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Unexpected filter clotting is a major problem in continuous renal replacement therapy (CRRT). Reduced solute clearance is observed prior to filter clotting. This single-center, retrospective, observational study aimed to determine whether reduced solute clearance of low- and medium-molecular-weight molecules in CRRT can predict filter clotting. Solute clearances of urea and myoglobin (Mb) were measured at 24 h after initiation of continuous hemodiafiltration (CHDF). Clearance per flow (CL/F) was calculated. The primary outcome was clotting of the filter in the subsequent 24 h, and 775 CHDF treatments conducted on 230 patients for at least 24 consecutive hours in our ICU were analyzed. Filter clotting was observed in 127 treatments involving 39 patients. Urea and Mb CL/F at 24 h were significantly lower in the patients who experienced clotting. Further analysis was limited to the first CHDF treatment of each patient to adjust for confounding factors. Multivariate logistic regression analysis revealed that both urea CL/F < 94% and Mb CL/F < 64% were significant predictors of clotting within the next 24 h. Lower urea and Mb CL/F measured at 24 h after CRRT initiation were associated with filter clotting in the next 24 h. Further study is necessary to ascertain whether measurement of urea and MB CL/F will help with avoiding unexpected filter clotting.

Abstract: Introduction : The optimal target of mean arterial pressure (MAP) during continuous renal replacement therapy (CRRT) is unknown. Method : We retrospectively collected the hourly MAP data in acute kidney injury patients requiring CRRT who admitted to the intensive care unit in the University of Tokyo hospital during 2011-2019. Patients who died within 48 h of CRRT start and whose average value of hourly MAPs during the first 48 h was <65 mm Hg were excluded. When the average value of MAP was ≤75 mm Hg or >75 mm Hg, patients were allocated to the low or high target group. We estimated the effect of MAP on mortality and RRT independence at 90 days, using multivariable the Cox regression model and Fine and Gray model. Result : Of the 275 patients we analyzed, 95 patients were in the low group. There are no differences in sex, baseline kidney function, and disease severity. At 90 days, the low target group had higher mortality with 38 deaths (40.0%) compared with 57 deaths (31.7%) in the high target group ( P < 0.05). The adjusted hazard ratio of the low target group (≤75 mm Hg) for mortality was 1.72 (95% CI, 1.08-2.74). In addition, the low target group had a lower rate of RRT independence, with 60 patients (63.2%) compared with 136 patients (75.6%) in the high target group ( P < 0.05). The multivariable analysis revealed that the adjusted hazard ratio of the low target group for RRT independence was 0.74 (95% CI, 0.54-1.01). Conclusion : This study found the association with low MAP and mortality. The association with low MAP and delayed renal recovery was not revealed., (Copyright © 2023 by the Shock Society.)

Purpose: Estimating the baseline renal function of patients without prior creatinine measurement is crucial for diagnosing acute kidney injury (AKI). This study aimed to incorporate AKI biomarkers into a new AKI diagnosis rule when no premorbid baseline is available., Methods: This prospective observational study was conducted in an adult intensive care unit (ICU). Urinary neutrophil gelatinase-associated lipocalin (NGAL) and L-type fatty acid-binding protein (L-FABP) were measured at ICU admission. An AKI diagnostic rule was composed by classification and regression tree (CART) analysis., Results: A total of 243 patients were enrolled. In the development cohort, CART analysis composed a decision tree for AKI diagnosis selecting serum creatinine and urinary NGAL at ICU admission as predictors. In the validation cohort, the novel decision rule was superior to the imputation strategy based on Modification of Diet in Renal Disease (MDRD) equation regarding misclassification rate (13.0% vs. 29.6%, p = 0.002). Decision curve analysis demonstrated that the net benefit of the decision rule exceeded the MDRD approach in a threshold probability range of 25% and higher., Conclusions: The novel diagnostic rule incorporating serum creatinine and urinary NGAL at ICU admission showed superiority to the MDRD approach in AKI diagnosis without baseline renal function data., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)

Background: Reference blood pressure (BP) values for Japanese children based on a large number of measurements by auscultation have not yet been established., Methods: This was a cross-sectional analysis of data from a birth-cohort study. The data from the sub-cohort study conducted for children at the age of 2 years in the Japan Environment and Children's Study from April 2015 to January 2017 were analyzed. BP was measured via auscultation using an aneroid sphygmomanometer. Each participant was measured in triplicate, and the average value of two consecutive measurements with a difference of less than 5 mmHg was recorded. The reference BP values were estimated using the lambda-mu-sigma (LMS) method and compared with those obtained via the polynomial regression model., Results: Data from 3361 participants were analyzed. Although the difference between the estimated BP values by the LMS and the polynomial regression model was small, the LMS model was more valid based on the results of the fit curve of the observed values and regression models for each model. For 2-year-old children with heights in the 50th percentile, the 50th, 90th, 95th, and 99th percentile reference values of systolic BP (mmHg) for boys were 91, 102, 106, and 112, and that for girls were 90, 101, 103, and 109, respectively, and those of diastolic BP for boys were 52, 62, 65, and 71, and that for girls were 52, 62, 65, and 71, respectively., Conclusion: The reference BP values for 2-year-old Japanese children were determined based on auscultation and were made available., (© 2023. The Author(s).)

