Increasing Living Donor Kidney Transplantation Numbers in Budapest H. Bäcker, L. Piros, and R.M. Langer ABSTRACT Living related kidney donations (LRD) have had a significant impact on therapy of kidney diseases. Due to their ease of scheduling in the general surgery program and better half-life of about 21.6 versus 13.8 years for deceased donor kidneys, this approach has revolutionized nephrology and transplantation medicine. Since the first Hungarian LRD which was performed in 1974 in Budapest, Hungary, donations have expanded especially in the last 3 years. This has been followed in 2000 by living unrelated kidney donations (LURD). Since 2000 LURD can be also performed in Hungary. From the 251 LRD in our country in the last 3 years, 79 living donations have accounted for nearly one-third of the cases. In comparison of 2008, and 2011 the absolute numbers of LRD as well as LURD have more than doubled from 9 to 20 and 6 to 14 respectively. Based on international ranking data from the global observatory on donation and transplantation Budapest has improved from 1.20 in 2000 to 6.20 LRD per million persons (p.m.p.) in 2010. The increase in LURD has also led to some side effects: an increase in recipient age from 26 years in 2000 to 46 in 2011 and greater HLA mismatches. In 2010, Budapest ranked higher than Croatia or Portugal but still behind Germany (8.13 LRD p.m.p.) and the leading countries: the Netherlands (28.49 LRD p.m.p.) and Norway (16.94 LRD p.m.p.). Because of the tremendous progress in LRD, the gap between today’s leading countries and Budapest is closing.

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N DECEMBER 18, 1952, the first living related kidney transplantation was performed at the Hôpital Necker by Jean Hamburger and Louis Michon in Paris, France.1 Due to the lack of immunosuppressive drug therapy, the kidney was rejected at 3 weeks. Two years later Joe Murray successfully transplanted a kidney between identical twins in Boston.2 The onset of immunosuppressive drug therapy revolutionized transplantation and facilitated the use of deceased donors. The first living related donor (LRD) kidney transplantation was performed in Hungary was performed in Szeged by Dr. András Németh in 1962.3 This event was followed by the establishment of the Budapest an transplantation program by Dr Ferenc Perner on November 16, 1973; about 1 year later the first (LRD) occurred there. The 2 Hungarian programs joined the Eastern Block transplantation exchange, “Intertransplant,” which lasted until 1989.4 During three decades about 5% of all renal transplants were LRD in Hungary. Up to today, the half-lives and postsurgery infections as well as remember of these cases have shown improvements. In 2009, the new head of the Budapest department emphasized living renal transplantations, because of their higher quality, longer half-life,

and greater genetic concordance decreasing the rate of rejection episodes compared with deceased donor kidneys. The procedure was further facilitated by laparoscopic donor explantation introduced in 2008. PATIENTS AND METHODS Beginning in 1974, the time of the first living donor kidney transplantation, we collected data for comparison with those of Eurotransplant International Foundation member countries, primarily The Netherlands, which is the leading country worldwide, and Germany5 plus Norway’s Oslo Universitetssykehos6 since 1995 as well as the rankings from the Global Observatory on Donation and Transplantation (GODT)7 since 2000. To calculate the numbers of cases per million persons (p.m.p.) based upon commuter size, in Budapest we assumed 5 million people. However, the p.m.p values may vary due to center effects.

From the Department of Transplantation and Surgery, Semmelweis University, Budapest, Hungary. Address reprint requests to Robert M. Langer, Department of Transplantation and Surgery, Semmelweis University, Baross u 23, Budapest, H-1082, Hungary. E-mail: [email protected]

0041-1345/13/$esee front matter http://dx.doi.org/10.1016/j.transproceed.2013.10.001

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Transplantation Proceedings, 45, 3678e3681 (2013)

