Organ Donation in Croatia: The Importance of a National Champion, a Comprehensive Plan, and International Collaborations.

The Republic of Croatia is a global leader in organ donation and transplantation despite having fewer resources and more modest healthcare expenditures than other countries in the European Union. The results of an extensive literature review were combined with expert input in an iterative multi-step data collection and evaluation process designed to assess trends in Croatian organ donation and transplantation and identify key elements, policy changes, and drivers of the system that have contributed to its success. Multiple sources of evidence were used in this study, including primary documents, national and international transplantation reports, and insights from critical informants and content experts. The results highlight several key organizational reforms that have substantially improved the performance of the Croatian transplant program. Our findings emphasize the importance of strong central governance led by an empowered national clinical leader acting under the direct auspices of the Ministry of Health and a comprehensive and progressive national plan. The Croatian transplant system is notable for its integrated approach and efficient manner of managing scarce health resources. Collectively, the results suggest that Croatia has become nearly self-sufficient due to its systematic implementation of the guiding principles for organ donation and transplantation.

Factors influencing kidney transplantation rates: a study from the ERA Registry.

BACKGROUND: Large international differences exist in kidney transplantation (KT) rates. We aimed to investigate which factors may explain the total, deceased donor and living donor KT rates over the last decade. METHODS: KT experts from 39 European countries completed the Kidney Transplantation Rate Survey on measures and barriers and their potential effect on the KT rate in their country. In the analyses, countries were divided into low, middle and high KT rate countries based on the KT rate at the start of study period in 2010. RESULTS: Experts from low KT rate countries reported more frequently that they had taken measures regarding staff, equipment and facilities to increase the total KT rate compared with middle and high KT rate countries. For donor type-specific KT, the largest international differences in measures taken were reported for deceased donor KT, with middle and high KT rate countries taking more measures, such as the use of expanded criteria donor kidneys, the presence of transplantation coordinators and (inter)national exchange of donor kidneys. Once a measure was taken, experts' opinion on its success was similar across the low, middle and high KT rate countries. Experts from low KT rate countries more often reported potential barriers, such as patients' lack of knowledge and distrust in the healthcare system. CONCLUSIONS: Particularly in low KT rate countries, the KT rate might be stimulated by optimizing staff, equipment and facilities. In addition, all countries may benefit from measures specific to deceased and living donors.

The Reality of Inadequate Patient Care and the Need for a Global Action Framework in Organ Donation and Transplantation.

BACKGROUND: Transplant therapy is considered the best and often the only available treatment for thousands of patients with organ failure that results from communicable and noncommunicable diseases. The number of annual organ transplants is insufficient for the worldwide need. METHODS: We elaborate the proceedings of the workshop entitled "The Role of Science in the Development of International Standards of Organ Donation and Transplantation," organized by the Pontifical Academy of Sciences and cosponsored by the World Health Organization in June 2021. RESULTS: We detail the urgency and importance of achieving national self-sufficiency in organ transplantation as a public health priority and an important contributor to reaching relevant targets of the United Nations Agenda for Sustainable Development. It details the elements of a global action framework intended for countries at every level of economic development to facilitate either the establishment or enhancement of transplant activity. It sets forth a proposed plan, by addressing the technical considerations for developing and optimizing organ transplantation from both deceased and living organ donors and the regulatory oversight of practices. CONCLUSIONS: This document can be used in governmental and policy circles as a call to action and as a checklist for actions needed to enable organ transplantation as treatment for organ failure.

Access of non-residents to transplantation of deceased donor organs: practices and strategies in the European setting.

The access of non-resident patients to the deceased donor waiting list (DDWL) poses different challenges. The European Committee on Organ Transplantation of the Council of Europe (CD-P-TO) has studied this phenomenon in the European setting. A questionnaire was circulated among the Council of Europe member states to inquire about the criteria applied for non-residents to access their DDWL. Information was compiled from 28 countries. Less than 1% of recipients of deceased donor organs were non-residents. Two countries never allow non-residents to access the DDWL, four allow access without restrictions and 22 only under specific conditions. Of those, most give access to non-resident patients already in their jurisdictions who are in a situation of vulnerability (urgent life-threatening conditions). In addition, patients may be given access: (i) after assessment by a specific committee (four countries); (ii) within the framework of official cooperation agreements (15 countries); and (iii) after patients have officially lived in the country for a minimum length of time (eight countries). The ethical and legal implications of these policies are discussed. Countries should collect accurate information about residency status of waitlisted patients. Transparent criteria for the access of non-residents to DDWL should be clearly defined at national level.

