The number of people diagnosed with heart failure (HF) is increasing. Current therapies improve survival for HF with reduced ejection fraction, but a result has been to increase the number of HF patients who progress to advanced disease. Heart transplantation (HTx) offers the best survival for patients with end-stage heart failure. However, with the scarcity of donor organs, the waiting time to transplant continues to lengthen, leading to an increase in the proportion of patients with a left ventricular assist device (LVAD) in Japan. As is widely known, serial assessment of evaluating patients’ candidacy, managing long-term LVAD therapy and intensive perioperative/long-term treatment after HTx are essential to achieve a favorable prognosis. The amount of specialized knowledge and skill required to care for the growing number of patients with HF, including those who require mechanical circulatory supports and/or cardiac transplantation. Accordingly, there is an increasing need for well-trained cardiologists to manage these complex patients.

Lung transplant (LTX) has evolved dramatically over the last decades and has become a valuable option for patients with advanced pulmonary disease. Because of the limited number of LTX, all transplant processes starting from listing candidates, followed by a transplant procedure, to immunosuppressive therapy after transplantation have been managed only by thoracic surgeons in Japan. Given the current increase in the number of LTX, there is a growing demand for transplant physicians who take care of the non-surgical management of candidates and recipients. To this end, we have surveyed how devoted thoracic surgeons are to pre-, peri- and post-transplant management and how respirologists are currently involved in LTX in all transplant centers. This report presents an overview of the workload in LTX management on both thoracic surgeons and respirologists. Additionally, we document the training program specialized for lung transplant physicians that was established at Tohoku University Hospital in 2021. Although Japan has taken steps towards an increasing number of LTX, there remains a challenge to explore how respirologists participate in transplant care in Japan.

In Japan, the yearly number of liver transplantations reached the highest level of 570 cases in 2005, and decreased thereafter to 395. One-year survival after liver transplantation increased from 79.4% in deceased donors and 83.2% in living donors to 89.2% and 85.4%, respectively. To overview the present status of transplant hepatologists at transplant centers in Japan, a nation-wide survey was conducted in 2020 to both transplant surgeons and hepatologists at 14 facilities which performed more than 10 cases of liver transplantation in 2017. Although hepatologists performed preoperative evaluation and consultation at outpatient clinics, surgeons did not recognize the fact. As hepatologists were interested in preoperative treatment, postoperative immunosuppressant control and lifestyle-related chronic disease, the constitution of cooperation systems and training systems is mandatory to securely train transplant hepatologists.

There are currently 14,000 kidney transplant patients in Japan. While transplantation surgeons typically take care of the post-transplant patients and living kidney transplant donors, participation of nephrologists and internal physicians has the potential to achieve satisfactory outcome by caring for kidney transplant recipients and donors from before to after transplant surgery. Medical management of the kidney transplant recipient seems to be challenging to the general nephrologists who are unfamiliar with the medical nuances of caring for these patients. This includes immunosuppressive drugs, rejection, infections, and malignancies. In these situations, it is mandatory to establish a kidney transplant education system in Japan. In this article, I will discuss the current situation and the issues of a Japanese transplant nephrology fellowship.

The first kidney transplantation was carried out in Peter Bent Brigham Hospital (1954. 12. 23., the night prior to Christmas Eve). The transplantation team at that time was composed of surgeon, nephrologist and urologist. In the U.S., the renal physician follows up many transplant patients even now. Although the U.S. has about 4,000 transplant physicians, there are few in Japan. The transplant physician’s training is behind that of the U.S. by about 40 years. In this paper, we demonstrate that a wide quest of transplantation physicians’ training and recruiting through the Japanese Society of Internal Medicine is mandatory in order to care the transplant recipients and living donors.

In Japan, organ donor shortage is a chronic problem in transplantation; therefore, the proportion of living-related organ transplantations is higher than that of deceased donor transplantations. For the development of living-related organ transplantation, guaranteeing the health of transplantation donors is crucial, and further donor evaluation and treatment after organ donation are required. Therefore, transplant physician intervention would be desired not only for recipient complication treatment but also for donor treatment throughout transplantation.

【Objective】 Heart transplant (HTx) recipients often have a lower exercise capacity than normal healthy age-and-gender-matched controls in the early period or long after HTx. We try to elucidate the effects of the recipient and donor risk factors on the patient’s exercise capacity early after HTx.

【Methods】 Forty-one HTx recipients who underwent the procedure from April 2010 to November 2016 at the National Cerebral and Cardiovascular Center (NCVC) and participated in our 3-month cardiac rehabilitation (CR) program were reviewed retrospectively for clinical parameters, including demographics of the recipient, recipient nutritional risk factors, demographics of the donor and other risk factors for the donor heart. Each recipient underwent a symptom-limited cardiopulmonary exercise test at the entry and the end of the 3-month program.

