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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.Forty-three pediatric recipients were classified as those with an eGFR-1 M ≥ 90 mL/min/1.73 mThe 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 mThe 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.

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.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.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 mThe 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.

Background Major symptoms of progressive chronic kidney disease (CKD) are similar to those of hypothyroidism. Hidden symptoms of hypothyroidism underlying CKD are often observed in clinical practice. This study aimed to ascertain the frequency of hypothyroidism complicated by CKD, and to analyze factors impacting thyroid function. Methods During the period from April 2012 through October 2016, 510 CKD patients at our outpatient clinic were measured thyroid and kidney function for diagnosing hypothyroidism (overt hypothyroidism, OH; subclinical hypothyroidism, SH; non-thyroidal illness, NTI) and evaluating the stage of CKD. All patients were over 15 years of age. Results There were significant differences in age, estimated glomerular filtration rate (eGFR), urinary protein (UP), and serum albumin (Alb) among patients with OH, SH, and NTI compared to the normal group in univariate and multivariate analyses. UP showed the highest odds ratio of OH, SH, and NTI but no differences were recognized in gender in each group. Frequency distribution showed that the prevalence of thyroid dysfunction was greater among more severe stage of CKD with higher amount of UP. OH and SH did not show high positive ratio of anti-thyroglobulin antibody (TgAb) and anti-thyroid peroxidase antibody (TPOAb). NTI and normal subjects showed higher positive ratio as 50.0% and 42.9% of TgAb and TPOAb than OH and SH. Conclusions Hypothyroidism complicated by CKD exhibited a high prevalence. Age, eGFR, UP, and serum Alb were related to the prevalence of hypothyroidism, whereas gender was not and this was contradicted to the prevalence of hypothyroidism in general population. The prevalence of OH and SH was higher among patients with higher stage of CKD with increased UP. Hypothyroidism complicated by CKD may involve different onset mechanisms unrelated to antithyroid antibodies (ATAb). In CKD patients, assessments of OH and SH, as well as NTI, are needed for proper diagnosis.

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.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).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.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.

Background Recurrence of SRNS is a major challenge in KT. Several clinical factors, including initial steroid sensitivity, have been associated with increased post-transplant SRNS recurrence risk. However, conflicting data have been reported, possibly due to the heterogeneous pathophysiology of SRNS and the lack of genetic testing of SRNS patients. Furthermore, the response to immunosuppressive therapies has not been evaluated. Methods Seventy patients aged 1-15 years at SRNS onset who underwent KT between 2002 and 2018 were enrolled. Patients with secondary, familial, syndromic, and genetic forms of SRNS and those who were not treated with steroid were excluded. This study aimed to assess the risk factors for post-transplant recurrence, including treatment responses to initial steroid therapy and additional therapies with immunosuppressive agents, rituximab, plasmapheresis, and/or LDL-A. Results Data from 36 kidney transplant recipients were analyzed. Twenty-two (61%) patients experienced post-transplant SRNS recurrence, while 14 patients did not. The proportion of patients who achieved complete or partial remission with initial steroid therapy and/or additional therapies with immunosuppressive agents, rituximab, plasmapheresis, and/or LDL-A was significantly higher in the SRNS recurrence group (19/22, 86%) than in the group without SRNS recurrence (6/14, 43%; p = .01). Conclusion This study suggests that the response to steroid treatment, other immunosuppressive agents, rituximab, plasmapheresis, and/or LDL-A may predict post-transplant SRNS recurrence.

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. 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. 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

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.

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.

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.