INCREASING LIVING DONORS IN BUDAPEST

RESULTS

From 1974 to 2011, we performed 251 living donations, including 38 living unrelated donation (LURD) since its introduction in 2000. In the first 20 years (1974 to 1994), only 72 living donor kidneys were transplanted (average ¼ 3.6 cases per year). The maximal numbers during this period were performed in 1988, namely 10 procedures; whereas, in 1974, 1981, 1982, and 1992, there was only 1 LRD case each. Thus there were between 0% and 2% per million Hungarian inhabitants. Between 1995 and 2008, there was a small increase, namely, 100 kidneys transplanted during the 13-year interval (7.69% per annum), including 15 LURD since 2000. In 2005 and 2008, 3 kidneys p.m.p. were transplanted which was below international activities. In comparison, Germany performed up to 6.9 living donations, p.m.p. (2007); Norway, 19.7 p.m.p. (2008); and The Netherlands, 24.6 (2008) p.m.p, a performance that was second worldwide only behind Cyprus (37.8 p.m.p) due to the small number of inhabitants. In 2008; our 15 living donations with 40% LURD placed Budapest 35th worldwide. In 2009 the new director of the Department of Transplantation and Surgery in Budapest stimulated the program. By 2011 we transplanted 79 living donor kidneys (31.5% of all Budapest living donors). Budapest currently performs about 75% of Hungarys LRD (Fig 1). In addition, the

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numbers of LURD increased from 20% in 2000 to 35.9% of all living donations in 2009, and 41.2% in 2011. However, it should be noted that there were decreases to 20% in 2005 and 12.9% in 2010. In absolute numbers, 14 LD (2.8 p.m.p.) were transplanted in 2009; 31 (6.2 p.m.p.) in 2010; and 34 (6.8 p.m.p.) in 2011. Comparison With Other European Countries

This activity has closed the gap with German transplant centers, which averaged 7.3 p.m.p. in 2009; 8.1 p.m.p. in 2010; and 9.7 p.m.p. in 2011. Germany is below the Eurotransplant average: 9.3 p.m.p. (2009); 10.3 p.m.p. (2010); and 10.9 p.m.p. (2011). However, these numbers are still far less than the world’s leading country, the Netherlands, with 25 LD p.m.p. in 2009; 28.4 p.m.p. in 2010; and 26.4 p.m.p. in 2011. Norway performs well albeit with a slight decrease from 2009 (20.8 LD p.m.p.) to 2011 (14.6 p.m.p.), considering that only Universitetssykelios Oslo performs all cases in Norway. Therefore Universitetssykelios Oslo is one of the most effective transplanting centers worldwide based on numbers per center. When examining LRD percentages per all transplantations (deceased donation and LURD and LRD), the differences between Budapest and other countries are even smaller. Since 2002, the percentage of LRD among all kidney transplantations (deceased donations plus living

Fig 1. Kidney transplantation in Hungary, 1973e2012.

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donation) has increased from 3.9% to 9.5% in 2009 and 24.1% in 2011 in Budapest as well as in Germany. The Eurotransplant average went from 19.1% to 22.8% in 2002; 21.6% to 32.3% in 2009; and 27.9% to 37.4% in 2011. These enormous increases in living donations are still well behind the Netherlands: 34.5% in 2002; 51.2% in 2009; and 51.2% in 2011. However, Norway has shown a consistent decrease: 49.5% in 2002; 37.7% in 2009; and 25.8% in 2011, a change associated with an increase in deceased donor transplantations. In terms of LURD, Budapest has shown fluctuating numbers: in 2003 and 2008, each 40.0%; 2009, 35.7%; and 2011, 41.2%. During these years Norway performed 18.4% (2003), 24.5% (2008), 26.0% (2009), and 24.7% (2011) LURD among all LRD. In 2000 as well as 2005 and 2007, 20.0% LURD were performed but none of these cases in 2001, 2002, and 2006. The decrease to 12.9% in 2010 was followed by a record of 41.2% in 2011. Since 2008, the Netherlands has transplanted more than 50%: 51.1% in 2008, 52.8% in 2009, 52.0% in 2010, and 50.6% in 2011. Germany as well as the Eurotransplant average revealed more than 40.0% of these cases performed since 2004. Due to better techniques, greater graft life expectancy, and the increase in LURD, recipient as well as donor ages increased from 29.0 and 18.6 years in 2002 to 47.4 and 45.7 in 2011 respectively. Related to the increase in LURD, the relation of donor to recipient has shifted from mother to children to between spouses and partners. DISCUSSION

