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Background: The coronavirus disease 2019, caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has become a global epidemic. There are concerns regarding the severity of SARS-CoV-2 infections in kidney transplant (KTx) recipients. However, there is limited data on how the epidemic has affected the treatment and prognosis of these patients. Therefore, we aimed to report the changes in the treatment and outcomes of KTx recipients infected with SARS-CoV-2 during each wave at our institution., Methods: A total of 282 KTx recipients who were infected with SARS-CoV-2 during the study period were followed up at Tokyo Women's Medical University between March 2020 and August 2022. We investigated the outcomes and treatments of infected KTx recipients., Results: Nineteen (6.7%) patients showed severe outcomes, including eight SARS-CoV-2 infection-related deaths. Risk factors associated with severe outcomes included underlying conditions, such as diabetes mellitus, heart disease, and liver disease (odds ratios, 2.09, 2.88, and 5.52, respectively). Treatment strategies changed throughout the epidemic in response to changes in the SARS-CoV-2 variants. Antiviral drugs were gradually administered as soon as they were approved for use., Conclusions: Treatment strategies for KTx recipients were gradually established over the course of the epidemic. Although the proportion of infected KTx recipients decreased compared to that of the general population throughout the epidemic, many patients still followed a severe course., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Poor post-vaccination production of antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a concern among solid organ transplant (SOT) recipients. Furthermore, the timing and kinetics of antibody titers after the second vaccine dose are unknown. We conducted a multicenter prospective observational study that included 614 SOT recipients: 460 kidney, 53 heart, 50 liver, 20 lung, and 31 simultaneous pancreas-kidney (SPK). The participants received two doses of the mRNA vaccine (Pfizer BNT162b2 or Moderna mRNA-1273), as indicated. Serum samples were collected before the first and second vaccinations and at 1, 3, and 6 months after the second vaccine dose, which were then assessed for SARS-CoV-2 antibodies. The overall seropositivity rate was 43% at 1 month after administration of the second vaccine dose; it gradually increased to 68% at 3 months after second dose administration and to 70% at 6 months. In addition, recipient of kidney, lung or SPK transplants had lower antibody titers at the 3- and 6-month time points than did the other recipients. SOT recipients acquired SARS-CoV-2 S-IgG antibodies slowly, and the peak titer differed significantly from that of the general population., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yoshio Hirota reports financial support was provided by Health Labor Administration. Yoshio Hirota reports a relationship with Japan Health Labor Administration that includes: funding grants. The authors of this manuscript have no conflicts of interest to disclose as described by the Vaccine. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The number of marginal living kidney donors has increased. Medically complex donors who have hypertension, older age, or low estimated glomerular filtration rate (eGFR) have been more likely to be used., Methods: We conducted a retrospective cohort study of living kidney donors at a single center. We analyzed 309 living donors and divided them into three groups: group with older donors (aged ≥70 years) (n = 41), middle-aged (aged 46-69 years) (n = 239), and young donors (aged <46 years) (N = 29). Donor factors associated with chronic kidney disease (CKD) stage 3b or worse within 5 years post-donation were investigated., Results: Of the 309 live donors, 86 (27.8%) developed CKD stage3b or worse within 5 years post-donation. The incidence of CKD stage3b or worse within 5 years post-donation was significantly higher in older donor (p < 0.01). Cox regression models revealed that older donor ages and lower eGFR were significantly related to the development of CKD stage3b or worse, independent of comorbidities such as obesity and hypertension [hazard ratio (95% CI); 4.59 (1.02-20.6), p = 047, 0.95 (0.94-0.96), p ≤ 0.01, respectively]. However, recovery of eGFR 4-5 years after donation was noted in the middle-aged and older donor groups, whereas the level of eGFR remained unchanged in the young group., Conclusions: Older donors tend to develop CKD stage3b within 5 years post-donation but with the potential of recovery. Healthy older people (aged ≥70 years) could be candidates for living donors under careful monitoring of kidney function after donation., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Objectives: To compare the efficacy and safety of hypoxia-inducible factor prolyl-hydroxylase inhibitors (HIF-PHis), a novel agent for management of anemia in chronic kidney disease (CKD), between transplant recipients and nontransplant individuals., Methods: A retrospective analysis was conducted on nondialysis-dependent CKD stage 3 to 5 patients treated with the HIF-PHi roxadustat or daprodustat at a single institution. Patients were categorized as kidney transplant recipients (KTRs) and non-KTRs. Efficacy outcomes (hemoglobin and creatinine levels) and safety profiles (rate of adverse events [AEs], descriptions, and discontinuations due to AEs) were assessed 3 months before and 6 months after HIF-PHi initiation within and then between the groups., Results: The study comprised 82 patients (KTR: 43, non-KTR: 39). Median ages significantly differed between the KTR (52.7 years) and non-KTR (82.9 years) groups (P < .001). Roxadustat was predominantly used in the KTR group (88.4%), while daprodustat was used in the non-KTR group (94.9%, P < .001). Both groups exhibited significant increases in Hb levels at 1, 3, and 6 months post-HIF-PHi initiation (P for trend, <.001), with a relative increase in Hb level at 6 months of 16% for KTRs and 13% for non-KTRs. Creatinine levels showed no significant changes over 6 months. Although no difference was observed in drug discontinuation due to AEs, the KTR group experienced a significantly higher rate of thrombotic events (18.6 vs 2.6%, P = .049)., Conclusions: HIF-PHis demonstrate comparable efficacy for managing anemia in CKD, regardless of transplant status. However, heightened vigilance for thrombosis events is necessary during follow-up for KTRs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Kidney transplantation is a well-established alternative in renal replacement therapy. Compared with hemodialysis, low-immunological-risk kidney transplantation can reduce the medical treatment costs associated with end-stage renal disease. However, there are few reports on whether high-immunological-risk kidney transplantation reduces the financial burden on governments. We investigated the medical costs of high-immunological-risk kidney transplantation in comparison with the cost of hemodialysis in Japan., Methods: We compared the medical costs of high-immunological-risk kidney transplantation with those of hemodialysis. 15 patients who underwent crossmatch-positive and/or donor-specific antibody-positive kidney transplantations between 2020 and 2021 were enrolled in this study. The patients received intravenous immunoglobulin, plasmapheresis, and rituximab as desensitizing therapy., Results: Acute antibody-mediated rejection was detected in nine (60%) recipients, while there were no indications of graft function deterioration during the follow-up. For each patient, the transplant hospitalization cost was 38 428 ± 8789 USD. However, the cumulative costs were 59 758 ± 10 006 USD and 79 781 ± 16 366 USD, at 12 and 24 months, respectively. Compared with hemodialysis (34 286 USD per year), high-immunological-risk kidney transplantation tends to be expensive in the first year, but the cost is likely to be lower than that of hemodialysis after 3 years., Conclusions: Although kidney transplantation is initially expensive compared with hemodialysis, the medical cost becomes advantageous after 3 years even in kidney transplant recipients with high immunological risk., (© 2024 The Japanese Urological Association.)

