Kidney360 Publish Ahead of Print, published on May 12, 2021 as doi:10.34067/KID.0002542021

Global Perspective on Kidney Transplantation: Turkey Oya Andacoglu1* and Fazil Tuncay Aki2

1 Koc University Organ Transplantation Center, Istanbul, Turkey 2 Hacettepe University, Department of Urology, Ankara, Turkey * Corresponding Author Oya Andacoglu, MD Abdominal Transplant Surgeon Koc University Organ Transplantation Center, Istanbul, Turkey [email protected]

Abbreviations ESRD End-Stage Renal Disease IRODaT International Organ Registry in Organ Donation and Transplantation pmp per million population TND Turk Nefroloji Dernegi (Turkish Society of Nephrology) USA United States of America

Copyright 2021 by American Society of Nephrology. Introduction The first renal transplant in Turkey was performed in 1968 at Istanbul University Medical School (1). However patient expired due to ventricular fibrillation at post-operative 7th hour (1). First successful renal transplant in Turkey was performed by Dr. Mehmet Haberal and his colleagues in 1975, at Hacettepe University from a mother to her child followed by the first deceased donor kidney transplantation in 1978, using an organ supplied by Eurotransplant (2). The law on har- vesting, storage, and transplantation of organs and tissues was enacted in 1979; later that year, the first local deceased donor kidney transplantation was performed by the same team. The Turk- ish Ministry of Health established the National Coordination Center to promote transplantation activities, and the deceased donor organ procurement in 2001 (3). Currently, Organ Transplanta- tion Regulatory Unit is a subdivision within the Ministry of Health. To date, including year of 2020, a total of 33.028 renal transplants and 13.135 liver transplants were performed as com- pared to 728 heart transplants, 276 lung transplants, 65 pancreas transplants since 2008 accord- ing to the publicly available online registry of Ministry of Health (4). Despite large volume of living donor renal and liver transplant performance in Turkey, heart, lung, pancreas or intestinal programs and overall deceased donor transplant activity are quite behind due to various factors including low rates of deceased donation compared to Europe or the USA. According to the most recent International Organ Registry in Organ Donation and Transplantation (IRODaT) reports, Turkey ranked 1st for overall living donor rate (53,02 per million population [pmp]) and for liv- ing donor renal transplant activity (36,64 pmp) globally however ranked 42nd with only 7,54 pmp rate for deceased donor rates compared to the top 3 countries (Unites States, Spain and Por- tugal; 38,35, 37,40 and 33,80 pmp, respectively) (5,6). Deceased donor kidney transplant rate was 10,45 pmp (6).

Current Status of Renal Transplant in Turkey Renal transplant annual volume has been increasing steadily in Turkey (Figure 1). There were 20.857 patients listed for renal transplant as of 2020 (4). As of 2021, there were 78 renal trans- plant programs and 6 pancreas transplants programs listed in the country (4). There has been some major changes in the transplant regulations: First, there has been major increase in the fi- nancial incentives by the Ministry of Health towards the kidney transplant programs during 2008-2010. Secondly, the Ministry of Health gave permission and license to perform kidney transplants to the private hospitals. Former to this regulations, only state hospital and state uni- versities were eligible to perform transplant. Third, three has been increase in the educational activities regarding donation for medical providers as well as public. Given these major changes, annual renal transplant volume has increased dramatically around the time of these changes 2010 (figure 1). All transplant programs and all transplant activities are closely monitored and strictly reported to the Ministry of Health. Another important data source is the Turkish Society of Nephrology (TND) which was founded in 1970. TND initiated a reporting system in 1990 and collects data from participating centers and annual reports are publicly available. Caveat to that is, not all centers in the country are included in the TND reports. With all these limitations in mind, 1 year renal graft survival was 94,14% according the latest TND report from 2019 (7). This was 96,2% for living donor renal transplants and 86,34% for deceased donors renal transplants (Table 1). Of all renal transplants in 2019, only 805 (20,87%) were from deceased donor whereas remaining 3053 (79,13%) were from living donors. Majority (63.2%) of the living donations were from relatives and 21.9% were from unrelated donors in 2019 (7). The distribution of living and deceased donor renal transplants for the last 2 decades is demonstrated in figure 2. Deceased donor rates further decreased in 2020 due to the COVID-19 pandemic in addition to increased organ discard rates. Donor exchange is legally allowed in Turkey but a national paired exchange program is still un- der preparation and is not active as of 2021. Individual kidney exchange is possible between families and is facilitated within each individual transplant program. Rate of paired exchange in 2019 was 5.7% which was similar to 2018 (7). The rate of pre-emptive transplantation was higher in 2019 compared to that of 2018 (46.2% vs. 43.9%). It was stated in the same TND report that the high rates of pre-emptive renal transplant raise concerns about the timing of transplantation (7). Half of the patients were on hemodialysis and only 3,63 % were on peritoneal dialysis.

Pediatric Renal Transplant According to the TND report, 13 centers participated for pediatric transplant registry in 2019 (7). There were 89 pediatric patients who underwent renal transplants in 2019. On the other hand, it is also stated that according to the Ministry of Health data, there were 329 total pediatric renal transplants for 2019, which means only 27% of all pediatric cases were captured in the TND re- port. Despite the sampling limitation, further info is provided as following: Of these 89 pediatric patients, 91% were living donor, and 28,9% were pre-emptive. While there were 3 graft losses, patient survival was 100% at 1 year. Top 3 etiologies of renal failure in pediatric patients were as following: Vesicoureteral reflux and recurrent urinary tract infections (22,89%), primary glo- merulonephritis (20,48%), and other category (26,50%) (7).