Background Cytomegalovirus (CMV) infection is one of the major factors that affect morbidity and mortality in kidney transplant (KTx) patients. The rate of CMV seropositivity in children before KTx is lower than that in adults; therefore, pediatric KTx patients have a higher risk of CMV infection. In Japanese pediatric KTx patients, preemptive therapy for CMV infection is a main conventional therapy. This study investigated whether this preemptive treatment would affect kidney function at 2 years post-KTx. Methods A total of 163 patients, that is approximately half of the Japanese pediatric KTx patients nationwide, were recruited to participate in our study. We compared the values of the sequential estimated glomerular filtration rate (eGFR) at two years post-KTx and other influencing factors in CMV viremia, CMV disease, and no-infection groups. Results Cytomegalovirus infection after KTx occurred in 75 patients (46.0%), 38.7% of whom developed CMV disease. The sequential eGFR values post-KTx did not differ significantly between the three groups. CMV infection was not significantly correlated with other factors, other infections (including Epstein-Barr [EB] virus infection), acute rejection (AR), or adverse events. Only prolonged duration of total hospitalization was significantly associated with CMV infection (P = .002). In the multivariate analysis, younger age, CMV infection, and adverse effects were independently significantly related to prolonged total hospitalization. Conclusion Preemptive therapy for CMV infection evidenced by viremia and disease did not significantly influence kidney function in Japanese pediatric KTx patients at two years after the operation.

Extensive data have been accumulated for adults who have undergone ABO-incompatible (ABOi)-living kidney transplantation (LKT). In contrast, available published data on pediatric recipients who underwent ABOi-LKT from the early to middle 2000s is very limited. Thus, pediatric ABOi-LKT has remained relatively rare, and there is a lack of large, multicenter data.We analyzed data from the Japanese Kidney Transplant Registry to clarify the patient and graft outcomes of pediatric recipients who underwent ABOi-LKT from 2002 to 2015. A total of 102 ABOi and 788 ABO-compatible (ABOc) recipients were identified in this study. All recipients had received basiliximab and a triple immunosuppressive protocol comprising calcineurin inhibitors, mycophenolate mofetil, and steroids. The ABOi recipients also received preconditioning therapies including B-cell depletion by a splenectomy or rituximab treatment and therapeutic apheresis.Death rates for ABOi and ABOc recipients were 0.17 versus 0.17 deaths per 100 patient-years. Graft loss rates for ABOi and ABOc recipients were 1.58 versus 1.45 events per 100 patient-years. No particular causes of death or graft loss predominantly affected ABOi or ABOc recipients.The results of this registry analysis suggest that pediatric ABOi-LKT can be performed efficiently. Although further studies are clearly required to perform pediatric ABOi-LKT more safely and less invasively, ABOi-LKT is now an acceptable treatment for pediatric patients with end-stage renal disease.

Background We investigated whether serum uric acid (SUA) levels before kidney transplantation predict new-onset diabetes after kidney transplantation (NODAT) and compared SUA levels with known risk factors for NODAT by prospective cohort study. Methods A total of 151 adult kidney recipients without diabetes (84 men, 67 women) who underwent living-donor kidney transplantation between 2001 and 2011 were followed in this study. The Cox proportional hazards model was used to analyse the risk of NODAT. Results During the follow-up period (median 3.3 years, range 0–10 years), 32 (21.2%) adult kidney recipients without diabetes developed NODAT, and an incidence rate was 5.6 per 100 person-years and a 10-year cumulative incidence of 26.9%. When subjects were stratified by SUA levels into tertiles, the patients in the highest tertile (> 8.6 mg/dl for men, > 7.7 mg/dl for women) had a significantly higher risk of NODAT than the patients in the lower 2 tertiles (log-rank test, P = 0.03). In the univariate analysis, increased level of SUA was associated with NODAT (hazard ratio 1.27 [95% CI 1.04–1.55], P = 0.01). In the multivariate analysis, increased level of SUA was significantly associated with NODAT after correction by any factors, e.g. (age, sex, family history of diabetes, BMI, HbA1c, serum creatinine, tacrolimus, HCV) factors directly affecting the SUA value (1.26 [1.02–1.56], P = 0.03), risk factors for T2DM onset (1.34 [1.10–1.64], P = 0.03), and factors previously reported risk factors for NODAT (1.36 [1.11–1.66], P = 0.003). Conclusion SUA independently predicts NODAT in living-donor kidney transplantation patients.

