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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.)

Background: Letermovir is approved for cytomegalovirus (CMV) prophylaxis in adult allogeneic hematopoietic cell transplantation recipients worldwide and is also approved in the United States for CMV prophylaxis in adult high-risk (D+/R-) kidney transplant recipients (KTRs). The safety and efficacy of letermovir for CMV prophylaxis in adult Japanese KTRs are reported here., Methods: In this Phase 3, single-arm, open-label study, adult Japanese KTRs with CMV serostatuses D+/R-, D+/R+, and D-/R+ received letermovir 480 mg daily orally within 7 days post-transplant through Week 28. Participants were followed through Week 52. The primary objective was to evaluate letermovir safety and tolerability. Efficacy was a secondary objective, measured by CMV disease, CMV disease or infection requiring intervention, and quantifiable CMV DNAemia. All CMV disease cases were confirmed by an independent adjudication committee., Results: Among 22 participants (12 were D+/R-) who received letermovir prophylaxis, 20 (90.9%) experienced ≥ 1 AE through Week 28. Most AEs were mild to moderate in severity; no deaths were reported. During the prophylaxis period through Week 28, one transient case of quantifiable CMV DNAemia was detected, but no CMV disease or infection requiring intervention was reported. Through Week 52, four D+/R- participants met the endpoint of CMV disease or infection requiring intervention, of whom two had committee-confirmed CMV syndrome; all recovered with CMV therapy. A total of 5 participants had quantifiable CMV DNAemia through Week 52., Conclusion: Letermovir was generally well tolerated, and the data support its use for the prevention of CMV disease/infection in adult Japanese KTRs., Trial Registration: ClinicalTrials.gov NCT04129398., (© 2024. Merck & Co., Inc., Rahway, NJ, USA and its affiliates, Hideki Ishida, Norihiko Goto, Ryoichi Imamura, Hajime Sasaki, Kohei Unagami, Kenta Futamura 2024.)

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.)

Background/aim: Occasionally, candidate renal transplant recipients (RTRs) are incidentally diagnosed with prostate cancer (PCa) during pre-transplant screening examinations; however, their clinical course remains unclear. This study aimed to clarify the clinical course of RTR diagnosed with PCa during pre-transplant screening tests., Patients and Methods: Between April 2008 and April 2022, 15 candidates for RTRs were newly diagnosed with PCa during the screening test. We analyzed the patients' treatment choices, initial treatment results, waiting duration for renal transplantation, and whether they finally underwent transplantation., Results: The median patient age was 64 years (range=52-75 years). The median prostate-specific antigen level was 6.9 ng/ml (5.2-56.9 ng/ml). According to D'Amico risk stratification, one, 10, and four patients were at low, intermediate, and high risk, respectively. As for treatment choice, 13 patients chose surgery. Moreover, intensity-modulated radiotherapy and hormone therapy were chosen by one patient each. Of these, seven patients underwent transplantation, with a median waiting time from initial treatment to transplantation of 20.3 months (9.2-40.0 months). One patient discontinued transplantation owing to poor cancer control, four patients had donor issues (change in mind, aging, or disease), and one patient waited because pathological findings revealed locally invasive cancer., Conclusion: PCa diagnosis in candidate RTRs during the pre-transplant screening test impacts the candidate's clinical course., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The coronavirus disease-19 (COVID-19) vaccine efficacy and immunogenicity in the immunocompetent population are well established. However, in solid organ transplant (SOT) recipients, because of their use of immunosuppressive medication, the immunogenicity of these severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines remains suboptimal. Both BNT162b2 and mRNA1273 have been used for some time, but their immunogenicity has not been directly compared in this immunocompromised patient group. We performed a post-hoc analysis of a previous prospective cohort study. The inclusion criteria were adult SOT recipients with active grafts at least 1 month after SOT. After giving consent, participants chose to receive either BNT162b2 or mRNA1273 vaccine. Anti-spike-protein-S antibody against SARS-CoV-2 was measured. Propensity scores were calculated via logistic regression to transform the probability of having received either BNT162b2 or mRNA1273 vaccine, and a model was developed. We enrolled 623 SOT recipients. In the propensity score-matched analysis, 100 recipients were selected for BNT162b2 and 100 for mRNA1273. SARS-CoV-2 anti-spike protein antibody positivity with BNT162b2 versus mRNA1273 at 3 weeks after the first dose, 1 month after the second dose, 3 months after the second dose, and 6 months after the second dose were 10% versus 19% (P = .07), 51% versus 58% (P = .30), 74% versus 88% (P = .01), and 78% versus 87% (P = .13), respectively. We conducted a propensity score-matched comparison of BNT162b2 and mRNA1273 vaccines as the primary series of COVID-19 vaccines in SOT recipients. We found significantly better immunogenicity with the mRNA1273 vaccine than with BNT162b2., (© 2023 The Scandinavian Foundation for Immunology.)

