Kidney transplantation is the treatment of choice for patients with end-stage renal disease. However,
it took years and numerous attempts to achieve success, for the kidney to function well and for the patient to survive after the transplantation. Following this breakthrough made by Murray in 1954, the introduction of immunosuppressive therapy and tissue typing has significantly improved this program. Today we have new challenges in maintaining or improving a kidney transplant program, one of which is COVID-19 infection. This review presents the history and current status of kidney transplantation, emphasizing the Croatian Kidney Transplant Program

Bašić Jukić, Nikolina

Hauptman, Dinko

Hudolin, Tvrtko

Jurić, Ilija

Kaštelan, Željko

Lipšinić, Jana

Mokos, Ivica

Pasini, Miriam

Pavlović, Oliver

English

Hrčak - Portal of scientific journals of Croatia

Review ArticleRAD 548. Medical Sciences 56-57 (2021) : 84-88                       www.rad-med.com 84 December 2021   -   Vol 548 = 56-57Abstract:Kidney transplantation is the treatment of choice for patients with end-stage renal disease. However, it took years and numerous attempts to achieve success, for the kidney to function well and for the patient to survive after the transplantation. Following this breakthrough made by Murray in 1954, the introduction of immunosuppressive therapy and tissue typing has significantly improved this program. Today we have new challenges in maintaining or improving a kidney transplant program, one of which is COVID-19 infection. This review presents the history and current status of kidney transplantation, emphasizing the Croatian Kidney Transplant Program.Keywords: kidney transplantation, history of transplantation, Croatia, EurotransplantSažetak:Transplantacija bubrega, kratka povijest i hrvatsko iskustvoTransplantacija bubrega je metoda izbora liječenja završnog stadija kronične bubrežne bolesti. Međutim, bilo je potrebno puno godina i pokušaja da bi se napravila uspješna transplantacija bubrega, odnosno da bi bubreg profunkcionirao, a bolesnik preživio transplantaciju. Prvu uspješnu transplant-aciju je napravio Murray 1954, a daljnji napredak omogućen je uvođenjem imunosupresivne terapije i tipizacije tkiva. Danas imamo nove izazove u održavanju i napretku programa transplantacije bubrega, a jedna od njih je COVID-19. U ovom radu prikazujemo povijest i sadašnju situaciju s transplantaci-jom bubrega s naglaskom na program transplantacije bubrega u Republici Hrvatskoj. Ključne riječi: transplantacija bubrega, povijest transplantacije, Hrvatska, EurotransplantKidney transplantation, brief  history and Croatian experience Tvrtko Hudolin1, Nikolina Bašić Jukić2, Dinko Hauptman1, Ivica Mokos1, Jana Lipšinić3, Ilija Jurić1, Miram Pasini4, Oliver Pavlović5, Željko Kaštelan1    1 Department of urology, Clinical Hospital Center Zagreb, Croatia2 Department of dialysis, Clinical Hospital Center Zagreb, Croatia 3 Emergency medicine department of Krapina, Zagorje County, Croatia4 Department of pediatric surgery and urology, Clinical Hospital Center Zagreb, Croatia5 Department of urology, Clinical Hospital Center Osijek, Croatia OPEN ACCESSCorrespondence:Tvrtko Hudolintvrtkohudolin@gmail.com This article was submitted to RAD CASA - Medical Sciencesas the original articleConflict of Interest Statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a poten-tial conflict of interest.Received: 28 October 2021Accepted: 15 November 2021Published: 24 December 2021Citation:Hudolin T, Bašić Jukić N, Hauptman D, Mokos I, Lipšinić J, Jurić I, Pasini M, Pavlović O, Kaštelan Ž. Kidney transplantation, brief history and Croatian experienceRAD CASA - Medical Sciences. 