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Current Status and Future Aspects of Kidney Transplantation in Japan Atsushi Aikawa

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Current Status and Future Aspects of Kidney Transplantation in Japan Atsushi Aikawa Aikawa Renal Replacement Therapy (2018) 4:50 https://doi.org/10.1186/s41100-018-0186-3 REVIEW Open Access Current status and future aspects of kidney transplantation in Japan Atsushi Aikawa Abstract In Japan, there are very few cases of organ donation, including kidneys. The number of deceased donor kidney transplants (DDKTs) is much less than that of other developed Asian and Western countries, although donation after brain death is increasing slowly. Living donor kidney transplants (LDKTs) are more popular than DDKTs in Japan. However, the number of LDKTs per million population was still less than that in Korea, the UK, and the USA. Living donor ABO-incompatible kidney transplants have been performed in Japan since 1989, and long- term outcomes proved similar to those for ABO-compatible kidney transplants. Preemptive kidney transplants comprised 30% of LDKTs. In spite of the small number of kidney transplants, patient, and graft survival rates in Japan are superior to those of any other country. The infusion of regulatory T cells may induce immunotolerance in kidney transplants although acute rejection frequently occurred when immunosuppression was withdrawn and anti-donor-specific antibodies (DSAs) production could not always be suppressed. Combined kidney and bone marrow transplantation may induce immunotolerance, although a few recipients produced DSA. Kidney regeneration has become a reality. Nephron progenitor cells have been generated from human-induced pluripotent stem cells, readily reconstituting three-dimensional nephrons, including vascularized glomeruli with podocytes. The niche method has been used to generate kidney, urinary tract, and bladder tissue. Many Japanese scientists are researching kidney regeneration, and a kidney regenerated from a recipient’scellscould be transplanted without immunosuppression in the near future. Keywords: Kidney transplantation, Deceased donor, Living donor, Regulatory T cell, Kidney regeneration, Japan Background in Japan. A research group funded by the Japanese Min- The realization of the current status of kidney trans- istry of Health, Welfare and Labor is considering a new plantation in Japan compared to that of other countries approach of optional presentation of organ donation as is very important [1]. In particular, deceased organ do- a terminal care procedure, provided by a qualified so- nation, including a kidney in 2016 occurred much less cial medical worker [5]. often in Japan than in other Asian developed countries, The number of living donor kidney transplants (LDKTs) such as Korea and Taiwan, as well as Western countries has increased steadily in Japan; however, the number of [2]. Therefore, the mean waiting time for a deceased LDKTs per million population (pmp) in 2016 in Japan was donor kidney transplant (DDKT) in adults is > 12 years 11.6, lagging behind that of South Korea (23.0), the UK [3]. Medical staff and donor coordinators do not always (15.6), and the USA (18.0) [6]. ensure a terminal patient’s will for organ donation and The number of ABO-incompatible kidney transplants do not always present the option of organ donation to was approximately 30% of all LDKTs [7], and patient and the patient’s family in an intensive care unit and emer- the graft survival rates in ABO- incompatible kidney gency department [4]. These factors appeared to be the transplants were similar to those of ABO-compatible major causes of the extremely low organ donation rate transplants [8–10]. The number of preemptive kidney transplants (PEKT) was > 30% of LDKTs [11]. A nephrolo- Correspondence: [email protected] gist, nurse, and coordinator cooperating with an early re- Department of Nephrology, Toho University Faculty of Medicine, 6-11-1 ferral of patients with chronic kidney disease (CKD) to a Omorinishi, Otaku, Tokyo 〒143-8541, Japan © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Aikawa Renal Replacement Therapy (2018) 4:50 Page 2 of 12 kidney transplant center could increase and provide better Furthermore, metanephroi with a bladder were retrieved outcomes of PEKT. successfully [20]. Kidney regeneration may become real in The patient and graft survival rates of DDKT and the near future for use as a transplant graft. LDKT are better than those of any other countries des- pite the small numbers of kidney transplants [12, 13]. In Japan, kidney transplantation, as well as peritoneal Current status of kidney transplantation in Japan dialysis, compared to hemodialysis, was rarely pre- DDKT sented as an option for renal replacement therapy Deceased organ donation (RRT) [14]. Kidney