The last 2 years have witnessed successful implementation of living donation procedures worldwide. Budapest especially has augmented the numbers of living donation particularly in the last 3 years: 79 in this period among a total of 251 living donations since 1974. In comparison to 2008, the numbers of LRD as well as LURD have more than doubled from 15 to 34 in 2011 from 6 in 2008 and 14 in 2011. In 2011, 24.1% of all deceased and living donor kidney transplantations were from LRD; whereas in 2008 it was only 10.6%. This shift in the numbers of living donor kidney transplantations has led to various effects. There has been a slight decrease in deceased donation cases. Politics, policies, and internal regulations are undergoing modifications not only in Budapest but also worldwide. Today medicine is becoming more subject to economic calculations to evaluate individual cases. This not only improves efficiency, but also the quality of transplantation. It is likely that the subscription of Hungary into Eurotransplant will lead to better performances. The Eurotransplant International Foundation headquarters is located in the Netherlands and Rotterdam placed first among Eurotransplant member and worldwide centers. The impact of LURD kidney transplantation will likely increase steadily due to the demographic changes of greater recipient ages as

BÄCKER, PIROS, AND LANGER

well as better pretransplant treatment that reduces the risks and complications of surgery. Compared with deceased donation procedures, living donor transplantation has fewer complications, such as rejection, because of better HLA matching, and less infectious diseases because of the lower doses of immunosuppressants. These surgeries are more economical and efficient, because of the easier planning and integration into the normal surgery schedule. However, there may be a greater chance for tumor emergence among recipients on the one hand, and potential adverse psychological effects, greater vulnerability to kidney diseases, and as the need for lifelong post-transplantation medical examinations in living donors on the other hand. To prevent illegal situations associated with these procedures, such as economic transactions, bioethical committees must evaluate every donor, particularly those individuals who are not directly related to the recipient, such as spouses and partners. Because of the importance of bioethical committees and laws that vary among countries and even among centers within a country, there are multiple regulations for admission criteria. It must be taken into account that the above calculations were based on average commuter belts, such as Budapest with 5 million people. They may not reflect the exact number of individuals due to center effects as may apply to Rotterdam and Nijmegen (both Dutch), Berlin and Heidelberg (both German), and Oslo (Norway). Inconsistent data from GODT and Hungary, as well as the variable numbers of inhabitants, make it difficult for comparisons and calculations. Some countries like Cyprus (1.1 million in 2011) or Iceland (300,000 in 2011) have very few inhabitants, which may lead to higher rates of kidney transplantation per million people. Other important factors are the health systems and government spending. In comparison with Germany, the Netherlands, and Norway, the Hungarian government spending is lower, a circumstance that restricts possibilities, for example ABO incompatible LRD. In conclusion, living related kidney donations have had a significant impact on the treatment of kidney diseases. Due to their ease of scheduling in the general surgery program and better half-life of about 21.6 versus 13.8 years for deceased donor kidneys,8 this approach has revolutionized nephrology and transplantation medicine. Since 1974 and especially during the last 3 years, Budapest has undertaken programs in LRD and LURD to improve the quality and length of recipient life in relation to patients on dialysis.

REFERENCES 1. Michon L, Hamburger J, Oeconomos N, et al. Une tentative de transplantation renale chez 1’homme. Aspects Medicaus et Biologiques Presse Med. 1953;61:1419. 2. Merrill JP, Murray JE, Harrison JH, et al. Successful homotransplantation of the human kidney between identical twins. JAMA. 1956;160:277.

INCREASING LIVING DONORS IN BUDAPEST 3. Nemeth A, Petri G, Gal G, et al. Kidney homotransplantations in 2 brothers. Orv Hetil. 1963;104:2017e2023. 4. Langer RM, Kalmár NK. New Chances for Hungarian TransplantationdPreface to the 12th Congress of the Hungarian Transplantation Society. Transplant Proc. 2011;43(4):1219e1220. 5. Data from Eurotransplant International Foundation Annual reports 1995 to 2010. Available at: www.eurotransplant.org, 2301 CH Leiden; The Netherlands.

3681 6. Personal communication from Torbjørn Leivestad, MD, from the Oslo University Hospital, Norway. 7. Global Observatory on Donation and Transplantation (GODT) data, produced by the WHO-ONT collaboration. Available at: http://issuu.com/o-n-t/docs/2010?e¼4461754/2592072. 8. Kaufman B. Renal Transplantation (Medical) eMedicine. Mulloy LL, et al. (eds). Medscape. Available at: emedicine. medscape.com/article/429314-overview. Accessed January 15, 2013.

Increasing living donor kidney transplantation numbers in Budapest.

Living related kidney donations (LRD) have had a significant impact on therapy of kidney diseases. Due to their ease of scheduling in the general surg...
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