548=56-57 (2021): 84-88DOI: 10.21857/mwo1vcjq4yCopyright (C) 2021 Hudolin T, Bašić Jukić N, Hauptman D, Mokos I, Lipšinić J, Jurić I, Pasini M, Pavlović O, Kaštelan Ž. This is an open-access article distributed under the terms of the Creative Commons Attribu-tion License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owners(s) are credited and that the original publication in this journal is cited, in accordance whit accepted adacemic practice. No use, distribu-tion or reproduction is permitted which does not comply with these terms. Review ArticleRAD 548. Medical Sciences 56-57 (2021) : 84-88                       www.rad-med.com 85 December 2021   -   Vol 548 = 56-57The road to a successful kidney transplant took more than half a century and was filled with many obstacles that needed to be addressed. The first important step forward was made by Alexis Carrel, a French surgeon born in 1873 in Sainte-Foy-lès-Lyon. In 1904 he moved to the United States, first to Chicago and then in 1906 to New York, where he became a member of the Rockefel-ler Institute for Medical Research. He mainly focused on vascular surgery, tissue and organ transplantation, for which he received the Nobel Prize in 1912.1 His discovery of a successful vascular anas-tomosis technique that was the basis for transplantation of all solid organs, but also the development of vascular surgery in general, was followed by several decades of kidney transplantations from various animal species, including goats, sheep, pigs and monkeys to humans. The lack of options for prolonging the life of patients with end-stage renal failure led surgeons to these attempts, which, we now know, were doomed to failure in advance.Yurii Voronoy did the first human allograft kidney transplanta-tion described in medical literature in Kherson in Ukraine. The donor was a 60-year-old male who died of head trauma and the recipient was a 26-years-old female who tried suicide by mercury poisoning. The warm ischemia time was more than 6 hours, and the kidney was transplanted in the right thigh area with its blood vessels anastomosed with the femoral blood vessels and the ureter connected to the skin. The renal function was never regained, and the patient died after 48 hours.2 After Voronoy’s transplan-tation, several transplantations were published in medical or newspaper articles, but the results were disappointing. Neither adequate renal function was established, nor did the recipient survive the procedure, i.e., death occurred shortly after trans-plantation. It is also important to mention Rene Küss, a French urologist and transplant surgeon born in 1913 in Paris. He described and standardized the techniques which we are using today. In this technique, the kidney was placed in the iliac fossa and the renal vessels were anastomosed with iliac vessels and the ureter was anastomosed with the urinary bladder. The technique was developed, among other things, due to using the organs of pris-oners who were guillotined. His role was not only important as a surgeon, but to develop transplantation he also founded several organizations such as “Paris Transplant”, “French Transplant” and “French Transplantation Society”.3The first successful kidney transplantation was performed by Jo-seph E. Murray, an American surgeon born in 1919 in Milford, along with his associates in 1954 in Boston, United States.4 The donor and recipient were genetically identical twins, brothers Richard and Ronald, which made it possible to overcome the immunological problems that were the reason for the failure of most previous transplantations. The transplantation lasted about five hours, and Richard (the brother who received the kidney) survived with a functional kidney for eight years. It is an inter-esting anecdote that he got not only a kidney but also a wife, because the nurse who took care of him fell in love and became his wife.5 In the following years, the development and use of immunosuppressive drugs and tissue typing techniques made a huge contribution to organ transplantation that entered the field of deceased and unrelated living donor transplantations.6 Croatian Kidney Transplantation ProgramThe first kidney transplantation in Croatia was performed by Vinko Frančišković and his associates in Rijeka in 1971. The donor was a mother who gave her son a kidney and the kidney functioned normally for 14.5 years.7 In 1973, the first kidney transplant was performed at the Clinical Hospital Center in Zagreb. The donor was a sister who gave her brother a kidney (Fig. 1.). After these initial transplantations, the kidney trans-plant program in Croatia has significantly improved both in the number of kidney transplantations (living and