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We aimed to compare the outcomes of pediatric kidney transplantation (KT) between preemptive KT (PEKT) and non-PEKT in children aged < 6 years. Seventy-four pediatric recipients aged < 6 years who underwent KT were divided into the PEKT and non-PEKT groups. They were retrospectively evaluated for patient and graft survival, graft function, growth, and cytomegalovirus (CMV) infection. Comparison of the groups (PEKT, n = 14; non-PEKT, n = 60) revealed no significant differences between them in terms of distribution of sex, age, weight, primary disease, or population of pre-transplant CMV immunoglobulin G-positive patients. The median estimated glomerular filtration rate before KT in the PEKT and non-PEKT groups was 11.4 and 7.3 (mL/min/1.73 m2) (P < .001), respectively, and the median duration of dialysis was 2.7 years in the non-PEKT group. Graft survival at 5 years was 100% and 95% in the PEKT and non-PEKT groups, respectively (P = .634). One patient in the non-PEKT group had vascular complications, with subsequent early graft loss. Incidence of CMV infection was significantly lower in the PEKT group (P = .044). There were no significant differences in post-transplant estimated glomerular filtration rate, acute rejection, or growth. The height standard deviation score showed catch-up growth after KT in both groups. There was no significant difference in transplant outcomes in recipients aged < 6 years, with or without pre-transplant dialysis, except for the incidence of CMV infection. Therefore, PEKT in younger children should be performed aggressively by experienced multi-disciplinary teams., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Coronavirus disease (COVID-19) vaccination is recommended for patients undergoing renal replacement therapy (RRT), including hemodialysis (HD), peritoneal dialysis (PD), and kidney transplantation (KT). However, the difference in the immune response between RRT patients and healthy individuals after mRNA vaccines remains uncertain., Methods: This retrospective observational study evaluated the anti-severe-acute-respiratory-syndrome-coronavirus-2 (anti-SARS-CoV-2) IgG antibody acquisition, titers and their changes, normal response rate (reaching titers of healthy individuals), factors associated with a normal response, and effectiveness of booster vaccination in Japanese RRT patients., Results: Most HD and PD patients acquired anti-SARS-CoV-2 IgG antibodies after the second vaccination; however, their antibody titers and normal response rates (62-75%) were low compared with those of healthy subjects. Approximately 62% of KT recipients acquired antibodies, but the normal response rate was low (23%). Anti-SARS-CoV-2 IgG antibody waning occurred in the control, HD, and PD groups, while negative or very low titers remained in KT recipients. Third booster vaccination was effective in most HD and PD patients. However, the effect was mild in KT recipients - only 58% reached a normal response level. Multivariate logistic regression analyses demonstrated that younger age, higher serum albumin level, and RRT other than KT were significantly associated with a normal response after the second vaccination., Conclusions: RRT patients, particularly KT recipients, exhibited poor vaccine responses. Booster vaccination would be beneficial for HD and PD patients; however, its effect in KT recipients was mild. Further COVID-19 vaccinations using the latest vaccine or alternative procedures should be considered in RRT patients., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Nephrology.)

Background: Arteriovenous fistula (AVF) due to renal allograft biopsy is mechanical trauma resulting from the penetration of small arteries and veins by a core needle. Most AVFs are reported to resolve asymptomatically and spontaneously. This report presents a patient with acute kidney injury (AKI) due to urinary tract obstruction caused by a bleeding AVF in a renal allograft., Case Presentation: A 22-year-old Japanese woman who underwent living-donor kidney transplantation (KT) at 3 years due to end-stage renal disease caused by focal segmental glomerulosclerosis (FSGS) presented with a renal transplant AVF (gourd-shaped; 42 × 19 × 20 mm). The AVF was unexpectedly discovered by ultrasound before a surveillance biopsy at 10 years after KT. The patient had a history of recurrent FSGS, had undergone several renal allograft biopsies after KT, and did not experience symptoms or growth of the AVF for years. Nineteen years after KT, the patient developed AKI with sudden, asymptomatic, gross hematuria and anuria. Plain computed tomography revealed a hematoma in the pelvis of the renal allograft and bladder tamponade. The AVF was successfully treated by coil embolization. Hemodialysis was performed for AKI, and graft function was gradually recovered., Conclusions: Unexpected bleeding from a renal transplant AVF may lead to transplant dysfunction. Angiographic embolization against the ruptured renal transplant AVF may prevent rebleeding and rescue the renal allograft., (© 2023. The Author(s).)

Background: The role of fibroblast growth factor 23 (FGF23) levels in mineral metabolism before and after kidney transplantation in pediatric patients is poorly understood., Methods: We prospectively evaluated 24 patients under 18 years of age (4.5 [3.3-9.8] years) who underwent living kidney transplantation between July 2016 and March 2018, and measured intact FGF23 and serum αKlotho levels, and other parameters of mineral metabolism before and after transplantation (Day 7, 1 and 4 months, and 1 year). Relationships between parameters were examined by linear analysis., Results: FGF23 level was 440.8 [63.4-5916.3] pg/ml pre-transplant and decreased significantly to 37.1 [16.0-71.5] pg/ml at Day 7 post-transplant (-91.6%, p < .001). Thereafter, it remained at normal levels until 1 year. αKlotho level was 785 [568-1292] pg/ml pre-transplant and remained low at Day 7 and 1 month post-transplant, with an increasing trend at 4 months. Post-transplant phosphorus levels were significantly decreased compared with pre-transplant, with a lowest level of 1.7 [1.3-2.9] mg/dl, -5.7 [-6.8, -3.8] SD at Day 4, followed by gradual recovery. Phosphorus levels and the ratio of tubular maximum phosphate reabsorption were significantly and negatively associated with pre-transplant FGF23 until 4 months of post-transplant. Pre-transplant αKlotho was negatively associated with pre-transplant FGF23 but not FGF23 or other parameters after transplantation., Conclusion: FGF23 in pediatric kidney transplant patients decreased rapidly after transplantation and associated with post-transplant hypophosphatemia and increased phosphorus excretion. Post-transplant αKlotho was low early post-transplant but tended to increase subsequently. Post-transplant αKlotho was unaffected by pre-transplant FGF23 or other factors, suggesting pre-transplant chronic kidney disease status has no effect., (© 2022 Wiley Periodicals LLC.)

The outcomes of COVID-19 in kidney transplant recipients have shown high mortality. In addition to their immunocompromised states, kidney transplant recipients frequently have certain exacerbation risk comorbidities of COVID-19, such as diabetes mellitus, hypertension, and chronic kidney disease. Several concomitant diseases develop during the course of COVID-19, one of which is thromboembolism, which can potentially lead to a critical condition. However, thromboembolic complications in kidney transplant recipients with COVID-19 have not been fully addressed in previous studies. A 62-year-old man, who underwent kidney transplantation 17 years ago, was diagnosed with COVID-19 and was admitted to our hospital. Although the patient was in remission at the start of the hospitalization, his condition became severe on day 7 after admission, with fever, elevated white blood cell counts (10,000/μL) and a high C-reactive protein level (6.9 mg/dL). Although the patient was not under forced bed rest, an ultrasound study on day 10 detected deep venous thrombosis (DVT), with an elevated D-dimer level (6.2 µg/dL). We withdrew the mycophenolate mofetyl and the tacrolimus dosage but did not administer any specific treatment for COVID-19. The patient achieved successful clearance of SARS-CoV-2 on day 16. The DVT disappeared after systematic heparin treatment and oral rivaroxaban for 2 months. DVT occurred in a kidney transplant recipient with COVID-19 who was not bedridden and might manifest when the clinical status was exacerbated during hospitalization., (© 2022. The Author(s) under exclusive licence to The Japan Society of Nephrology.)