Background: There are limitations in treating advanced prostate cancer (PC), especially castration-resistant (CR) cases, in renal transplant recipients (RTRs). We describe the case of RTR with metastatic CRPC (mCRPC) treated with docetaxel., Case Report: A 60-year-old man with end-stage renal disease due to autosomal-dominant polycystic kidney disease (ADPKD) underwent living-related kidney transplantation. A year later, he was diagnosed with PC (prostate-specific antigen level: 998 ng/mL). Prostate biopsy revealed prostatic adenocarcinoma with a Gleason score of 4 + 4 = 8. Radiographic examination revealed seminal vesicle invasion and multiple bone and lymph node metastases. Combined androgen blockade therapy was initiated; however, the patient was diagnosed with CRPC 6 months later. Triweekly docetaxel therapy was administered 28 months after diagnosis. The patient successfully completed 7 cycles of this therapy without major adverse events. However, after the 7th cycle, he developed a high fever caused by an infection of ADPKD-associated renal cysts. Therefore, docetaxel was discontinued, and enzalutamide was started, followed by abiraterone, but without any effect. We then introduced cabazitaxel but discontinued it because of hepatic dysfunction. Hence, the patient underwent a docetaxel rechallenge. He was administered the PEGylated form of the recombinant human granulocyte colony-stimulating factor for neutropenia prophylaxis. After 6 cycles of rechallenge docetaxel therapy, the patient accidentally fell, resulting in a cervical spine fracture and subsequent death due to respiratory failure., Conclusions: Docetaxel can be safely delivered to patients with CRPC after renal transplantation who are taking oral immunosuppressants. It can be a good treatment option for them., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Recent developments in intensive desensitization protocols have enabled kidney transplantation in human leukocyte antigen (HLA)-sensitized recipients. However, cases of active antibody-mediated rejection (AABMR), when they occur, are difficult to manage, graft failure being the worst-case scenario. We aimed to assess the impact of our desensitization and AABMR treatment regimen and identify risk factors for disease progression. Among 849 patients who underwent living-donor kidney transplantation between 2014 and 2021 at our institution, 59 were diagnosed with AABMR within 1 year after transplantation. All patients received combination therapy consisting of steroid pulse therapy, intravenous immunoglobulin, rituximab, and plasmapheresis. Multivariable analysis revealed unrelated donors and preformed donor-specific antibodies as independent risk factors for AABMR. Five-year death-censored graft survival rate was not significantly different between patients with and without AABMR although 27 of 59 patients with AABMR developed chronic AABMR (CABMR) during the study period. Multivariate Cox proportional hazard regression analysis revealed that a donor age greater than 59 years and microvascular inflammation (MVI) score (g + ptc) ≥4 at AABMR diagnosis were independent risk factors for CABMR. Our combination therapy ameliorated AABMR; however, further treatment options should be considered to prevent CABMR, especially in patients with old donors and severe MVI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Banno, Hirai, Oki, Yagisawa, Unagami, Kanzawa, Omoto, Shimizu, Ishida and Takagi.)

An 18-year-old man underwent allogenic bone marrow transplantation (BMT) for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). Ph+ALL relapsed 3 months after the first BMT, and the patient underwent a second BMT. However, Ph+ALL relapsed 4 months after the second BMT, and he received a haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) from his father. Molecular complete remission was confirmed 29 days after haplo-PBSCT. However, the patient needed dialysis for end-stage renal disease due to thrombotic microangiopathy 3 years and 2 months after haplo-PBSCT. He received a kidney transplantation from his father 7 years and 10 months after haplo-PBSCT, and got off dialysis after the kidney transplantation. Immunosuppressive therapy with methylprednisolone, tacrolimus, and mycophenolate mofetil was started for kidney transplantation, but the dose of immunosuppressive agents was reduced successfully without rejection soon after kidney transplantation. The patient has maintained long-term remission since the haplo-PBSCT, and his kidney function was restored by the kidney transplantation from his father.

Pregnancy in kidney transplantation (KT) recipients has been challenging because of the high risk of maternal, fetal, and renal complications. Although patients with immunoglobulin A nephropathy (IgAN)-chronic kidney disease (CKD) are at a high risk for hypertension in pregnancy (HIP), the maternal risk in KT recipients with IgAN as the etiology remains unclear. We retrospectively reviewed the medical records of pregnant KT recipients who delivered at our hospital. The incidence of maternal and fetal complications and the impact on kidney allografts between the group with IgAN as the primary kidney disease and the group with other primary diseases were compared. The analysis included 73 pregnancies in 64 KT recipients. The IgAN group had a higher incidence of HIP than the non-IgAN group (69% vs. 40%, p = 0.02). IgAN as primary kidney disease and interval from transplantation to conception were associated with HIP (OR 3.33 [1.11-9.92], p = 0.03, OR 0.83 [0.72-0.96], p < 0.01, respectively). The 20-year graft survival or prevention of CKD stage 5 in group with IgAN was lower than that in the group with other primary disease ( p < 0.01). KT recipients should be informed of the risk of HIP and possibility of long-term worsening of postpartum renal function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Oki, Unagami, Kakogawa, Beppu, Banno, Yagisawa, Kanzawa, Hirai, Omoto, Kitajima, Shirakawa, Hoshino, Takagi and Ishida.)

Objectives: To evaluate the 10-year efficacy and safety of a prolonged-release tacrolimus-based combination immunosuppressive regimen on longer-term outcomes in living donor kidney transplantation., Methods: Data from Japanese living donor kidney transplant recipients (n = 410) maintained on continuous prolonged-release tacrolimus-based immunosuppression from 2009-2013 were analyzed with a median follow-up of 9.9 years., Results: A prolonged-release, tacrolimus-based combination regimen provided death-censored graft failure and all-cause death rates at 10 years of 7.0% and 6.8%, respectively. In multivariable analyses, acute and chronic rejection and 'throughout' (new-onset plus preexisting) diabetes mellitus were risk factors for death-censored graft failure. Recipient age ≥ 65 years, throughout diabetes mellitus and malignancy were common risk factors for all-cause death. Throughout diabetes mellitus was the most common risk factor for both death-censored graft failure and all-cause death. Additional analyses showed 10-year cumulative rates of death-censored graft failure were 14.0% and 5.4% for recipients with or without preexisting diabetes mellitus, respectively (log-rank test: p = 0.009). All-cause death rates were 12.7% and 5.4% in the preexisting and non-diabetes mellitus groups, respectively (log-rank test: p = 0.023)., Conclusions: In this real-world, retrospective, living donor kidney transplantation study, a prolonged-release tacrolimus-based immunosuppressive combination regimen provided 10-year death-censored graft failure rates of 14.0% and 5.4% in diabetes mellitus and non-diabetes mellitus patients, respectively; Similarly, 10-year all-cause death rates were 12.7% and 5.4% in diabetes mellitus and non-diabetes mellitus patients, respectively. To our knowledge, the data in this study are the first to provide 10-year transplant outcomes in living donor kidney transplant recipients under prolonged-release tacrolimus-based regimen., (© 2023 The Japanese Urological Association.)