Organ donation and transplantation: a multi-stakeholder call to action.

Although overall donation and transplantation activity is higher in Europe than on other continents, differences between European countries in almost every aspect of transplantation activity (for example, in the number of transplantations, the number of people with a functioning graft, in rates of living versus deceased donation, and in the use of expanded criteria donors) suggest that there is ample room for improvement. Herein we review the policy and clinical measures that should be considered to increase access to transplantation and improve post-transplantation outcomes. This Roadmap, generated by a group of major European stakeholders collaborating within a Thematic Network, presents an outline of the challenges to increasing transplantation rates and proposes 12 key areas along with specific measures that should be considered to promote transplantation. This framework can be adopted by countries and institutions that are interested in advancing transplantation, both within and outside the European Union. Within this framework, a priority ranking of initiatives is suggested that could serve as the basis for a new European Union Action Plan on Organ Donation and Transplantation.

The effect of differing kidney disease treatment modalities and organ donation and transplantation practices on health expenditure and patient outcomes.

The Effect of Differing Kidney Disease Treatment Modalities and Organ Donation and Transplantation Practices on Health Expenditure and Patient Outcomes (EDITH) aims to obtain information on long-term kidney transplant outcomes, long-term health outcomes of living kidney donors and detailed outcomes and costs related to the different treatment modalities of end-stage kidney disease. Nine partners from seven European Union countries will participate in this project.

Management of Patients Who Receive an Organ Transplant Abroad and Return Home for Follow-up Care: Recommendations From the Declaration of Istanbul Custodian Group.

Eradicating transplant tourism depends on complex solutions that include efforts to progress towards self-sufficiency in transplantation. Meanwhile, professionals and authorities are faced with medical, legal, and ethical problems raised by patients who return home after receiving an organ transplant abroad, particularly when the organ has been obtained through illegitimate means. In 2016, the Declaration of Istanbul Custodian Group convened an international, multidisciplinary workshop in Madrid, Spain, to address these challenges and provide recommendations for the management of these patients, which are presented in this paper. The core recommendations are grounded in the belief that principles of transparency, traceability, and continuity of care applied to patients who receive an organ domestically should also apply to patients who receive an organ abroad. Governments and professionals are urged to ensure that, upon return, patients are promptly referred to a transplant center for evaluation and care, not cover the costs of transplants resulting from organ or human trafficking, register standardized information at official registries on patients who travel for transplantation, promote international exchange of data for traceability, and develop a framework for the notification of identified or suspected cases of transnational transplant-related crimes by health professionals to law enforcement agencies.

Improvement in kidney transplantation in the Balkans after the Istanbul Declaration: where do we stand today?

Due to the limited access to kidney transplantation (KTx) in developing countries, desperate patients have engaged in the purchase and sale of kidneys. In 2004, the World Health Assembly urged member states to protect the poor and vulnerable from being exploited through practices of illegal organ trafficking that had become widespread throughout the world. In 2008, the international transplant community convened a summit of transplant professionals, legal experts and ethicists to combat organ trafficking, transplant tourism and transplant commercialism that resulted in the Declaration of Istanbul (DOI). The South-Eastern Europe Health Network (SEEHN) represents a nine country multigovernmental collaboration on health systems. The Regional Health Development Centre on Organ Donation and Transplant Medicine (RHDC) was established in 2011 in Croatia to facilitate cooperation among south-eastern European countries to improve organ transplantation within the Balkan region. Since 2011, a collaboration between the RHDC, the Custodian Group of the DOI (DICG) and SEEHN professionals has enhanced strategic planning and definition of country-specific action plan priorities on organ donation and transplantation. Data of kidney transplantation provided in this report show a significant increase in transplantation activities in a 4-year period in Macedonia, Moldova, Bosnia and Hercegovina, Romania and Montenegro. The success of the donation and transplantation programmes was influenced by the engagement of key professionals and the establishment of organizational infrastructure with the implementation of an appropriate funding model. In conclusion, the DOI has provided an ethical framework for engagement of health professionals from south-eastern European countries. The newly established SEEHN RHDC as a technical coordinating body greatly contributed in building institutional capacity and strengthening regional collaboration between health authorities and professionals within these countries for improvement of transplant activities in the Balkans.