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

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.

Summary 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 Study design We performed a retrospective cohort study on pediatric kidney transplant recipients, weighing 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 Discussion We assessed the long-term outcomes of the surgical approaches used for pediatric patients weighing Conclusion The transplant approach did not influence the long-term outcomes in children weighing Summary Table . Comparison of surgical complications by surgical approach. Variables IPA group (n = 62) EPA group (n = 38) P-value Early surgical complications 15 (24%) 1 (3%) Urinary leak 3 0 Urinary stenosis 1 0 Ileus 2 0 Renal artery thrombosis 1 0 Renal vein thrombosis 1 0 Anastomotic bleeding 1 0 Lymphocele 1 0 Wound infection 1 0 Renal allograft compression syndrome 4 1 Late surgical complications 9 (15%) 1 (3%) 0.08 Ileus 6 0 Bowel obstruction 2 0 Urinary stenosis 0 1 Bladder stone (due to sutures) 1 0 Total 24 (39%) 2 (6%) Surgical reintervention 10 (16%) 1 (3%) 0.05 EPA, extraperitoneal approach; IPA, intraperitoneal approach; KTx, kidney transplantation. Values are presented as numbers (%). Early surgical complications were identified within 30 days post-KTx. Late surgical complications were defined as complications occurring more than 1 month post-KTx.

Congenital nephrotic syndrome is difficult to manage, particularly the Finnish type (CNF), with patients experiencing severe edema, sepsis and thrombosis before kidney transplantation. Further, nephrosis and thrombosis remain problematic after transplantation. Of 22 CNF patients managed at our hospital, 14 who underwent kidney transplantation were retrospectively studied. CNF was diagnosed according to standard criteria. The study population consisted of 3 males and 11 females. Mean gestation period was 36 ± 1.4 weeks and mean birth weight was 2442 ± 454 g (mean placenta to body weight ratio: 0.4). All patients started dialysis at 2.4 ± 1.3 years and underwent kidney transplantation at 5.2 ± 2.0 years. The kidneys were donated by the parents (n = 13), and cadaver (n = 2), including overlap. Mean follow-up period after transplantation was 14.3 ± 8.9 years, and mean age at last observation was 19.5 ± 8.5 years. Two patients had recurrent proteinuria after kidney transplantation; one underwent retransplantation following graft failure and eventually required dialysis, while the second had complete remission after intensive immunosuppressive therapy. There were no cases of thrombosis or serious infections. Mean eGFR at the time of last observation was 57.3 ± 16.5 ml/min/1.73 m2, while mean height SD score was − 2.1 ± 0.9 at the time of transplantation and − 1.5 ± 1.5 at last observation. Long-term outcome in these 14 CNF patients showed satisfactory graft survival, improved height SD score, and favorable development. Although recurrent proteinuria after transplant was not predictive, it was associated with graft survival rate.

WDR19 has been reported as a causative gene of nephronophthisis-related ciliopathies. Patients with WDR19 mutations can show various extrarenal manifestations such as skeletal disorders, Caroli disease, and retinal dystrophy, and typically display nephronophthisis as a renal phenotype. However, there is limited information on the renal phenotypes of patients with WDR19 mutations. We report two Japanese infants with Sensenbrenner syndrome caused by WDR19 mutations who demonstrated different features in renal ultrasound and histopathological results, despite several common extrarenal manifestations. Patient 1 had normal sized and hyperechogenic kidneys with several small cysts and histopathological findings compatible with infantile nephronophthisis. Renal ultrasound of Patient 2 showed enlarged kidneys with diffuse microcysts resembling those of autosomal recessive polycystic kidney disease. Her renal histopathology revealed dysplastic kidney with diffuse glomerular cysts. Genetic testing identified compound heterozygous mutations in WDR19 in both patients (Patient 1: c.953delA, c.3533G > A, Patient 2: c.2645 + 1G > T, c.3533G > A). Our patients suggest that WDR19 mutations can cause dysplastic kidney in addition to nephronophthisis pathologically. In addition, differences in pathology of the kidneys from WDR19 mutations may result in heterogeneous features in renal ultrasound findings. Renal phenotypes from WDR19 mutations may thus be more diverse than previously reported. Extrarenal manifestations and genetic testing can therefore help to diagnosis this disease more precisely.