Background: Kidney transplantation (KTx) after urinary tract conversion surgery is extremely difficult due to several complications. In our case, KTx was performed after multiple operative procedures, including diversion urethrostomy., Case Report: The patient was a 46-year-old woman with a right atrophic kidney, an ectopic opening of the left ureter, and urethral dysplasia since birth. The patient underwent a right nephrectomy, left ureteral sigmoidostomy, Stamey surgery, augmentation ileocystoplasty, and left ureteroileostomy. Thereafter, she underwent nephrostomy, ileal conduit diversion, open sigmoid colectomy, and total cystectomy because of persistent urinary incontinence, sigmoid colon cancer, and recurrent cystitis. Her renal function gradually deteriorated, and hemodialysis was initiated. Before the KTx, she underwent laparoscopic left nephrectomy, an intraperitoneal adhesion debridement, and left ileal conduit resection. We dissected the left ileal conduit in the abdominal cavity and penetrated the anorectal side of the free ileal conduit into the wall of the right side of the abdomen. Thereafter, a kidney from a living donor was transplanted into the right iliac fossa through the existing right ileal conduit when the patient was 46 years old. The allograft function was stable without rejection for 2 years., Conclusions: We report the case of a patient who underwent multiple urethral modifications followed by ileal conduit transfer and living donor KTx, which progressed without major postoperative complications., Competing Interests: Declaration of Competing Interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: We report a case of suspected hyperacute rejection during living kidney transplantation., Case Report: A 61-year-old man underwent kidney transplantation in November 2019. Before the transplantation, immunologic tests revealed the presence of anti-HLA antibodies but not donor-specific HLA antibodies. The patient was intravenously administered 500 mg of methylprednisolone (MP) and basiliximab before perioperative blood flow reperfusion. After blood flow restoration, the transplanted kidney turned bright red and then blue. Hyperacute rejection was suspected. After the intravenous administration of 500 mg of MP and 30 g of intravenous immunoglobulin, the transplanted kidney gradually changed from blue to bright red. The initial postoperative urine output was good. On the 22nd day after the renal transplantation, the patient was discharged with a serum creatinine level of 2.38 mg/dL, and the function of the transplanted kidney gradually improved., Conclusions: In this study, non-HLA antibodies may have been a cause of the hyperacute rejection, which was managed with additional perioperative therapies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Herein, we discuss clinicopathological analyses of cases of chronic renal allograft arteriopathy (CRA) after renal transplantation and clarify the mechanisms underlying the development and prognostic significance of CRA., Methods: CRA was diagnosed in 34 renal allograft biopsy specimens (BSs) obtained from 27 renal transplant patients who were followed up at the Department of Urology and Transplant Surgery, Toda Chuo General Hospital, between January 2010 and December 2020., Results: CRA was diagnosed at a median of 33.4 months post-transplantation. Of the 27 patients, 16 had a history of rejection. Among the 34 BSs showing evidence of CRA, CRA was mild (cv1 in Banff's classification) in 22, moderate (cv2) in 7, and severe (cv3) in 5 patients. We then classified the 34 BSs showing evidence of CRA based on their overall histopathological features as follows: cv alone seen in 11 (32%) BSs, cv + antibody-mediated rejection (AMR) in 12 (35%), and cv + T-cell-mediated rejection (TCMR) in 8 (24%). Loss of the renal allograft occurred during the observation period in 3 patients (11%). Of the remaining patients with functioning grafts, deterioration of renal allograft function after biopsies occurred in 7 cases (26%)., Conclusions: Our study results suggest that AMR contributes to CRA in 30-40% of cases, TCMR in 20-30% of cases, isolated v lesions in 15% of cases, and cv lesions alone in 30%. The intimal arteritis was a prognostic factor in CRA., (© 2023 S. Karger AG, Basel.)

Objectives: Many researchers have demonstrated that the seropositivity rate after SARS-CoV-2 coronavirus vaccination is lower in patients receiving oral immunosuppressants. In this article, we report on a comparative study on the seropositivity rate after 2 doses of coronavirus vaccine before or after kidney transplant., Materials and Methods: We studied 111 recipients vaccinated after transplant, 19 patients vaccinated before transplant, and 10 healthy patients. We retrospectively measured antibody titers using preserved serum samples. The antibody testing was performed 1 month and 3 months after vaccination. The measurement was via LABScreen COVID Plus, which enables simultaneous determination of 5 coronavirus protein antigens., Results: Seropositivity to coronavirus antibodies was observed in all 19 patients vaccinated before transplant (100%) and in all the 10 healthy patients (100%). Forty- six of the 111 recipients (42%) vaccinated after transplant developed seropositivity. Analyzed at each time point after vaccination, the mean fluorescence intensity of antibodies was unchanged between 1 month and 3 months after vaccination in transplant recipients who were vaccinated after transplant and developed seropositivity. On the other hand, the antibody mean fluorescence intensity in patients vaccinated before transplant was markedly lower at 3 months (posttransplant)., Conclusions: All patients with renal failure who were vaccinated before transplant showed a high seropositivity rate, similar to that in healthy patients. The seropositivity rate for each of the viral fragment antibodies in patients vaccinated before transplant was maintained, as seen in healthy patients. However, in patients vaccinated before transplant who tested positive for antibody production at 1 month after vaccination,the antibody mean fluorescence intensity at 3 months after vaccination (posttransplant) was remarkedly lower than the mean fluorescence intensity at 1 month, which was probably caused by the types of immunosuppressive regimens used atthe time of transplant.

Background: Patients undergoing organ transplantation are immunosuppressed and already at risk of various diseases. We report about a patient who underwent ABO-incompatible kidney transplantation after coronavirus disease 2019 (COVID-19) without a recurrence of infection., Case Report: A 68-year-old woman presented with end-stage renal failure owing to primary autosomal dominant polycystic kidney disease; accordingly, hemodialysis was initiated in September 2020. Her medical history included bilateral osteoarthritis, lumbar spinal stenosis, hypertension, and hyperuricemia. In mid-January 2021, she contracted severe acute respiratory syndrome coronavirus 2 infection from her husband. Both of them were hospitalized and received conservative treatment. Because their symptoms were mild, they were discharged after 10 days. The patient subsequently underwent ABO-incompatible kidney transplantation from her husband who recovered from COVID-19 in March 2021. Before kidney transplantation, her COVID-19 polymerase chain reaction test was negative, confirming the absence of pre-existing COVID-19 immediately before the procedure. Computed tomography revealed no pneumonia. Initial immunosuppression was induced by administering tacrolimus, mycophenolate mofetil, methylprednisolone, basiliximab, rituximab, and 30 g of intravenous immunoglobulin. Double-filtration plasmapheresis and plasma exchange were performed once before ABO-incompatible kidney transplantation. The renal allograft functioned immediately, and the postoperative course was normal without rejection. COVID-19 did not recur. In addition, her serum creatinine levels and renal function had otherwise remained stable., Conclusion: Living kidney transplantation was safely performed in a patient with COVID-19 without postoperative complications or rejection. During the COVID-19 pandemic, the possibility of severe acute respiratory syndrome coronavirus 2 infection during transplantation surgery must be considered., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Casirivimab-imdevimab is a cocktail of 2 monoclonal antibodies designed to prevent infection by SARS-CoV-2, the virus that causes COVID-19. Casirivimab-imdevimab has been approved in Japan for treating mild to moderate COVID-19; however, to our knowledge, there are no reports of its use after kidney transplant from a live donor. Everolimus, an antineoplastic chemotherapy drug, is expected to be effective in inhibiting the spread of SARS-CoV-2 and preventing its replication, which may facilitate treatment. Here, we report a case of COVID-19 infection after kidney transplant that was initially treated with casirivimab-imdevimab and mycophenolate mofetil but was later changed to everolimus., Case Report: A 47-year-old man underwent living donor kidney transplant from his mother in 2017. Immunosuppression therapy was underway through the administration of tacrolimus, mycophenolate mofetil, and methylprednisolone. In early September 2021, he was diagnosed as having COVID-19 and was hospitalized on day 3. On hospitalization, mycophenolate mofetil was discontinued and casirivimab-imdevimab and heparin were started. The patient started an everolimus regimen on day 5. The clinical course was successful without rejection. There was no exacerbation of COVID-19; the patient's serum creatinine levels and renal function had otherwise remained stable., Conclusions: We could safely treat a patient with casirivimab-imdevimab after kidney transplant. It is suggested that casirivimab-imdevimab can prevent COVID-19 from becoming severe and can be administered without worsening renal function. In addition, everolimus may have inhibited the spread of the virus and prevented it from replicating., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Coronavirus disease 2019 (COVID-19) infection may become more severe in those who have undergone kidney transplantation than in the general population. False-negative reverse transcription-polymerase chain reaction (RT-PCR) results have been reported for COVID-19 infection. Patients might carry infection even though RT-PCR results are negative., Case Report: A 65-year-old man with a 19-year history of ABO-incompatible kidney transplantation presented with fever and arthralgia. Although the RT-PCR result was negative, a focal slit-glass shadow in the left upper lobe on computed tomography (CT) suggested COVID-19 pneumonia. His symptoms did not improve until after 10 days, and CT showed multiple slit-glass shadows in the bilateral lung fields. However, RT-PCR remained negative. The patient was admitted, and mycophenolate mofetil was discontinued. Anticoagulants were administered on the third day of hospitalization. Because of poor oxygenation, the patient was intubated in the intensive care unit on the fifth day, and sivelestat sodium was administered. The patient was extubated on the 12th day after improvement in oxygenation. There was no exacerbation, and CT showed improvements on day 51., Conclusion: We report a case of pneumonia with suspected COVID-19 infection 18 years after living donor kidney transplantation. If COVID-19 is suspected, infection control and aggressive therapeutic interventions should be undertaken while considering the possibility of a positive result., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Although the effectiveness of vaccines in protecting the host from infection has been proven, few surveys have been conducted on changes in antibody levels after vaccination of kidney transplant recipients in Japan., Materials and Methods: We analyzed serological responses in kidney transplant recipients after BNT162B2 COVID-19 mRNA vaccine with the use of a reagent capable of simultaneously specifying the antibody response to 5 proteins: a full-spike protein (extracellular domain), 3 individual domains of the spike protein (S1, S2, and receptor-binding domain), and nucleocapsid. The analysis involved 111 patients who had follow-up over 1 month after having received the second of 2 coronavirus vaccines after kidney transplant., Results: Antibodies were detected in 46 of 111 patients (41%). The antibody-positive rate in the kidney transplant group tended to be lower than that in the healthy control group, which showed an antibody- positive rate of 100%. When the antibody-positive rate was analyzed by the type of immunosuppressor used, the rate was 36% (37/100) for patients who used tacrolimus at the time of vaccination and 90% (9/10) for patients who used cyclosporine. Patients administered CD20 antibody (rituximab) before and/or after transplant showed a lower production of antibodies, which was supported by a smaller number of CD19- and CD20-positive cells in the peripheral blood as well as a shorter period between rituximab administration and vaccination. The percentage of responding viral fragments varied greatly among individual patients and showed no uniformity in the kidney transplant group, whereas the mean fluorescence intensity of individual fragments showed a certain tendency in the control group., Conclusions: The appropriate timing of vaccination should be considered in transplant recipients who use tacrolimus-mycophenolate mofetil combination and rituximab as these drugs are deeply related to a lower antibody response to SARS-CoV-2 BNT162b2 vaccination.