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/aim: Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney is a rare histological type of renal cell carcinoma (RCC). There are few reports of MTSCC occurring in renal transplant recipients (RTRs). The aim of this study was to report a case of long-term survival of a RTR with metastatic MTSCC of the kidney with sarcomatoid changes., Case Report: A 53-year-old male with a left retroperitoneal tumor was referred to our department. He had been receiving hemodialysis since 1991 and underwent kidney transplantation in 2015. Computed tomography (CT) revealed suspected RCC, and a radical nephrectomy was performed in June 2020. Pathological findings revealed MTSCC with sarcomatoid changes. After the surgery, multiple metastases appeared in the bilateral adrenals, skin, para-aortic lymph nodes, muscles, mesocolon, and liver. We treated the patient with metastasectomy, radiation therapy, and sequential systemic therapy with tyrosine kinase inhibitors (TKI). Two years after the initial surgery, the patient died of cancer while controlling its progression., Conclusion: We report a RTR with aggressive and metastatic MTSCC with sarcomatoid changes, resulting in a longer survival time relative to multimodal therapy., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Transplant recipients (TRs) are at high risk for severe coronavirus disease 2019 (COVID-19). Neutralizing monoclonal antibodies (mAbs) are used for treating mild-to-moderate COVID-19. However, reports comparing the efficacy of COVID-19 treatment without/with mAbs in TRs are limited. We assessed the efficacy of casirivimab/imdevimab against mild-to-moderate COVID-19 in TRs., Methods: Forty-one patients were retrospectively evaluated. The duration until defervescence, oxygen (O 2 ) requirement ≥5 L, and neutralizing antibody levels were compared in TRs with COVID-19 without/with casirivimab/imdevimab., Results: Casirivimab/imdevimab was correlated with shorter duration until defervescence and non-requirement of O 2  ≥ 5 L in TRs with COVID-19 [mean: without/with: 6 vs. 2; P = 0.0002, hazard ratio (HR) = 0.3333, 95% confidence interval (CI) = 0.1763-0.6301; 15 vs. 8; P < 0.0001, HR = 0.5333, 95% CI = 0.2878-0.9883; P = 0.0377, HR = 0.1502, 95% CI = 0.02511-0.8980]. Casirivimab/imdevimab was associated with early defervescence after adjusting for sex and age (P = 0.013, HR = 0.412, 95% CI = 0.205-0.826). The antibody levels between patients without/with casirivimab/imdevimab on the day of hospitalization were not significantly different (P = 0.1055), including 13 TRs with vaccination. Antibody levels were higher in patients with casirivimab/imdevimab at 3-5 days after hospitalization than in those without, at 7-9 days after hospitalization (P < 0.0001, mean, without/with: 414.9/40000 AU/mL)., Conclusion: Casirivimab/imdevimab was effective and increased the neutralizing antibody in TRs with mild-to-moderate COVID-19, it may contribute toward preventing the progression., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Solid organ transplant recipients have an increased risk of developing severe coronavirus disease 2019 (COVID-19). Although SARS-CoV-2 mRNA vaccination has been strongly recommended for solid organ transplant recipients, its efficacy and safety have remained unknown., Methods: We performed an observational prospective cohort study in 18 lung transplant recipients who received two doses of SARS-CoV-2 mRNA vaccine, including BNT162b2 (n = 17) or mRNA-1273 (n = 1), between June and October 2021. The titers of IgG antibodies against the SARS-CoV-2 spike protein (S-IgG) were measured in serum samples collected before the prime dose, three weeks after the prime dose, and four weeks after the booster dose. Reactogenicity and adverse events were evaluated after vaccination., Results: There were no recipients with previous SARS-CoV-2 infection prior to vaccination. S-IgG levels were elevated in 2/18 (11.1%) recipients after the prime dose and in 5/18 recipients (27.8%) after the booster dose (31.7 ± 30.6 U/ml). The time from transplantation to vaccination tended to be longer in the seropositive group than the seronegative group [7.5 (3.9-10.2) vs 2.8 (1.9-4.0) years, p = 0.059]. Maintenance dose of mycophenolate mofetil tended to be lower in the seropositive group than in the seronegative group [500 (250-500) vs 1000 (1000-1000) mg/day, p = 0.088]. Regarding the adverse events after vaccination, the development of chronic lung allograft dysfunction (CLAD) or antibody-mediated rejection (AMR) were observed in two seropositive patients., Conclusions: The antibody response to the SARS-CoV-2 mRNA vaccine was quite poor in lung transplant recipients. We experienced cases that developed clinical CLAD or AMR that was likely related to SARS-CoV-2 vaccination., (© 2022. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

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.

