【Objective】 Expanded criteria donors (ECD), or marginal donors including donation after cardiac death (DCD), are now accepted as a one of the most important solutions for the shortage of organ donors in the world. A greater risk of severe ischemic reperfusion injury may lead delayed graft function (DGF), primary non-function (PNF), and poor graft survival. The aim of this study is to access the possibility of experimental kidney transplantation with warm chemically-injured kidney graft preserved with a machine perfusion system.

【Methods】 Domestic pigs weighing 30 kg were used in this study. A 30-minute warm ischemic time (WIT) was induced by clamping the renal artery. Group 1; Kidney was preserved with simple cold storage (CS) in UW solution for 22 hrs. Group 2; Kidney was preserved with CS for 5 hrs and perfused with a hypothermic machine perfusion preservation (HMP) system. Kidney was reperfused by ex vivo autologous blood transfusion and evaluated for 30 minutes. The hemodynamic parameters and urine volume were measured. In addition, histological and immunohistochemical findings were investigated.

【Results】 The serum creatinine level was remarkably lower in the HMP group than in the CS group. An initial urine volume was found in the HMP group, but not in the CS group. Histological findings revealed severe degeneration in tubular cells in the CS group compared to the HMP group. Additionally, immunohistological findings demonstrated endothelial cells were significantly exfoliated to a more severe extent and platelet aggregation occurred more frequently in the CS group than in the HMP group.

【Conclusion】 Using machine perfusion is the preferred preservation approach for warm ischemic kidney with long cold preservation time.

【Objective】 Pediatric kidney transplant (KTx) recipients receive medication under their parents’ supervision. However, once they reach adolescence, they may be given the responsibility of managing their own medication with the support of their family and medical staff. Previous research has shown that medication nonadherence (NA) in KTx recipients is influenced by psychosocial aspects of the recipients and their family. The present study sought to assess the prevalence of NA and its association with psychosocial issues in KTx recipients and family-related factors.

【Materials and Methods】 Between January 2000 and March 2019, 220 pediatric KTx were performed at our institution. The present study enrolled 193 recipients who underwent a psychological and intelligence test before transplantation. NA was defined as stating that the recipients had incorrectly taken immunosuppressive drugs more than twice a week with renal malfunction or renal graft rejection.

【Results】 The NA rate was found to be 15.5%. The timing of NA was age 17.4±3.6 years, with bimodal peaks at puberty (n＝21) and young adulthood (n＝9). The pre-KTx intelligence quotient (IQ) was 90.4±14.1 in the nonadherence group and 78.9±25.9 in the good-adherence group, with the IQ of the nonadherence group being significant lower in puberty-onset group (PG) than in the young adult-onset group (YG) (85.6±11.8 and 101.7±13.0). The cause of nonadherence differed between the PG and YG; 11 patients in the former had poor self-management, four required enforcement of self-management, three refused medication, and three had poor medication understanding. Six patients in the YG experienced disturbances in their life rhythm, one experienced depression, and two had poor medication understanding. Of the patients with NA, 43.3% had poor support from their family; six were from a single-parent household (20%) and four experienced parental neglect (13.3%). In the same group two had a poor understanding of their treatment (6.7%), and one had a poor relationship with the parents (3.3%).

【Conclusion】 NA was present in 15.5% of the subjects, most of whom were in the PG. The pre-KTx IQ of the PG was significantly lower than that of the YG. The PG had potential high prevalence of cognitive problems and insufficient familial support. Meanwhile, the YG had the psychosocial problem of adaptation to social change. To reduce NA, the PG needed a pre-KTx personality assessment and familial support while the YG needed psychosocial support.

【Objective】 Immunosuppressant drugs such as cyclosporine (CSA), tacrolimus (TAC) and everolimus (EVR) are often used in transplantation therapy. Their concentrations need to be monitored carefully. This study aimed to evaluate the analytical performance of the CLAM^TM-2030 connected with LCMS^TM-8060 based on the liquid chromatography with tandem mass spectrometry method (LC-MS/MS), which has been newly developed to measure the immunosuppressant drugs in whole blood.