Pediatric renal transplantation is associated with various surgical complications due to the complexity of the technique and the often-fragile condition of patients with end-stage renal disease. We evaluated the surgical complications associated with renal transplantation via the extraperitoneal approach in pediatric recipients. This retrospective study enrolled 280 patients younger than 16 years old who underwent renal transplantation via the extraperitoneal approach: 216 patients underwent transplant placement in the iliac fossa like in adults, and 64 underwent transplant placement in the distal part of the original renal lower pole (the extraperitoneal cavity). On the basis of the Clavien-Dindo classification, 30 patients (10.7%) showed grade 2 complications and 12 patients (4.3%) showed grade 3 or higher complications. None of the patients showed gastrointestinal complications. In a Cox regression analysis, grade 2 or higher complications were significantly associated with weight less than 15 kg (P = .027) and operative times longer than 245 minutes (P = .029). Among the 49 patients weighing less than 15 kg with an allograft placed in a distal portion of the original renal lower pole, only 3 patients (6.1%) developed surgical complications. Thus, allograft placement in the extraperitoneal cavity can be performed safely in children weighing less than 15 kg., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: We reviewed the results of cases of kidney transplant (KTx) that were conducted at the Toda Chuo General Hospital, a private hospital located in Saitama, Japan., Methods: A total of 312 patients with end-stage renal failure underwent KTx between January 1992 and December 2019 at Toda Chuo General Hospital. There were 191 men and 121 women. Their mean age was 45.7 years. Of the 312 cases, 310 were living-related KTx, while 2 were deceased donor KTx. The immunosuppressive treatment protocol mainly consisted of 4-drug therapy with methylprednisolone, tacrolimus, mycophenolate mofetil, and basiliximab., Results: Patient survival was 99.7% at 1 year, 99.3% at 5 years, and 97.3% at 10 years. Renal allograft survival was 98.4% at 1 year, 91.7% at 5 years, and 86.5% at 10 years. However, death-censored renal allograft survival was 98.7% at 1 year, 92.4% at 5 years, and 89.0% at 10 years. Among the 312 patients, 33 grafts were lost during the observation period. The loss was because of chronic antibody-mediated rejection in 19 patients, death with function in 6 patients, and acute antibody-mediated rejection in 2 patients., Conclusions: The prognosis of patients and their grafts, which were managed following the immunosuppression protocol at our institute, was relatively good. KTx in a private hospital in Japan is at par with the global standard., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: Antibody-mediated rejection in patients with positive crossmatches can be severe and result in sudden onset of oliguria, leading to graft loss. In an attempt to prevent posttransplant oliguria, we adopted a preoperative desensitization protocol involving the use of high-dose intravenous immunoglobulin/plasmapheresis and the anti-CD20 antibody, rituximab, in 41 transplant recipients with positive crossmatch test results., Materials and Methods: We retrospectively examined the clinical courses of the 41 kidney transplant recipients, paying special attention to renal graft function, urine volume, and changes in the titers of donor-specific antibodies., Results: Four grafts were lost during an average of 4.5-year follow-up. Average graft function was excellent, with a serum creatinine level of 1.3 ± 0.4 mg/dL. Sufficient urine output, with no oliguria or anuria, was achieved postoperatively in 40 of the 41 patients. However, among the 34 patients who underwent graft biopsies, the biopsies revealed acute antibody-mediated rejection in 21 patients (62%), and chronic antibodymediated rejection in 10 patients (30%)., Conclusions: The high-dose intravenous immunoglobulin treatment included in our desensitization protocol was shown to be safe and effective for achieving successful transplant outcomes and allowed the avoidance of more aggressive B-cell-targeted treatments, such as C5 inhibitors and/or proteosome inhibitors, for preventing posttransplant oliguria and anuria.

Background: We present a rare case of de novo renal cell carcinoma that developed in an allograft kidney 14 years after transplantation., Case Report: A 39-year-old man underwent living donor kidney transplantation from his mother. After 14 years, routine screening ultrasonography revealed a solid mass of 30-mm diameter in the kidney allograft. Partial nephrectomy was performed by clamping the renal artery under in situ cooling. Tissue histology revealed clear cell carcinoma with negative surgical margins. We explored the tumor's genetic origin using fluorescence in situ hybridization to analyze the X and Y chromosomes of the tumor cells. Postoperative hemodialysis was avoided, and the patient's serum creatinine level remained stable., Conclusions: Fluorescence in situ hybridization clearly indicated that the tumor originated from the donor and that the tumor vasculature originated from the recipient. The patient recovered well and remains without any tumor recurrence., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Tacrolimus (TAC) is a key immunosuppressant drug for kidney transplantation (KTx). However, the optimal serum trough level of TAC for good long-term outcomes remains unclear. This study aimed to investigate the relationship between the maintenance TAC trough level and the appearance of de novo donor-specific anti-human leukocyte antigen (HLA) antibodies (dnDSAs)., Methods: A total of 584 KTx recipients were enrolled in this study, of whom 164 developed dnDSAs during the follow-up period and 420 did not., Results: We found no significant relationship between TAC trough level during the follow-up period and dnDSA incidence. Patients who developed dnDSAs had a significantly greater number of HLA-A/B/DR mismatches (3.4 ± 1.3 versus 2.8 ± 1.5; P < 0.001), were more likely to have preformed DSAs (48.2% versus 27.1%; P < 0.001) and showed poor allograft outcome., Conclusions: There was no clear relationship between TAC trough level and dnDSA incidence for KTx recipients whose TAC trough levels were kept within the narrow range of 4-6 ng/mL during the immunosuppression maintenance period., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Little is known about the outcome of living-donor kidney transplantation (LDKT) performed in low-volume centers lacking the services of full-time transplant surgeons. This retrospective cohort study assessed the outcome of LDKT performed in a low-volume center by visiting transplant surgeons from a high-volume center and managed perioperatively by transplant nephrologists., Methods: We compared Japanese adult patients who had no donor-specific antibodies and underwent LDKT between 2006 and 2015 either in a low-volume (n = 31) or high-volume (n = 481) center. In the low-volume center, visiting transplant surgeons from the high-volume center conducted LDKT and transplant nephrologists managed the recipients peri- and postoperatively. The primary outcome was the composite of infection, cardiovascular disease, or cancer during 1-year follow-up. The outcomes of the low- and high-volume centers were compared using 1:2 propensity score matching., Results: After matching, 9 of 29 patients in the low-volume center (31.0%) and 16 of 58 patients in the high-volume center (27.6%) experienced the primary composite outcome (risk ratio = 1.13; 95% confidence interval, 0.57-2.23). There were no significant differences between the 2 groups in graft function at 1 year, all-cause graft loss, biopsy-proven rejection, and urological complications. However, the median duration of post-LDKT hospitalization was significantly longer in the low-volume center than in the high-volume center (23 and 16 days, respectively)., Conclusions: Among Japanese patients without preformed donor-specific antibodies, LDKT conducted at a low-volume center by visiting transplant surgeons from a high-volume center and managed clinically by transplant nephrologists was not associated with significantly higher risk of postoperative complications., (Copyright © 2021. Published by Elsevier Inc.)