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.

Proliferative glomerulonephritis with monoclonal immunoglobulin IgG deposits (PGNMID) is an already described form of renal involvement by monoclonal gammopathy. PGNMID is known to recur in kidney allografts. Bortezomib has shown clinical success in the treatment of multiple myeloma. However, its effect for recurrent PGNMID in kidney allografts has rarely been reported. We present the case of a 61-year-old woman who developed recurrent PGNMID 3 weeks after kidney transplantation. This patient was initially treated with steroid pulses (500 mg/day for 2 days) and two cycles of rituximab therapy (200 mg/body). However, disease progression was observed with mesangial matrix expansion and subendothelial deposits by light microscopy and stronger staining for IgG3 and kappa in the mesangial area by Immunofluorescence (IF) microscopy. Thus, we started treatment with bortezomib therapy (1.3 mg/m2, once weekly, on days 1, 8, 15, and 22 in a 5-week cycle, for a total of six cycles). Bortezomib therapy reduced massive proteinuria, although monoclonal immune deposits on IF and the serum creatinine level did not change during the treatment period. Seven months after completion of the first bortezomib course, we decided to prescribe a second course of bortezomib with the same regimen. Each course resulted in a > 50% reduction of proteinuria. Bortezomib may delay the progress of PGNMID in kidney allograft patients., (© 2022. The Author(s).)

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.)

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: Nephron-sparing surgery is required for patients with kidney transplant with organ-confined renal cell carcinoma (RCC) in the allograft kidney to preserve renal function. Robot-assisted laparoscopic partial nephrectomy (RAPN) is expected to be the optimal surgical approach for these patients, as in the general population. However, RAPN for RCC arising in the allograft kidney is rarely reported. Here, we report 2 cases of patients who underwent RAPN for allograft RCC., Case Presentation: Two patients were diagnosed with RCC in the renal allograft based on enhanced computed tomography findings. Case 1 was a 69-year-old man with a 32-mm mass in the middle portion of the right iliac fossa renal allograft, and case 2 was a 55-year-old man with a 24-mm mass in the lower pole of the right iliac fossa renal allograft. In each patient, RAPN was performed for the renal mass through a transperitoneal approach, with clamping of the renal artery. No major perioperative complications occurred in either patient, negative surgical margins were achieved, and no significant changes in kidney function were observed during either surgery. Pathologic findings showed clear cell RCC in case 1 and papillary RCC in case 2., Conclusion: RAPN can be a feasible and effective treatment option for allograft RCC., (Copyright © 2021 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: Cardiovascular disease (CVD) is a major cause of death in kidney transplant (KT) recipients. To improve their long-term survival, it is clinically important to estimate the risk of CVD after living donor KT via adequate pre-transplant CVD screening., Methods: A derivation cohort containing 331 KT recipients underwent living donor KT at Kyushu University Hospital from January 2006 to December 2012. A prediction model was retrospectively developed and risk scores were investigated via a Cox proportional hazards regression model. The discrimination and calibration capacities of the prediction model were estimated via the c-statistic and the Hosmer-Lemeshow goodness of fit test. External validation was estimated via the same statistical methods by applying the model to a validation cohort of 300 KT recipients who underwent living donor KT at Tokyo Women's Medical University Hospital., Results: In the derivation cohort, 28 patients (8.5%) had CVD events during the observation period. Recipient age, CVD history, diabetic nephropathy, dialysis vintage, serum albumin and proteinuria at 12 months after