Background: This study aimed to evaluate the change in graft function in two groups stratified by the estimated glomerular filtration rate (eGFR) at 1 month after transplantation (eGFR-1 M) in pediatric living donor kidney transplant recipients., Methods: Forty-three pediatric recipients were classified as those with an eGFR-1 M ≥ 90 mL/min/1.73 m 2 (n = 19; high eGFR group) or those with an eGFR-1 M of 60-89 mL/min/1.73 m 2 (n = 24; middle eGFR group). In the two groups, changes in the eGFR were retrospectively evaluated for 5 years after kidney transplantation., Results: The mean recipient age at transplantation in the high/middle eGFR group was 6.1 ± 3.4/7.8 ± 4.0 years (P = 0.14). The mean eGFR-1, -12, and -60 M (mL/min/1.73 m 2 ) in the high/middle eGFR group were 106.8 ± 2.99/78.5 ± 1.52 (P < 0.001), 79.3 ± 3.22/62.7 ± 2.38 (P < 0.001), and 73.1 ± 4.16/59.2 ± 2.79 (P = 0.006), respectively. The change in the mean eGFR remained mostly parallel in the two groups. In both groups, the eGFR significantly decreased only between 1 and 12 months after transplantation (P < 0.0001). Approximately 70% of the patients had an eGFR-60 M ≥ 60 mL/min/1.73 m 2 ., Conclusions: The high and middle eGFR groups showed a rapid decline in the eGFR by 1 year after transplantation, but the change thereafter was gradual. In pediatric living donor kidney transplant recipients, the eGFR was relatively well maintained up to 5 years after transplantation. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Introduction: This study aimed to determine if immune or nonimmune and acute or chronic lesions associated with mesangiolysis (MGLS) occurred in biopsy-proven pathological chronic active antibody-mediated rejection (P-CAABMR) in kidney transplant biopsies., Methods: We evaluated MGLS in 41 patients with biopsy findings of P-CAABMR from January 2016 to December 2019. Histological scoring was evaluated by Banff classification. Multivariate logistic regression analysis was performed using a forward selection method., Results: Fifteen of the 41 P-CAABMR biopsies (36.6%) cases showed MGLS. The estimated glomerular filtration rate (eGFR) was significantly lower in the MGLS-positive compared with the MGLS-negative group, and proteinuria was significantly higher in the MGLS-positive compared with the MGLS-negative group. In the clinical model, multivariate analysis was performed using covariates of eGFR and duration after transplantation significantly correlated with MGLS by simple analysis, in addition to type of calcineurin inhibitor use (tacrolimus or cyclosporine), donor-specific antibodies, diabetes, and hypertension grade defined by use of antihypertensive therapy or/and blood pressure level. Only hypertension grade was significantly correlated with MGLS. In the pathological model, multivariate analysis was performed using the presence of FSGS and the aah and cg scores significantly correlated with MGLS by simple analysis, in addition to g and ptc scores. The cg score was significantly correlated with hypertension grade, duration after transplantation, g, ah, and aah., Conclusion: Lower graft function and higher proteinuria was observed in MGLS of P-CAABMR. The Banff cg score was independently related to MGLS in multivariate analysis. Sustained glomerulitis, calcineurin inhibitor nephrotoxicity, and hypertension may cause Banff cg lesions, leading to MGLS in P-CAABMR., (© 2023 S. Karger AG, Basel.)

BK polyomavirus-associated nephropathy is one of serious complications in transplant recipients. Everolimus-a mammalian target of rapamycin inhibitor-has been shown to reduce the incidence of BK polyomavirus infection in transplant recipients. In this study, the effects of everolimus were examined on viral replication and the spread of infection in BK polyomavirus-infected cultures. BK polyomavirus replicated in renal and pulmonary cells, contrary to that in hepatocytes, and spread as diffusely scattered patterns of infected cells, unlike plaque formation through the cell-to-cell mode. BK polyomavirus is stable to heat up to 65 °C with a particle per infectivity ratio of 5000, and the replication cycle was for approximately 34 h. Everolimus administration remarkably reduced the viral replication to 20% in cells treated with 0.1-10 ng/mL, the concentration at which everolimus reached the serum of transplant recipients. In addition, it reduced the amount of viral capsid protein 1 at 5 ng/mL without reducing the ratio of viral capsid protein 1 versus β-actin, and it also retained the pattern of viral capsid protein 1 localization in the nuclei. Everolimus suppressed the number of infected cells to 32.8% during a 14-day treatment, indicating the reduction of BK polyomavirus-infected cell mass to 18.8% of untreated cultures by modifying cellular functions. The reduction in the total number of BK polyomavirus infected cells by everolimus indicates that everolimus alleviates BK polyomavirus infection, including nephropathy in transplant recipients., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: There are certain criteria for selecting living kidney donors. However, the association between clinical characteristics of these criteria and kidney biopsy findings in living kidney donors have not yet been elucidated. Thus, we investigated the association between kidney biopsy findings and clinical characteristics defined in the Japanese guidelines for living kidney donors., Methods: A retrospective multicentre study was conducted on donors and their recipients who underwent kidney transplantation between July 2014 and June 2017. Multiple linear regression analysis and multiple logistic regression analysis were performed to investigate the association between biopsy findings and clinical characteristics., Results: A total of 240 donors and 240 recipients were included. Age was significantly correlated with global glomerulosclerosis and intimal thickening in multiple linear regression analysis and multiple logistic regression analysis, whereas diabetes was correlated with tubular atrophy in multiple linear regression analysis after multiple imputation and multiple logistic regression analysis., Conclusions: Amongst the clinical factors investigated in our study, age was positively correlated and diabetes was possibly correlated with kidney tissue injury in living kidney donors. Age and diabetes may be more important for selecting suitable living kidney donors than other clinical factors., (© 2021. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Objectives: Several controversies regarding desensitization strategies for successful ABO-incompatible (ABOi) kidney transplantation still exist. This study aimed to investigate whether pretransplant anti-A/B antibody removal is mandatory in an ABOi kidney transplant recipient with low baseline isoagglutinin titers., Methods: We adopted a modified desensitization protocol with two doses of rituximab (RTX, 100 mg/body) without pretransplant antibody removal for ABOi kidney transplant recipients with a titer of ≤1:64 (group A; n = 35) and investigated the feasibility of this protocol by comparing it with the clinical outcomes of patients undergoing standard pretransplant plasmapheresis (group B; n = 21)., Results: There was no significant difference in the rate of antibody-mediated rejection within the first month after transplantation between the two groups (11.4% in group A vs. 2% in group B, p = 0.6019). Moreover, no differences were observed in the short- and long-term graft outcomes between the groups. However, two major critical acute antibody-mediated events occurred in group A; one patient lost the graft due to hyperacute rejection, and the other patient developed thrombotic microangiopathy after surgery. Risk factors predicting these perioperative complications were not identified., Conclusions: We conclude that not only B-cell depletion using RTX but also pretransplant antibody removal is still recommended even for patients with low isoagglutinin titers. In addition, a new diagnostic tool is needed for accurate risk stratification., (© 2022 The Japanese Urological Association.)

Background: Patient and graft survival rates after pediatric kidney transplantation have improved recently. Therefore, the quality of life or social outcome after kidney transplantation has become important for patients and their families., Methods: Patients who underwent kidney transplantation at < 18 years old and were observed for > 10 years were included in this study. The median age at first kidney transplantation was 9.2 (interquartile range [IQR] = 5.6-13.0) years; there were 56 males and 50 females. The median age at last follow-up was 29.9 (IQR = 22.2-36.0) years. We evaluated the patients' renal function, growth, professional status, and marital status at the last follow-up., Results: The percentage of functioning grafts at the last follow-up was 81.1%; 73 patients (68.9%) had a first graft. The mean estimated GFR was 51.0 ± 20.5 mL/min/1.73 m 2 . Twenty patients received dialysis for graft failure. The mean final heights of the males and females were 158.1 ± 9.2 cm (- 2.2 standard deviations) and 149.1 ± 6.4 cm (- 1.7 standard deviations), respectively. Excluding 23 students, 63 patients (75.9%) were employed. Office worker was the most common profession. Twelve patients (14.5%) were unemployed. Of patients > 20 years old, 14 (16.7%), three males and 11 females, were married. Five females had one child each., Conclusions: The graft survival rate was favorable. The final height was short, particularly in male. The rate of employment was relatively high. The rate of marriage and having children were still low. Improving the social outcome is an important problem after pediatric kidney transplantation., (© 2021. Japanese Society of Nephrology.)

Background: Malignancy after kidney transplantation (KT) is one of the most serious post-transplant complications. This study aimed to investigate the incidence, type, and outcomes of malignancy after pediatric KT., Methods: We performed a retrospective cohort study on pediatric kidney transplant recipients aged 18 years or younger who received their first transplant between 1975 and 2009., Results: Among the 375 children who underwent KT, 212 were male (56.5%) and 163 were female (43.5%) (median age at KT, 9.6 years [interquartile range {IQR}] 5.8-12.9 years). The incidence of malignancy was 5.6% (n = 21). The cumulative incidences of cancer were 0.8%, 2.5%, 2.8%, 4.2%, 5.5%, and 15.6% at 1, 5, 10, 15, 20, and 30 years post-transplantation, respectively. Of 375 patients, 12 (3.2%) had solid cancer and nine (2.4%) had lymphoproliferative malignancy. The median age at the first malignancy was 21.3 years (IQR 11.5-33.3 years). The median times from transplant to diagnosis were 22.3 years (IQR 12.3-26.6 years) for solid cancer and 2.2 years (IQR 0.6-2.8) for lymphoproliferative malignancies. During follow-up, five recipients died due to malignancy. The causes of death were hepatocellular carcinoma in one patient, squamous cell carcinoma in the transplanted kidney in one patient, malignant schwannoma in one patient, and Epstein-Barr virus-related lymphoma in two patients. The mortality rate was 0.79 per 1000 person-years (95% confidence interval 0.38, 1.85)., Conclusions: Early diagnosis and treatment of malignancies in transplant recipients is an important challenge. Therefore, enhanced surveillance and continued vigilance for malignancy following KT are necessary., (© 2021. The Author(s).)