Aim: We discuss the clinicopathologic analyses of cases of biopsy specimens (BS) after renal transplantation and clarify the mechanisms underlying the development and prognostic significance of chronic vascular rejection (CVR)., Patients: CVR was diagnosed in 30 renal allograft BS obtained from 23 renal transplant patients being followed up at the Department of Urology and Transplant Surgery, Toda Chuo General Hospital, between January 2010 and August 2017., Results: CVR was diagnosed at a median of 33.1 months post-transplantation. Among the 23 patients, 14 had a history of rejection. Among the 30 BS showing evidence of CVR, the CVR was mild (cv1 on Banff's classification) in 19, moderate (cv2) in 6, and severe (cv3) in 5. We then classified the 30 BS showing evidence of CVR by their overall histopathologic features as follows: cv alone was seen in 9 (30%), cv + antibody-mediated rejection (AMR) in 11 (37%), and cv + T-cell-mediated rejection (TCMR) in 8 (27%). Loss of the renal allograft occurred during the observation period in 2 patients (9%). Of the remaining patients with functioning grafts, deterioration of the renal allograft function after the biopsies occurred in 6 (26%)., Conclusions: Our study results suggest that AMR contributes to CVR in 30% to 40% of cases, TCMR in 20% to 30% of cases, isolated v lesions in 10% of cases, and cv lesions alone in 30%. The prognosis of the graft exhibiting CVR was not too poor even under the present immunosuppressive protocol., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Although minimally invasive procedures have been established as the standard for a donor nephrectomy, there are many different surgical techniques described in the literature. The aim of this study is to compare the outcomes of kidney transplant procedures using the pure retroperitoneoscopic donor nephrectomy (PRDN) and hand-assisted retroperitoneoscopic donor nephrectomy (HARDN) techniques., Methods: A retrospective study involving 1508 transplant procedures was conducted; 874 were PRDN procedures; and 634 were HARDN. We reviewed the outcomes of the PRDN and HARDN groups, which were performed at two different centers over an identical time period., Results: Donors in the PRDN group had a longer operation time (P < 0.0001), reduced estimated blood loss (P < 0.0001), less open conversion (P = 0.0002), lower postoperative serum C-reactive protein levels (P < 0.0001), and a shorter postoperative hospital stay (P < 0.0001) than the HARDN group. Recipients in the PRDN group had lower serum creatinine levels at postoperative day 1-6 and the decreased incidence of slow graft function (P = 0.0017) than the HARDN group. The HARDN procedure was an independent risk factor for the incidence of acute rejection (P = 0.0211) and graft loss (P = 0.0193)., Conclusions: Our study suggests that the PRDN procedure is less invasive for donors as it results in reduced blood loss, lower postoperative serum CRP levels, and a shorter postoperative stay than the HARDN procedure. Additionally, PRDN provides a better outcome for recipients as it lowers the incidence of acute rejection and improves graft survival compared to HARDN.

Background: No studies using a valid, standardized method to measure post-donation satisfaction levels among living kidney donors (LKDs) have been published., Methods: Donor satisfaction levels were measured using the Japanese version of the Client Satisfaction Questionnaire-8 (CSQ-8), a validated, self-report questionnaire. To identify factors related to post-donation satisfaction levels, we compared donors' sociodemographic and psychological characteristics and health-related quality of life (HRQoL), using the Short Form-36 Health Survey (SF-36), as well as recipients' clinical characteristics and SF-36 scores between donors with and without low satisfaction. In addition, donors' perceptions of the donation results and transplant procedure were assessed using measures that we developed., Results: The mean (standard deviation [SD]) CSQ-8 score for the 195 participants was 26.9 (3.4). Twenty-nine (14.9%) respondents with total scores < 1 SD below the mean CSQ-8 score were placed into the low satisfaction group. Multiple logistic regression analysis demonstrated that lower perceptions of receiving adequate information prior to transplantation (odds ratio [OR] = 0.17; 95% confidence interval [CI] = 0.079-0.379; p < 0.001), lower optimism according to the Life Orientation Test (OR = 1.24; 95% CI = 1.045-1.470; p = 0.014), and increased serum creatinine levels in the paired recipient (OR = 0.05; 95% CI = 0.250-1.011; p = 0.054) independently increased the odds of having less satisfaction with donation., Conclusions: Our findings suggest that careful pre-donation education and more detailed informed consent may be needed, especially in LKDs with low constitutional optimism.

Objectives: To investigate the cumulative return-to-work (RTW) rate and to identify predictors of employment after kidney transplantation (KT)., Design: Retrospective, outpatient-based cohort study., Setting: This was a single-centre study of the largest Japanese kidney transplant centre., Participants: We selected Japanese kidney transplant recipients aged 20-64 years who were employed in paid jobs at the time of transplantation and who visited an outpatient clinic from December 2017 to March 2018. From 797 patients, we evaluated 515 in this study., Interventions: We interviewed patients at an outpatient clinic and investigated the timing and predictors of RTW using logistic regression models., Primary and Secondary Outcome Measures: The primary outcome was the cumulative RTW rate, and the secondary outcome was to investigate the predictors of RTW after KT., Results: Among the 515 included recipients, the cumulative overall partial/full RTW rates at 2, 4, 6 and 12 months were 22.3%, 59.0%, 77.1% and 85.0%, respectively. The median duration from transplantation to RTW was 4 months. Regarding partial/full RTW, according to the multivariable analysis including all variables, male sex was a greater predictor for RTW than female sex (OR 2.05, 95% CI 1.32 to 3.20), and a managerial position was a greater predictor than a non-managerial position (OR 2.23, 95% CI 1.42 to 3.52). Regarding full RTW, male sex (OR 1.95, 95% CI 1.25 to 3.06) and managerial position (OR 1.95, 95% CI 1.25 to 3.06) were also good predictors., Conclusions: The cumulative RTW rate was 85.0% 1-year post-transplantation. Given that cumulative RTW rates varied by sex and position, transplant and occupational physicians should support kidney transplant recipients in the aspect of returning to work., Trial Registration Number: UMIN000033449., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate the 10-year biopsy-proven recurrence rates and risk factors for immunoglobulin A nephropathy recurrence in kidney transplant recipients., Methods: We included 299 kidney transplant recipients from 1995 to 2015, who had biopsy-proven underlying immunoglobulin A nephropathy and underwent zero-hour biopsy. The primary end-point was recurrence of immunoglobulin A nephropathy. We compared clinical, treatment and graft failure among those with and without recurrent immunoglobulin A nephropathy. A time-to-recurrence analysis was carried out using the competing risk analysis and time-dependent Cox model., Results: Of 299 recipients, 80 had recurrent immunoglobulin A nephropathy (66.3% with clinical biopsy and 33.7% with protocol biopsy, post-transplant biopsy rate: 90.6%). The 10-year recurrence rate was 34.3% (95% confidence interval 27.6-41.1). Related-donor transplantation (hazard ratio 2.28, P = 0.009) and post-transplant increased proteinuria (hazard ratio 1.59, P < 0.001) were identified as potential risk factors for immunoglobulin A nephropathy recurrence. The 10-year rates were 41.5% in related donor recipients and 16.3% in unrelated donor recipients. There was no conclusive evidence that the calcineurin inhibitor, antimetabolites, basiliximab and rituximab reduce immunoglobulin A nephropathy recurrence. Immunoglobulin A nephropathy recurrence was associated with an increased risk of death-censored graft failure (hazard ratio 5.29, 95% confidence interval 1.39-20.17, P = 0.015). However, related donor itself was not associated with an increased risk of graft failure., Conclusions: The present results have clinical implications in that the signs of recurrent immunoglobulin A nephropathy should be evaluated carefully in recipients receiving related-donor transplants. There is a need for further studies related to genetic and/or familial interactions in kidney transplant recipients with immunoglobulin A nephropathy and related donors., (© 2019 The Japanese Urological Association.)