Background: Wide variations in facility staffing may lead to differences in care, and consequently, adverse outcomes such as hospitalizations. However, few studies focused on types of occupations. Therefore, we aimed to examine the association between a wide variety of facility staffing and potentially avoidable hospitalizations of nursing home residents in Japan., Methods: In this retrospective cohort study using long-term care and medical insurance claims data in Ibaraki Prefecture from April 2018 to March 2019, we identified individuals aged 65 years and above who were newly admitted to nursing homes. In addition, facility characteristic data were obtained from the long-term care insurance service disclosure system. Subsequently, we conducted a multivariable Cox regression analysis and evaluated the association between facility staffing and potentially avoidable hospitalizations., Results: A total of 2909 residents from 235 nursing homes were included. The cumulative incidence of potentially avoidable hospitalizations at 180 days was 14.2% (95% confidence interval [CI] 12.7-15.8). Facilities with full-time physicians (adjusted hazard ratio [HR]: 0.59, 95% CI: 0.37-0.94) and a higher number of dietitians (HR: 0.72, 95% CI: 0.54-0.97) were significantly associated with a lower likelihood of potentially avoidable hospitalizations. In contrast, having nurses or trained caregivers during the night shift (HR: 1.72, 95% CI: 1.25-2.36) and a higher number of care managers (HR: 1.37, 95% CI: 1.03-1.83) were significantly associated with a high probability of potentially avoidable hospitalizations., Conclusions: We revealed that variations in facility staffing were associated with potentially avoidable hospitalizations. The results suggest that optimal allocation of human resources, such as dietitians and physicians, may be essential to reduce potentially avoidable hospitalizations. To provide appropriate care to nursing home residents, it is necessary to establish a system to effectively allocate limited resources. Further research is warranted on the causal relationship between staff allocation and unnecessary hospitalizations, considering the confounding factors., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Paralytic ileus as tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS) is extremely rare. We herein report a 44-year-old man with pulmonary and renal tuberculosis who developed paralytic ileus 14 days after starting antituberculosis therapy (ATT) despite an initial favorable response to ATT. Paralytic ileus was successfully managed with conservative care. He initially required hemodialysis because of obstructive uropathy due to renal tuberculosis, but he was able to withdraw from dialysis after placement of ureteral stents. TB-IRIS can affect organs other than the original sites of tuberculosis, and the combined use of steroids may be effective for its prevention and treatment.

Objectives: The objective was to investigate the microscopic artifacts made in the uterus of cervical high-grade squamous intraepithelial lesion (HSIL) resected by hysterectomy through minimally invasive (H-MI) procedures and to verify whether these specimens are suitable for histopathological assessment., Materials and Methods: This single-center retrospective study analyzed 28 patients with cervical HSIL, consisting of 21 premenopausal and seven postmenopausal women, who underwent H-MI. The proportion of the cervical mucosa covered by intact surface epithelium (residual ratio [RR]) was measured on microscopically. Surgical margin's status was also verified., Results: All cases developed detachment of the cervical surface epithelium to a varying extent. The RR was significantly higher in the premenopausal patients (median: 75.5%) than in the postmenopausal patients (median: 37.6%). Among the premenopausal patients, the RR was lower in the cases on whom uterine manipulator (UM) was used (median: 70.5%) than in the cases without UM use (median 92.7%). Among the 21 cases whose resected uterus contained HSIL, the vaginal resection margin was not assessable in three (14.2%) of the seven postmenopausal cases due to the artifact., Conclusion: Although transvaginal manipulation of the uterus causes detachment of the cervical surface epithelium, H-MI for cervical HSIL provides an acceptable specimen for histological assessment in premenopausal patients, even if UM is used. In postmenopausal women, H-MI easily develops artifactual loss of cervical surface epithelium, sometimes providing an unfavorable specimen for microscopic assessment., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Gynecology and Minimally Invasive Therapy.)

Competing Interests: The authors have nothing to disclose.