Physiologically based pharmacokinetic (PBPK) modeling is useful for evaluating differences in drug exposure among special populations, but it has not yet been employed to evaluate the absorption process of tacrolimus. In this study, we developed a minimal PBPK model with a compartmental absorption and transit model for renal transplant patients using available data in the literature and clinical data from our hospital. The effective permeability value of tacrolimus absorption and parameters for the single adjusting compartment were optimized via sensitivity analyses, generating a PBPK model of tacrolimus for renal transplant patients with good predictability. Next, we extrapolated the pharmacokinetics of tacrolimus for liver transplant patients by changing the population demographic parameters of the model. When the physiological parameters of a population with normal liver function were changed to those of a population with impaired hepatic function (Child-Pugh class A) in the constructed renal transplant PBPK model, the predicted tacrolimus concentrations were consistent with the observed concentrations in liver transplant patients. In conclusion, the constructed tacrolimus PBPK model for renal transplant patients could predict the pharmacokinetics in liver transplant patients by slightly reducing the hepatic function, even at three weeks post-transplantation., Competing Interests: Declaration of competing interest None of the authors have any competing interests to declare., (Copyright © 2021 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)

Introduction: Kidney transplantation (KTx) is the most effective treatment for end-stage renal disease in children., Objectives: We aimed to compare the long-term outcomes and surgical complications of the intraperitoneal approach (IPA) and extraperitoneal approach (EPA) for KTx in children weighing <15 kg., Study Design: We performed a retrospective cohort study on pediatric kidney transplant recipients, weighing <15 kg, who received their first living-related kidney transplant between January 1987 and December 2015. Patients were divided into two groups based on the surgical approach (IPA or EPA) during transplant, and clinical data were extracted from the medical records., Results: The median follow-up duration was 14.1 years (interquartile range, 9.0-19.2). Comparing the two groups (IPA group, n = 62; EPA group, n = 38), the median age and body weight were significantly lower in the IPA group (4.2 vs. 4.8 years, P = 0.03; 11.7 vs. 13.0 kg, P < 0.01). There were 26 surgical complications (26%) in 19 patients during the follow-up period. The surgical complication rate was higher in the IPA group (39% vs. 6%)., Discussion: We assessed the long-term outcomes of the surgical approaches used for pediatric patients weighing <15 kg who underwent KTx and received a size-mismatched adult donor kidney. There was no significant difference in renal transplantation prognosis using the surgical approach, but IPA-related complications were more frequent in the long term. Therefore, our data suggest that in cases of donor-recipient size mismatch in pediatric KTx, the EPA, associated with fewer surgical complications, is preferable to the IPA if the patient's body size has sufficient space for allograft placement., Conclusion: The transplant approach did not influence the long-term outcomes in children weighing <15 kg, but EPA had fewer surgical complications and was technically safe., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Anemia and vitamin D deficiency are associated with allograft failure, and hence, are potential therapeutic targets among kidney transplant recipients (KTRs). We conducted a multicenter, two-by-two factorial, open-label, randomized clinical trial to examine the effects of anemia correction and vitamin D supplementation on 2-year change in eGFR among KTRs (CANDLE-KIT). We enrolled 153 patients with anemia and >1-year history of transplantation across 23 facilities in Japan, and randomly assigned them to either a high or low hemoglobin target (>12.5 vs. <10.5 g/dl) and to either cholecalciferol 1000 IU/day or control. This trial was terminated early based on the planned interim intention-to-treat analyses (α = 0.034). Among 125 patients who completed the study, 2-year decline in eGFR was smaller in the high vs. low hemoglobin group (i.e., -1.6 ± 4.5 vs. -4.0 ± 6.9 ml/min/1.73 m 2 ; P = 0.021), but did not differ between the cholecalciferol and control groups. These findings were supported by the fully adjusted mixed effects model evaluating the rate of eGFR decline among all 153 participants. There were no significant between-group differences in all-cause death or the renal composite outcome in either arm. In conclusion, aggressive anemia correction showed a potential to preserve allograft kidney function., (© 2021 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Background: Renal transplantation improves the quality of life (QOL) of end-stage renal disease (ESRD) patients with renal failure. However, it remains unclear which renal disease-specific QOL aspects determine general health-related QOL of ESRD patients. This study aimed to identify these QOL items by examining the QOL of ESRD patients using the Kidney Disease Quality of Life-Short Form (KDQOL-SF), version 1.3, and EuroQoL-5 dimension-5 levels (EQ-5D-5L) questionnaires., Methods: We conducted QOL surveys with 67 renal transplant recipients at our hospital. EQ-5D-5L, which evaluates general health-related QOL, was the response variable, and KDQOL-SF, which includes the renal disease-specific instrument and general health-related QOL SF-36 instrument, was the explanatory variable. We analyzed the effects of each KDQOL-SF domain on EQ-5D-5L using Pearson correlation coefficient., Results: Regarding the general health-related QOL assessed by SF-36, physical health aspects, such as physical functioning (R = 0.749) and daily functioning physical (R = 0.603), showed a strong correlation with EQ-5D-5L, and the domains related to the psychological and social aspects of QOL showed a limited correlation. Regarding kidney disease-specific scales, symptoms/problems related to physical function showed a good correlation (R = 0.691) with EQ-5D-5L, whereas other scales, including burden of kidney disease (R = 0.168), quality of social interaction (R = 0.284), and those related to the mental and social aspects of QOL showed a low correlation with EQ-5D-5L., Conclusion: Among kidney transplant recipients, the physical health aspects of QOL, such as symptoms/problems, were the major factors influencing overall QOL as assessed by EQ-5D-5L., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To evaluate long-term outcomes and risk factors for graft loss in pediatric kidney transplantation over a 30-year period., Methods: We retrospectively assessed 400 consecutive kidney transplants carried out in 377 children during 1975-2009. Patients were stratified according to the immunosuppressive regimen (era 1: methylprednisolone and azathioprine; era 2: calcineurin inhibitor-based therapy, including methylprednisolone and azathioprine or mizoribine; era 3: basiliximab induction therapy, including calcineurin inhibitors, methylprednisolone and mycophenolate mofetil)., Results: The median age and bodyweight at transplantation were 9.7 years and 20.6 kg, respectively. In total, 364 (91.0%) children received a living related donor transplantation. The acute rejection rate within 1 year post-transplant decreased significantly from 61.0% in era 1 to 14.5% in era 3 (P < 0.001). For transplant eras 1-3, 1-year graft survival was 81%, 93% and 95%; 5-year graft survival was 66%, 86% and 93%; and 10-year graft survival was 47%, 79% and 89%, respectively. The overall 5-, 10- and 20-year patient survival rates were 96%, 93% and 88%, respectively. A Cox multivariate analysis identified cold ischemia time (hazard ratio 1.385, 95% confidence interval 1.251-1.603), acute rejection (hazard ratio 1.682, 95% confidence interval 1.547-3.842), re-transplant (hazard ratio 2.680, 95% confidence interval 1.759-3.982) and donor type (hazard ratio 2.957, 95% confidence interval 1.754-4.691) as independent risk factors for graft loss at 10 years post-transplant., Conclusions: The progress of immunosuppressive therapy has led to a low incidence of acute rejection and a high graft survival rate across 30 years of pediatric transplantation., (© 2019 The Japanese Urological Association.)

Background: Because of the severe shortage of suitable deceased donors, ABO-incompatible living donor kidney transplantation (ABOi LDKT) is performed even in pediatric recipients in Japan. We performed pediatric ABOi LDKT using rituximab without anti-A/B antibody removal., Methods: Thirteen pediatric recipients (mean age 7.4, range 3.4-15.7, four females) whose baseline anti-A/B IgG titers were ≤ × 64 underwent ABOi LDKT without antibody removal and splenectomy between July 2013 and April 2017 at Toho University. Mycophenolate mofetil (MMF) was initiated on day - 10. Rituximab (100 mg) was administered twice. Basiliximab and triple maintenance immunosuppression (calcineurin inhibitor, MMF, and steroids) were administered. Protocol biopsy was performed at 3 months and 1 year after transplantation. We retrospectively compared the clinical outcomes between these recipients and 37 children (mean age 9.0, range 2.6-18.9, 15 female) who underwent ABO-compatible (ABOc) LDKT during the same period., Results: The mean follow-up periods of ABOi and ABOc groups were 31.9 ± 13.5 and 28.8 ± 14.4 months, respectively. In the ABOi group, no clinical acute rejection (AR) was noted and subclinical AR was observed in four patients without evidence of acute antibody-mediated rejection. In the ABOc group, clinical and subclinical AR developed in 3 and 10 patients, respectively. No significant difference was identified for the mean eGFR between the ABOi and ABOc groups (98.3 ± 48.8 vs. 86.9 ± 39.4, P = 0.452 at 3 months; 78.2 ± 21.2 vs. 79.7 ± 21.3, at 1 year, P = 0.830). Death-censored graft survival at follow-up was 100% in the ABOi group and 94.6% in the ABOc group. Patient survival during the follow-up period in both the groups was 100%. Late-onset neutropenia (LON) requiring granulocyte colony-stimulating factor occurred more frequently in the ABOi group than in the ABOc group (4 vs. 0 patients) (P < 0.001)., Conclusions: Pre- and post-transplantation antibody removal is not a prerequisite for successful pediatric ABOi LDKT, at least in patients with a low anti-A/B IgG antibody titer. However, LON caused by rituximab should be monitored.

