This report presents the Japanese status of organ procurement from deceased donors for organ transplantation in 2018. The Act on Organ Transplantation was established in July 1997 and amended in June 2009. After the enforcement of the amended Act on Organ Transplantation in July 2010, the number of brain-dead donors vastly increased. But the total numbers of deceased donors for organ transplantation, which were almost the same in 2010, 2011, and 2012, decreased in 2013 and 2014 and slightly increased in 2015, 2016 and 2017. But in 2018, incredibly, the total number of deceased donors decreased to 95. This fact is the biggest problem in organ transplantation in Japan. The lives, which are saved by the organ transplantation elsewhere the world, cannot be saved in Japan. The organ procurement for transplantation from deceased donors is supported by the efforts of procurement teams.

A total of 1,865 kidney transplants including 1,683 from living donors, 55 from non-heart-beating donors and 127 from heart-beating donors were performed in 2018 in Japan.

The data obtained from the Japanese Renal Transplant Registry are shown and analyzed in this annual report. The characteristics of recipients and donors such as relationships, original diseases, duration of dialysis therapy, blood transfusion, status of viral antigens and antibodies, pretransplant complications, causes of death of deceased donors, ischemic time and histocompatibilities are described. In addition, immunosuppressants used initially and other treatments are analyzed.

We also report the results of a follow-up survey for recipients and living donors.

As of December 31, 2018, a total of 9,643 liver transplants had been performed in 68 institutions in Japan. There were 507 deceased donor transplants (504 from heart-beating donors and 3 from non-heart-beating donors) and 9,136 living-donor transplants. The annual total of liver transplants in 2018 was 401 (60 deceased donor transplants and 341 living-donor transplants). The most frequent indication was cholestatic disease, followed by neoplastic disease and hepatocellular disease. As for hepatocellular disease in 2018, alcoholic cirrhosis and non-alcoholic steatohepatitis were the most common. Patient survival following transplantation from heart-beating donors (504 transplants: 1-year 89.0%, 3-year 85.7%, 5-year 82.8%, 10-year 75.7%, 15-year 67.0%, 20-year 61.4%) was similar to that from living-donors (9,136 transplants: 1-year 85.2%, 3-year 81.2%, 5-year 78.7%, 10-year 73.5%, 15-year 68.8%, 20-year 65.9%, 25-year 64.7%). Graft survival was very much the same as patient survival (heart-beating donors: 1-year 88.4%, 3-year 85.1%, 5-year 82.2%, 10-year 75.1%, 15-year 66.5%, 20-year 60.9%, living-donors: 1-year 84.4%, 3-year 80.2%, 5-year 77.6%, 10-year 71.8%, 15-year 66.6%, 20-year 63.3%, 25-year 62.0%). Survival data are reported according to age and sex of recipient, indication, graft type, age and sex of donor, ABO-compatibility, and other factors.

Since the Organ Transplantation Law was passed in October 1997, a total of 428 heart transplantations (HTx) have been performed in Japan as of December, 2018. Of those, 359 HTx were performed after activation of a revised Transplant Act, and 55 were performed in 2018. Most recipients had dilated cardiomyopathy; and the waiting condition of all patients was status 1 at HTx. The mean waiting time as status 1 continuously increased to 1310 days in 2018 from 873 days in 2014. After approval of the use of the implantable continuous flow ventricular assist device (cf-LVAD) for bridge-to-transplant (BTT) in 2011, BTTs, especially those using the cf-LVAD increased. In 2017, all adult patients were BTT cases, and 50 (100%) of them were supported by several types of cf-LVADs. Mean support duration also continuously increased to 1356 days in 2018 from 876 days in 2014. Thirty-three children underwent HTx and 26 (79%) of them were BTT cases (8 in Nipro VAD, 7 in EXCOR VAD, 6 in Jarvik and 3 in other cf-VADs). Most of patients received a modified bicaval method of operation with Celsior for cardiac preservation, and all recipients were administered triple therapy with calcineurin inhibitor (cyclosporine or tacrolimus), mycophenolate mofetil, and steroid as an initial immunosuppressive regimen. Patient survival at 10 and 15 years was 89.5% and 85.8%, respectively, which is superior to that of the international registry. This review documented that the results of HTx in Japan were excellent despite a severe shortage of donors and long waiting times with LVAD as BTT.

【Objective】 To scrutinize the status of lung transplantation in Japan, the Japanese Society of Lung and Heart-Lung Transplantation started to collect and present registry data from 2005. This is the 15th official registry report of Japanese lung transplantation.