Background: The interaction between post-transplant anemia (PTA) and allograft function in kidney transplantation has not been evaluated directly. PTA, defined by WHO/AST criteria, was investigated in 1307 adult kidney transplant recipients between 2000 and 2015 (median follow-up, 7 years)., Methods: We investigated the impact of hemoglobin (Hb) on graft failure (non-censored for death) and their interactions, time-dependent Cox model, and subgroup analysis were used., Results: PTA prevalence was 43.6% at 7 years and varied according to allograft function, recipient sex, and follow-up period. Decreased Hb considering the time-varying effect was associated with an increased risk of graft failure (hazard ratio = 1.83, 95% CI 1.66-2.02, P < 0.001). In subgroup analysis, allograft function (post-transplant time-averaged estimated glomerular filtration rate and cut point: 45 mL/min/1.73 m 2 ) had significant interaction (P = 0.032). The 7-year graft failure rate in recipients with PTA and high eGFR was 7.7% (HR 1.52, 95% CI 1.25-1.84), whereas in those with PTA and low eGFR was 19.9% (HR 2.00, 95% CI 1.74-2.31)., Conclusions: The unfavorable impact of PTA was significantly enhanced by low allograft function. PTA is likely to be associated with graft failure due to interaction with allograft function. Therefore, we should consider both Hb level and allograft function while determining the treatment strategy.

Background: Tubular basement membrane immune deposits (TBMID) has rarely been observed in renal allografts. It is usually found in BK virus nephropathy and immune complex glomerulonephritis; however, its significance is not well understood. We conducted a retrospective clinicopathological study on monoclonal immunoglobulin G (IgG) TBMID., Methods: We studied 7177 renal allograft biopsy specimens obtained from Tokyo Women's Medical University from 2007 to 2015 and performed light microscopic, electron microscopic and immunofluorescence studies., Results: Tubular basement membrane (TBM) deposits of IgG were found in 73 biopsies from 61 patients and the IgG subclass was obtained in 31 biopsies. There were no cases of monoclonal IgA or IgM TBMID. In total, 13 biopsies from 10 patients showed monoclonal IgG TBMID. Of these, seven showed monoclonal IgG1κ TBMID and one each showed monoclonal IgG2κ, IgG2λ and IgG3κ TBMID. Conversely, eight patients showed polyclonal IgG TBMID. In electron microscopy, large granular electron-dense deposits (EDDs) in the TBM were detected in all patients with monoclonal IgG1κ TBMID. EDDs were absent in TBM in patients with monoclonal IgG2κ, IgG2λ or IgG3κ TBMID. Progression of interstitial fibrosis and tubular atrophy (IFTA) was significantly higher in patients with monoclonal IgG1κ TBMID than in those with polyclonal IgG TBMID (P < 0.05). There were no significant differences in the other clinical parameters between monoclonal IgG1κ and polyclonal IgG TBMID., Conclusions: This is the first study of patients with monoclonal IgG TBMID in renal allografts. We found that monoclonal IgG1κ TBMID was associated with EDD formation in TBM and IFTA progression., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA.)

Regulatory T cells (Tregs) play a significant role in immune tolerance. Since Treg function deeply depends on Interleukin-2 signaling, calcineurin inhibitors could affect their suppressive potentials, whereas mammalian target of rapamycin (mTOR) inhibitors may have less impact, as mTOR signaling is not fundamental to Treg proliferation. We previously reported a novel mixed hematopoietic chimerism induction regimen that promotes Treg proliferation by stimulating invariant natural killer T cells under CD40 blockade. Here, we use a mouse model to show the impact of tacrolimus (TAC) or everolimus (EVL) on the establishment of chimerism and Treg proliferation in the regimen. In the immunosuppressive drug-dosing phase, peripheral blood chimerism was comparably enhanced by both TAC and EVL. After dosing was discontinued, TAC-treated mice showed gradual graft rejection, whereas EVL-treated mice sustained long-term robust chimerism. Tregs of TAC-treated mice showed lower expression of both Ki67 and cytotoxic T lymphocyte antigen-4 (CTLA-4), and lower suppressive activity in vitro than those of EVL-treated mice, indicating that TAC negatively impacted the regimen by interfering with Treg proliferation and activation. Our results suggest that the usage of calcineurin inhibitors should be avoided if utilizing the regimen to induce Tregs in vivo for the establishment of mixed hematopoietic chimerism., (© 2018 Steunstichting ESOT.)

Background: The safety of kidney transplantation (KT) for end-stage kidney disease (ESKD) after haematopoietic stem cell transplantation (HSCT) for haematological disease has not been investigated thoroughly., Methods: In this retrospective multicentre study, we investigated the clinical courses of six ESKD patients that received KT after HSCT for various haematological diseases. Data for six such patients were obtained from three institutions in our consortium., Results: Two patients with chronic myeloid leukaemia, one with refractory aplastic anaemia and another one with acute lymphocytic leukaemia received bone marrow transplantation. One patients with acute lymphocytic leukaemia received umbilical cord blood transplantation, and one with mantle cell lymphoma received peripheral blood stem cell transplantation. The patients developed ESKD at a median of 133 months after HSCT. Two patients who received KT and HSCT from the same donor were temporarily treated with immunosuppressive drugs. The other patients received KT and HSCT from different donors and were treated with antibody induction using our standard regimens. For one patient with ABO-incompatible transplantation, we added rituximab, splenectomy, and plasmapheresis. In the observational period at a median of 51 months after KT, only one patient experienced acute T-cell-mediated rejection. Four patients underwent hospitalization because of infection and fully recovered. No patient experienced recurrence of their original haematological disease. All patients survived throughout the observational periods, and graft functions were preserved., Conclusions: Despite the high infection frequency, survival rates and graft functions were extremely good in patients compared with previous studies. Therefore, current management contributed to favourable outcomes of these patients.