Aim: Medullary ray injury was recently reported in renal transplant biopsies. This study was performed to clarify the clinicopathological features of medullary ray injury in paediatric living renal transplant recipients., Methods: Paediatric recipients who completed a 5-year follow-up after living renal transplantation were enroled. We evaluated the clinical and pathological parameters of the presence or absence of medullary ray injury in their 1-year protocol biopsies., Results: Of 48 1-year protocol biopsies, 18 (37.5%) showed histological evidence of medullary ray injury. The 48 paediatric recipients were classified as those with medullary ray injury (n = 18; MRI-1Y [+] group) and those without medullary ray injury (n = 30; MRI-1Y [-] group) in the 1-year protocol biopsies. The prevalence of histological evidence of calcineurin inhibitor (CNI) nephrotoxicity, chronic obstruction or reflux nephropathy, and imaging findings of vesicoureteral reflux was 66.7, 22.2, and 7.7% in the MRI-1Y (+) group and 33.3, 13.3, and 15.4% in the MRI-1Y (-) group, respectively. Only the prevalence of CNI nephrotoxicity was significantly different between the 2 groups. There was no significant difference in the mean estimated glomerular filtration rate at 1, 3, or 5 years after transplantation between the 2 groups., Conclusion: In total, 37.5% of 1-year protocol biopsies showed histological evidence of medullary ray injury. This finding suggests that CNI nephrotoxicity might be the main contributor to medullary ray injury in 1-year protocol biopsies. The presence of medullary ray injury had little influence on renal function, at least during the first 5 years after transplantation., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Aim: This study evaluated the clinicopathological findings of acute/active antibody-mediated rejection (AABMR) according to the Banff 2013 classification., Methods: We analyzed 345 biopsies of 269 kidney transplant recipients. Pathological AABMR (PAABMR) was defined as histological evidence of acute tissue injury and endothelial injury by light microscopy regardless of donor-specific antibodies (DSAs)., Results: Among the 345 biopsies, 29 (8.4%) were diagnosed as PAABMR. The mean g score was 1.17 ± 0.60, the mean ptc score was 1.97 ± 1.32, and DSA positivity was found in 69% of PAABMR. The mean duration after transplantation was 22.9 ± 26.7 months. Among 3 groups (DSA-high, mean fluorescence intensity (MFI) ≥ 5,000; DSA-low, MFI < 5,000 to ≥1,000; below cutoff), ABO incompatibility in DSA-high was significantly lower and second transplantation in DSA-high was significantly higher. We found 83% of PAABMR by the protocol biopsy (subclinical AABMR [SAABMR]). The short-term clinical and light microscopical changes in 8 cases of SAABMR did not show worsening during follow-up period (9-24 months). However, ultrastructural finding, including glomerular endothelial swelling, subendothelial electron-lucent widening, and early glomerular basement duplication, were found by electron microscopy (EM) in the first biopsies, and half of the SAABMR cases developed de novo circular peritubular capillary multilayering in the follow-up biopsies., Conclusion: PAABMR was mainly found by the protocol biopsy. The short-term follow-up of SAABMR patients did not show worsening clinically and light microscopically, but ultrastructural examination by EM was useful to detect early lesions of endothelial injury and progression of glomerular and peritubular capillary basement membrane alterations., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Aim: Low-vacuum scanning electron microscopy (LVSEM) has been reported to aid in diagnosis of renal biopsy. This study evaluated early transplant glomerulopathy in kidney transplant recipients using LVSEM., Methods: We selected 4 biopsies of cg0, 5 biopsies of cg1a, 5 biopsies of cg1b, and 4 biopsies of cg2 lesions that had been evaluated by light microscopy (LM) and transmission electron microscopy from recipients with acute/active or chronic, active antibody-mediated rejection (AABMR or CAABMR). Renal allograft paraffin sections (1 µm thickness) were stained with periodic acid-methenamine silver and observed using LVSEM. The cg score was based on the Banff classification. The parameter "percentage of duplicated capillary number" was calculated as follows: in 1 glomerulus with glomerular basement membrane (GBM) duplication, the total duplicated capillary number/the total number of capillaries ×100., Results: In all 4 biopsy specimens with AABMR showing cg0, LVSEM revealed GBM duplication not identified by LM. The average percentage of duplicated capillary number per glomerulus with GBM duplication was higher when observed by LVSEM than when observed by LM in all cg1b and cg2 biopsy specimens., Conclusion: LVSEM revealed early GBM duplication in AABMR. Early GBM duplication might progress in the very early phase of AABMR. GBM duplication was more frequently detected by LVSEM than by LM in biopsy specimens with early chronic, active antibody mediated rejection. Thus, LVSEM may be useful in diagnosis of early transplant glomerulopathy., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

A man in his 70's who had undergone left radical nephrectomy for kidney cancer had the right renal artery ablated unexpectedly during pancreatoduodenectomy for a huge duodenal tumor. For this intraoperative emergency, an autologous kidney transplantation was performed with the right kidney being removed, perfused, and transplanted into the right iliac fossa. Warm ischemic time was over 2 hours. The patient developed postoperative hemorrhagic infarction of a renal artery branch, which was successfully treated with intravascular intervention. The patient was weaned off hemodialysis and was discharged in 16 weeks postoperatively.

LVH is a significant risk factor for the development of cardiovascular morbidity. However, few studies have evaluated the changes in cardiac function that occur in pediatric patients with ESRD undergoing RTx. Therefore, we assessed the changes in parameters associated with LVH in children within the first year after RTx. We retrospectively evaluated patients aged < 18 years who underwent initial RTx from April 2014 to December 2016. The patients were divided into 2 groups according to the presence of LVH before RTx. Clinical, biochemical, and echocardiographic parameters including the LVMI before and 1 year after RTx were evaluated in both groups. Twenty-six patients were included in this study. Seven of the 26 patients had LVH before RTx. Among the echocardiographic parameters, the LVMI was significantly improved 1 year after RTx in the initial LVH group (57.79 ± 11.86 vs 42.20 ± 6.03 g/cm 2.7 , P = .018), while no change was observed in the initial non-LVH group (32.66 ± 7.52 vs 35.17 ± 12.86 g/cm 2.7 , P = .376). Improvement of the ejection fraction was also observed only in the initial LVH group (66.5% ± 5.3% vs 72.2% ± 5.2%, P = .042). Children who had LVH before RTx showed significant improvements in the LVMI and ejection fraction even within 1 year after RTx. To minimize aggravation of cardiac function, early RTx should be considered for patients with LVH., (© 2019 Wiley Periodicals, Inc.)

Background: Securing postdonation renal function in the lifetime of donors is a consequential subject for physicians, and precise prediction of postdonation renal function would be considerably beneficial when judging the feasibility of kidney donation. The aim of this study was to investigate the optimum model for predicting eGFR at 1 year after kidney donation., Methods: We enrolled 101 living-related kidney donors for the development cohort and 44 for the external validation cohort. All patients in each cohort underwent thin-sliced (1 mm) enhanced computed tomography (CT) scans. We excluded individuals with diabetes, glucose intolerance, or albuminuria from this study. We evaluated preoperative factors including age, sex, hypertension, body mass index (BMI), serum uric acid, baseline eGFR, and body surface area (BSA)-adjusted preserved kidney volume (PKV) by using 3-dimensional reconstruction of thin-sliced enhanced CT images. To detect independent predictors, we performed multivariable regression analysis., Results: The multivariable regression analysis revealed that age, BMI, predonation eGFR, and BSA-adjusted PKV were independent predictors of eGFR at 1 year after kidney donation (correlation coefficient: -0.15, -0.476, 0.521, 0.127, respectively). A strong correlation between predicted eGFR and observed eGFR was obtained in the development cohort (r = 0.839, P < .0001). The significance of this predictive model was also confirmed with the external validation cohort (r = 0.797, P < .0001)., Conclusions: Age, BMI, predonation eGFR, and BSA-adjusted PKV may be useful for precisely predicting eGFR at 1 year after living kidney donation and be helpful to determine the feasibility of kidney donation from marginal donors., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Although an association between body weight mismatch and impaired graft function has been reported, few histologic studies have evaluated this issue, especially using electric microscopic analysis. During routine observations, we have noted a thin glomerular basement membrane (GBM) in the 1-hour biopsy specimen in cases with an overweight recipient and a lightweight donor. Therefore, we hypothesized that donor-recipient body weight mismatch affects the GBM thickness in the 1-hour biopsy specimen. The aim of the present study was to clarify the effect of donor-recipient body weight mismatch on the GBM thickness of the 1-hour biopsy specimen measured using electron microscopy., Methods: We used an electron microscope to measure the GBM thickness of specimens at 1-hour post-transplantation (n = 24) and at 1 year post-transplantation (n = 17). The GBM thickness of cases with donor-recipient body weight mismatch was compared with those without mismatch. In accordance with a previous study, we defined a donor/recipient body weight ratio of less than 0.9 as donor-recipient body weight mismatch and a ratio of more than 0.9 as no mismatch., Results: At 1-hour post-transplantation, the mean GBM was significantly thinner in the mismatch group than in the nonmismatch group. However, at 1-year post-transplantation, the mean GBM thickness did not significantly differ between the 2 groups., Conclusions: The GBM thickness at 1-hour post-transplantation is thinner in cases with donor-recipient body weight mismatch than in cases without mismatch. This implies that donor-recipient body weight mismatch may have to be considered when assessing donor-derived thin GBM disease using the 1-hour biopsy specimen., (Copyright © 2019 Elsevier Inc. All rights reserved.)