【Design and Methods】 The data of cadaveric lung transplantation and living-donor lobar lung transplantation performed by the end of 2018 were registered in the database and analyzed with respect to the number of transplants, recipient survival rates, recipient functional and working statuses, and causes of death after transplantation. Survival rates were calculated by the Kaplan-Meier method.

【Results】 A total of 447 cadaveric lung transplantation (231 single, 216 bilateral), 221 living-donor lobar lung transplantation and 3 heart-lung transplantation procedures were performed by the end of 2018. Five-year and 10-year survival rates for cadaveric lung transplantations were 71.9% and 57.8%, which were superior to those in the International Registry. Five-year and 10-year survival rates for living-donor lobar transplantations were similar to those for cadaveric lung transplantation at 74.0% and 63.3%. The recipients of 3 heart-lung transplantations are alive. The functional status of more than 80% of recipients was restored to a mMRC scale of grade 0 or 1 after transplantations. Infection has been the leading cause of death after lung transplantation. Chronic lung allograft dysfunction and primary graft dysfunction account for about 18% of the causes of death after cadaveric and living-donor lung transplantations.

【Conclusion】 The outcomes of Japanese lung transplantation are so far satisfactory. Efforts must be made, however, to overcome early deaths resulting from primary graft dysfunctions and chronic lung allograft dysfunction. The modified Japanese transplantation law has been enforced since July 2010, and an increase in the number of cadaveric organ transplantations has been achieved thereafter. The Japanese Society of Lung and Heart-Lung Transplantation will continue to present annual reports of Japanese lung transplantations.

A total of 388 cases of pancreas transplantation from deceased, non-heart beating and living-related donors have been performed in 18 institutions in Japan as of the end of 2018 since April, 2000. The following donor- and recipient-related factors were analyzed: age and gender of donor and recipient, cause of death, histories of diabetes and dialysis, waiting period, total cold ischemic time, operative procedure, immunosuppression and survival rates of patient and graft. We showed the current status of pancreas transplantation in Japan. Although the donor conditions have improved every year, they were still mostly marginal. However, the outcome of pancreas transplants was considered to be comparable to that of the US and Europe. The patient survival is 96.3% and 94.9% at 1 and 5 years, respectively. Pancreas graft survival for SPK is 90.8% and 86.7% at 1 and 5 years, respectively. The most critical problem is that the pancreas graft survivals of PAK and PTA were significantly poorer than that of SPK. Another is that the early graft loss rate within 90 days after pancreas transplantation is 8.9%.

We should propose our original safety criteria for pancreas transplants to reduce the early graft loss and achieve a long-term graft survival.

Islet transplantation is promising to be capable of relieving glucose instability and improving the QOL of type 1 diabetic patients with uncontrollable severe hypoglycemic unawareness. A phase II clinical trial of islet transplantation for type 1 diabetes patients has been under way using ATG induction and TNF-α inhibition protocol since 2012 in Japan. Primary endpoints for this trial are the proportion of subjects with HbA1c<7.4% and who are free of severe hypoglycemic events one years after the first islet cell infusion. This trial will play an important role in establishing islet transplantation in Japan.

Thirty intestinal transplants were performed since 1996 in 6 institutions. There were 17 deceased donor and 13 living donor transplants. Primary causes of intestinal transplants were short gut syndrome (n=12), intestinal mobility function disorder (n=14), others (n=1) and re- transplantation (n=3). One-year patient survival was 89%, and 10-year patient survival was 54%. They were excellent results for a standard therapeutic option for intestinal failure if patients failed to maintain total parental nutrition.

Hematopoietic stem cell transplantation (HSCT) offers potentially curative treatment for a wide range of otherwise fatal hematologic disorders, and the number of HSCTs has continued to increase over the last 20 years; more than 5,000 allogeneic and autologous HSCTs have been performed annually in recent years. A constant increase of allogeneic HSCTs for older (aged over 50) patients, and an increase in the variety of donor/stem cell sources such as cord blood from unrelated donors have led to this constant increase of HSCT in Japan. The transplant survival outcome also continues to improve and the assets for the improvement include better supportive care, innovative transplant approaches, and the considerable contribution of a well-established transplant outcome registry to a variety of clinical studies.

【Objective】 Few studies have investigated the incidence of abnormalities in electroencephalography (EEG) in pediatric renal transplant patients. The aim of this study was to evaluate EEG before transplantation and investigate the incidence of seizures following transplantation.

【Design】 case control study.

【Methods】 We evaluated the EEG of 235 patient (average age 10.0±5.8 years old) before kidney transplantation.