【Results】 The peak VO₂ was significantly increased after the 3-month program in patients irrespective of recipient and donor risk factors including several nutritional factors. Younger recipient age, higher serum choline esterase and higher blood lymphocyte counts at the entry were significantly associated with higher peak VO₂ at the entry and end of the 3-momth program.

【Conclusion】 These data suggested that nutrition management before HTx and entry into a 3-month CR program early after HTx play a significant role in increasing peak VO₂ for HTx recipients.

【Objective】 To improve the Japanese guideline for HTLV-1 infection in organ transplantation published in 2019, we investigated the awareness of the guideline and actual management in Japan.

【Methods】 In February 2020, we sent a questionnaire about the guideline and the actual management of HTLV-1 infection to 220 hospitals in which kidney and/or liver transplantations were performed. Transplant doctors anonymously answered and returned it by mail.

【Results】 The questionnaire was returned from 106 (48%) hospitals and 46% of them had already known the guideline. More than 90% supported or were somewhat supportive of the contents of the guideline. The indication policy for an HTLV-1-positive donor to a negative recipient (D+/R−) kidney transplantation, which is contraindicated in the guideline, was: ‘no contraindication,’ 0%; ‘relative contraindication,’ 15%; ‘absolute contraindication,’ 73%; ‘not determined,’ 6%. That of D+/R− liver transplantation, which is not an absolute contraindication, was: ‘no contraindication,’ 0%; ‘relative contraindication,’ 35%; ‘absolute contraindication,’ 35%; ‘not determined,’ 19%. Regarding D+/R+ and D−/R+ transplantations, which are not contraindicated, the answers were similar for kidney and liver: ‘no contraindication,’ ∼50%; ‘relative contraindication,’ ∼10%; ‘absolute contraindication,’∼10%; ‘not determined,’∼20%. Regarding pretransplant HTLV-1 screening, nearly 90% routinely performed the screening test; however, only 48% knew that the confirmatory test is necessary to diagnose HTLV-1 infection.

【Conclusion】 Most hospitals agreed with the guideline; however, the indication policies were substantially different, suggesting that D+/R− transplantation sometimes cannot be avoided because of the donor shortage. Doctors also had concern about the safety of transplantation for HTLV-1-positive recipients. More evidence is required for this patient population.

【Objective】 We report the developmental trend of infants who received heart transplantation after using the ventricular assist device (VAD).

【Design】 To evaluate the infants development, the KIDS Infant Development Scale was conducted on parents of four infants who received heart transplantation after implanting the VAD, the term of VAD usage being August 2012 to December 2016.

【Methods】 The age of infants at VAD implantation and the age of infants at the time of heart transplantation in months were: Cases A to D: 15/25, 11/20, 10/22, and 21/30. Developmental evaluations were performed at 3 time points: before transplantation, 1 year after transplantation, and later at the time of postal mail inquiry (Case A to D: 5 years 5 months, 2 years 4 months, 2 years, and 2 years 5 months).

【Results】 In all cases, overall developmental was slower than the chronological age at the pre-transplant evaluation, and the overall developmental index (DQ) was around 50 (Cases A to D: 36.0, 60.0, 45.5, and 53.3). Development showed a catch up trend at one year after transplantation (Cases A to D: 48.6, 62.5, 14.7, and 107.1). Development was further promoted at the time of postal mail evaluation which was more than 2 years after transplantation, wherein 2 patients reached DQ100 (Cases A to D: 93.3, 106.3, 21.7, and 175.0).

【Conclusion】 The development of patients with severe heart failure seeking transplantation was delayed. After transplantation, development showed a trend of catching up.

【Objective】 We examined the degree to which the prerequisites for brain death were met, and examine the actual conditions and factors that led to the loss of organ donation even though the prerequisites for brain death were met, if possible donors, who were likely to become brain dead, were selected automatically at the time of admission, as in Spain, which was the world’s No. 1 country in terms of the number of organ donations.

【Design】 cohort study.

【Methods】 This was a single-center, retrospective study of patients under 75 years of age who met criteria for possible donors and were discharged dead from the emergency department. We investigated the prerequisites for brain death, the conditions that could be considered brain death, and the percentage of patients who were offered the option of organ donation, and then examined the factors that contributed to these patients’ conditions at the time of admission and the treatment and patient care after admission.

【Results】 One-third of the possible donors died and were discharged from the hospital, and the possibility of organ donation gradually decreased with each step, with only 3% of the possible donors eventually becoming organ donors. The diagnosis of brain death was influenced by the post-hospitalization treatment and the understanding of transplantation medicine by the attending physician.