RTx of adult-size kidneys presents a size mismatch in small pediatric recipients, and there are potential surgical complications. This study reveals the outcomes of intra- and extraperitoneal RTx in low-weight (less than 15 kg) pediatric recipients. We studied 51 pediatric patients weighing less than 15 kg who received a living-related donor renal transplant between 2009 and 2017. The intraperitoneal (group A, n = 24) and extraperitoneal (group B, n = 27) approaches were compared. In group A, the mean age, Ht, and weight were 3.8 ± 1.6 years, 83.7 ± 6.5 cm, 10.5 ± 1.8 kg; in group B, 5.0 ± 1.9 years, 95.3 ± 7.3 cm, and 13.0 ± 1.4 kg. Single renal artery grafts (21 in group A and 16 in group B) and double renal artery grafts (three in group A and 11 in group B) were performed. Of the patients with double renal artery transplants, one in group A and six in group B underwent ex vivo arterial reconstruction. The eGFR (mL/min/1.73 m 2 ) at 1-week post-transplant in group A was significantly higher than that in group B; the eGFRs at 4 weeks post-transplant did not differ. One graft was lost in group B because of vascular thrombosis. Post-transplant complications included ileus and transplant ureteral stenosis. There was no significant difference in 5-year graft survival rate (group A 100%, group B 91.7%). Both transplant approaches are feasible to adapt to a size mismatch between the adult-size donor kidney and low-weight pediatric recipients., (© 2019 Wiley Periodicals, Inc.)

Background: Lipofuscin is an indicator of aging. We examined the clinicopathologic significance of lipofuscin deposition in the renal tubules of renal allografts., Method: We analyzed allograft biopsy specimens from living kidney transplantations from January to December 2015. For controls, we analyzed native kidney biopsy specimens obtained from January 2015 to December 2016. We identified granules with a yellow-to-tan shade in renal tubules as lipofuscin., Results: The donor age at transplantation was significantly older in lipofuscin deposition biopsy specimens than in those without, whereas the time after transplantation age was not different between the 2 groups with renal allografts. In native kidney biopsies, age at biopsy was significantly older in lipofuscin deposition biopsy specimens than in those without. We compared "massive lipofuscin deposition," defined as lipofuscin deposition on both sides of 3 or more renal tubules, and donor-age matched control allograft biopsies without lipofuscin deposition. Comparing these 2 groups, recipient age at transplantation was significantly older in the massive lipofuscin deposition group., Conclusion: Lipofuscin deposition on tubular epithelium is not a surrogate marker of aging of kidneys allografts, although lipofuscin deposition was significantly greater in older tissues from native kidneys. The older age of recipients may be associated with massive lipofuscin deposition in renal allografts., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aim: Epstein syndrome is a hereditary disease characterized by macrothrombocytopaenia and progressive nephritis. The abnormality of the MYH9 gene has a strong relationship to the severity of the disease. Severe Epstein syndrome progresses to end-stage renal disease rapidly after adolescence. There is no established therapy. We sought to clarify appropriate management of Epstein syndrome nephropathy., Methods: Epstein syndrome patients who underwent renal transplantation at our institution between March 2009 and March 2017 were enrolled. Epstein syndrome was diagnosed based on clinical features and genetic testing. Patient medical records were reviewed retrospectively., Results: Four male patients with Epstein syndrome, all with severe MYH9 gene mutations (p.R702C in three and p.S96L in one), were enrolled. Despite treatment with renin-angiotensin system blockers, nephropathy was refractory and progressed rapidly, and the patients required dialysis or renal transplantation after adolescence. Early preparation for treatment based on early and accurate diagnosis of Epstein syndrome enabled two patients to undergo pre-emptive renal transplantation. For these patients, we kept the platelet count above 100 × 10 9 /L until day 7 after renal transplantation with platelet transfusions for macrothrombocytopaenia, and no postoperative bleeding episodes occurred., Conclusion: Epstein syndrome nephropathy due to a severe MYH9 gene mutation can be refractory and progress rapidly; therefore, early and accurate diagnosis is important for safer therapeutic options including pre-emptive renal transplantation. By keeping the platelet count above 100 × 10 9 /L during the perioperative period, renal transplantation can be a safe treatment option for severe Epstein syndrome nephropathy., (© 2018 Asian Pacific Society of Nephrology.)

Objectives: Living donor kidney transplant relieves the disease burden of patients with end-stage renal disease but may shorten donor life expectancy; however, their quality of life (QOL) is preserved. Nevertheless, the magnitude of the net gain of this procedure is unknown. We evaluated the QOL of both donors and recipients concurrently and calculated the net utility gain., Methods: We recruited 210 subjects who visited the kidney transplantation clinic of a university hospital. Subjects were asked to complete the 5-level EQ-5D-based questionnaire, and patient characteristics were extracted from their medical records. We performed multivariate tobit models analysis to evaluate the QOL change caused by transplant surgery and subsequently ran computational simulations to determine the net utility gains of donors and recipients. We also performed sensitivity analyses., Results: After excluding 16 answers with missing data, we analyzed 203 answers in total. After the transplant surgery, recipients gained 0.07 in utility value while donors lost 0.04. In the net utility analysis, we found that the quality-adjusted life years gained ranged from 7.2 to 7.8 in the most favorable case observed in the combination of middle-aged recipients and elderly donors. Assuming no utility discount, the most favorable combination was that with older donors and younger recipients., Conclusions: These findings indicated that the QOL improvement in recipients was larger than the loss among donors. When calculating the net utilities, a combination of middle-aged recipients and elderly donors yielded the largest net utility, but this was likely derived from assumption in the discount of QOL., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Recipients of organ transplants are immunosuppressed and at high risk of oral infection. Oral diseases are often neglected compared with infections of other organs that typically confer higher morbidity. However, severe local symptoms hinder oral intake, decrease quality of life, and are sometimes lethal. Here we describe a case of a 57-year-old woman who developed recurrent aphthous stomatitis after kidney transplantation; the cause of the infection was complex and included cytomegalovirus, herpes simplex virus, and Candida species. Since misdiagnosis of oral diseases impairs patient quality of life and increases morbidity, clinicians should be aware of possible etiologies of oral infections in renal transplant recipients., (Copyright © 2019. Published by Elsevier Inc.)

Objectives: Rituximab treatment strategies vary in ABOincompatible pediatric kidney transplant recipients. Here, we present the efficacy of 2 doses of rituximab and subsequent outcomes in ABO-incompatible pediatric kidney transplant patients., Materials and Methods: Our study of ABO-incompatible pediatric kidney transplant recipients included 21 who were pretreated with desensitization that included 2 doses of 100 mg rituximab (rituximab group) at 10 and 1 day pretransplant and 14 who received splenectomy without rituximab (splenectomy group). Both groups received immunosuppression. Basiliximab was administered during transplant and 4 days posttransplant. Double-filtration plasmapheresis and/or plasma exchange procedures were performed pretransplant in those with higher antidonor antibody titers. CD19-positive and CD20-positive B cells were measured sequentially in the rituximab group. Maximum titers of antidonor antibody pre- and posttransplant, patient and graft survival, biopsy-proven rejection, and complications/infections were compared between groups., Results: In the rituximab group, CD19- and CD20-positive B cells were depleted on transplant, persistently depleted at 3 months, and under 5% until 1 year posttransplant. Maximum titers of antidonor antibodies decreased significantly posttranplant in the rituximab (P < .001) but not in the splenectomy group (P = .174), with maximum titers posttransplant significantly lower than shown in the splenectomy group (P < .001). No rituximab patients had clinical rejection, but 5 splenectomy group patients had clinical T-cell-mediated rejection, with 2 also having antibody-mediated rejection. Six in the rituximab group had cytomegalovirus viremia but no cytomegalovirus disease; however, 5 splenectomy group recipients had cytomegalovirus disease and viremia. In the rituximab group, 3 had late-onset neutropenia. One child died of hypertrophic cardio myopathy with a functioning graft; all others survived with no failed grafts. All splenectomy group children survived, although 2 had deteriorated graft function., Conclusions: Two doses of rituximab were effective in long-term B-cell depletion to suppress antidonor antibodies. The possibility of late-onset neutropenia must be considered.

Objectives: We investigated outcomes in living-donor kidney transplant recipients with preformed donor-specific antibodies (detected with flow cytometry and specified with the LABScreen single antigen test) under desensitization pretransplant and immunosuppression posttransplant., Materials and Methods: Of 15 recipients included, 8 had ABO-incompatible kidney transplant. Six patients had sensitization caused by pregnancy, 8 by blood transfusion, 5 by previous transplants, and 1 by unknown cause. Desensitization was initiated using calcineurin inhibitors, methylprednisolone, and mycophenolate mofetil 30 days pretransplant, with rituximab administered 1 and 10 days pretransplant. Patients underwent plasmapheresis 1, 3, and 5 days pretransplant. Antithymocyte globulin was admi nistered for 5 days posttransplant as induction therapy. At 3 and 12 months posttransplant, all recipients underwent protocol renal allograft biopsies, with donor-specific antibodies simultaneously measured with the single antigen test., Results: T-cell complement-dependent cytotoxicity crossmatch was negative in all 15 recipients, but T-cell and B-cell flow cytometry was positive in 8 and 14 recipients, respectively. Anti-HLA class I antibodies became negative, except in 1 recipient 3 months posttransplant. Class II antibodies remained positive in 8 recipients 3 months posttransplant. No clinical or subclinical T-cell-mediated rejection occurred, but 1 recipient experienced clinical acute antibody-mediated rejection. At 3 and 12 months posttransplant, 8 and 5 recipients had subclinical acute antibody-mediated rejection. Cytomegalovirus test showed positivity in 14 recipients, but none developed cytomegalovirus disease. BK viremia was detected in 2 recipients, with 1 developing BK virus nephropathy, which was reversed by reducing immunosuppression., Conclusions: Transplant patients with preformed donor-specific antibodies showed good outcomes in terms of desensitization and immunosuppression. However, most anti-HLA class II donor-specific antibodies remained, and microvascular inflammation score could indicate long-term risk of renal allograft dysfunction.