Few previous studies have reported immune-complex nephropathy that has not been classified as a specific phenotype in kidney allografts. We report a case of a de novo subclinical "full-house" pattern of deposition in a pediatric transplantation recipient with possible donor-derived IgA deposition. A five-year-old boy underwent living kidney transplantation due to congenital kidney and urinary tract anomalies. A one-hour implantation biopsy revealed IgA deposition. A four-month protocol biopsy finding showed less intense IgA deposition, in contrast with the one-hour biopsy, and trace para-mesangial deposits. A one-year protocol biopsy demonstrated a full-house deposition pattern and massive electron-dense deposits with minor glomerular changes. At the time of the one-year biopsy, kidney function was stable, with no urinalysis abnormalities. No evidence of systemic lupus erythematosus was observed in clinical and serologic examinations. Mesangial IgG, IgM, C3, and C1q deposition was codominant, and IgA deposition was weaker. We diagnosed this case as C1q nephropathy combined with remaining donor-derived IgA deposition. Few studies have reported C1q nephropathy in kidney allograft; further accumulation of cases is required. To distinguish between donor-derived and de novo glomerular lesions, it is important to assess the serial histologic findings of immunofluorescence and electron microscopy. Here, we report a rare case of subclinical C1q nephropathy with possible donor-derived IgA nephropathy., Competing Interests: DISCLOSURES Written informed consent for this publication was obtained from the patient. All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Adolescents and young adults face various socio-emotional and behavioral challenges that can affect their medical and psychosocial outcomes. Pediatric patients with end-stage kidney disease (ESKD) often have extra-renal manifestations, including intellectual disability. However, limited data are available regarding the impact of extra-renal manifestations on medical and psychosocial outcomes among adolescents and young adults with childhood-onset ESKD., Methods: Patients born between January 1982 and December 2006 that had developed ESKD in 2000 and later at age < 20 years were enrolled in this multicenter study in Japan. Data for patients' medical and psychosocial outcomes were retrospectively collected. Associations between extra-renal manifestations and these outcomes were analyzed., Results: In total, 196 patients were analyzed. The mean age at ESKD was 10.8 years, and at last follow-up was 23.5 years. The first modality of kidney replacement therapy was kidney transplantation, peritoneal dialysis, and hemodialysis in 42, 55 and 3% of patients, respectively. Extra-renal manifestations were documented in 63% of patients and 27% had intellectual disability. Baseline height at kidney transplantation and intellectual disability significantly impacted final height. Six (3.1%) patients died, of which five (83%) had extra-renal manifestations. Patients' employment rate was lower than that in the general population, especially among those with extra-renal manifestations. Patients with intellectual disability were less likely to be transferred to adult care., Conclusions: Extra-renal manifestations and intellectual disability in adolescents and young adults with ESKD had considerable impacts on linear growth, mortality, employment, and transfer to adult care., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Nephrology.)

Background: Icodextrin has a lower absorption rate, and icodextrin peritoneal dialysate contributes to more water removal than glucose dialysate in patients with high peritoneal permeability. There are limited data on icodextrin dialysate use in children., Methods: This study included all pediatric patients who received peritoneal equilibration tests and peritoneal dialysis with icodextrin dialysate at the study center. The factors related to ultrafiltration volume with icodextrin dialysate with long dwell time were statistically analyzed. Then the ultrafiltration volume with icodextrin and medium-concentration glucose dialysate was compared in individual cycles in the same patients., Results: Thirty-six samples were included in the icodextrin group, and nine samples were used to compare the ultrafiltration volume with icodextrin and glucose dialysate. Dwell time, D/P-creatinine, D/D 0 -glucose, age, height, and weight correlated significantly with the ultrafiltration volume of icodextrin dialysate (p < 0.05). A dwell volume equal to or more than 550 mL/m 2 was associated with a significantly higher ultrafiltration volume than a lower dwell volume (p = 0.039). Multiple regression analysis revealed that dwell time (p = 0.038) and height (p < 0.01) correlated with ultrafiltration volume significantly. In addition, the ultrafiltration volume was superior (p < 0.01), and dwell time was longer (p = 0.02), with icodextrin dialysate than with medium-concentration glucose dialysate., Conclusions: The ultrafiltration volume with icodextrin dialysate decreases in patients with small stature. Providing sufficient dwell time and volume is important for maximal water removal even in children. Ultrafiltration volume is superior with icodextrin than medium-concentration glucose dialysate for long dwell times. 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.)