The results were classified into three groups according to EEG: Seizures group, who had a history of seizures; Abnormal EEG group, who had abnormal EEG before transplantation with no history of seizure; and Normal group, who had normal EEG with no history of seizures. We compared the patient background, frequency of perioperative seizures and reversible leukoencephalopathy (PRES) among the three groups. The Abnormal EEG group were administered sodium valproate prophylactically to prevent postoperative seizures.

【Results】 According to this study, 235 patients were classified into the Seizures group 28 (11.9%), abnormal EEG group 44 (18.7%), and normal group 163 (69.4%). In the Abnormal EEG grope, the proportion of patients under 12 years old was high (p=0.037). Eighteen (7.6%) of 235 patients were complicated by seizures. The incidence of PRES was not different among the three groups (p=0.970). Seventy-five-point-nine percent of the Abnormal EEG group patients improved their EEG after transplantation.

【Conclusion】 Asymptomatic electroencephalogram abnormalities were found in 18.7% of children before kidney transplantation. Three quarters of asymptomatic electroencephalogram abnormalities improved after transplantation. There were no differences in the incidence of PRES among the three groups.

【Objective】 This study assessed Japanese citizens’ attitudes toward organ transplantation and the acceptability of being offered the option to donate organs upon death, to gain insights into the most appropriate approach to offering this option in Japan.

【Design】 Cross-sectional quantitative survey study.

【Methods】 An internet panel survey was conducted in 2018. Two thousand Japanese respondents (1,208 male, 792 female) aged 18-79 years were included. Respondents were selected by proportional distribution based on residential prefectures. All data were gathered anonymously. Statistical analyses were conducted using IBM SPSS Statistics 25 and included descriptive statistics and chi-square tests. Significance was set at p<0.05.

【Results】 Interest in the topic of organ transplantation was reported by 42.8% of respondents; however, only 24.4% indicated having discussed organ donation with their families. Nearly one-third responded that they would donate their own organs upon death. Regarding acceptability of medical personnel presenting the option of organ donation as a general practice, 81.7% thought it was good or rather good practice, but only 23.2% indicated that they would themselves like to be presented with the option to donate or not donate a family member’s organs when the family member’s death was imminent. People interested in organ transplantation were significantly more likely to prefer having the option of organ donation when a family member’s death was imminent (p<0.001).

【Conclusion】 These results indicate that Japanese find being given the option of organ donation acceptable. People interested in organ transplantation show positive attitudes toward being offered the organ donation option. Increasing public awareness of organ transplantation could therefore help build positive attitudes toward donation.

【Objective】 Spain with 47.0 donors per million people (pmp.) per year is known as the eminent “transplant superpower” in the world. In Japan, the number of donors remains at 0.8 donors pmp. every year. We investigated the organ donation system of Spain to increase the donations of Japan.

【Design and Methods】 We interviewed the chief of staffs of a local hospital, a regional donation coordination office, and university hospital in Spain about education concerned with donation and their in-house organ-providing system from Apr. 9 to 11, 2018.

【Results】 As a result of an Organ Procurement Team managing all duties in-hospital in the beginning of “possible donor detection”, various burdens, e.g. on organ donation choice presentation and daily duties in each hospital, were eliminated. It became possible to transfer hospitals to aimed organ donation from the hospital in the surrounding area by burden eliminated, so the number of organ donation was increased dramatically. The university hospital established a regional alliance system centered on the hospital based on the incentive of abundant organs. It is an educational program known as the Transplant Procurement Management (TPM) training course, and has had a great influence on these organ-providing systems, indispensable to the process of organ donation as the common language in the organ procurement.

【Conclusion】 We think that it is an urgent challenge and response measure to establish and spread an educational program such as the TPM training course to increase the number of donors.

This retrospective observation study was performed in order to uncover the current status of desensitization therapy in renal transplantation recipients with donor-specific antibodies using intravenous immunoglobulin in Japan.

A primary survey was conducted at facilities that carried out renal transplantation from 2014 to 2016. From the survey it was revealed that desensitization therapy is based on the combination of multiple drugs and therapies, and in particular rituximab, plasma exchange, and mycophenolate mofetil were found to be frequently used. In addition, it was found that there is a demand for the use of intravenous immunoglobulin as part of the combination therapy in order to achieve more successful desensitization.

Subsequently, a secondary survey was performed regarding desensitization cases that used intravenous immunoglobulin from 2014 to 2016. In the cases where living-donor renal transplant was performed after desensitization therapy, rejection occurred in 40% of cases, but the graft survival rate at 2 years after transplantation was estimated to be 100%. This result was considered satisfactory regarding renal transplantation in recipients with donor-specific antibodies.