rose only from 4% to 8.3%, and the percentage of donors who died due to cranial trauma remained stable at around 40% (4).

Figure 1.

Organ donors in Spain: evolution of the number and rate per million population (1989–2002) (10).

Figure 2.

Organ donors in Spain: evolution of the different groups of age (1992–2002) (10).

Figure 3.

Organ donors in Spain: cause of death (1992–2002) (10).

What the coordinating network has done is to dramatically increase the number of potential referred donors from all hospitals: not only big reference centers, but also small hospitals without neurosurgery facilities; and not only young donors from trauma, but also older donors who died from cerebrovascular accidents.

As a result, the organ donation rate (donors from whom at least one solid organ has been grafted) is around 30 pmp. The percentage of discarded kidneys has remained stable in the last 3 years – it varies around 22% (Table 3). There are an important number of donors (between 140 and 160) from whom both kidneys are discarded, but the liver is effectively grafted (11). In less than 5% of all discarded kidneys, the reason for discarding is related to technical problems that could have been avoided. The main reasons for discarding kidneys are related to glomerular sclerosis (16%), atheromatosis (16%) or malignancies (12%). The older the donor, the higher the percentage of discarded kidneys (39% from donors between 60 and 69 and 56% from donors over 70 years). Twenty per cent and 6% of all effective kidney donors had hypertension or diabetes, respectively (11). Organs procured from those older donors are associated with worse graft survival and they are therefore labeled as ‘marginal’ or ‘expanded’ donors. A higher percentage of discarded kidneys among those expanded donors has been reported (12). However, it has also been underlined that what is important is to refer all potential donors and to identify donor factors associated with graft failure. This analysis will help to optimize the utilization of retrieved kidneys. It is definitely better to discard after careful examination than not to have any possibility since the potential donor has been previously discarded. It has been reported that even kidneys with more than 20% glomerular sclerosis can be safety and effectively grafted into selected patients (13). Reduced ischemia times or HLA match improvement can improve graft outcomes of the so-called expanded donor kidneys (12). Besides, many patients are ready to accept such organs if it reduces the time on the waiting list. Even transplantation of expanded donor kidneys may provide acceptable survival rates over maintenance on dialysis (14).

Table 3.  Organ donors – efficient donors and kidneys reviewed and grafted in Spain 1998–2001 (10)
 19981999200020012002
Million population39.639.639.641.214.8
Organ donors (OD)12501334134513351409
Efficient OD11621217121412001267
Organ donors pmp31.533.133.932533.7
Efficient OD pmp29.330.730.629.230.3
Kidneys retrieved24312587255025172660
Kidneys grafted20162049198219502059
Kidneys discarded415538568567601
% of discarded kidneys1720.72222.522.5

The critical shortage of organs and the morbidity and mortality in patients who await transplantation have also mandated careful reconsideration of other potential donors who are not ideal candidates due to positive serology or a history of malignancy. Transplantation of livers and kidneys with positive hepatitis C virus (HCV) and hepatitis B virus (HBV) serologic tests into recipients with appropriate serological and viral profile has been accepted by some transplant teams. However, in many instances organs with positive viral markers are discarded due to the lack of adequate recipients (11).

The use of organs from donors with malignancies has been precluded by international bodies (15). In less than 1% of all potential donors referred after the medical evaluation, we discovered the presence of an unknown malignancy during the surgical procedure in some of the retrieved organs (10). In this situation, usually all organs are discarded. However, the decision to use or not to use organs of such donors should be based upon the known biological behavior of those tumors, always keeping in mind the benefit not only for individuals but also for the entire waiting transplant community (16).

The evolution of the Spanish transplantation figures, as a consequence of the increase in the organ donor rates, is shown in Table 4.

Table 4.  Transplantation activity in Spain.
 1990199119921993199419951996199719981999200020012002
Cadaveric donors6817788328699601.0371.0321.1551.2501.3341.3451.3351411
pmp17,720.221.722.6252726.82931.533.633.932.533.7
% Multiorgan donors51%64%69%70.5%77%83%79.5%82.3%84.5%85.3%83%84% 
Cadaveric kidney transplants122413551477147316131.7651.6851.8411.9772.0061.9191.8931998
pmp31.835.238.438.4424643.846.449.850.648.446.047.8
Living related kidney transplants16161515203522201917193134
pmp0.40.40.40.40.50.90.60.50.50.40.50.80.8
Liver transplants3134124684956146987007908999609549721.033
pmp8.110.712.1131618.118.22022.624.224.123.624.7
Heart transplants164232254287292278282318349336353341310
pmp4.666.67.57.67.27.388.88.58.98.37.4
Heart-lung transplants421 174546
Single lung-double lung transplants231016+417+1917+2827+4926+8226+10240+9547+9138+10538+123
pmp   0.50.91.11.72.73.23.43.53.53.8
Pancreas transplants19212624162424272825486069
pmp0.50.50.70.60.40.60.60.60.70.61.21.51.6

The mandatory Renal Registry in Catalonia offers the opportunity to review the evolution of the integrated treatment of end-stage renal failure in our country.