The Oral Cavity State in Renal Transplant Recipients.

AIM: Patients with a solid organ transplant can have many different complications in the mouth, as a result of immunosuppression and side effects of drugs. The aim of this study was to examine the frequency and type of oral lesions in renal transplant patients, dental status, oral hygiene, oral lesions related to drugs which patients take and the time of transplantation as well as the frequency of patient's visits to the dentist in the post-transplant period. MATERIAL AND METHODS: The study was performed in a period of two years and included 100 subjects with a renal transplant during their regular control visits to the Department of Nephrology and Dialysis, Clinical Hospital Centre Zagreb and the Department of Oral Medicine, School of Dental Medicine, University of Zagreb and 100 randomly selected control subjects at the Department of Endodontics and Restorative Dentistry, School of Dental Medicine, University of Zagreb. RESULTS: Results showed a significantly higher incidence of oral lesions in patients with renal transplant (31%) compared to control subjects. The most frequent were erythematous (inflammatory changes), keratotic lesions and gingival hyperplasia. The average DMFT index was significantly lower in patients with renal transplant than in the control group. One third of patients had a subjective feeling of dry mouth. Oral hygiene was poor overall, and only a small number of subjects used the additional sustainers for oral hygiene. Most patients did not visit the dentist after the transplantation. CONCLUSION: Renal transplant patients need a comprehensive and regular dental care during the pre- and post-transplant period and a doctor of dental medicine should be part of a multidisciplinary team of medical specialists.

Development of the Croatian model of organ donation and transplantation.

During the past ten years, the efforts to improve and organize the national transplantation system in Croatia have resulted in a steadily growing donor rate, which reached its highest level in 2011, with 33.6 utilized donors per million population (p.m.p.). Nowadays, Croatia is one of the leading countries in the world according to deceased donation and transplantation rates. Between 2008 and 2011, the waiting list for kidney transplantation decreased by 37.2% (from 430 to 270 persons waiting for a transplant) and the median waiting time decreased from 46 to 24 months. The Croatian model has been internationally recognized as successful and there are plans for its implementation in other countries. We analyzed the key factors that contributed to the development of this successful model for organ donation and transplantation. These are primarily the appointment of hospital and national transplant coordinators, implementation of a new financial model with donor hospital reimbursement, public awareness campaign, international cooperation, adoption of new legislation, and implementation of a donor quality assurance program. The selection of key factors is based on the authors' opinions; we are open for further discussion and propose systematic research into the issue.

Current status of transplantation and organ donation in the Balkans--could it be improved through the South-eastern Europe Health Network (SEEHN) initiative?

Organ donation and transplantation activity in the majority of Balkan countries (Albania, Bosnia and Herzegovina, Croatia, Macedonia, Moldova, Montenegro, Serbia, Romania and Bulgaria) are lagging far behind international averages. Inadequate financial resources, unclear regional data and lack of government infrastructure are some of the issues which should be recognized to draw attention and lead to problem-solving decisions. The Regional Health Development Centre (RHDC) Croatia, a technical body of the South-eastern Europe Health Network (SEEHN), was created in 2011 after Croatia's great success in the field over the last 10 years. The aim of the RHDC is to network the region and provide individualized country support to increase donation and transplantation activity in collaboration with professional societies (European Society of Organ Transplantation, European Transplant Coordinators Organization, The Transplantation Society and International Society of Organ Donation and Procurement). Such an improvement would in turn likely prevent transplant tourism. The regional data from 2010 show large discrepancies in donation and transplantation activities within geographically neighbouring countries. Thus, proposed actions to improve regional donation and transplantation rates include advancing living and deceased donation through regular public education, creating current and accurate waiting lists and increasing the number of educated transplant nephrologists and hospital coordinators. In addition to the effort from the professionals, government support with allocated funds per deceased donation, updated legislation and an established national coordinating body is ultimately recognized as essential for the successful donation and transplantation programmes. By continuous RHDC communication and support asked from the health authorities and motivated professionals from the SEEHN initiative, an increased number of deceased as well as living donor kidney transplantations in the future should be more realistic.

Increased donor rate at Sestre milosrdnice University Hospital.