Trends of End-Stage Renal Disease Turkey is ranked 23rd for the incidence of End-Stage Renal Disease (ESRD) according to the most recent USRDS Annual Data Report (8). Average annual change in the incidence of treated ESRD by country or region, 2009-2010 versus 2017-2018 demonstrated ESRD incidence de- creased in Israel, Norway, Sweden, Italy, Bosnia and Herzegovina, Colombia, Chile, and Turkey (6). Etiology of ERSD in Turkey were as following: Diabetes (20,94%), Glomerulonephritis (20,35%), hypertension (18,48%), polycystic kidney disease (5,96%), obstructive nephropathy (5,38%), Tubulointerstitial nephritis (2,92%), Amyloidosis (2,81%), and unknown etiology (16,49%) (7).

Transplant Surgery and Post-Transplant Care Out of 78 centers in Turkey, urology performs kidney transplants primarily at 16 (20%) centers. High volume centers (i.e. 100 renal transplant per year) would constitute 20% or less of all pro- grams. The training for renal transplant surgery and certification process is undertaken through the Ministry of Health. General surgeons, urologists or pediatric surgeons can apply for any insti- tution listed at the Ministry of Health. Surgeons collect points in the following criterion for the certification process: (1) Minimum 6 months of work at a center where at least 15 renal trans- plants per year is performed, (2) first assistance and primary surgeon role for recipient operation, (3) participation in donor nephrectomy surgery, (4) academic activity (peer reviewed article, re- view or book chapter) with a focus on renal transplant. Each category has a different contribution points for the certification. Final approval is performed by the Ministry of Health. Transplant nephrology remains a rotation within nephrology fellowship for internal medicine specialty. They also have a similar certification system. Follow up of renal transplant patients are per- formed mainly by transplant nephrologists. Recipient and donor costs are covered by the univer- sal health care system including lifelong immunosupression. Lodging or travel expenses are not included.

Conclusion Despite the limited access to long term patient and graft survival data, 1 year graft and patient survival is excellent after living donor kidney transplant and is good after deceased donor renal transplant in Turkey. Turkey ranks 1st globally for living donor renal transplant rates. Countries with interest to expand living donor transplants, could probably focus on the incentive part. While this may not be an easily achievable goal, there could be other external resources for this purpose (i.e. private funds or donations). Turkey has significant experience in living donor trans- plants, however deceased donor system should be augmented, prioritized and perhaps incentiv- ized in financial and non-financial ways. Possible areas to improve could be summarized as: in- crease public awareness, increase training and education among medical providers and medical staff, formation of independent personnel to approach to families, implementing regulations fa- cilitating or promoting deceased donation, consideration for specific donor management teams (either within the same institute or independent teams). This way we could expand other lifesav- ing organ transplants including heart, lung, pancreas and intestine. It would require systematic, long term commitment both from Ministry of Health and from transplant providers’ end. We can further strengthen the system with publicly available long term graft and patient results. This will not only allow patients to be able to choose where they wish to have their transplants done, but will also raise the quality bar by pushing the centers to reach better long term outcomes and de- cease the outcome variations among centers. Lastly, a standardized national transplant fellowship curriculum, structured by professional transplant societies and formal board certifications, and recognition of “transplantation” as a formal subspecialty both in medicine and surgery are man- datory. We believe this would further raise the bar in transplant quality nationally.

Disclosures: Both authors have nothing to disclose.

Funding: None

Acknowledgement: The content of this article reflects the personal experience and views of the author(s) and should not be considered medical advice or recommendation. The content does not reflect the views or opinions of the American Society of Nephrology (ASN) or Kidney360. Re- sponsibility for the information and views expressed herein lies entirely with the author(s).

Author contributions: O Andacoglu: Conceptualization; Data curation; Investigation; Method- ology; Writing - original draft; Writing - review and editing F T Akı: Methodology; Supervision; Writing - review and editing REFERENCES 1- Turk Nefroloji Tarihi. Ankara, Turkey. Editor: Prof. Dr. Ayla San. 2002. Publisher: Anadolu Bobrek Vakfi. Vakif Yayin No:27 2. Karakayali H, Haberal M. The history and activities of transplantation in Turkey. Transplant Proc. 2005 Sep;37(7):2905-8. doi: 10.1016/j.transproceed.2005.07.025. PMID: 16213257. 3- Haberal M. Transplantation in Turkey. Clin Transpl. 2013:175-80. PMID: 25095506. 4- https://organkds.saglik.gov.tr/dss/PUBLIC/PublicDefault2.aspx 5-https://www.irodat.org/?p=publications 6- https://www.irodat.org/img/database/pdf/Newsletter%20Dec%202020%20.pdf 7- National Nephrology, Dialysis and Transplantation Registry Report of Turkey 2018. ISBN 978-605-62465-0-0 http://www.nefroloji.org.tr/folders/file/REGISTRY_2018.pdf 8- https://adr.usrds.org/2020/end-stage-renal-disease/11-international-comparisons

Table 1. Outcomes of renal transplants performed in 2019. Adapted from TND (7)

n %

Functioning graft (all transplants) 3632 94,14

Returned to dialysis 45 1,17

Re-transplant 16 0,41

Death 165 4,28

Total 3858 100,00

Functioning graft (living donor) 2937 96,20

Returned to dialysis 26 0,85

Re-transplant 3 0,10

Death 87 2,85

Total 3053 100,00

Functioning graft (deceased donor) 695 86,34

Returned to dialysis 19 2,26

Re-transplant 13 1,61

Death 78 9,69

Total 805 100,00

Figure 1 Figure 2