Background: Severe congenital anomalies of the kidney and urinary tract (CAKUT) progress to infantile kidney failure with replacement therapy (KFRT). Although prompt and precise prediction of kidney outcomes is important, early predictive factors for its progression remain incompletely defined., Methods: This retrospective cohort study included patients with CAKUT treated at 12 centers between 2009 and 2020. Patients with a maximum serum creatinine level ≤ 1.0 mg/dL during the first 3 days, patients who died of respiratory failure during the neonatal period, patients who progressed to KFRT within the first 3 days, and patients lacking sufficient data were excluded., Results: Of 2187 patients with CAKUT, 92 were finally analyzed. Twenty-five patients (27%) progressed to KFRT and 24 (26%) had stage 3-5 chronic kidney disease without replacement therapy during the median observation period of 52.0 (interquartile range, 22.0-87.8) months. Among these, 22 (24%) progressed to infantile KFRT. The kidney survival rate during the infantile period was significantly lower in patients with a maximum serum creatinine level during the first 3 days (Cr-day3-max) ≥ 2.5 mg/dL (21.8%) compared with those with a Cr-day3-max < 2.5 mg/dL (95.2%) (log-rank, P < 0.001). Multivariate analysis demonstrated Cr-day3-max (P < 0.001) and oligohydramnios (P = 0.025) were associated with higher risk of infantile KFRT. Eighty-two patients (89%) were alive at the last follow-up., Conclusions: Neonatal kidney function, including Cr-day3-max, was associated with kidney outcomes in patients with severe CAKUT. Aggressive therapy for severe CAKUT may have good long-term life outcomes through infantile dialysis and kidney 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.)

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.)

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.)

Purpose: Patients with chronic kidney disease (CKD) complicated by hypothyroidism exhibit a higher prevalence of urine protein than that in the general population. This study was aimed at investigating thyroid hormones and thyroid hormone-binding proteins excreted in urine to elucidate the urine protein-associated underlying mechanisms of hypothyroidism., Methods: Between November 2016 and August 2018, thyroid function (serum free T3 [sFT3], free T4 [sFT4], and thyroid-stimulating hormone [sTSH]), kidney function (estimated glomerular filtration rate [eGFR]), thyroid antibodies and albumin (Alb) were evaluated in 99 Japanese CKD patients with proteinuria at our outpatient clinic. A urine examination was also performed to assess the following parameters: total T3, total T4, TSH, Alb, preAlb, thyroid-binding globulin, and protein., Results: The median patient age at study recruitment was 60 years; 50 patients (50.5%) were male. The median eGFR and Alb level were 20.3 ml/min/1.73 m 2 and 3.8 g/dL, respectively. 21 patients (21.2%) were diagnosed with nephrotic syndrome (NS). The median sFT3, sFT4, and sTSH levels were within normal limits. Approximately 70% of the patients had thyroid dysfunction and 51.5% had overt or subclinical hypothyroidism without predominantly antibody positive. Regarding NS and non-NS patients, age and Alb were significantly different between these groups, while sex and eGFR were not significant, but the urinary T4 and TSH levels were higher in the NS group; thus, more severe hypothyroid., Conclusion: We found a significant association between hypothyroidism and NS regardless of sex and antibodies. Urinary loss of thyroid hormones must be a factor influencing hypothyroidism independent of autoimmunity.