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.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.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.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.

Background The aim of this study was to assess the differences in pharmacokinetic (PK) profiles after the 1:1 ratio-based conversion from a twice-daily to a once-daily tacrolimus formulation (TD-TAC and OD-TAC, respectively) in pediatric recipients of kidney transplants. Methods TD-TAC was initially administered to 29 pediatric patients who underwent kidney transplantations between April 2010 and September 2015 and were then subsequently switched to OD-TAC. The switch dose ratio was 1:1, and the 24-hour complete PK parameter assessment was performed before and after the regimen was changed from TD-TAC to OD-TAC. Results The mean total daily dose at baseline was 5.5 ± 2.9 mg (0.18 ± 0.10 mg/kg body weight). Consecutive PK studies revealed no significant difference in the mean time to achieve maximum concentrations and the area under the concentration–time curve from 0 to 24 hours (AUC 0–24 ) of both drug formulations. However, the mean trough concentration (C min ) and the maximum concentration of OD-TAC were 22% and 6% lower and higher, respectively, than those of TD-TAC. Therefore, a better correlation was observed between the AUC 0–24 and C min of OD-TAC than between those of TD-TAC. Conclusions After the change from TD-TAC to OD-TAC, the AUC 0–24 values were equivalent despite a 22% reduction in C min . C min may therefore be an excellent predictor in the therapeutic drug monitoring of OD-TAC because of its superior correlation with AUC 0–24 .

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.

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

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.

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.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.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).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.

Cryptococcosis is an invasive fungal infection that is common among organ transplant recipients, and it is challenging to treat among these patients because of their immunocompromised status. Fluconazole (FLCZ) is recommended as a first-line treatment modality for pulmonary cryptococcosis in organ transplant recipients. However, cases of FLCZ resistance among Cryptococcus neoformans isolates have been reported from the Asia Pacific region. Previous studies have reported the efficacy of voriconazole (VRCZ) in patients with FLCZ-resistant fungal infections. Herein, we report a case of FLCZ-resistant pulmonary cryptococcosis after renal transplantation that was successfully treated with VRCZ combined with amphotericin B-liposome (L-AMB). The patient was a-23-year-old woman who underwent living-donor kidney transplantation at age 20 years. She has attended our hospital since before for mental retardation, epilepsy, and dilated cardiomyopathy. At age 23 years, she presented to our hospital with fever and cough. She was diagnosed with pulmonary cryptococcosis based on positive-serum cryptococcal antigen. Chest radiography showed bilateral consolidations. Fosfluconazole (F-FLCZ) was administered, and her condition improved. However, she developed cough and fever again on day 60 of hospitalization. Cryptococcosis recurrence was suspected due to the high degree of cryptococcal antigen titers showed (1:2048) taken on the same day. Therefore, L-AMB was added, and F-FLCZ was substituted with VRCZ. Her condition improved, but L-AMB was discontinued due to hyponatremia, hypokalemia, and elevated serum creatinine. This indicates that VRCZ caused the remission. She was discharged after 6 months of admission. In conclusion, this case shows the efficacy of VRCZ combined with L-AMB for refractory pulmonary cryptococcosis.