Background/aims: To examine the relationship of extracellular fluid (ECF) volume and osmotic excess with treatment modality, we retrospectively analyzed spontaneous body weight loss and osmotic excretion versus true body weight after kidney transplantation in peritoneal dialysis (PD) patients and preemptive transplant recipients compared with hemodialysis (HD) patients. We also examined maximum bladder volume in other transplant recipients on PD., Methods: From 2005 to 2011, 42 PD patients underwent kidney transplantation at our institution. Patients aged <12 years and cadaveric transplantations were excluded; we enrolled 27 PD patients (PD group; age 35.7 ± 14.4 years at transplantation; dialysis duration 36.5 ± 31.2 months) and 14 adult preemptive kidney transplant patients (preemptive group; age 31.7 ± 15.7 years; estimated glomerular filtration rate 8.26 ± 1.8 mL/min/1.73 m2 at transplantation). From 2005 to 2006, 29 adult living-related donor kidney transplant recipients on HD support (HD group) were enrolled as controls (age 36.4 ± 11.3 years; dialysis duration 37.5 ± 55.2 months)., Results: Percentage body weight loss at 1 month after transplantation was 5% from ideal body weight for the PD group (51.2 ± 14.3 to 48.6 ± 13.0 kg, p = 0.002), 5.1% for the preemptive group (56.7 ± 17.4 to 53.8 ± 16.5 kg, p = 0.0005), and 1% for the HD group (52.9 ± 12.4 to 52.1 ± 12.5 kg, p = 0.079); post-transplantation 24-h osmotic excretion was greater in the PD and preemptive groups (387.3 ± 175.7 mOsm) groups than in HD (250 ± 124 mOsm; p = 0.006. Another 69 adult living-related donor kidney transplant recipients (PD and HD support) with dialysis duration ≤5 years were examined. Mean dialysis duration differed in the HD (17.5 ± 13.1 months) and PD (29.6 ± 20.4 months, p = 0.015) groups; mean urine volume and maximum desire to void (MDV) were similar., Conclusion: ECF volume and osmotic excess occurred in the PD and preemptive groups compared with the HD group pre-transplantation. Although PD maintains MDV and residual and total urine volume, ECF volume and osmotic excess should be monitored before transplant; pre-transplant HD support should always be considered in PD and preemptive transplant patients., (© 2019 S. Karger AG, Basel.)

Background: Caregivers of patients with chronic kidney disease experience great burdens. Changes in these caregivers' quality of life (QOL) before and after their children underwent kidney transplantation (KTx) were evaluated in this prospective study., Methods: The sequential QOL scores of 31 caregivers (median age 38.5 years) whose children (5.8 years) underwent KTx from 2012 to 2014 were studied. The same questionnaires were administered before and 1, 3, and 12 months after KTx. We evaluated whether the following factors were associated with QOL: pre-transplant dialysis, recipient's mental and/or motor disability, and acute rejection or infections after KTx., Results: The average QOL score before KTx (3.40) was higher than that of the general population (3.23). Despite a temporal decrease at 1 month (3.15), the final QOL scores were maintained at 3 months (3.40) and 1 year (3.42) after KTx. The mean QOL scores were significantly higher for caregivers of patients with than without dialysis before KTx [3.46 vs. 3.28 (p = 0.041) at 3 months and 3.53 vs. 3.18 (p = 0.001) at 1 year, respectively]. Conversely, these scores were significantly lower for caregivers of patients with than without disabilities [2.97 vs. 3.20 (p = 0.021) at 1 month, 3.18 vs. 3.46 (p = 0.006) at 3 months, and 3.10 vs. 3.50 (p = 0.001) at 1 year, respectively]., Conclusion: Dialysis of children before KTx was a particularly larger burden for caregivers. The child's comorbidities and social adaptation problems might be focused after KTx, we need to evaluate for more long-term QOL of caregivers.

Accurate interpretation of renal allograft biopsy is necessary to guide therapy, especially when an episode biopsy is taken to rescue the graft. Contrarily, a protocol biopsy is carried out routinely to identify baseline conditions (biopsy at 0 or 1 h), subclinical rejection, histological change under current immunosuppression regimen, drug nephrotoxicity, viral infection, and recurrence of glomerulonephritis. Semiquantitative scoring for active lesions including tubulitis, glomerulitis, capillaritis, arteritis, arteriopathy, and others such as polyomavirus infection are key factors in transplant pathology. Recently, the Banff classification has proposed several novel concepts focused on antibody-mediated rejection (ABMR). This review presents the interpretation of transplant pathology from rejection to infection, recurrence of glomerulonephritis, and drug nephrotoxicity, with a description of ABMR according to the 2013 and 2017 Banff classification., (© 2018 Asian Pacific Society of Nephrology.)

Aim: The present study was performed to examine the clinicopathological significance of hyaline deposits in the smooth muscle of the interlobular artery (interlobular hyaline arteriopathy [IHA]) in renal allografts., Methods: Tissue specimens that included the interlobular artery from biopsies performed from January 2012 to December 2015, as well as specimens from biopsies performed ≥1 year after living kidney transplantation were analyzed. Biopsies of recipients with new-onset diabetes mellitus after transplantation were excluded, as well as those of recipients who had undergone transplantation because of diabetic nephropathy. Arteriolopathy was evaluated using the aah score determined by the Banff 2007 classification., Results: In total, 51 specimens with IHA lesions were identified among 381 biopsies obtained from 243 recipients performed ≥1 year after kidney transplantation. Among these 51 biopsies, 18 specimens had a score of aah3, 29 had a score of aah2, and four had a score of aah1. The incidence of IHA lesions was 3.6% at ≥1 to <4 years, 18.5% at ≥4 to <8 years, and 54.1% at ≥8 years. Older kidney grafts exhibited more IHA lesions. Among the biopsy specimens obtained ≥8 years after transplantation, no significant differences in the recipient or donor age, duration after transplantation, or prevalence of hypertension were observed between the IHA and non-IHA groups. The aah scores were significantly higher in the IHA group ≥8 years after transplantation as determined by the mean score test (P < 0.01)., Conclusion: IHA in renal allografts is associated with severe arteriolopathy., (© 2018 Asian Pacific Society of Nephrology.)