deceased donors) and in the number of centers that perform this challenging procedure. Many conditions need to be fulfilled to establish an excellent renal transplant program, especially from deceased donors. One of the most important is the legislation. In Croatia, there is presumed consent, which means that all persons with a brain death are considered potential deceased donors, un-less during their lifetime they have objected to organ donation, about which they can declare themselves, i.e. sign a statement with the selected primary care physician or at the Ministry of Health of the Republic of Croatia.8 This approach allows for many more potential donors compared to some other countries in which only those who have declared themselves to be so dur-ing their lifetime (informed consent) are considered deceased donors.9,10 The presumed donors have enabled Croatia to have a high number of deceased donors per million inhabitants for many years. (Fig. 2.).11 Other essential conditions are public and religious support. Despite some differences between religions, more precisely between some isolated groups within different religions, mainly in discouraging deceased, but in some cases even live kidney transplantations, no religion formally forbids one to donate or receive organs or is against transplantation from living or deceased donors.12 Also important is the cost of trans-plantation, including hospitalization, treatment, and the cost of diagnostic procedures performed on the donor as well as the cost of hospital coordinators, surgical teams, but also all other physi-cians and other staff involved in the transplantation. Further-more, there are costs for possible complications and immunosup-pressive medications that patients must take at least while they have a kidney. Although these costs are not small, they are still significantly lower compared to the costs of dialysis, especially if we include the costs of dialysis-related complications, reduced quality of life, but also the survival of patients with end-stage renal disease in general, which is even more pronounced after long-term follow-up.13 These findings were recently confirmed in a systematic review by Fu R. et al., although it has been shown Review ArticleRAD 548. Medical Sciences 56-57 (2021) : 84-88                       www.rad-med.com 86 December 2021   -   Vol 548 = 56-57Figure 1. Documents of our first kidney transplant from 1973 (archive of the Department of Urology the Clinical Hospital Center Zagreb). a). Newspaper article “Sister’s kidney lives in a brother” and “Successfully transplanted kidney”.b). Angiography showing renal blood vessels.Figure 2. Eurotransplant. Deceased donors per million population, by year, by country.    Review ArticleRAD 548. Medical Sciences 56-57 (2021) : 84-88                       www.rad-med.com 87 December 2021   -   Vol 548 = 56-57Figure 3. Eurotransplant. Active kidney waiting list, median time, by year, by country. that they are less prominent for patients with older age, comor-bidities, and long wait times.14 It has also been shown that there are differences inside the kidney transplanted group itself, where living donor kidney transplantation is clearly showing best cost-savings.15 In our country, these costs outside the hospital limit are covered by the Croatian Health Insurance Fund.In 2007, Croatia became a member of Eurotransplant, an international organization of 8 countries (Austria, Belgium, Croatia, Germany, Hungary, Luxembourg, the Netherlands and Slovenia). Since then, we have significantly improved our kidney transplant program, liver and heart transplantations and, more recently, lung transplantations. In 2010, we had the larg-est number of kidney transplantations in our institution (157) since its establishment. Clinical Hospital Center Zagreb is the largest kidney transplant center that has supported and helped other hospitals in Croatia and other hospitals abroad to start and develop their own kidney transplant program. Most of our trans-plantations are deceased donor kidney transplantations, but we also perform living donor kidney transplantations and transplan-tations in children. Our patients have the shortest waiting