transplantation should be intro- There is a global shortage of organ donations. Com- duced to patients who qualify as recipients. Such deliv- pared to that of other developed Asian, as well as West- ered information about RRT to patients with CKD was ern countries, the number of organ donations is too recently approved to be covered by medical insurance. small in Japan (Fig. 1)[2]. The number of deceased Recently, donor-specific immunosuppression and kid- organ donors pmp in 2016 was 0.8 in Japan and 4.5, ney regeneration has been developed as future aspects 6.3, 11.2, 21.4, 28.7, 31.0, and 46.7 in Taiwan, Hong of kidney transplantation in Japan. Regulatory T cell Kong, South Korea, the UK, France, the USA, and (Treg) therapy was almost successful in liver trans- Spain, respectively (Fig. 1)[2]. The concept of brain plants, although anti-donor-specific antibodies (DSAs) death is accepted in the younger Japanese generation. were produced in two of 10 recipients [15]. Immunoto- According to research conducted by the cabinet office lerance is more difficult to induce in kidney than in of the government of Japan in 2017, 41.8% of the popu- liver transplants. However, clinical trials of Treg ther- lation had a will specifying organ donation in cases of apyinkidneytransplantationareongoinginJapan,as brain death and cardiac arrest [21]. Notably, 69.6% of well as the USA [16, 17]. the approximately 18–20-year generation had a positive Human-induced pluripotent stem cells are being donation will compared to 34.2% of the 60-year gener- used to study kidney regeneration is now being stud- ation [21]. In spite of this, the actual number of organ ied using iPSCs [18]. The nephron progenitors were donations is far less. This discrepancy might not be re- successfully generated and completely replaced native alized by doctors and transplant coordinators, and may nephron progenitor cells with donor cells from the be the reason why very few present the option of organ mixture cells produced by the niche method [19]. donation to the family of brain-dead patients. The Fig. 1 Worldwide deceased organ donations pmp in 2016. pmp: per million population. This figure was referred as reference [2]. Yellow; Asian countries, red; Japan Organ donation pmp in Japan in 2016 was lower than Asian developed countries such as South Korea, Taiwan, Hong Kong, and Western countries Aikawa Renal Replacement Therapy (2018) 4:50 Page 3 of 12 United States Routine Inquiry Laws on Organ Donation compared to 7.9, 8.2, 20.7, 35.3, 45.1, 55.9, and 62.8 in (required request laws) request consent of potential candi- Taiwan, Hong Kong, South Korea, the UK, the USA, dates or their families for donation or at least inform France, and Spain, respectively (Fig. 3)[1]. Since the re- people of the option [22]. In European countries, in-house vision of the Japanese transplant law in 2010, kidney donor coordinators ask potential donors’ families to do- transplantation after brain death has increased slowly. nate organs in terms of transplant procurement manage- In contrast, kidney transplantation after cardiac arrest ment [23]. However, the option for organ donation from has decreased remarkably since 2010 (175) to 42 in patients with brain death is not regulated by law and de- 2015, the lowest number to date [25, 26]. Terminal care pends on the decision of charged doctors in Japan [24]. In remains unpopular in Japan. Very few medical staff ac- a research study of medical record reviews of 3898 cases tively discontinue ventilation, even in brain-dead pa- as the Donor Action Program in donor hospitals, the rate tients. Donation after circulatory death (DCD) is either of optional presentation of organ donation to the family controlled or uncontrolled, as per the Maastricht classi- was 18.9% only [4]. Consequently, organs were donated fication [27]. Uncontrolled DCD refers to organ re- from 0.1% of brain-dead patients and 3.4% of patients with trieval following an unexpected cardiac arrest from cardiac arrest [4]. To mitigate this low rate of organ dona- which the patient cannot or should not be resuscitated. tion, Yokota’s research group, founded by the Japanese In contrast, controlled DCD takes place after death fol- Ministry of Health, Welfare, and Labor, suggested that ter- lowing the planned withdrawal of life-sustaining treat- minal and grief care includes an optional presentation of ments that have been considered of no overall benefit organ donation mediated by qualified medical social to a critically ill patient in the intensive care unit or workers [5]. emergency department. In Japan, the number of con- trolled DCDs is low, because although life-sustaining treatments usually continue or are minimized, respira- The number of DDKTs and kidney donations tory support is not withdrawn until cardiac arrest.
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