KT were significant predictors of CVD. A prediction model consisting of integer risk scores demonstrated good discrimination (c-statistic 0.88) and goodness of fit (Hosmer-Lemeshow test P = 0.18). In a validation cohort, the model demonstrated moderate discrimination (c-statistic 0.77) and goodness of fit (Hosmer-Lemeshow test P = 0.15), suggesting external validity., Conclusions: The above-described simple model for predicting CVD after living donor KT was accurate and useful in clinical situations., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Diagnostic criteria for chronic active T cell-mediated rejection (CA-TCMR) were revised in the Banff 2017 consensus, but it is unknown whether the new criteria predict graft prognosis of kidney transplantation. We enrolled 406 kidney allograft recipients who underwent a 1-year protocol biopsy (PB) and investigated the diagnostic significance of Banff 2017. Interobserver reproducibility of the 3 diagnosticians showed a substantial agreement rate of 0.68 in Fleiss's kappa coefficient. Thirty-three patients (8%) were classified as CA-TCMR according to Banff 2017, and 6 were previously diagnosed as normal, 12 as acute TCMR, 10 with borderline changes, and 5 as CA-TCMR according to Banff 2015 criteria. Determinant factors of CA-TCMR were cyclosporine use (vs tacrolimus), previous acute rejection, and BK polyomavirus-associated nephropathy. In survival analysis, the new diagnosis of CA-TCMR predicted a composite graft endpoint defined as doubling serum creatinine or death-censored graft loss (log-rank test, P < .001). In multivariate analysis, CA-TCMR was associated with the second highest risk of the composite endpoint (hazard ratio: 5.42; 95% confidence interval, 2.02-14.61; P < .001 vs normal) behind antibody-mediated rejection. In conclusion, diagnosis of CA-TCMR in Banff 2017 may facilitate detecting an unfavorable prognosis of kidney allograft recipients who undergo a 1-year PB., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objectives: To compare the long-term outcome and complications of living-kidney grafts with arteriosclerosis to those without abnormal findings diagnosed using pretransplant graft biopsy, and to assess the impact of the arteriosclerosis in living-donor kidneys., Methods: The influence of arteriosclerosis in pretransplant biopsy on long-term outcomes and complications was evaluated in both unmatched (n = 1351, without arteriosclerosis n = 788 vs with arteriosclerosis n = 563) and propensity score-matched cohorts (n = 984, without arteriosclerosis n = 492 vs with arteriosclerosis n = 492) of adults who underwent living-kidney transplant., Results: In both the unmatched and matched cohort, there was no significant difference in patient and death-censored graft survival at 10 years between the without arteriosclerosis and with arteriosclerosis groups. The with arteriosclerosis group had a higher incidence rate of overall rejection than did the without arteriosclerosis group in both the unmatched (P = 0.026) and matched (P = 0.060) cohorts. The with arteriosclerosis group had significantly higher chronic antibody-mediated rejection than did the without arteriosclerosis group (P = 0.006) in the unmatched cohort. The with arteriosclerosis group had a significantly lower estimated glomerular filtration rate in recipients, but there was no significant difference after matching. The incidence rates of calcineurin inhibitor nephrotoxicity and post-transplant anemia were significantly higher in the with arteriosclerosis group than in the without arteriosclerosis group in both the unmatched and matched cohorts. Long-term postoperative kidney function of living donors was lower in the with arteriosclerosis group., Conclusions: Kidney graft with arteriosclerosis might affect the incidence of rejection, complications and postoperative kidney function of donors. Long-term careful observation is required for both the recipients who received grafts with arteriosclerosis and the donors who had kidneys with arteriosclerosis., (© 2020 The Japanese Urological Association.)