【Methods】 The assay precision, the stability of calibration, linearity, lower limit of quantitation (LOQ), and correlation of immunoassay method with LC-MS/MS were examined using residual whole blood samples from transplantation patients who were being treated with CSA, TAC, or EVR. Furthermore, we measured the metabolites of EVR.

【Results】 The CLAM^TM-2030 connected with LCMS^TM-8060 showed satisfactorily analytical performance. Regarding the EVR correlation, the difference between two immunoassay methods and LC-MS/MS was revealed (n＝84, r＝0.936, y＝1.172x＋0.799, n＝84，r＝0.979，y＝0.871x−0.661). The result of including the everolimus metabolites was a shift of the correlation slope from 0.871 to 1.026.

【Conclusion】 It is possible to measure CSA, TAC, and EVR simultaneously without pretreatment using CLAM^TM-2030 connected with LCMS^TM-8060. It may be suitable for routine measuring of immunosuppressant drugs in the clinical laboratory.

【Objective】 Flow cytometric crossmatch (FCXM) and complement-dependent cytotoxic crossmatch (CDC) are usually used for the lymphocyte crossmatch to detect donor specific HLA antibodies (DSA). However, the results are often different at FCXM and CDC for lymphocyte crossmatch. We have reported that the cause of this discrepancy is based on the difference in the complement-binding ability of anti-HLA antibody. (Design) We studied the complement non-binding DSA which exists in the sera of long-term graft survival kidney transplant.

【Methods】 Seventy-nine subjects were chosen from the recipients of kidney graft surviving longer than 15 years who had undergone a PRA-screening test between 2016 and 2019. DSA of these recipient sera were detected using the LABScreen Single Antigen Test (SA).

【Results】 Of these, 62 subjects had serum creatinine (Cre) of 2.0 mg/dL or less, 32 cases were negative for anti-HLA antibodies, non-DSA numbered 14 cases and DSA positive 16 cases. Six cases were Class1-DSA only positive, and 4 cases of these measured higher than 8000 nMFI; 5 cases were DR-DSA only positive, and 4 of these were higher than 10000 nMFI. In five cases, DQ-DSA antibodies were only positive; 4 of these were higher than 17000 nMFI, but all these DSA were CDC negative. Of those 33 years beyond the transplant, nMFI of DSA-B51 was 13299 nMFI, but the present kidney functions were Cre 0.83 mg/dL and eGFR 61.4 mL/min. The longest graft survival case was 36 years, and that DSA-A24 was 8241 nMFI, but the present kidney function was Cre 1.76 mg/dL and eGFR 31.1 mL/min.

【Conclusion】 Even if DSA are present, it is considered possible for the transplanted kidney to survive for the long term if it is complement- non-binding DSA.

【Objectives】 This is a second survey conducted with the aim of understanding the actual situation of rituximab use in pancreas transplantation in Japan after a first survey for all organ transplantation.

【Methods】 A second survey on efficacy and safety was conducted, which included 4 cases from 3 institutions in which rituximab was used for the treatment of antibody-related rejection after pancreas transplantation from August 2001 through December 2016.

【Results】 Although pancreatic graft biopsies were not performed in any case, kidney graft biopsy was performed in 3 cases for the diagnosis of AMR. After the diagnosis of rejection, two were positive for DSA class II, and two were positive for both DSA class I and II. As a treatment for AMR, one patient received 50 mg/m² of rituximab, and the other three patients received 200 mg/body. The pancreatic graft prognosis after AMR was graft loss in 3 of the 4 cases. As an adverse event after AMR treatment, antigenemia due to cytomegalovirus (n＝1) and bone marrow suppression (n＝2) were observed as adverse events; however, none of these adverse events was serious and all cases recovered.