Tacrolimus (TAC) is available as a twice-daily capsule (TAC-BID), once-daily capsule (TAC-QD), and once-daily tablet. Recipients with ABO-incompatible/anti-human leukocyte antigen (HLA)-incompatible transplantation were excluded in previous trials and have thus not been evaluated. We conducted a 5-year trial to determine whether TAC-QD is noninferior to TAC-BID for transplant outcomes. Adults who underwent de novo living kidney transplantation were randomly assigned (62 TAC-QD; 63 TAC-BID). We did not exclude ABO-/HLA- incompatible transplantation. TAC was initiated 7 days preoperatively (0.10 mg/kg/d). Mycophenolate mofetil, methylprednisolone, and basiliximab were administered. The primary endpoint was graft failure (non-censored for death). We performed a noninferiority test. The noninferiority margin was 10% in risk difference. Five-year graft failure rates were 6.5% and 9.5% for TAC-QD and TAC-BID, respectively (noninferiority, P = 0.009). The estimated glomerular filtration rates were similar between the groups (noninferiority, P < 0.001). TAC-QD did not have point estimates of risk difference above the inferiority margin in any assessed endpoints. However, a tendency of interaction was observed between biopsy-proven acute rejection and the follow-up period. In a living kidney transplant population with 40% of patients with ABO/HLA incompatibility, the effect of TAC-QD was not appreciably worse on various clinical transplant outcomes than that of TAC-BID over 5 years., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Plasma cell-rich acute rejection (PCAR) is a rare type of allograft rejection characterized by the presence of mature plasma cells. In general, the prognosis of PCAR is poor, and its clinical and pathological features remain unclear., Methods: We performed a retrospective observational study and compared allograft survival between kidney transplant recipients who developed PCAR and those who did not develop PCAR. We further analyzed clinical and pathological risk factors for allograft failure in PCAR patients., Results: Of 1956 recipients, 40 developed PCAR. There was a higher prevalence of deceased donor transplants (27.5% vs 11.7%, P = 0.0059), longer median total ischemia time (99 minutes; interquartile range, 71-144 vs 77 minutes; interquartile range, 59-111; P = 0.0309), and lower prevalence of ABO-incompatible transplantation (7.5% vs 22.5%; P = 0.0206) in patients with PCAR than in those without PCAR.Multivariate Cox regression analysis showed that development of PCAR was associated with allograft loss (hazard ratio, 8.03; 95% confidence interval, 3.89-14.80; P < 0.0001).We classified PCAR according to the Banff 2015 criteria into a borderline change group, a T cell-mediated rejection (TCMR) group, an antibody-mediated rejection (AMR) or suspected of having AMR (AMR/sAMR) group, and a mixed rejection (TCMR/AMR) group. The AMR/sAMR group was associated with a lower rate of allograft survival without significant difference (log-rank test, P = 0.1692)., Conclusions: The results indicated that PCAR was an independent risk factor for allograft loss. PCAR presented with all types of rejection in the Banff 2015 criteria, and AMR/sAMR was associated with poor allograft survival.

Transplant tolerance induction makes it possible to preserve functional grafts for a lifetime without immunosuppressants. One powerful method is to generate mixed hematopoietic chimeras in recipients by adoptive transfer of donor-derived bone marrow cells (BMCs). In our murine transplantation model, we established a novel method for mixed chimera generation using sublethal irradiation, CD40-CD40L blockade, and invariant natural killer T-cell activation. However, numerous BMCs that are required to achieve stable chimerism makes it difficult to apply this model for human transplantation. Here, we show that donor-derived splenic T cells could contribute to not only the reduction of BMC usage but also the establishment of complete chimerism in model mice. By cotransfer of T cells together even with one-fourth of the BMCs used in our original method, the recipient mice yielded complete chimerism and could acquire donor-specific skin-allograft tolerance. The complete chimeric mice did not show any remarks of graft versus host reaction in vivo and in vitro. Inhibition of the apoptotic signal resulted in increase in host-derived CD8 + T cells and chimerism brake. These results suggest that donor-derived splenic T cells having veto activity play a role in the depletion of host-derived CD8 + T cells and the facilitation of complete chimerism., (© 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: In hematological malignancy patients intended to receive rituximab, hepatitis B virus (HBV) serology screening, viral reactivation monitoring, are recommended. However, the effect of single-dose rituximab (RIT) on HBV reactivation in kidney transplant patients with previous HBV infection is still unclear., Methods: In this retrospective cohort study consisting of 1294 kidney transplant patients, we identified 76 patients showing preoperative hepatitis B surface antigen-negative, hepatitis B core antibody-positive, and HBV-DNA-negative results. A rituximab dose of 200 mg/body was administered to 48 patients, 46 of whom did not receive prophylaxis (RIT+ group). Twenty-eight patients received neither rituximab nor prophylaxis (RIT- group). We monitored HBV-DNA by polymerase chain reaction every 1 to 3 months, and HBV reactivation was defined as detectable HBV-DNA., Results: HBV reactivation was found in 1 patient in the RIT+ group (2.2%) and 1 patient in the RIT- group (3.6%) at 6 weeks and 5.5 years posttransplant, respectively, but spontaneously cleared. Both patients showed positive hepatitis B surface antibody preoperatively. HBV reactivation was not found in 6 patients lacking anti-hepatitis B surface preoperatively., Conclusions: Low-dose RIT administration in kidney transplant patients without prophylaxis is associated with low incidence of HBV reactivation. However, the comparisons among standard-dose RIT, low-dose RIT, and controls with high-quality study design is necessary.

Objectives: Universal prophylaxis and preemptive therapy are used to prevent cytomegalovirus (CMV) disease post-transplantation. Data regarding which strategy is superior are sparse, especially in high-risk recipients (donor CMV seropositive (D+) and recipient CMV seronegative (R-))., Methods: This retrospective, single-center cohort study included recipients who underwent kidney transplantation between 2009 and 2015. The incidence of CMV infection/disease and patient and graft outcomes were analyzed and compared between high-risk recipients (D+/R-) and intermediate-risk recipients (D+/R+ or D-/R+), all managed with preemptive therapy., Results: Of 118 kidney transplant recipients, 21 were high-risk and 97 were intermediate-risk. Over a median follow-up period of 3 years, asymptomatic CMV infection developed significantly more frequently in high-risk patients than in intermediate-risk patients (38.1% vs. 16.5%, p=0.04), and CMV disease developed in a similar manner (28.6% vs. 3.1%, p<0.01). Among high-risk patients, CMV infection developed within the first 3 months post-transplantation and CMV disease within the first 9 months post-transplantation. Kaplan-Meier analysis showed no difference in the probability of mortality (log-rank p=0.63) or graft loss (log-rank p=0.50) between the patient groups. Graft rejection occurred more frequently in high-risk than in intermediate-risk patients, but the difference was not significant (log-rank p=0.24)., Conclusions: These results suggest that further studies on universal prophylaxis in high-risk patients are needed to elucidate whether preventing CMV infection/disease during the early post-transplant period leads to better outcomes, especially in terms of reducing graft rejection., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: In ABO-incompatible kidney transplantation, the diagnostic criteria for antibody-mediated rejection remain controversial because C4d deposition is commonly observed. Thus, we investigated microvascular inflammation (MVI score ≥ 2) within 1 year as a predictor of graft outcome., Methods: A total of 148 recipients without preformed or de novo donor-specific anti-HLA antibody were stratified based on MVI score less than 2 (n = 117) and MVI score of 2 or greater (n = 31)., Results: We found that 5-year graft survival was significantly lower (P = 0.0129) in patients with MVI (89.8%) than in patients without MVI (97.0%). Graft function, as characterized by serum estimated glomerular filtration rate, was also significantly worse for patients with MVI than it was for patients without MVI, between 3 months and 10 years after transplantation (P = 0.048). Multivariate analysis indicated that HLA class II mismatch (P = 0.0085) was an independent marker of MVI., Conclusions: Microvascular inflammation score of 2 or greater is significantly associated with poor graft outcome after ABO-incompatible kidney transplantation. We suggest that MVI score of 2 or greater in ABOi transplantation be used as a basis to diagnose antibody-mediated rejection.

Competing Interests: The authors declare no funding or conflicts of interest.

Competing Interests: The authors declare no funding or conflicts of interest.

Transplantation-associated thrombotic microangiopathy (TA-TMA) is relatively rare and requires immediate intervention to avoid irreversible organ damage or death; however, consensus regarding the treatment approach is lacking. Atypical haemolytic uraemic syndrome (aHUS) is a rare disease caused by dysregulation of the alternative complement pathway resulting in TMA. aHUS is histologically similar to TA-TMA; approximately 60% of TA-TMA patients have complement dysregulation. Eculizumab, a humanized anti-C5 monoclonal antibody, inhibits terminal membrane-attack complex formation and TMA progression. Eculizumab has been successfully used to treat aHUS post-transplant. We present two cases of kidney TA-TMA due to unknown causes, suspected antibody-mediated rejection, or calcineurin inhibitor (CNI)-related toxicity that developed on day 1 or 2 post-kidney transplantation. Low platelet count and haemoglobin level with red cell fragments were detected. Despite steroid pulse, plasma exchange (PE), and intravenous immunoglobulin therapy, TA-TMA did not improve; therefore, eculizumab was administered despite no genetic testing. Laboratory data, including renal function, improved immediately. TA-TMA treatment primarily involves PE initiation or CNI discontinuation; eculizumab can be used to safely treat TA-TMA and then be ceased in the short term. Therefore, eculizumab administration might be beneficial for kidney TA-TMA as early as the diagnosis of refractory to PE., (© 2016 Asian Pacific Society of Nephrology.)