Background: Renin-angiotensin system blockers (RASBs) reduce end-stage kidney disease and cardiovascular event (CVE) development in chronic kidney disease. However, whether RASBs improve long-term prognosis in kidney transplant (KT) recipients remain unknown., Method: We investigated 900 kidney transplant patients in a multicenter retrospective cohort study in Japan and compared death-censored graft survival and CVE (total, cardiac events, stroke) based on RASB use within 12 months after KT. The associations were examined using a Cox hazard model and propensity score-matching analysis., Results: The cohort comprised 375 patients treated with RASBs (RASB group) and 525 patients without RASBs (control group). The median observational period was 82 months, with 68 patients reaching graft loss: 79 total CVE, 36 cardiac events, 26 stroke. In a matching cohort comprising 582 patients, death-censored graft survival, total CVE, and cardiac events were not different between the two groups. Only stroke incidence rate was significantly lower in the RASB group compared with the control group (1.4 vs. 6.4 per 1000 patients/year, log-ranked P = 0.005). In a multivariable analysis, stroke events were also significantly lower in the RASB group compared with the control group (Hazard ratio and 95% confidence interval, 0.20 [0.04-0.62])., Conclusion: Thus, RASBs potentially reduce stroke events in KT recipients.

Background: A higher prevalence of bladder cancer is reported in solid organ recipients, and advanced cancer requires radical cystectomy combined with urinary diversion. Surgery is technically challenging in kidney transplant recipients because of urinary tract abnormalities. Here, we describe the use of a robot-assisted approach in a kidney transplant recipient., Case Presentation: The etiology of the patient's end-stage renal disease was bilateral hypoplastic kidney. The patient started to receive hemodialysis at 19 years of age and underwent living-related kidney transplant at 23 years of age. Thirteen years later, he was diagnosed with invasive urothelial carcinoma and underwent robot-assisted radical cystectomy with extracorporeal neobladder construction under open laparotomy. Surgery was indicated to enhance suture flexibility and dissection of the peribladder tissues. Although the patient had an intraperitoneal infection caused by leakage from the vesicourethral anastomosis site and required drainage of the abscess, his condition stabilized after antibiotic treatment., Conclusion: This case outlines the effectiveness of the robot-assisted approach in patients with urinary tract abnormalities, such as kidney transplant recipients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Extra efferent arterioles, also known as polar vasculosis (PV), are often observed in the glomerular vascular pole and are associated with glomerular hypertrophy, indicating early recurrent diabetic kidney disease (DKD) in renal allografts. However, its significance in patients without diabetes remains uncertain., Methods: A total of 9,004 renal allograft biopsy specimens obtained between January 2007 and December 2017 at Tokyo Women's Medical University were retrospectively analyzed to examine the clinical and pathological significance of PV in renal allografts. PV was identified in 186 biopsy specimens obtained from 165 patients. The PV group comprised 46 patients; 35 patients without DKD and 11 patients with DKD as the initial cause of ESRD, whose clinical information was available and treated with the calcineurin inhibitor (CNI) tacrolimus. The non-PV group comprising patients with renal allografts matched for age and postoperative day included 93 patients without DKD and 16 patients with DKD as the initial cause of ESRD., Results: In patients with nondiabetic renal allografts, systolic blood pressure was significantly higher in the PV group than in the non-PV group. The trough tacrolimus levels during the overall study period and at 2 weeks, 1 month, and 2 years after transplantation were significantly higher in the PV group compared with the non-PV group. Glomerulomegaly was significantly more common. Moreover, ah and aah scores in Banff score were significantly higher in the PV group than in the non-PV group. In those with diabetic renal allografts, although the clinical parameters and tacrolimus trough levels in all time periods were not significantly different between the PV and non-PV groups, the ah score was significantly higher in the PV group., Conclusion: PV was associated with CNI toxicity in nondiabetic but not in diabetic renal allografts. The pathogenesis of PV in renal allografts is considered to be multifactorial., (© 2020 S. Karger AG, Basel.)

Objectives: To examine the association of response to rituximab and the incidence of antibody-mediated rejection in preconditioning of rituximab and plasma exchange without post-transplant plasmapheresis in patients undergoing ABO-incompatible living kidney transplantation., Methods: A total of 115 patients who underwent ABO-incompatible living kidney transplantation at Tokyo Women's Medical University Hospital, Tokyo, Japan, were divided into two groups based on the response to rituximab: good response (n = 75) or poor response (n = 40). The rituximab good response and poor response patients were defined as patients whose CD19 + cells were non-detected (0%) and detected on the day of transplantation (2-5 days, median 3 days, after rituximab administration), respectively., Results: Rituximab response and anti-A/B blood antibody titer after plasmapheresis were significant risk factors for antibody-mediated rejection (P = 0.036, 0.045, respectively). The occurrence of antibody-mediated rejection was higher in the poor response group than in the good response group (22.5% vs 8.0%; P = 0.028). The 14-day, 3-month and 1-year cumulative incidence of antibody-mediated rejection was 2.7%, 5.3% and 8.0% in the good response group, and 17.5%, 20.0% and 22.5% in the poor response group after ABO-incompatible living kidney transplantation. The patient survival was not significantly different between the two groups. However, graft survival 1 month after transplantation was lower in the poor response group. There is no significant difference in graft function and in the incidence of complications, including infection, after transplantation between the two groups., Conclusions: Antibody-mediated rejection after ABO-incompatible living kidney transplantation was significantly associated with the response to rituximab in our preconditioning protocol., (© 2019 The Japanese Urological Association.)

The occurrence of acute antibody-mediated rejection (ABMR) is higher in flow cytometric crossmatch (FCXM)-positive patients despite desensitization. Accumulating evidence suggests a correlation between the complement-binding ability of donor-specific antibodies (DSAs) and the risk of ABMR. Here, we investigated the correlation between complement C3d-fixing ability of preformed DSA and ABMR risk, the efficacy of a desensitization protocol for patients with C3d-fixing DSA, and the risk of ABMR in 21 DSA- and FCXM-positive patients. We retrospectively analyzed the C3d-fixing ability and mean fluorescence intensity (MFI) of preformed DSA before and after desensitization. Six patients had non-C3d-fixing DSA and 15 had C3d-fixing DSA. The presence of C3d-fixing DSA before desensitization was correlated with the incidence of acute ABMR within 1 year after transplantation (p = .04) and chronic ABMR (p = .03). Moreover, the MFI of preformed DSA differed between responder and non-responder C3d-fixing DSA after desensitization (p < .0001). The C3d-fixing ability of preformed DSA with low MFI disappeared after desensitization. These results indicate that measuring DSA C3d-fixing ability may identify patients with a high risk of ABMR, especially before desensitization. CLINICAL TRIAL NOTATION: UMIN Clinical Trials Registry (UMIN-CTR) number: UMIN000033449., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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.