Aneurysm of autogenous arteriovenous fistula is a common complication in patients receiving hemodialysis. We present a novel method for repair of a case of aneurysm of arteriovenous fistula resulting from stenosis. A 52-year-old woman presented with aneurysm formation of the left upper arm arteriovenous fistula, with related numbness in the left hand. Clinical examination revealed a tense, pulsatile aneurysm above the brachiocephalic anastomosis. Ultrasound examination revealed an aneurysm (50 mm × 25 mm) with proximal stenosis and an arteriovenous fistula flow rate above 1200 mL/min. An incision was made lateral to the aneurysm from the brachiocephalic anastomosis to the proximal stenosis through the antecubital fossa. After exposure of the entire aneurysmal arteriovenous fistula, the narrowed segment, and the proximal cephalic vein, the aneurysm outflow was ligated and the narrowed segment was removed. A U-shaped incision was made on the aneurysm to create an aneurysmal flap (75 mm × 20 mm). The flap was tubularized after calibration of the lumen with a 14-Fr cannula. End-to-end anastomosis was performed between the distal tubularized flap and the proximal cephalic vein. Intra- and postoperative arteriovenous fistula flow rates were below 900 mL/min. After surgery, the remodeled arteriovenous fistula was immediately usable for hemodialysis with normal arteriovenous fistula flow in the upper arm. The repair technique achieved not only aneurysmorrhaphy but also created an autologous vascular graft as the bypass after removal of the narrowed segment. Moreover, this technique achieved reduced arterial inflow and is suitable for patients with conditions similar to those of this case.

We examined the clinicopathologic significance of hyalinosis in the vasa recta in the medulla of allograft kidney biopsies. We analyzed biopsy specimens from January 2010 to December 2015, obtained from both the cortex and medulla (including the vasa recta) ≥ 1 year after living-donor kidney transplantation. We excluded biopsy specimens from recipients who had undergone transplantation due to diabetic nephropathy or who had diabetes mellitus after transplantation. We evaluated hyaline arteriolopathy in the cortex using the aah score determined by the Banff 2007 classification. Among 381 biopsy specimens obtained from 248 transplant recipients ≥ 1 year after transplantation, 36 specimens obtained from 34 recipients showed vasa recta hyalinosis (VRH) in the medulla. Among these 36 specimens, 17 had a score of aah3, 16 had a score of aah2, and 3 had a score of aah1. The incidence of VRH was 1.9% at ≥ 1 to

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.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.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 to4 years, 18.5% at ≥4 to8 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 (P0.01).IHA in renal allografts is associated with severe arteriolopathy.

Lower urinary tract abnormalities are difficult to resolve in pediatric kidney transplant patients. Measure of residual urine, voiding cystourethrography, retrograde urethrography, cystometry, electromyography of urethral external sphincter muscle, urethrometry, and uroflowmetry are the primary methods for evaluation of lower urinary tract abnormalities. Endoscopic resection or ablation of urethral valves is required in children with posterior urethral valve to treat obstruction, but bladder function does not always recover and may deteriorate to end-stage renal failure even after the obstruction is released. This bladder dysfunction in posterior urethral valve defines valve bladder syndrome. Vesicoureteral reflux caused by high vesical pressure can cause even worse renal graft function posttransplant. In our patient group, urinary diversion occurred with Mitrofanoff conduit using an appendix in 6 children, a Yang-Monti channel conduit using ileum in 1 patient, with cystostomy in 3 children, and with augmented cystoplasty in 9 children before or simultaneously with kidney transplant. These procedures should be selected based on the type of lower urinary tract abnormality including bladder function. Recently, we have preferred a continent diversion for self-catheterization in children with lower urinary tract abnormalities. We have conducted 9 augmented cystoplasty procedures using a portion of the sigmoid colon or ileum. Seventeen children retained their own bladders when the transplant ureter was implanted. Most patients needed clean intermittent catheterization, depending on the residual urine volume and a bladder function. Ten-year graft survival rate in kidney transplant in our department is 98% in 36 children with lower urinary tract abnormalities. Lower urinary tract abnormality is not always a risk factor for pediatric kidney transplant; however, a preoperative evaluation is important to choose the best option for urinary diversion.