【Conclusion】 Early multidisciplinary intervention in possible donors may lead to transplantation care with less burden on both medical personnel and families.

【Objective】 Due to the COVID-19 pandemic, transportation and movement of people are restricted, and organ recovery, including the movement of surgeons, may also be restricted. We conducted a questionnaire survey to improve the system of organ recovery.

【Methods】 A questionnaire survey was conducted as part of a welfare and labor science special research project entitled, “Survey research for organ transplantation from brain dead donors and donors after cardiac death during the pandemic of COVID-19”, and was distributed electronically to 206 transplant centers (heart, n=11; lung, n=10; liver, n=25; kidney, n=130; pancreas, n=18; small intestine, n=12).

【Results】 We received questionnaire responses from 177 of the 206 centers (response rate: 86%). Fifty-four centers (31%) had helped recover organs for other centers. Forty-eight centers (27%) had received help from other centers to recover organs. Nineteen (95%) of the thoracic organ transplant centers were willing to participate in nationwide organ distribution and recovering graft organ by own their staff. Eighty-five (55%) abdominal organ transplantation centers were willing to undertake nationwide organ distribution and recovering graft organ by other centers close to the donor’s hospital.

【Conclusion】 Due to the COVID-19 pandemic, it may be necessary to review the organ recovery system in Japan, and the results of this questionnaire are considered helpful for making such changes.

【Objective】 Lipid metabolism disorder worsens in many patients after kidney transplantation depending on the immunosuppressive agents administered. Thus, this study aimed to examine the safety and efficacy of using monoclonal antibodies that inhibit proprotein convertase subtilisin-kexin type 9 (PCSK9) and have a potent effect on lowering low-density lipoprotein cholesterol (LDL-C) levels in patients who have undergone kidney transplantation.

【Design】 Case series study.

【Methods】 Patients who received PCSK9 inhibitors, Evolocumab or Alirocumab, and had an inadequate control of LDL-C levels despite being under statin therapies were investigated. The data obtained before and after the patients were administered these agents were compared to investigate the LDL-C lowering effects and adverse event occurrences.

【Results】 Of the patients, 11 were treated with PCSK9 inhibitors (8 men and 3 women, median age: 63 years; interquartile range [IQR] 59-68). A significant LDL-C reduction (from median 112 mg/dL [IQR 116-130] to median 31 mg/dL [IQR 1.6-2.5]) was observed, and the efficacy lasted for a 1-year treatment period. No significant changes were noted in the creatinine levels of the patients or trough concentrations of the calcineurin inhibitor drugs. Moreover, new-onset episodes of rejections or diabetes mellitus were not observed in any patient, and no patients developed additional cardiovascular events during the observation period.

【Conclusion】 The present study showed that PCSK9 inhibitors significantly lowered LDL-C levels in kidney transplant patients, and no adverse effects that interfered with the management of the transplanted kidneys were observed.

【Objective】 To report the activities of an in-hospital coordinator who changed to a multidisciplinary system to build a system that can connect the intention of organ donation.

【Methods】 The in-hospital coordination was changed from a nurse-only system to a system including an emergency physician, a clinical laboratory technician, and a clinical engineer. In addition, a urologist and a clinical recipient transplant coordinator were added as support staff.

【Results】 A multidisciplinary hospital coordinator system was established, and a system for organ donation was put in place within the hospital. Since the change to the multidisciplinary coordination system, we have experienced seven cases of organ donation under brain death. The multidisciplinary collaboration system has strengthened team ties and facilitated cooperation when dealing with organ donation cases.

【Conclusion】 The number of cases of brain-dead organ donation increased due to the improvement of teamwork through multidisciplinary cooperation and the improvement of the hospital system.

【Objective】 The author investigated the reasons why organ donation has not developed sufficiently in Japan, especially focusing on the educational practices and policies of medical institutions.

【Design】 Questionnaire survey and observations.

【Methods】 The author analyzed the reports of medical students and the general public at lectures about organ donation, and also observed the activities of the emergency organizations, as well as transplantation organizations for fifteen years.

【Results】 The legal definition of brain death, and the rules and procedures of organ donation remain misunderstood by the general public. The emergency medical institutions were passive or less motivated regarding donation because they were concerned that actively encouraging donation may cause the patients’ families to feel pressured to donate the organs of their loved ones. The transplantation organizations stressed brain death too strongly. Consequently, the general public is currently unable to have a clear, informed view on donation. Moreover, transplantation organizations did not clearly explain requirements for organ donation to the general public because they were also concerned that those requirements may be criticized as inducing or forcing donation.

【Conclusion】 All facets regarding organ donation must be clearly explained to the general public. Medical students and staff should be educated to participate in organ donation professionally.