Introduction: At present, there is limited evidence of the histological impact of vesicoureteral reflux (VUR) on pediatric kidney allografts. In this study, we aimed to investigate the relationship between VUR diagnosed by voiding cystourethrography (VCUG) and 1-year protocol biopsy results., Methods: One hundred thirty-eight pediatric kidney transplantations were performed in Toho University Omori Medical Center between 2009 and 2019. We included 87 pediatric transplant recipients who were evaluated for VUR by VCUG prior to or at the time of the 1-year protocol biopsy and underwent a 1-year protocol biopsy after transplantation. We evaluated the clinicopathological findings of the VUR and non-VUR groups, and histological scores were evaluated using the Banff score. Tamm-Horsfall protein (THP) within the interstitium was identified by light microscopy., Results: Of the 87 transplant recipients, 18 cases (20.7%) were diagnosed with VUR by VCUG. The clinical background and findings were not significantly different between the VUR and non-VUR groups. The pathological findings revealed a significantly higher Banff total interstitial inflammation (ti) score in the VUR group than in the non-VUR group. Multivariate analysis indicated a significant relationship between the Banff ti score and THP within the interstitium, and VUR. The 3-year protocol biopsy results (n = 68) revealed a significantly higher Banff interstitial fibrosis (ci) score in the VUR group than in the non-VUR group., Conclusion: VUR caused interstitial fibrosis in the 1-year pediatric protocol biopsies, and interstitial inflammation at the 1-year protocol biopsy may affect interstitial fibrosis at the 3-year protocol biopsy., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Introduction: Severe acute kidney injury (AKI) requiring renal replacement therapy (RRT) has been associated with an unacceptably high mortality of 50% or more. Successful discontinuation of RRT is thought to be linked to better outcomes. Although functional and structural renal markers have been evaluated in AKI, little is known about their roles in predicting outcomes at the time of RRT discontinuation., Methods: In this prospective single-center cohort study, we analyzed patients who received continuous RRT (CRRT) for AKI between August 2016 and March 2018 in the intensive care unit of the University of Tokyo Hospital (Tokyo, Japan). Clinical parameters and urine samples were obtained at CRRT discontinuation. Successful CRRT discontinuation was defined as neither resuming CRRT for 48 h nor receiving intermittent hemodialysis for 7 days from the CRRT termination. Major adverse kidney events (MAKEs) were defined as death, requirement for dialysis, or a decrease in the estimated glomerular filtration rate (eGFR) of more than 25% from the baseline at day 90., Results: Of 73 patients, who received CRRT for AKI, 59 successfully discontinued CRRT and 14 could not. Kinetic eGFR, urine volume, urinary neutrophil gelatinase-associated lipocalin (NGAL), and urinary L-type fatty acid binding protein were predictive for CRRT discontinuation. Of these factors, urine volume had the highest area under the curve (AUC) 0.91 with 95% confidence interval [0.80-0.96] for successful CRRT discontinuation. For predicting MAKEs at day 90, the urinary NGAL showed the highest AUC 0.76 [0.62-0.86], whereas kinetic eGFR and urine volume failed to show statistical significance (AUC 0.49 [0.35-0.63] and AUC 0.59 [0.44-0.73], respectively)., Conclusions: Our prospective study confirmed that urine volume, a functional renal marker, predicted successful discontinuation of RRT and that urinary NGAL, a structural renal marker, predicted long-term renal outcomes. These observations suggest that the functional and structural renal makers play different roles in predicting the outcomes of severe AKI requiring RRT., (© 2023 S. Karger AG, Basel.)

Objective: Clinically amyopathic dermatomyositis (CADM) patients frequently develop refractory interstitial lung disease (ILD), with a poor prognosis. We aimed to verify the efficacy and safety of plasma exchange (PE) treatment for ILD in CADM., Method: A retrospective case-control study was conducted to compare clinical outcomes with and without PE treatment in CADM-ILD patients refractory to combination therapy of high-dose glucocorticoids, calcineurin inhibitors, and cyclophosphamide. Among 19 enrolled patients, 11 were further treated with PE. We compared survival rates and other clinical characteristics. PE consisted of either fresh-frozen plasma or albumin as a replacement solution., Results: Basal clinical characteristics at diagnosis, including age, gender, serum ferritin, Krebs von den Lungen-6 (KL-6), C-reactive protein, and respiratory function tests, did not differ between the two groups. The survival rate for treatment with PE was higher than for treatment without PE (91% and 50%, respectively, p < 0.05). Among PE-treated patients, anti-melanoma differentiation-associated gene-5 (anti-MDA-5) antibody titre, ferritin, and KL-6 as serological activity markers were sustainably reduced only after initiating PE. Therapeutic intervention with PE reduced the frequency of exacerbation of ILD requiring methylprednisolone pulse therapy. The occurrence of bacterial, fungal, and cytomegalovirus infection did not differ between the groups with and without PE, and adverse events associated with PE resolved with appropriate intervention., Conclusion: Combination therapy with PE was associated with an improved survival rate, and may be effective for the management of refractory ILD in CADM patients. A personalized therapeutic strategy including PE could be introduced for fatal rapidly progressive ILD.

Instruction: High mobility group box 1 (HMGB1) is a pro-inflammatory cytokine that reportedly causes kidney injury and other organ damage in rodent acute kidney injury (AKI) models. However, it remains unclear whether HMGB1 is associated with clinical AKI and related outcomes. This study aimed to evaluate the association with HMGB1 and prognosis of AKI requiring continuous renal replacement therapy (CRRT)., Methods: AKI patients treated with CRRT in our intensive care unit were enrolled consecutively during 2013-2016. Plasma HMGB1 was measured on initiation. Classic initiation was defined as presenting at least one of the following conventional indications: hyperkalemia (K ≥6.5 mEq/L), severe acidosis (pH &lt;7.15), uremia (UN &gt;100 mg/dL), and diuretics-resistant pulmonary edema. Early initiation was defined as presenting no conventional indications. The primary outcome was defined as 90-day mortality., Results: A total of 177 AKI patients were enrolled in this study. HMGB1 was significantly associated with the primary outcome (hazard ratio, 1.06; 95% CI, 1.04-1.08). When the patients were divided into two-by-two groups by the timing of CRRT initiation and the HMBG1 cutoff value obtained by receiver operating curve (ROC) analysis, the high HMGB1 group (&gt;10 ng/mL) with classic initiation was significantly associated with the primary outcome compared with the others, even after adjusting for other factors including the nonrenal serial organ failure assessment (SOFA) score., Conclusion: HMGB1 was associated with 90-day mortality in AKI patients requiring CRRT. Notably, the highest mortality was observed in the high HMGB1 group with classic initiation. These findings suggest that CRRT should be considered for AKI patients with high HMGB1, regardless of the conventional indications., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