ABO-incompatible kidney transplantation (ABO-ILKT) has been reported to have a higher rate of early complications and higher medical costs than ABO-compatible kidney transplantation (ABO-CLKT). We aimed to compare the clinical outcomes, complications, and medical costs between ABO-ILKTs and ABO-CLKTs at 2 years post-transplantation. We included 65 ABO-ILKTs and 94 ABO-CLKTs in this retrospective analysis. The patient survival, graft survival, rejection incidence, and graft function were similar between ABO-CLKT and ABO-ILKT. The hospitalization costs for ABO-CLKT and ABO-ILKT were 26 544 ± 4168 USD and 34 906 ± 18 732 USD, respectively (P = 0.0001). Total 2-year medical costs were 77 117 ± 15 609 USD and 85 325 ± 33 997 USD for ABO-CLKT and ABO-ILKT, respectively, indicating that the medical costs of ABO-ILKT recipients were non-significantly higher than those of ABO-CLKT recipients at 2 years post-transplantation (P = 0.0866). ABO-ILKT and ABO-CLKT recipients showed similar infectious adverse events and complications. In conclusion, medical cost at 2 years post-transplantation, including transplant hospitalization cost, and the frequency of early complications were not significantly higher in the ABO-ILKT group than in the ABO-CLKT group. ABO-ILKT is an acceptable treatment for patients with ESRD and is comparable to ABO-CLKT not only in terms of outcomes but also in terms of medical cost., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

ABO-incompatible living kidney transplantation (ABO-ILKT) is an effective option for increasing living kidney transplant opportunities. ABO-ILKT has been conducted in our institution since 1989 to widen the indication for living kidney transplantation. ABO-ILKT is considered to require extra treatment, and it has increased risks compared with ABO-compatible living kidney transplantation (ABO-CLKT). In the past two decades, some protocols have removed anti-blood-type antibodies to prevent the production of antibodies. Additionally, we have made considerable changes to our ABO-ILKT protocol as new immunosuppressive agents have been developed. Consequently, increased immunosuppression and immunological understanding have helped shape recent desensitization protocols. Herein, we review the history, therapeutic strategy, pathology, and future directions of ABO-ILKT. Our standard immunosuppressive regimen and desensitization protocol for ABO-ILKT recipients consist of low doses of tacrolimus (TAC), mycophenolate mofetil (MMF), and rituximab; several sessions of double filtration plasmapheresis; and basiliximab induction. We do not use thymoglobulin induction, intravenous immunoglobulin, or prophylactic post-transplant plasmapheresis. Recently, ABO-ILKT has been recognized as a useful alternative therapy for end-stage kidney disease with ABO-incompatibility, and its outcome is comparable to that of ABO-CLKT., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background/aims: Although hypomagnesemia was found to be a risk for cardiovascular diseases in the general population, the relationship between serum magnesium (Mg) levels and prognosis of patients on maintenance hemodialysis (MHD) has not been extensively studied. This study sought to determine the relationship of serum Mg levels with aortic arch calcification (AoAC) and mortality in Japanese MHD patients., Methods: We measured serum Mg levels in a cohort of 392 patients on MHD, classified the patients into 3 groups according to these levels, and followed their course for 4 years. AoAC was assessed using chest-X-rays., Results: During follow-up, there were 117 deaths. Kaplan-Meier analyses showed that the high serum Mg group tended to have better survival rates than the low and middle serum Mg groups but this did not reach statistical significance. We also found that patients in the high serum Mg group had better nutritional status associated with higher serum albumin, triglyceride, and phosphate levels and had a significantly lower serum C-reactive protein level. In total, 83 patients (59.3%) in the high serum Mg group had been prescribed Mg oxide (MgO)., Conclusions: Hypermagnesemia tended to be associated with better survival and a higher prescription rate of MgO. Interventional studies are needed to clarify whether Mg supplementation is beneficial for improving patient prognosis., (© 2019 S. Karger AG, Basel.)