Objective: To investigate whether sodium restriction alters the nocturnal urine volume (NUV) and the ratio of NUV to 24-hour urine of renal allograft recipients (RARs)., Materials and Methods: This prospective, single-center study analyzed 38 of the 59 RARs who were followed up for more than 6 months in our hospital. All patients underwent 3 sessions of dietary counseling performed by a board-certified dietitian. Before and after these 3 sessions, 24-hour urine samples were collected, along with voiding frequency volume charts., Results: Of the 38 included RARs, 23 (60.5%) were diagnosed as having nocturnal polyuria (NP, NUV >10 mL/kg). After counseling the RARs with NP, their 24-hour sodium excretion was reduced from 169.5 to 125.6 mEq (P = .0066), their NUV from 862 to 709 mL (P = .021), and the ratio of NUV to 24-hour urine volume from 38.9% to 33.0% (P = .023). In contrast, these parameters were not significantly changed by dietary counseling in RARs without NP. Reduced sodium excretion and decreased NUV were significantly correlated (Spearman rho = 0.45, P = .005)., Conclusion: Excess intake of sodium is considered a cause of NP in RARs. Dietary counseling on sodium restriction is effective in reducing NUV in RARs. Prospective studies are needed to evaluate the general population with NP., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Despite restoration of fertility after kidney transplantation, the benefit is limited in female kidney recipients. Our objective is to determine the reasons for this discrepancy., Methods: We evaluated 315 women who underwent kidney transplantation from 1983 to 2015 (a median of age at transplantation [10th-90th percentile] of 32 years [7-55 years]); 230 recipients between the ages of 15 to 49 years old as of March 2016 were observed., Results: We experienced 10 abortions and 21 live births from our 23 recipients and 2 abortions and 7 live births in 7 recipients from other transplant center. The live birth rate was 8.9 per 1000 female transplant recipients of childbearing age. Seven recipients received either treatments of artificial insemination or in vitro fertilization. Average age at pregnancy was 33.2 ± 3.2 years old, and the fertile period post-transplantation was longer in recipients with live births than those without live births (14.1 ± 7.1 vs 9.9 ± 7.3 years, P < .05). In 42.9% of recipients with live birth, pregnancy-induced hypertension was observed in the last trimester. The gestational age and the average birth weight were 32.8 ± 5.0 months and 2184 ± 632 g, respectively. During follow-up of 14.5 years, there was one case of graft loss, which is a rate of 2.5 per 1000 female recipients., Conclusion: Although pregnancy complications are often observed in kidney recipients, graft survival is less influenced by pregnancy. Importantly, kidney disease at childbearing age disrupts pregnancy even after kidney transplantation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Transplant recipients are supposedly in a more anemic, catabolic, and even inflammatory state at re-entering hemodialysis due to chronic rejection. The goal of this study was to clarify how transplant recipients can re-enter dialysis safely by focusing on control of anemia., Methods: From 2012 to 2014, a total of 29 transplant recipients re-entered hemodialysis because of chronic rejection (ie, the chronic kidney disease with transplant [CKDT] group). At the same time, in 2014, a total of 30 patients with chronic kidney disease without transplantation entered dialysis as the control group (ie, the CKD group). CKDT recipients (mean ± standard deviation age, 41.9 ± 11.8 years; 18 male subjects, 10 female subjects; frequency of diabetes, 10%; duration of graft survival, 12.5 ± 4.3 years) were younger and fewer had diabetes compared with the CKD group (age, 53.2 ± 10.5 years; 21 male subjects, 9 female subjects; frequency of diabetes, 36%). Patient characteristics at entering dialysis in both groups were analyzed according to retrospective chart review., Results: At entering dialysis, there were no significant differences between the CKD and CKDT groups in terms of the following: dose of darbepoetin; concentrations of hemoglobin, albumin, and C-reactive protein; cardiothoracic ratio; blood urea nitrogen and creatinine levels; estimated glomerular filtration rate; initial ultrafiltration; and duration of hospitalization for initiation of dialysis. The only difference between groups was mean weight at entry to dialysis (CKDT group, 58.5 ± 15.1 kg; CKD group, 67.1 ± 14.8 kg; P = .03). The darbepoetin dose per kilogram of weight did not differ between groups (CKDT, 2.28 ± 2.03 μg/kg; CKD, 2.12 ± 1.6 μg/kg; P = .95) in the final month before entry to dialysis., Conclusions: Safe re-initiation of dialysis is important for recipient survival. Although anemia is supposedly higher in transplant recipients due to immunosuppression, this single-center analysis found no difference in anemia in CKD with or without transplantation, caused by good use of erythropoietin-stimulating agents in both groups., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Sodium retention causes posttransplant hypertension, and sodium restriction is recommended in kidney allograft recipients. However, there have been few studies on the impact of dietary counseling on sodium intake and blood pressure (BP) in this population., Objective: To determine the effect of dietary counseling on sodium intake and consequent BP control in kidney allograft recipients., Design, Setting, and Participants: A prospective single-arm study to determine the effect of dietary counseling on sodium intake. Enrolled were renal allograft recipients with sodium intake >100 mEq/d, BP >130/80, antihypertensive use, or body mass index >25 kg/m 2 . Of 53 renal transplant recipients who met the criteria, 48 participated in the present study. Sodium intake was estimated based on 24-hour urinary sodium excretion before and after 3 sessions of dietary counseling by a board-certified dietitian., Results: Sodium intake was significantly decreased after dietary counseling (158.7 vs 129.6 mEq/d; P = .005). Systolic BP was significantly decreased from 124 mm Hg (interquartile range: 122-134) before counseling to 121 mm Hg (interquartile range: 117-128) after counseling ( P < .001). The number of patients with systolic BP >130 mm Hg was decreased by 30% (n = 19-13; P = .07). Among 34 patients on antihypertensive medications, 8 (23.5%) ceased or reduced their drugs due to improvement in BP, whereas 2 increased or changed the drugs due to poor control of BP., Conclusion: Dietary counseling showed a short-term efficacy of reducing sodium intake and clinically relevant BP improvement in renal allograft recipients.

We report a 40-year-old man with end-stage renal disease due to IgA nephropathy who underwent deceased donor kidney transplantation. The donor was diagnosed to be brain-dead due to cerebral hemorrhage after her second liver transplantation for non-viral liver cirrhosis. Intraoperative 1-hour biopsy of the graft kidney revealed moderate global glomerular sclerosis (22%) and interstitial fibrosis (40%) consistent with underlying nephrosclerosis or calcineurin inhibitor nephrotoxicity. Although hemodialysis was needed until the graft began functioning several days after the kidney transplantation, the postoperative clinical course thereafter was uneventful and the graft functioned well with stable serum creatinine levels around 2.4 mg/dl at 6 monthspos toperatively.

Background: Due to the shortage of deceased donor kidneys, we have expanded the indications for living-donor kidney transplantation (LKT) including ABO-incompatible (ABO-i) donors in Japan. In this study, the utility of protocol biopsies was discussed in ABO-i LKT., Methods: Protocol biopsies have been performed on kidney graft 1 hour, 3 weeks, and 1 year after LKT in our institution. The relationship between biopsies and clinical courses was considered retrospectively in 38 cases of ABO-i LKT. The immunosuppressive regimen consisted of anti-CD20 antibody, mycophenolate mofetil, prednisolone, calcineurin inhibitor (cyclosporine or tacrolimus), and anti-CD25 antibody. Anti-ABO blood type antibody removal by plasmapheresis was performed before LKT up to 32 times. The post-transplantation regimen consisted of mycophenolate mofetil or mizoribine as an antimetabolite., Results: Episode biopsies have been performed in 6 cases within 3 weeks post-transplantation. Each pathological diagnosis was as follows: antibody-mediated rejection (AMR; 5 cases) and calcineurin inhibitor (CNI) nephrotoxicity (1 case). Subclinical chronic active AMR was found at 1 year post-transplantation follow-up biopsies in 4 of the 6 cases. Episode biopsies have been done in the other 6 cases from 1 month to 1 year post-transplantation. Each pathological diagnosis was as follows: acute T-cell-mediated rejection (TMR; 1 case), vesicoureteral reflux (VUR; 3 cases), CNI nephrotoxicity (2 cases), and VUR + CNI nephrotoxicity (1 case). AMR was also not found at 1 year post-transplantation follow-up biopsies in them. In all cases episode biopsies were performed based on pathological diagnosis and had no graft dysfunction after that., Conclusions: Pathological study revealed that acute AMR was found early (ie, within 3 weeks) following transplantation. Although appropriate treatment made AMR go into remission once, chronic active AMR was often found at 1-year follow-up biopsies., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In Japan, diabetic nephropathy accounted for 16,225 (43.7%) of the 38,473 patients who began hemodialysis in 2010 and the number increases year by year. In 1991, we started a kidney transplantation program for patients with diabetic nephropathy in our institution, and the ratio of patients who underwent kidney transplantation for diabetic nephropathy traces the course of increase. Among the 516 patients who underwent primary kidney transplantation in our institution from January 1991 to February 2013, we divided them into 2 groups. One group was the diabetes mellitus (DM) group, which included patients with primary disease of diabetic nephropathy, and the other group was the non-DM group. The DM group included 50 patients, and in our institution the ratio traces the course to increase. There was no significant difference for the 1-year and 5-year patient survival rates and graft survival rates between the DM group and the non-DM group. Moreover, the rate of acute rejection in the 2 groups was not significantly different. Furthermore, when we investigated the causes of death in the 2 groups, there was no significant difference with the mortality of cases due to heart vascular disease in the DM group and the non-DM group. Also, no case in which the graft lost function due to recurrence of diabetic nephropathy was observed. Although the early outcome of kidney transplantation for diabetic nephropathy in our institution did not have inferiority in comparison with kidney transplantation for the other primary disease, we think that careful diabetic control after kidney transplantation is required for long-term outcome., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Mizoribine (MZR) has been developed as an immunosuppressive agent in Japan, but has a less potent immunosuppressive effect up to 3 mg/kg/d. We previously reported that high-dose MZR, at 6 mg/kg/d, would be effective and safe for ABO-incompatible(ABO-i) living donor kidney transplantation (LDKT) patients when combined with cyclosporine (CsA) or tacrolimus(FK), anti-CD20 and anti-CD25 monoclonal antibodies, and corticosteroid without splenectomy in a 1-year study. Therefore, we observed these patients for 3 years., Methods: From 2007 to 2010, we encountered 24 cases of ABO-i LDKT using anti-CD20 and anti-CD25 monoclonal antibodies without splenectomy. The pretransplantation immunosuppressive regimen consisted of two doses of anti-CD20 antibody, mycophenolate mofetil (MMF, 25 mg/kg/d), prednisolone, calcineurin inhibitor (CNI; CsA 7 mg/kg or (FK 0.2 mg/kg) and two doses of anti-CD25 antibody. Antibody removal by plasmapheresis was performed before LDKT up to several times according to the antibody titer. The post-transplantation regimen consisted of high-dose MZR (6 mg/kg/d) instead of MMF (MZR group, N = 12) ., Results: The 3-year graft survival rates for the MZR and MMF groups were 91.7% and 100%, respectively. Serum creatinine levels for the MZR and MMF groups were 1.44 mg/dL and 1.31 mg/dL at 1 year, 1.55 mg/dL and 1.41 mg/dL at 2 years, and 1.51 mg/dL and 1.48 mg/dL at 3 years, respectively (not significant [NS]). The MZR group did not show a higher rate of elevated serum uric acid values. The percentage of patients who were administered anti-uric medication was 42.5% (5/12) in the MZR group and 50% (6/12) in the MMF group (P = NS) at the third year. Severe infection, such as cytomegalovirus, herpes zoster, was not observed at the second and third years in both groups., Conclusion: A high-dose MZR regimen including CNI (CsA or FK), steroid, and anti-CD20 and anti-CD25 antibodies without splenectomy was effective and safe in ABO-i renal transplantation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Since 2007, we have performed tonsillectomies for patients with recurrent immunoglobulin A nephropathy (IgAN) after kidney transplantation. Seven patients with primary IgAN showed biopsy-proven recurrent IgAN after living-donor kidney transplantation. They had persistent proteinuria or hematuria for an average of 40.3 months, and tonsillectomy was performed, on average, 75.6 months after kidney transplantation. In six patients with observation periods of more than one year, good remission of urinary findings was observed after tonsillectomy. We classified the seven patients into three types of renal injury based on histological findings: severe, moderate, and mild. Two patients classified with severe renal injury at the time of tonsillectomy had other problems, such as refractory hypertension and bilateral sinusitis. They followed a rapidly progressive clinical course. One case already had moderate histological renal injury. He demonstrated prompt amelioration of urinary findings after tonsillectomy but immediate deviation from remission of proteinuria and hematuria. In the four cases presenting mild renal injury at tonsillectomy, the improved urinary findings and serum creatinine value after tonsillectomy have persisted. In conclusion, tonsillectomy may be a favorable treatment for cases of mild-grade IgAN. However, other treatments such as antihypertensive agents and diet therapy may be necessary in other grades., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Mizoribine (MZR) at 3 mg/kg/d shows less potent immunosuppressive effects, but high-dose MZR (6 mg/kg/d) was effective and safe in a 2-year study in conjunction with a regimen of cyclosporine (CsA), basiliximab, and corticosteroids., Methods: We compared 40 living-related kidney recipients administered MZR (6 mg/kg/d), CsA (7 mg/kg/d), prednisolone (maintenance dose 10 mg/d), and basiliximab (20 mg/body) with control group (n = 38) treated with CsA, mycophenolate mofetil (MMF; 25 mg/kg/d), basiliximab, and corticosteroids., Results: The 4-year graft survival rates for the MZR vs MMF groups were 92.5% vs 94.7%, respectively, with serum creatinine levels of 1.66 ± 1.0 mg/dL vs 1.41 ± 0.42 mg/dL at 3 years, and 1.72 ± 1.16 mg/dL vs 1.56 ± 1.26 mg/dL at 4 years. There was no significant difference in serum creatinine levels between the 2 groups. The MZR group demonstrated a significantly higher rate of elevated serum uric acid values (29.7%). The numbers of patients treated with allopurinol at 4 years were 11/37 (29.7%) for MZR vs 2/36 (5.6%) for the MMF subjects (P < .05). Mean serum uric acid levels of the MZR vs MMF group at 4 years were 7.1 ± 1.9 mg/dL vs 7.0 ± 1.6 mg/dL, respectively (NS). There was no significant difference between the 2 groups regarding bone marrow suppression or liver dysfunction. Severe cytomegalovirus infection was not observed at 3 and 4 years in either group. There were no severe gastrointestinal symptoms among the MZR or the MMF group at 3 or 4 years., Conclusions: The combination of high-dose MZR with CsA, basiliximab, and corticosteroids displayed excellent results over a 4-year follow-up., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Mizoribine (MZR) has been developed as an immunosuppressive agent, but has a less potent immunosuppressive effect up to 3 mg/kg/day MZR. Therefore, we investigated whether high-dose MZR, at 6 mg/kg/day, would be effective and safe for kidney transplant patients in conjunction with cyclosporine (CsA), basiliximab, and corticosteroids., Methods: A total of 40 living related patients were administered MZR (6 mg/kg/day), CsA (7 mg/kg/day), prednisolone (maintenance dose 10 mg/day), and basiliximab (20 mg/body). A control group (n = 38) treated with CsA, mycophenolate mofetil (MMF, 25 mg/kg/day), basiliximab, and corticosteroids was also employed in this study., Results: The 2-year graft survival rates for the MZR and MMF groups were 100 and 94.7 %, respectively. The rejection rate in the MZR group (25 %) was not significantly higher than that in the MMF group (16 %). Serum creatinine level was not significant between the two groups. The number of patients who developed cytomegalovirus (CMV) disease was 0 (0 %) in the MZR group and 7 (18.4 %) in the MMF group (P < 0.05). The number of patients treated with ganciclovir was 3 (7.5 %) and 11 (28.9 %) (P < 0.05), respectively., Conclusions: The combination of high-dose MZR with CsA, basiliximab, and corticosteroids can establish not only satisfactory immunosuppression but also a low rate of CMV infection in vivo.