【Conclusion】 AMR after pancreas transplantation was associated with a poor pancreatic graft prognosis. However, treatment with rituximab has shown the potential to control AMR and avoid graft loss.

In addition, no fatal adverse events were observed, and the incidence of complications, such as viral infection, was not high.

【Objective】 To survey the details of treatment with rituximab for antibody-mediated rejection (AMR) after heart transplantation.

【Methods】 A retrospective study was conducted to survey outcomes in patients who underwent heart transplantation in Japan from August 2001 through December 2016 and were treated with rituximab for post-transplant AMR. A questionnaire was sent to medical institutions that have used rituximab for such treatment, and information on AMR treatment rituximab dosage, efficacy, and safety was collected.

【Results】 Three medical institutions reported a total of 4 patients (2 male and 2 female), 5 to 45 years of age at transplantation: 3 patients with dilated cardiomyopathy and 1 with a single ventricle. All had a history of blood transfusion. Records showed acute AMR in 3 cases, chronic AMR in 1 case, and T cell-mediated rejection (TCMR) as a comorbidity in 3 cases. All 4 patients tested positive for donor-specific antibodies (DSA). Two patients experienced 2nd AMRs each: 1 acute AMR and 1 suspected AMR. Rituximab was administered to both patients for the first rejection and to one patient for suspected AMR. Doses ranged from 368 mg/m² to 383 mg/m². All patients recovered from rejection and experienced successful engraftment of the transplanted organ. AMR treatments, including rituximab, were well tolerated. However, 1 of the 4 patients developed acute renal failure, pulmonary mycosis, and gastrointestinal bleeding, and eventually died from herpes zoster with a functioning graft.

【Conclusion】 Treatment containing rituximab is considered effective for AMR, but careful monitoring is required to prevent or reduce the development of infections.

【Objective】 We retrospectively surveyed the details of treatment with rituximab for antibody-mediated rejection (AMR) after lung transplantation.

【Design】 Case series.

【Methods】 This study was conducted to assess outcomes in patients who underwent lung transplantation in Japan from August 2001 to December 2016 and were treated with rituximab for AMR. A questionnaire was sent to medical institutions that had used rituximab for such treatment, and information on AMR treatment, including rituximab dosage, efficacy, and safety, was collected.

【Results】 Among the 525 patients undergoing lung transplantation during the study period in Japan, fourteen patients (2.7%; 1 child and 13 adults) were enrolled. Records showed definite clinical AMR in 3 patients, probable clinical AMR in 2 patients, possible clinical AMR in 8 patients and suspected AMR in 1 patient. All patients had allograft dysfunction, and 13 adult patients were positive for donor-specific antibodies (DSA). Two patients experienced rejection more than twice. Rituximab was administered to all patients. In one patient who experienced AMR twice, rituximab was administered for each AMR. The rituximab dose was 375 mg/m² in all but one patient, who received 348 mg/m². Eight patients recovered from AMR. AMR treatments, including rituximab, were well tolerated. However, 11 patients developed graft loss due to rejection, and 10 patients died from chronic lung allograft syndrome or sepsis.

【Conclusion】 Based on these findings, treatment containing rituximab was considered effective for AMR, but careful monitoring is needed to prevent or reduce the number of adverse events such as infection.

【Background】 The machine perfusion of marginal kidney grafts from donors after cardiac death (DCD) has become one of the standard therapies in the USA and Europe. We report the first case of Japanese clinical trials of the hypothermic machine perfusion of the kidney transplantation from DCD.

【Case】 The man was around 60 years old. He underwent hemodialysis for 26 years. We could perform the hypothermic machine perfusion of the kidney transplantation from DCD. The patient was withdrawn from the hemodialysis after transplantation and discharged on postoperative day 23. Now, his renal function is good (P-Cr＝1.7).

【Conclusion】 We performed kidney transplantation from DCD using the new machine perfusion system. This result helps the expansion of the kidney transplantation from DCD.