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 × 109 /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 × 109 /L during the perioperative period, renal transplantation can be a safe treatment option for severe Epstein syndrome nephropathy.

Glioblastoma 2 (GLI2) is a mediator of Sonic hedgehog signaling pathway that plays an important role in development of the central nervous system and limbs. Heterozygous GLI2 mutations have been associated with postaxial polydactyly, various pituitary dysfunction, and holoprosencephaly-like phenotype. Herein, we report a Japanese boy who presented with isolated growth hormone deficiency with ectopic posterior pituitary, postaxial polydactyly, atrioventricular septal defect, intellectual disability and dysmorphic facial features including mid-facial hypoplasia. The patient was also complicated with congenital urethral stricture with megacystis, hydronephrosis, and renal hypoplasia/dysplasia, which led to end-stage renal failure by the age of 8 years. Trio-whole-exome sequencing showed a novel de novo heterozygous frameshift mutation in GLI2 (c.3369delG, p.Met1123Ilefs*7) in the patient. This is the first report of possible association between GLI2 mutation and the phenotype of congenital anomalies of the kidney and urinary tract, and subsequent end-stage renal failure. Further studies on the urogenital phenotype in patients with GLI2 mutations may clarify a role of GLI2 in embryonic development of the urinary tract.

Background Pre-emptive kidney transplantation (PEKT) is beneficial for patients, improves graft survival and minimizes the complications associated with chronic kidney disease. Reports on pediatric PEKT, however, are limited, and little is known about the parathyroid hormone (PTH) abnormalities and calcium-phosphorus disorders (CPD) in this condition. This study was the first to report on mineral disorders in pediatric PEKT patients during a 1 year period. Methods We conducted a comparative examination of the abnormalities in calcium, phosphorus, calcium-phosphorus products and PTH before and 1 year after living donor kidney transplantation in PEKT and non-PEKT patients. Results Thirty-one patients were included. The patients were divided into two groups: PEKT (n = 11; 5 months in CKD stage 4-5) and non-PEKT (n = 20; 31.5 months in dialysis). Mean age at transplantation was 9.4 ± 5.0 years. Hypercalcemia and hyperphosphatemia were observed before and after transplantation in the PEKT and non-PEKT groups, and >15% of patients in each group had bone disorder and ectopic calcification associated with mineral disorder. Mineral disorder was present for approximately 3 months after transplantation in both treatment groups. Conclusions No significant differences in PTH or CPD were noted between PEKT and non-PEKT groups; moreover, normalization of abnormal values did not differ between the PEKT and non-PEKT groups. Compared with non-PEKT, PEKT did not improve the course of mineral metabolism disorders. Mineral and bone disorder treatment was likely insufficiently provided to pediatric PEKT patients. To obtain the maximum advantage of PEKT, calcium and phosphorus levels should be strictly controlled before kidney transplantation.

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. 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. 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]. 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.

Post-transplant recurrent nephritis is the third common complication that leads to graft loss, which affects the long-term graft survival of kidney transplant patients. Immunoglobulin A nephropathy (IgAN) is the most common for recurrent nephritis, with a recurrence rate of 13–53%. In this study, 12 patients diagnosed with recurrent IgAN were divided into two groups, one which underwent tonsillectomy and another which did not, to analyze the effect of treating IgAN recurrent with or without tonsillectomy. Urinary findings, estimated GFR (eGFR), and histopathological alteration (Banff and Oxford classifications) were examined for >5 years after kidney transplantation. We found that tonsillectomy protected graft function and prevented pathological alterations. The levels of urinary proteins increased in the no tonsillectomy group, whereas no difference was observed in the severity of hematuria between two groups. eGFR declined and mesangial hypercellularity score increased in the no tonsillectomy group. Tonsillectomy not only results in a favorable clinical outcome but also protects against the histological damage caused by recurrent IgAN after kidney transplantation.