The Catalan Experience on Renal Transplantation (17)

The incidence and prevalence of end-stage renal disease in Catalonia has gradually increased in the last decade (Figure 4). Catalonia with 6.5 million inhabitants is particularly active in organ procurement. The donation rate is consistently over 40 donors pmp and the annual cadaver kidney transplant rate is around 60 pmp. The organ donor profile has changed in Catalonia in the same way as in the whole Spanish state. At the same time, the recipient profile also changed. In the middle eighties, only 8% of the recipients were over 55 years of age. Today, more than 30% are older than 60 years of age, with 7% being older than age 70.

Figure 4.

Evolution of the incidence and prevalence rates of end-stage renal disease in Catalonia. Data are expressed in rates (17).

Recipients are selected from among those admitted to the local waiting list, depending on HLA matching and other medical conditions such as serological status, and primary disease (young diabetic patients, oxalosis, etc.). Pre-emptive transplantation is available for pediatric patients and in some adult units, where it accounts for around 10% of the activity.

At the end of 2001, 2838 patients with functioning kidney grafts were registered. Since 1990, some data have substantially changed. Donors and recipients have become older. In recent years, the trend has been to establish parity between donor and recipient age. Older organs are usually allocated to elderly recipients (20% of all grafts are the result of pairs of donors and recipients older than 60 years) (Figure 5). Both donor and recipient age are independent predictors of graft survival (Table 5). As expected, advanced donor and recipient ages entail an increased risk of graft failure. However, despite the reduced graft survival rates, the use of organs from older donors may have helped to stabilize or slightly decrease the number of patients on the waiting list despite an increasing incidence of end-stage renal disease in Catalonia. Besides, overall results are not worse than in previous periods: 5-year graft survivals between 1990 and 1995 and between 1996 and 2001 were 70% and 72%, respectively.

Figure 5.

Pairs of donors and recipients depending on their age (17).

Table 5.  Risk factors and graft survival rates in cadaver renal transplants in Catalonia (1990–2001; n = 4008) (Cox multivariate analysis) (17)
FactorN1-y survival5-y survivalRR
  1. Only factors showing RR over 1.4 or under 0.8 are shown.

Recipient's age (years)
 15–5425800.890.751
 >64 3550.790.551.59
Donor's age (years)
 <20 5120.880.801.
 40–49 5980.890.761.46
 50–59 7270.860.691.85
 60–69 5010.840.572.28
 >69 2030.800.502.61
DR matching
 0 4750.830.661
 124910.870.720.8
 2 6720.910.740.72
Period    
 1990–9723130.850.701
 1998–200113380.910.54
Chronic respiratory disease 2130.800.581.42

Opportunities for Improvement

Several alternatives have been proposed to bridge the gap between the supply of and the demand for organs (18). Improvement in the overall survival rates will reduce the need for second or third grafts, thus reducing the waiting lists. It must be emphasized that more than 20% of the kidney waiting-list patients have been already been grafted previously (4,17).

During recent years, and because of scarcity of available organs, living donation interest has been renewed – not only kidneys, but livers, lungs or pancreas have been grafted from living donors (4). Kidney transplants from living related and unrelated donors have been shown to be highly successful (19). Living related liver transplant activity is also increasing world wide with good results (20). However, lung or pancreas living transplantation remains anecdotal (4).

Strikingly, less than 1% of all kidney transplant activity comes from living donors in Spain. However, living donation should be improved and offered as an alternative if requested by the patients. This strategy may be very helpful to shorten the waiting time, especially in the case of young recipients. In contrast, liver transplants from living donors increase every year. During 2002, liver living activity was greater than for renal (10).

However, there is still room for increasing cadaver transplant activity. It has been said that the potential for organ donation has never been reached anywhere. Many potential donors are being lost due to lack of referral, lack of evaluation, management failures, or refusal to donate (21).

Implementation of hospital-based programs designed to evaluate and monitor the potential for organ donation and its outcome, can actively contribute to implement change in donation practices and create appropriate educational strategies. Donor-Action has proven to contribute to sustained increases in the organ donation rates up to 30% (22). Those initiatives have also proven a very good cost-benefit approach for evaluating the investment of its implementation (23).

Theoretical and actual capacity of organ procurement can be determined after the analysis of the ICU deaths by means of the medical record review or an external audit or both combined.

The Quality Control Program implemented in Spain combines the continuous monitoring and recording of all ICU death outcomes together with periodic external audits. This approach has the advantage of detecting under- or over-estimations that could arise during the internal evaluation. Currently, not more than 50% of all encephalic deaths are being transformed into actual donors, as recorded in the continuous internal monitoring of the process in the ICUs. However, external audits demonstrate that probably up to 60% of all encephalic death cases could be effective donors. If every potential donor is referred, management problems are minimized and only correct medical contraindications are applied (Table 6) (10).