Background: Mizoribine (MZR) has been developed as an immunosuppressive agent in Japan, but it shows less potent immunosuppressive effects at doses up to 3 mg/kg/d. In this study, we investigated whether high-dose MZR (6 mg/kg/d) was effective for ABO-incompatible (ABO-i) living donor kidney transplantation (LKT) using treatment with anti-CD25 and anti-CD20 monoclonal antibodies without splenectomy., Methods: Since 2007, we encountered 24 cases of ABO-i LKT using anti-CD20 and anti-CD25 monoclonal antibody without splenectomy. The pretransplant immunosuppressive regimen consisted of two doses of anti-CD20 antibody, mycophenolate mofetil (MMF), prednisolone, a calcineurin inhibitor (cyclosporine [7 mg/kg] or tacrolimus [0.2 mg/kg] and two doses of anti-CD25 antibody. Antibody removal by plasmapheresis was performed before LKT up to several times according to the antibody titer. The posttransplant regimen consisted of high-dose mizoribine (6 mg/kg/d) instead of MMF (MZR group, n = 12)., Results: The 1-year graft survival rates for the MZR and MMF groups were both 100%. The rejection rate in the MZR group (eight %) was not significantly higher than that in the MMF group (seventeen %) Serum creatinine level was not significantly different between the two groups. In the MZR group 6 (50%) patients developed CMV antigenemia-positivity versus 11 (92%) in the MMF group (P < .05). The number of patients who developed CMV disease was 0 in the MZR group and 1 (8%) in the MMF group. The number of patients treated with ganciclovir was 0% and 8%, respectively (not significant)., Conclusions: We obtain good clinical results with high-dose MZR in ABO-i LKT using anti-CD20 and anti-CD25 antibody treatment without splenectomy., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Due to the profound shortage of suitable deceased allografts, much effort has been made to investigate whether successful kidney transplantation (KT) is possible across the ABO blood group barrier even for pediatric recipients., Methods: We reviewed 52 consecutive ABO incompatible (ABOic) transplantation performed between September 1989 and March 2011. The mean age at transplantation was 10.6 ± 3.9 years (range, 4.4-19.7), with 35 boys and 17 girls. The donor-to-recipient ABO blood antigen incompatibility was as follows: A1/O (n = 17); B/O (n = 13); A1/B (n = 6); B/A1 (n = 1); A1B/B (n = 9); and A1B/A (n = 6). As a control group, data were collected from 271 pediatric ABO compatible (ABOc) living donor KT in the same period., Results: Overall acute rejection episodes (ARE) among the ABOic group were significantly higher than those of the ABOc group (44% vs 26%; P < .02). However, there was no difference in glomerular filtration rate (GFR) at 1 year after transplantation: 86 ± 31 mL/min for ABOic vs 99 ± 37 mL/min for ABOic, respectively. The 1-y, 5-y, and 10-year patient survival rates were 98%, 92%, and 92% in the ABOic group, respectively, and 99%, 98%, and 97% in the ABOc group, respectively (P = not significant [NS]). The overall 1-, 5-, 10-, and 15-year graft survival rates were 94%, 88%, 86%, and 86% in the ABOic group, respectively, and 95%, 92%, 88%, and 78% in the ABOc group, respectively., Conclusion: ABOic KT provided long-term allograft and patient survivals equivalent to ABOc live donor transplantations., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Due to the shortage of deceased donors, we have expanded the indications for living-donor kidney transplantation (LKT) to include ABO-incompatible (ABO-i) individuals. However, which patients with high-titer anti-blood-group antibody can be transplanted successfully is unclear., Methods: Since 2009 we have performed 2 high-titer ABO-i spousal LKT using anti-CD20 and anti-CD25 monoclonal antibody without splenectomy. In both cases, anti-type A antibody was 2048-fold before antibody removal. The immunosuppressive regimen consisted of 2 doses of anti-CD20 antibody (200 mg/body, day -14 to day -7), mycophenolate mofetil (1000 mg), prednisolone (10 mg starting from day -14), calcineurin inhibitor (cyclosporine [7 mg/kg] or tacrolimus [0.2 mg/kg] starting from day -7), and 2 doses of anti-CD25 antibody (20 mg/body, days 0 and 4). Antibody removal by plasmapheresis was performed up to 4 times before LKT according to the antibody titer. The posttransplantation regimen consisted of mycophenolate mofetil or mizoribine as antimetabolite. A protocol biopsy was performed at 1 month and 1 year after LKT., Result: The 60- and 62-year-old men had renal graft transplantation performed in the right hemipelvis without complication. After LKT, urinary output and serum creatinine decrease were within acceptable ranges without evidence of an acute rejection episode for 12 and 7 months, respectively. Patient and graft survival rates were 100%. A protocol biopsy at 1 month after LKT showed additional treatment to be unnecessary. Serious viral infection was not seen, even in the 1 patient who temporarily experienced positive changes in cytomegalovirus antigenemia., Conclusions: We obtained good clinical results among 2 high-titer ABO-i LKT using anti-CD20 and anti-CD25 antibodies without splenectomy, in conjunction with a calcineurin inhibitor plus mycophenolate mofetil or mizoribine., (Copyright © 2011 Elsevier Inc. All rights reserved.)