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: There have been few studies that have reported the influence of kidney transplantation on the quality of life (QOL) of patients of preemptive kidney transplantation (PKT) and nonpreemptive kidney transplantation (NPKT)., Material and Methods: Fifty patients of PKT and 49 patients of NPKT were employed as study subjects. A questionnaire survey using Short Form 36 and Kidney Disease QOL on patients' physical and psychological QOL was performed for these patients prior to transplantation and 1 month, 3 months, and 1 year after transplantation., Results: The analysis of results has revealed that transplantation clearly has improved the physical and psychological QOL in patients with end-stage renal disease. For the items regarding physical burdens incurred by the transplantation, patient QOL deteriorated on a single occasion 1 month after the transplantation while it was improved 1 year after the transplantation. For the items regarding psychological burdens, the mental condition of the patients was improved overall without deterioration over time. Concerning the "Effect of Kidney Disease" and "Burden of Kidney Disease," QOL was significantly better in PKT than NPKT at baseline before transplantation, although the significant difference gradually decreased 1 month and 3 months after the transplantation and disappeared after 1 year., Conclusion: Transplantation certainly improved the QOL of patients with end-stage renal disease. Before transplantation, PKT was clearly better than NPKT in the QOL items associated with "Burden of Kidney Disease." This indicated that patients of PKT have improved QOL compared to patients of NPKT, and that the overall awareness of kidney disease is decreased. A postoperative gap in mental and bodies was observed especially in PKT, however, could be overcome by nursing interventions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Patients with Alport syndrome (AS) develop progressive kidney dysfunction due to a hereditary type IV collagen deficiency. Survival of the kidney allograft in patients with AS is reportedly excellent because AS does not recur. However, several studies have implied that the type IV collagen in the GBM originates from podocytes recruited from the recipient's bone marrow-derived cells, suggesting the possibility of AS recurrence. Limited data are available regarding AS recurrence and graft survival in the Japanese population; the vast majority were obtained from living related kidney transplantation (LRKTx)., Methods: In this retrospective study, twenty-one patients with AS were compared with 41 matched patients without AS from 1984 to 2015 at two centers using propensity scores. Nineteen of the 21 patients with AS underwent LRKTx. The mean post-transplant follow-up period was 83 months in the AS group and 110 months in the control group. Histopathological AS recurrence was assessed by immunoreactivity of α5 (type IV collagen) antibody and electron microscopy., Results: The graft survival rate was equivalent between patients with and without AS (86.7% vs. 77.1% and 69.3% vs. 64.2% at 5 and 10 years; p = 0.16, log-rank test). Immunoreactivity to α5 antibody showed strong linear positivity with no focal defect in six patients. Electron microscopy showed no GBM abnormalities in two patients who were exhibiting long-term kidney allograft survival., Conclusions: We confirmed that α5 and the GBM structure were histopathologically maintained in the long term after kidney transplantation. The patient and graft survival rates were equivalent between Japanese patients with and without AS.

Objectives: We aimed to evaluate the feasibility and efficacy of surgical prostatectomy in renal transplant recipients (RTRs)., Methods: Between January 2008 and February 2017, we identified 13 RTRs who were diagnosed with localized prostate cancer and underwent radical prostatectomy. We reviewed all available clinicopathologic data for these 13 patients., Results: The median patient age was 61 years and median serum prostate-specific antigen (PSA) was 8.79 ng/mL. The mean period between transplantation and diagnosis of prostate cancer was 136 months. The sources for the kidney transplants included 10 living and 3 deceased donors. Biopsies indicated that the Gleason scores were 7 in 10 patients and 8 to 10 in 3 patients. Meanwhile, the D'Amico risk classification indicated an intermediate risk in 9 patients and a high risk in 4 patients. Eight patients were at stage cT1 and 5 were at stage cT2. The surgical procedure was retropubic radical prostatectomy in one recipient, laparoscopic radical prostatectomy in 3 recipients, and robot-assisted radical prostatectomy in 9 RTRs. Intraoperative complications were not noted in any patient, although one patient demonstrated postoperative complications (Clavien grade ≥ 3). An indwelling urinary catheter was required in 3 patients for over 3 weeks due to delayed wound healing. Biochemical recurrence evaluated by PSA monitoring occurred in four patients. Postoperative graft function was stable in all but one patient who required resumption of dialysis before prostatectomy; however, all patients are alive at the time of publication with 12 patients showing well-functioning renal allografts., Conclusion: Prostatectomy may be a feasible and effective technique as an initial treatment for RTRs with localized prostate cancer., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The cellular uptake of mizoribine (MZR), an immunosuppressant, and metabolism of MZR to MZR-5'- monophosphate (MZRP), an active metabolite, were evaluated in L5178Y-R mouse lymphoma cells and peripheral blood mononuclear cells (PBMCs) of rats and kidney transplant recipients (KTRs, n = 22). Real-time PCR analysis revealed the expression of ENT1 and ENT2 mRNAs, but not of CNTs, in L5178Y-R cells and rat's PBMCs. In L5178Y-R cells, the uptake of MZR was suppressed by adenosine, a substrate for ENT1 and ENT2, but not by 5-(4-nitrobenzyl)-6-thioinosine (0.1 μM), an ENT1 inhibitor. Saturable metabolism of MZR to MZRP was observed. In rats, peak plasma concentrations of MZR and peak concentrations of MZR and MZRP in PBMCs were observed 3 h after oral administration. MZR disappeared from PBMCs in parallel with plasma MZR, but the disappearance of MZRP from PBMCs appeared to be slow. In KTRs, the mean plasma concentration of MZR 3-4 h after ingestion was 3.14 μg/ml and the mean MZRP concentration in PBMCs was 16.8% of MZR, reflecting the involvement of ENT in the uptake of MZR. A linear relationship was observed between plasma MZR concentrations ranging from 1 to 6 μg/ml and PBMC's MZRP concentrations ranging from 90 to 200 ng/ml., (Copyright © 2018 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)