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 m2 ) 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.

An autosomal dominant hereditary disease, Epstein syndrome (ES) is characterized by sensorineural hearing impairment, macrothrombocytopenia, and hereditary nephritis, and can progress to end-stage kidney disease after puberty. Generally, kidney transplantation is difficult to perform in Epstein syndrome owing to the high risk of perioperative bleeding. Additionally, due to previous platelet transfusions, ES patients sometimes have antihuman leukocyte antigen (HLA) antibodies, including antiplatelet antibodies and donor-specific anti-HLA antibodies (DSA), which may result in refractoriness to platelet transfusion and antibody-mediated rejection (AMR). We report a case of successful kidney transplantation in a patient with ES who had DSA and antiplatelet antibodies. To prevent AMR, we used a desensitization protocol (a combination of plasmapheresis, rituximab, and basiliximab induction). Surveillance biopsy performed at 4 months and 1 year after transplantation showed no pathological findings suggesting AMR. To prevent perioperative bleeding complications, we infused the patient with HLA-matched platelets, thereby maintaining the platelet count at >10.0 × 10(4)/μL, and no postoperative episodes of bleeding occurred.

Background Recurrence of focal segmental glomerulosclerosis (FSGS) in pediatric kidney allografts is associated with poor graft survival. Several therapeutic regimens have been proposed, with conflicting results. Methods Ten pediatric patients with recurrent FSGS after kidney transplantation were treated with a protocol of methylprednisolone (MP) infusions in combination with cyclosporine (CsA)-based immunosuppression. The patients received a drug regimen with infusions of 20 mg/kg MP on three consecutive days at week 1, week 3, and week 5, and then monthly until six months after transplantation. If a complete or partial remission (PR) was obtained, MP pulse continued every three months until 24 months after transplantation. The CsA dose was adjusted according to AUC0–4. Results Seven of 10 patients (70%) achieved complete remission (CR) with stable renal function within 18 months of beginning of treatment. One of two patients with PR entered CR 3.5 yr after transplantation. One patient lost her graft due to recurrence four months after transplantation. After observation for 26–119 months, seven patients maintained remission with normal glomerular filtration rate. Few major side effects were observed in association with the high-dose MP infusion therapy. Conclusions MP infusion therapy in combination with CsA-based immunosuppression could be safe and effective in treating recurrent FSGS after kidney transplantation.

A girl aged 11 years and 3 months with occlusion of the inferior vena cava had experienced two renal transplant graft failures since birth. The third renal transplant from a live donor was carried out. Preoperative evaluation showed that the arteries from the right common to the right external iliac artery were absent, and the ilio-caval vein was occluded below the level of the renal vein. The donor's renal artery was anastomosed to the aorta. The donor's ovarian and large saphenous veins were used to extend the transplant renal vein to the recipient's patent inferior vena cava. The present report concludes that the extension of a short donor renal vein using other donor veins is a viable therapeutic option for pediatric patients with vascular occlusions.