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., (© 2021 Wiley Periodicals LLC.)

Congenital disorders characterized by the quantitative and qualitative reduction in the number of functional nephrons are the primary cause of chronic kidney disease (CKD) in children. We aimed to describe the alteration of urinary extracellular vesicles (uEVs) associated with decreased renal function during childhood. By nanoparticle tracking analysis and quantitative proteomics, we identified differentially expressed proteins in uEVs in bilateral renal hypoplasia, which is characterized by a congenitally reduced number of nephrons. This expression signature of uEVs reflected decreased renal function in CKD patients by congenital anomalies of the kidney and urinary tract or ciliopathy. As a proof-of-concept, we constructed a prototype ELISA system that enabled the isolation of uEVs and quantitation of expression of molecules representing the signature. The system identified decreased renal function even in its early stage. The uEVs signature could pave the way for non-invasive methods that can complement existing testing methods for diagnosing kidney diseases., Competing Interests: A patent application based on these results has been submitted by the University of Tokyo and Japanese Foundation for Cancer Research., (© 2022 The Authors.)

Frailty is associated with mortality in maintenance dialysis patients. For incident dialysis patients, we used the clinical frailty scale (CFS) to investigate frailty as related to mortality or hospitalization within 2 years. We retrospectively reviewed the medical records of patients initiating hemodialysis or peritoneal dialysis during 2016-2018. Based on those records, two dialysis nurses independently used a 9-point CFS (1 = "Very fit" to 9 = "Terminally ill") to assess each patient's frailty at dialysis initiation. Patients with a mean CFS value of 5 or higher were classified into the frail group. The 2-year survival rates or hospitalization-free rates after the initiation of dialysis were compared between the frail (mean CFS score ≥ 5) and non-frail (mean CFS score < 5) groups. The analysis included 155 incident dialysis patients with mean age of 66.7 ± 14.1 (71% male). Frailty was inferred for 39 (25%) patients at dialysis initiation. Kaplan-Meier analyses showed that the survival rate and hospitalization-free rate within 2 years were significantly lower in the frail group than in the non-frail group (p < 0.01). Cox proportional hazards regression analyses revealed the CFS score as associated with the occurrence of a composite outcome, independently of age (hazard ratio 1.34, 95% confidence interval 1.04-1.72). Frailty assessment based on clinical judgment using CFS might predict adverse outcomes in dialysis-initiated patients., (© 2022. The Author(s).)

Background: Short bowel syndrome (SBS) is a rare yet costly disease with an incidence rate of 3 per million people. Herein, we report a rare case of eosinophilic gastrointestinal disorders (EGIDs) with SBS after strangulated bowel obstruction., Case Presentation: A 5-year-old male had a necrotic intestine of 340 cm resected due to strangulated bowel obstruction caused by an intestinal mesenteric hiatal hernia. The length of the residual intestine was 51 cm. Bloody stools appeared 19 days postoperatively. Colonoscopy showed diffuse redness of the colonic mucosa, and pathological findings showed moderate chronic inflammatory cellular infiltration. On blood examination, the eosinophil count was > 30%. EGIDs with short bowel syndrome (SBS) were suspected. Because his symptoms did not improve with initial nutrition therapy, he was transferred to our hospital 5 months after the operation. Prednisolone was administrated at an initial dose of 1.4 mg/kg/day, 6 days after his transfer. Bloody stools disappeared after prednisolone administration. Seven months after discharge, he had no bloody stool recurrence., Conclusion: The risk of developing secondary EGIDs in children with SBS should be considered, and postoperative management should include attention to abdominal symptoms and elevated eosinophil counts on blood examination., (© 2022. The Author(s).)