Aim: Transplant glomerulopathy (TG) is a feature of chronic antibody-mediated injury in the glomerular capillaries in renal transplant recipients. TG is generally associated with proteinuria; however, renal function at the diagnosis of TG varies. This study aimed to determine which morphological abnormalities are associated with renal function and proteinuria at the diagnosis of TG., Methods: A total of 871 renal transplantations were performed at Tokyo Women's Medical University between 2005 and 2013. TG was diagnosed in 127 biopsies from 58 (6.7%) recipients. Renal function was evaluated by the estimated glomerular filtration rate (eGFR). Proteinuria was assessed by a dipstick test: positive for +1 and over., Results: At diagnosis, of 127 biopsies, 72, 37, and 18 had mild, moderate, and severe TG (Banff cg). The severity of TG was not associated with decreased eGFR at the time of biopsy (cg1: 36.1 ± 14.8, cg2-3: 38.8 ± 14.5 mL/min per 1.73 m(2) , P = 0.25), whereas the severity of interstitial fibrosis (IF) (Banff ci) was significantly associated with decreased eGFR (ci0-1: 42.75 ± 13.32, ci2-3: 27.69 ± 11.94 mL/min per 1.73 m(2) , P < 0.0001). The multivariate analysis revealed that IF was the only independent risk factors for decreased eGFR (OR = 4.38, P = 0.0006). Meanwhile, TG was identified as the only independent risk factor for the incidence of proteinuria (OR = 2.67, P = 0.014)., Conclusion: Interstitial fibrosis was a critical determinant of impaired renal function at the diagnosis of TG. The severity of TG was significantly associated with proteinuria, but did not contribute to renal dysfunction., (© 2016 Asian Pacific Society of Nephrology.)

Post-transplant lymphoproliferative disorder is a serious complication of solid organ transplantation; however, few large studies have been performed in Asian institutions. We review our single-center experience with post-transplant lymphoproliferative disorder patients in Japan. We retrospectively evaluated patients with post-transplant lymphoproliferative disorder following kidney transplantation between January 1985 and December 2013. The patients were divided into early-onset post-transplant lymphoproliferative disorder (<1 year) and late-onset post-transplant lymphoproliferative disorder (≥1 year) groups. Thirteen patients had the disorder, an incidence rate of 0.75% (13/1730). Early-onset post-transplant lymphoproliferative disorder (N = 3) had not occurred for the last two decades. In the late-onset group (N = 10), the median time of onset was 108.7 months. The Kaplan-Meier 10-year overall survival rates were 76.9% and 95.4% in patients with and without the disorder, respectively (P = 0.0001). Post-transplant lymphoproliferative disorder significantly affected transplant recipients' mortality. Late-onset occurred even > 10 years after transplantation; therefore, long-term monitoring of patients is needed., (© 2016 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Objectives: Cytomegalovirus infection is an important cause of morbidity and mortality among recipients undergoing hematopoietic stem cell and solid-organ transplant. The risk of cytomegalovirus infection is high in cytomegalovirus-seronegative recipients of cytomegalovirus-seropositive organs (donor positive/recipient negative) and recipients with strong immunosuppressive status such as those receiving rituximab induction or antirejection treatment. However, it remains unclear how rituximab affects patients with primary cytomegalovirus infection. We evaluated the effects of low-dose rituximab therapy on clinical and immunologic outcomes in recipients who were donor positive but recipient negative for primary cytomegalovirus infections., Materials and Methods: We conducted a retrospective review of patients with primary cytomegalovirus infections from January 2005 to March 2014. Patient outcomes were compared between groups administered given rituximab or given no intervention at the time of transplant., Results: Our study group included 49 recipients with primary cytomegalovirus infection, including 32 who received rituximab therapy (group 1) and 17 who did not (group 2). No significant differences were observed between groups in the duration of cytomegalovirus seroconversion (P = .0570) and initial cytomegalovirus immunoglobulin G titers (P = .8418)., Conclusions: Rituximab induction therapy does not affect clinical or immunologic outcomes of primary cytomegalovirus infection, even in high-risk recipients who are donor positive but recipient negative for primary cytomegalovirus infections.

Aim: Calcineurin inhibitors reduce the acute rejection rate and greatly improve renal allograft survival. However, they are associated with some adverse events, including nephrotoxicity, a risk factor for allograft failure. Chronic calcineurin inhibitor-induced nephrotoxicity causes irreversible damage to renal components, such as arteriolar hyaline thickening. The aim of this study is to investigate the risk factors for tacrolimus-induced chronic nephrotoxicity using zero-time biopsy specimens., Methods: Between January 2001 and December 2010, 483 patients who underwent living-related kidney transplantation and had also been placed on a tacrolimus-based regimen were enrolled in this study. There were 1859 specimens evaluated comprising 483 zero-time biopsy specimens and 1376 protocol and for-cause biopsy specimens. De novo arteriolar hyaline thickening due to tacrolimus-induced chronic nephrotoxicity was scored according to the Banff classification aah score. In this study, tacrolimus-induced nephrotoxicity was defined as a positive aah score., Results: Of the 483 patients, 108 patients (22.4%) had biopsy-proven tacrolimus-induced chronic nephrotoxicity. Multivariate analysis showed that interlobular arteriosclerosis proven by zero-time biopsy (OR: 2.23, 95%CI: 1.38-3.58, P < 0.01) and acute rejection episodes (OR: 1.58, 95%CI: 1.00-2.47, P = 0.04) were independent risk factors for tacrolimus-induced chronic nephrotoxicity. However, tacrolimus-induced chronic nephrotoxicity did not affect long-term graft survival., Conclusion: This is the first report showing that arteriosclerosis in zero-time biopsy specimens is a risk factor for histological tacrolimus-induced chronic nephrotoxicity., (© 2015 Asian Pacific Society of Nephrology.)

Focal segmental glomerulosclerosis commonly recurs following kidney transplantation. A 33-year-old man underwent living donor kidney transplantation. Proteinuria appeared two months after transplantation, and an episode biopsy on postoperative day 66 revealed recurrent focal segmental glomerulosclerosis lesions of the cellular variant by Columbia classification. We reviewed the native kidney biopsy and confirmed collapsing variant focal segmental glomerulosclerosis. Plasma exchange therapy was performed, and his proteinuria temporarily resolved. A second allograft biopsy performed on postoperative day 200 showed no evidence of focal segmental glomerurosclerosis. He experienced incomplete remission with a proteinuria of 0.5 g/day during the subsequent three years until his urinary protein level rose to 1.3 g/day. A third biopsy performed on postoperative day 1248 showed focal segmental glomerulosclerosis cellular variant lesions. Plasma exchange was resumed in combination with additional rituximab, but his proteinuria persisted. Intermittent plasma exchange was performed 42 times in total. However, his proteinuria continued, and his renal function gradually worsened. A fourth biopsy performed on postoperative day 2540 showed focal segmental glomerulosclerosis collapsing variant lesions with severe interstitial fibrosis and tubular atrophy. He ultimately required hemodialysis seven years after transplantation. Intensive therapy with long-term intermittent plasma exchange and rituximab suppressed proteinuria and preserved graft function for seven years, at which time graft failure occurred. We here present the clinical course and histological findings from consecutive allograft biopsies., (© 2015 Asian Pacific Society of Nephrology.)