The rate of organ donation reflects the level of the respective society and country development. In Croatia, attempts have been made to increase this rate. As a consequence, the number of potential donors with confirmed brain death was observed to have steadily increased during the 2004-2008 period. Data on all potential donors where the confirmation procedure for brain death was completed were retrieved and analyzed. The percentage of donors out of all persons diagnosed with brain death and all deaths recorded at the Central Intensive Care Unit and at all Hospital departments was calculated. The mean number or organs per donor was also calculated. During the 2004-2008 period, the number of donors perbrain death persons was 5/unknown, 6/10, 8/13, 11/13 and 18/20; mean age 51, 50, 39, 48 and 44; donor rate per Central Intensive Care Unit deaths 5.9%, 5.6%, 5.8%, 10.4% and 12.1%; donor rate per all hospital deaths 0.4%, 0.5%, 0.5%, 1.5% and 1.9%; and number of organs per donor 1.6, 2.4, 2.6, 3.0 and 2.7, respectively. Study results showed a steady increase in the number of donors and organs per donor at Sestre milosrdnice University Hospital during the 2004-2008 period. More intensive education should be organized at medical schools and for medical professionals to identify brain death persons and potential donors. In addition, mass media campaigns should improve public awareness and perception of the issue.

[New Croatian legislation on tissue banking]. / Novi hrvatski propisi O tkivnom bankarstvu.

Human tissues and cells are increasingly used in transplantation, and have also a very promising potential as starting material for tissue engineering and cell therapy. Due to their biological origin, tissues and cells also carry the risks of disease transmission, which need to be reduced as far as possible. Safety and quality standards for tissues and cells have to be concurrent with EU standards in all member states. EU standards in this area have been regulated by the Directive 2004/23/EC, which determines safety and quality standards for human tissues and cells. Two other directives support its implementation regulating technical requirements regarding different process phases of handling tissues and cells. Directive 2006/17/EC regulate technical requirements for donation, procurement and testing of human tissues and cells, whereas technical requirements concerning coding, processing, preservation, storage and distribution of human tissues and cells are regulated by Directive 2006/86/EC. Legal implementations of these directives throughout the European Union take places at different dynamic levels. Countries like Spain, Ireland, Denmark and Bulgaria have successfully completed this process. However, some countries have not met this challenge yet (e.g., Italy, The Netherlands, Latvia, Belgium, Luxembourg, Austria, Slovenia and Sweden), and others are only half-way through (e.g. Slovakia, Rumania, Portugal, Norway, Great Britain, et aI.). Some Member States indicated problems in the implementation of the Directive due to the limited number of experts in the field. In Croatia, the field of tissue and cell transplants is regulated by the Act of Conditions for Removal and Transplantation of Human Body Parts for Therapeutic Purposes (Official Gazette 177/04) and other decrees, which help regulating quality and safety for human tissues and cells, defining authorization systems for tissue and cell banks as well as supervising their work and determining the compliance regarding quality and safety for procurement, testing, processing and distribution of human tissues and cells for therapeutic purposes according to the required standards; Ordinance on Storing Personal Data of Donors and Recipients of Human Body Parts (OG 141/05), Ordinance on Cooperation with Related Foreign and International Organisations for the Purpose of Exchanging Organs and Human Tissues for Transplantation (OG 141/05), Ordinance on Measures to Ensure Safety and Quality of Human Body Parts for Medical Use COG 143/05), Ordinance on Distribution Principles of Unrelated Allogeneic Hematopoietic Cells and the Register of Potential Bone Marrow Donors COG 151/05), Ordinance on Distribution Criteria of Human Body Parts and Compilation of a National Waiting List (OG 152/05), Ordinance on the Method of Storage and Transportation of Human Body Parts Intended for Transplantation COG 152/05), Ordinance on Keeping Medical Documentation on Performed Removals and Transplants of Human Body Parts COG 152/05), Ordinance on Notification Procedures of the Death of Eligible Human Body Part Donors for Therapeutic Purposes (OG 152/05), Ordinance on the Work of Tissue Banks with and Supervision over Health Care Institutes or Divisions of Health Care Institutes COG 1/06), Ordinance on Method, Procedure and Medical Criteria for Death Determination of Body Part Donors for Transplants COG 3/06), and Ordinance on the Work of Coordinators in the Procedure of Removal and Transplantation of Human Body Parts for Therapeutic Purposes COG 51/06). The Croatian legislation is greatly consistent with the legislation of the European Union regarding this field. In the above mentioned law and decrees, Croatia has a legal foundation for regulating this field in compliance with EU standards.