Background: The clinical spectrum of Henoch-Schönlein purpura nephritis (HSPN), now known as IgA vasculitis-associated nephritis (IgAVN), ranges from isolated microscopic haematuria to nephrotic syndrome, progressive glomerulonephritis, and kidney failure. The outcome also varies, and the management of IgAVN is controversial. The presence of nephrotic state at disease onset is thought to be a risk factor of a poor prognosis. However, not all patients with nephrotic state have a poor prognosis, and it is unclear whether they need early treatment., Methods: We herein retrospectively examined the clinical course of paediatric IgAVN cases with nephrotic state (serum albumin [sAlb]<3.0 g/dL and urine protein-creatinine ratio of >2.0 g/ gCr) without kidney injury treated at our hospital between 2010 and 2018., Results: Of the 216 patients with IgAVN identified, 17 met the inclusion criteria. The median follow-up period from disease onset to the last observation was 40.5 months (IQR:31.0-74.2). Eleven patients were male, the median age at onset was 5 years, the minimum serum Alb level was 1.9 g/dL, the maximum proteinuria value was 12.3 g/gCr, and the median minimum eGFR was 86.0 mL/min/1.73 m 2 in the acute phase. Eight patients (47%) achieved resolution of nephrotic state within 3 months and complete remission without treatment by the last observation. The patients with spontaneous resolution of nephrotic state had less severe hypoalbuminaemia (Alb<2.0 g/dL) and tended to show a quick increase in the serum albumin level., Conclusions: Our study found that half of paediatric patients with IgAVN with nephrotic state achieved spontaneous resolution without treatment and enjoyed a favourable short-term outcome. Consideration of the duration of nephrotic state and trends in the serum albumin level in children with IgAVN may allow unnecessary kidney biopsies and immunosuppressive therapy to be avoided., (© 2022 Asian Pacific Society of Nephrology.)

Background: The assessment of kidney size is essential for treating kidney disease. However, there are no reliable and sufficiently robust ultrasonographic reference values or prediction formulas for kidney length in Japanese children, based on a sufficient number of participants., Methods: We retrospectively analyzed kidney measurements by ultrasonography in children aged 18 years or younger from eight facilities throughout Japan between January 1991 and September 2018. Detailed reference values were developed by aggregating the left and right kidneys of boys and girls separately. Simple and practical reference values were developed by combining all the data from left and right kidneys and boys and girls. The estimation formulas for the average value and lower limit of the normal range for kidney length were developed based on regression analysis., Results: Based on the aggregated kidney length data of 1984 participants (3968 kidneys), detailed reference values and simple reference values for kidney length were determined. From the regression analysis, the formula for calculating the average kidney length was generated as "kidney length (cm) = body height (m) × 5 + 2", and that for predicting the lower limit of normal kidney length in children under 130 cm was calculated as "lower limit (cm) = 0.85 × [body height (m) × 5 + 2]"., Conclusion: Detailed ultrasonographic reference values of kidney length for Japanese children and simple reference values and estimation formulas for daily practice have been established., (© 2022. The Author(s).)

Background: Social withdrawal (hikikomori) has become an internationally recognized phenomenon, but its pathology and related factors are not yet fully known. We previously conducted a statistical case-control study on adolescent patients with hikikomori in Japan, which revealed the non-specificity of pathology in patients with hikikomori. Further, environmental factors, such as the lack of communication between parents and Internet overuse, were found to be significant predictors of hikikomori severity. Here, we aimed to conduct a similar preliminary case-control study in France and to compare the results with those from the study conducted in Japan., Methods: Parents of middle school students who underwent psychiatric outpatient treatment for hikikomori (n = 10) and control group parents (n = 115) completed the Child Behavior Checklist to evaluate their child's psychopathological characteristics and the Parental Assessment of Environment and Hikikomori Severity Scales, as in our previous study in Japan. We compared the descriptive statistics and intergroup differences in France with those from the previous study conducted in Japan. In the multiple regression analysis to find predictors of hikikomori severity in French and also Japanese subjects, the same dependent and independent variables were chosen for the present study (both differed from the previous study). These were used in order to make accurate intercountry comparisons., Results: The comparisons revealed no differences in the pathology of hikikomori between Japan and France. Specifically, both studies found similarly increased scores for all symptom scales, with no specific bias. However, the statistical predictors of hikikomori severity in France (lack of communication between parents and child and lack of communication with the community) differed from those in Japan (lack of communication between parents)., Conclusion: Hikikomori in Japan and France could be considered essentially the same phenomenon; moreover, our findings demonstrated the universal non-specificity and unbiasedness of the hikikomori pathology. This suggests that hikikomori is not a single clinical category with a specific psychopathology; instead, it is a common phenotype with various underlying pathologies. However, different strategies may be required in each country to prevent the onset and progression of hikikomori., (© 2022. The Author(s).)