Table 6.  Quality control program on the donation and retrieval process in Spain
Quality Control Program Spain. Hospitals with neurosurgery facilities (1998–2000)Internal evaluationExternal evaluation
  1. Data corresponding to internal audits were recorded between 1998 and 2000. The corresponding 1-year confirmatory external evaluation was done for 17 units. Only data from hospitals with 24-h neurosurgery service (reference hospitals) are shown (10).

  2. ICU: Intensive care unit. ED: Encephalic deaths. ICUD: Intensive care unit deaths.

Controlled hospitals3717
ICU deaths (ICUD)21 9944821
ICU encephalic deaths (ED)3173755
% ED/ICU D14.4%16.2%
% Unreferred ED/Total ED1.6%3.3%
% Medical contraindications/ED28.2%25.3%
% Incorrect medical contraindications/ED0.4%4%
%Hemodynamic management problems/ED3.2%3%
%Avoidable hemodynamic management problems/ED0.2%0.7%
% Relatives' refusals/ED16.3%14.8%
% Coroner refusals/ED0.3%0.4%
% No legal diagnostic of ED/ED0.2%0%
% Lack of adequate recipient/ED0.7%0.5%
% Organizational problems/ED0.6%0.8%
% Actual donors/ED (Global Effectivity)48.9% 
% Possible actual donors/ED (Theoretical Global Effectivity) 59.7%

Non-heart beating donors are currently being considered as an alternative and complimentary source for organ retrieval (24). Many teams are working in this field with acceptable results (25) – not only kidneys, but also livers (Personal communication Mañez and Valdecasas, Spain), and more recently lungs (26), have been successfully grafted.

The main problem that limits further increases in organ donation rates is the lack of consent to donation. Refusal rates between 20 and 60% of all relatives' interviews are recorded every year in all countries. Family refusals in Spain have been maintained around 20–23% over all interviews during recent years (10). The range between regions varies from 10 to 40%. Many regions, mainly in the north and the Canary Islands, consistently record refusals between 10 and 15%. If 15% refusal was the rate all over the country, organ donation rates could increase up to 37 or 38 donors per million. Not only public education, but also improvements in hospital practices and communication skills are necessary to reduce these refusal rates (27). There is considerable debate between experts supporting the absolute necessity for strict presumed consent laws, and authors supporting consultation with the relatives (28). Strict presumed consent laws seem to be helpful when fully accepted but difficult to apply, mainly because of reluctance within the medical community and an important social rejection. It is advisable to ascertain the public and health professionals' opinions about presumed or informed consent for organ donation before promoting legal changes that might be potentially risky (29). General trust in the donation and transplant system is a cornerstone to improving the positive perception of the general population. The system must be transparent and equitable. The need to organize organ procurement and allocation in such a way is evident. However, there are no universally accepted rules (30). Organ allocation and waiting list management can be patient oriented, which is the case in the USA and some European countries, or center oriented, as is mainly the case in other European countries (e.g. Spain), with both advantages and disadvantages (31). Besides, several strategies to manage the enlarging waiting lists have been proposed (3,32). In any case, allocation rules must be public and periodically evaluated to monitor their efficacy.

The Council of Europe Committee of Ministers has published a recommendation for the proper management of waiting lists. It highlighted the need to set up a public system with an officially recognized network of transplant centers and an official registry of patients on waiting lists for the different organs. The committee also recommended that such a system should provide complete information for health care professionals and for the general public. This information set should include criteria for registration and allocation, numbers and flows of registered patients, and average waiting times for the different groups of patients. The system must ensure, as far as possible, that no group of patients waits longer than any other group (33).

Conclusions

There is an increasing gap between the supply of and the demand for organs for transplantation. Various alternatives have been proposed to increase the number of available organs, including living donation, non-heart-beating donors or expanding the criteria for organ donor acceptance. After the implementation of a network of trained professionals working in all hospitals authorized to procure organs, the number of organ donors rose dramatically in Spain. In 1989, the organ donor rate was 14 pmp, while in 2002 the recorded organ donor rate was close to 34 pmp. Obstacles such as non-referred donors, donor evaluation or donor management problems have been partially overcome. Nevertheless, it must be stressed that the top donation rate has not been reached, since there are still areas for improvement, and refusals can be reduced. At the same time criteria for accepting donors have changed substantially. However, the Catalan experience shows how it is possible to maintain very good results with the use of organs from older donors or the so-called expanded donors. In Catalonia, with such policy, the renal waiting list could be stabilized or slightly decreased with a sustained activity close to 60 renal transplants pmp, despite an increasing prevalence of end-stage renal failure.

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