Aim: De novo membranous nephropathy (dnMN) contributes to graft failure, but the pathophysiology of the disease remains poorly understood. We defined cases exhibiting granular Immunoglobulin G (IgG) immunofluorescence staining but lacking dense deposits on electron microscopy as being of 'dnMN stage 0'; we studied the associated clinicopathological features., Methods: We studied 4653 allograft biopsy specimens (from 1747 cases treated in the Department of Urology, Tokyo Women's Medical University) and found 42 cases of allograft membranous nephropathy, of which 28 (1.6%) were diagnosed as dnMN. Of these, five cases (0.06%) fulfilled the criteria for dnMN stage 0., Results: All five cases were diagnosed based on biopsies indicating increased serum levels of creatinine. Proteinuria status varied from negative to 2+. The median period from transplantation to allograft biopsy was 4068 days. Four of the five cases exhibited suspicious antibody-mediated rejection together with dnMN. The glomerular capillaries of all cases were C4d-positive, as were the peritubular capillaries of three of the four ABO-compatible transplants. In terms of IgG subclass, IgG1 and IgG3 predominated in all cases, and phospholipase A2 receptor status (evaluated via immunoreactivity) was negative in all cases. We examined two cases by immunoelectron microscopy using anti-IgG and anti-C4d antibodies. We found subendothelial and intramembranous deposits expressing both IgG and C4d, corresponding to positivity in immunofluorescence analysis., Conclusion: We confirmed the existence of dnMN stage 0 by focusing on granular IgG immunofluorescence positivity., (© 2018 Asian Pacific Society of Nephrology.)

Proliferative glomerulonephritis with monoclonal immunoglobulin (Ig)G deposits (PGNMID) is a rare disease with a treatment that is not well established. Several cases of recurrent PGNMID after kidney transplantation have been documented, but almost all cases reported symptoms such as elevated serum creatinine and/or urinary protein levels; subsequently, episode biopsies were performed and a diagnosis was made. This is the case of a 27-year-old man who underwent living-donor kidney transplantation. The aetiology of renal failure was membranoproliferative glomerulonephritis type III, which had been diagnosed at the age of 9 years. Protocol biopsy performed on postoperative day 62 revealed isolated granular C3 deposits in the glomerular capillaries and mesangium. We reviewed the native kidney biopsy and confirmed IgG3 deposition alone, with strong glomerular staining for lambda light chains and negative staining for kappa light chains. Accordingly, we re-diagnosed the aetiology of his renal failure as PGNMID and suspected recurrent PGNMID in the early stage; therefore, we administered plasma exchange therapy. Thereafter, protocol biopsies were performed twice, which revealed persistent isolated C3 deposition; therefore, we made a diagnosis of recurrent PGNMID or C3 glomerulonephritis. Currently, the patient has normal renal function, with negative urine findings for >1 year. Here, we present the histological findings of consecutive allograft biopsies performed in this patient., (© 2018 Asian Pacific Society of Nephrology.)

Background: The number of kidney transplant recipients (KTRs) from diabetic nephropathy (DN) and with cardiovascular disease (CVD) history has increased worldwide. Nevertheless, epidemiologic evidence of CVD in KTRs remains limited., Methods: We investigated post-transplant CVD in 1614 adult KTRs between 1990 and 2014. CVD was defined according to the international classification of diseases (ICD-10). All-cause mortality was also investigated. Final follow-up was performed in March 2016. The KTRs were categorized into four groups according to DN and CVD at surgery., Results: During the follow-up period, 309 KTRs experienced CVDs and 124 KTRs died. The 15-year cumulative CVDs rate was 87% in KTRs with both DN and CVD history, and the rate in KTRs without those was 22.3%. DN and CVD were associated with increased risk of post-transplant CVD [hazard ratio (HR), 3.44; 95% confidence interval (CI), 2.03-5.82; P < 0.001], and the impact marked increased after 7.5 years follow-up period (HR, 16.56; 95% CI, 6.56-41.8; P < 0.001). DN and CVD in KTRs were associated with mortality (HR, 3.32; 95% CI, 1.34-8.22; P = 0.009), and post-transplant CVD was the leading cause (35.5%) of overall death. However, DN and CVD were not associated with increased graft failure rate., Conclusions: The risk of post-transplant CVDs incidence in KTRs with DN and CVD history is high, and it increases during the late transplant period. Appropriate routine cardiovascular screening and evaluation are needed to reduce late-onset CVD incidence.