WDR19 has been reported as a causative gene of nephronophthisis-related ciliopathies. Patients with WDR19 mutations can show various extrarenal manifestations such as skeletal disorders, Caroli disease, and retinal dystrophy, and typically display nephronophthisis as a renal phenotype. However, there is limited information on the renal phenotypes of patients with WDR19 mutations. We report two Japanese infants with Sensenbrenner syndrome caused by WDR19 mutations who demonstrated different features in renal ultrasound and histopathological results, despite several common extrarenal manifestations. Patient 1 had normal sized and hyperechogenic kidneys with several small cysts and histopathological findings compatible with infantile nephronophthisis. Renal ultrasound of Patient 2 showed enlarged kidneys with diffuse microcysts resembling those of autosomal recessive polycystic kidney disease. Her renal histopathology revealed dysplastic kidney with diffuse glomerular cysts. Genetic testing identified compound heterozygous mutations in WDR19 in both patients (Patient 1: c.953delA, c.3533G A, Patient 2: c.2645 + 1G T, c.3533G A). Our patients suggest that WDR19 mutations can cause dysplastic kidney in addition to nephronophthisis pathologically. In addition, differences in pathology of the kidneys from WDR19 mutations may result in heterogeneous features in renal ultrasound findings. Renal phenotypes from WDR19 mutations may thus be more diverse than previously reported. Extrarenal manifestations and genetic testing can therefore help to diagnosis this disease more precisely.

An immunosuppressive agent, mizoribine, is excreted predominantly in the urine. The aim of this study was to investigate the pharmacokinetic variability of mizoribine in pediatric recipients of renal transplantation.Pharmacokinetic data for population analysis were collected from 51 recipients (32 males and 19 females) treated with oral administration of mizoribine (0.83-5.56 mg/day/kg). The population pharmacokinetic parameters of mizoribine were estimated using a nonlinear mixed effects model program.The pharmacokinetics of mizoribine in pediatric recipients of renal transplantation was well described by a one-compartment model with first-order absorption. The mean value of the absorption lag time (ALAG) and absorption rate constant (K (A)) was estimated to be 0.363 h and 0.554 h(-1), respectively. Apparent volume of distribution (V/F) was modeled as a function of body weight (WT), and the mean value was estimated to be 1.03 · WT L. Oral clearance (CL/F) was modeled as a function of creatinine clearance (CL(cr)), and the mean value was estimated to be 2.81 · CL(cr) · 60/1000 L/h. In addition, there was a positive correlation between CL(cr)-corrected CL/F and WT-corrected V/F in the pediatric recipients, indicating large interindividual variability in the bioavailability (F) of mizoribine.The present findings indicated that the rate of renal excretion and also the extent of intestinal absorption of mizoribine are responsible for the large interindividual pharmacokinetic variability of the drug.

国内小児腎移植におけるミコフェノール酸モフェチル (MMF) の有効性・安全性，薬物動態を評価するために，多施設共同オープンラベル臨床試験を行った。 小児腎移植患者25例に，多剤免疫抑制薬併用下にMMF (600∼1,200mg/m2/日 分2経口投与) を1年間投与し，経過観察した。評価項目は，腎移植後6か月の拒絶反応発現割合，腎移植後1年の生着割合および生存割合，有害事象発現頻度とした。AUC0-12，Cmax，Tmaxなどの薬物動態態パラメータを算出した。 腎移植後6か月の拒絶反応発現割合は24%，腎移植後1年の生着割合は100%であった。有害事象発現頻度は68%であった。MMF投与後3か月時平均AUC0-12は，48.7±27.6μg hr/mLであった。推定AUC0-12の経時的推移は，米国小児腎移植患者と同様であった。 本試験には試験デザインと登録症例数が少ないという制限があるものの，国内小児腎移植患者における，MMFの拒絶反応抑制効果と安全性が示唆された。また国内小児腎移植患者は，国内成人患者，米国小児患者と同様の薬物動態を示すことが認められた。

Various urological complications in VATER association require careful management. A 15-year-old boy with VATER association, including a hypoplastic lower urinary tract and diphallia, presented with chronic kidney disease and incontinence after a right loop ureterostomy. In order to acquire urinary continence without renal function impairment, an ileocecal reservoir with umbilical catheterizable stoma was created as a urinary reconstruction. The ectopic posterior penis was resected for cosmetic reasons, and the stump of the hypoplastic urethra was opened at the perineal skin. Clean intermittent self-catheterization through the umbilicus using disabled bilateral limbs was then achieved. This report describes the management of VATER association in a patient with complicated urological anomalies.