time for the kidney in Eurotransplant (Fig. 3).Since 2012, we have participated in the national kidney trans-plant program in Podgorica, Montenegro, significantly decreas-ing transplant tourism in Montenegro.16 Urologists, nephrolo-gists, transplant surgeons, anesthesiologists, immunologists and all other medical staff involved in kidney transplantation from various European, but also Asian and African countries visited our department for the purpose of education or to share with us their experiences with kidney transplantation. Although the recent situation with COVID-19 has decreased the number of kidney transplantations in our institution, as well as in other institutions in Europe and the world17 we continue to carry out kidney transplantation in these challenging times, taking in consideration situation with COVID-19. In the future, we plan to improve our kidney transplant pro-gram not only in the surgical part by improving or introducing new minimally invasive donor nephrectomies, i.e. transplan-tation using a robotic system, but also further advances in diagnostic methods, immunosuppressive protocols and the introduction of other types of kidney transplantations. Review ArticleRAD 548. Medical Sciences 56-57 (2021) : 84-88                       www.rad-med.com 88 December 2021   -   Vol 548 = 56-57References:1. https://www.nobelprize.org/prizes/medicine/1912/carrel/biographical/.2. Matevossian E, Kern H, Huser N, Doll D, Snopok Y et al. Surgeon Yurii Voronoy (1895-1961) - a pioneer in the history of clinical transplantation: in memoriam at the 75th anniversary of the first human kidney transplanta-tion. Transpl Int. 2009;22:1132-9. doi: 10.1111/j.1432-2277.2009.00986.x.3. Kc Cooper D. The forgotten French: The ‘heroic’ era of kidney transplantation. J Med Biogr. 2017;25:234-239.doi: 10.1177/0967772015608056.4. Shampo MA, Kyle RA. Joseph E. Murray - Nobel Prize for organ transplantation. Mayo Clin Proc. 2001;76:240. doi: 10.4065/76.3.240.5. https://hms.harvard.edu/magazine/science-emotion/fight-life6. 6 Synder A. Joseph E Murray. Lancet. 2012;381:110.7. Orlic P. The history of kidney transplantation in the world and in Croatia. Med Vjesn. 2005;371:37-41.8. Republika Hrvatska. Zakon o presađivanju ljudskih organa u svrhu liječenja. NN 144/129. Ugur ZB. Does Presumed Consent Save Lives? Evidence from Europe. Health Econ. 2015;24:1560-72. doi: 10.1002/hec.3111. Epub 2014 Oct 2. 10. Gay S and Adabie A. The impact of presumed consent legislation on cadaveric organ donation: a cross-country study. J Health Econ. 2006;25:599-620. doi: 10.1016/j.jhealeco.2006.01.003.11. https://www.eurotransplant.org/wp-content/up-loads/2021/09/ETP_AR2020_opmaak_LR2.pdf.12. Bruzzone P. Religious Aspects of Organ Transplantation. Transplant Proc. 2008;40:1064-7. doi: 10.1016/j.transpro-ceed.2008.03.049. 13. Jarl J, Desatnik P, Peetz Hansson U, Prütz KG and Ger-dtham UG. Do kidney transplantations save money? A study using a before-after design and multiple register-based data from Sweden. Clin Kidney J. 2018;11:283-288. doi: 10.1093/ckj/sfx088. 14. Fu R, Sekercioglu N, Berta W and Coyte PC. Cost-effec-tiveness of Deceased-donor Renal Transplant Versus Dialysis to Treat End-stage Renal Disease: A Systematic Review. Transplant Direct. 2020;6: e522.15. Axelrod DA, Schnitzler MA, Xiao H, Irish W,Tuttle-Newhall E, Chang SH et al. An economic assessment of contemporary kidney transplant practice. Am J Transplant. 2018;18:1168-1176. doi: 10.1111/ajt.14702. 16. Ratkovic M, Basic Jukic N, Kastelan Z, Radunovic D, Kavaric P, Brezak J et al. Development of the National Transplant Program Has Significantly Decreased but Not Ended Transplant Tourism in Montenegro. Transplant Proc. 2018;50:1236-1237. doi: 10.1016/j.transpro-ceed.2018.03.024.17.  Boyarsky BJ, Werbel WA, Durand CM, Avery RK, Jack-son KR, Kernolde AB et al. Early national and center-level changes to kidney transplantation in the United States during the COVID-19 epidemic. Am J Transplant. 2020;20:3131-3139. doi: 10.1111/ajt.16167. 

Kidney transplantation, brief history and Croatian experience

Kidney transplantation, brief history and Croatian experience

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