Background: Little is known about the epidemiology of Henoch-Schönlein purpura nephritis (HSPN)., Methods: We conducted a nationwide epidemiological survey of Japanese children aged 1 to 15 years with HSPN. Children who were newly diagnosed with HSPN by biopsy between January 2013 and December 2015 were eligible for the survey to clarify the incidence of HSPN. We also conducted an institutional survey on kidney biopsy criteria and treatment protocols., Results: A total of 353 of 412 institutions (85.7%) responded to the questionnaire. Of the 353 institutions, 174 reported to perform kidney biopsies at their institutions, and 563 children were diagnosed with HSPN. Considering the collection rate, the estimated incidence of biopsy-proven HSPN was 1.32 cases/100,000 children per year. The median age at biopsy was 7.0 years, and the male-to-female ratio was 1.2:1. The kidney biopsy criteria and treatment protocols for HSPN were as follows. Patients with acute kidney injury underwent biopsy at least one month after onset. For patients without kidney dysfunction, the timing for biopsy was determined by the amount of proteinuria. Regarding the treatment of HSPN, there were certain commonalities among the treatment protocols, they eventually differed depending on the institutions involved., Conclusions: The incidence of biopsy-proven HSPN was 1.32 cases/100,000 children per year in Japan. The male-to-female ratio and date of diagnosis of HSPN were similar to those in previous studies. The kidney biopsy criteria and treatment protocols for HSPN varied among institutions. Further studies are warranted to establish an optimal treatment policy based on the prognosis., Competing Interests: RH received research funding from Teijin Pharma Ltd. and was a stockholder in Mitsubishi Tanabe Pharma Co.. IT received research funding from Takeda Pharmaceutical Co., Ltd., Ono Pharmaceutical Co. Ltd., Bayer Yakuhin, Ltd., and Sunny Health Co., Ltd. and lecture fees from Takeda Pharmaceutical Co., Ltd. and Novartis Pharma K.K.. KI received research funding from Zenyaku Kogyo Co. Ltd. and subsidies or donations from Daiichi Sankyo Co. Ltd.. SI received research funding form Teijin Pharma, Ltd. and lecture fees from Sanofi K.K. and Alexion Pharmaceuticals Inc. The other authors have no conflicts of interest to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare. None of the research funding received by individual researchers mentioned in the Competing Interests statement are relate to this current study.

Objective: Osteoarthritis (OA) is more prevalent in females. We hypothesized that changes in articular cartilage (AC) constituents with aging may cause differences. Herein, we aimed to compare the changes in AC constituents with aging in male and female normal rats., Design: The glycosaminoglycan (GAG) and collagen (COL) contents of the AC in knee, hip, and shoulder joints of male and female rats were quantified and compared between age groups and sexes., Results: The amount of GAG was decreased in multiple joints in both males and females with aging. In females, it had a significant decrease in all joints measured. The decrease in GAG with aging was more severe in females than in males. Even in young rats, the amount of knee joint GAG was significantly less in females than in males. The amount of COL in the AC was unchanged with aging in both sexes., Conclusions: The drastic GAG decrease with aging in female normal rats may explain the higher prevalence and more severe OA in females.

Although the concept of chronic kidney disease (CKD) in children is similar to that in adults, pediatric CKD has some peculiarities, and there is less evidence and many factors that are not clearly understood. The past decade has witnessed several additional registry and cohort studies of pediatric CKD and kidney failure. The most common underlying disease in pediatric CKD and kidney failure is congenital anomalies of the kidney and urinary tract (CAKUT), which is one of the major characteristics of CKD in children. The incidence/prevalence of CKD in children varies worldwide. Hypertension and proteinuria are independent risk factors for CKD progression; other factors that may affect CKD progression are primary disease, age, sex, racial/genetic factors, urological problems, low birth weight, and social background. Many studies based on registry data revealed that the risk factors for mortality among children with kidney failure who are receiving kidney replacement therapy are younger age, female sex, non-White race, non-CAKUT etiologies, anemia, hypoalbuminemia, and high estimated glomerular filtration rate at dialysis initiation. The evidence has contributed to clinical practice. The results of these registry-based studies are expected to lead to new improvements in pediatric CKD care., (© 2021. IPNA.)

Background: Approximately 30% of children with steroid-resistant nephrotic syndrome (SRNS) have causative monogenic variants. SRNS represents glomerular disease resulting from various etiologies, which lead to similar patterns of glomerular damage. Patients with SRNS mainly exhibit focal segmental glomerulosclerosis (FSGS). There is limited information regarding associations between histologic variants of FSGS (diagnosed using on the Columbia classification) and monogenic variant detection rates or clinical characteristics. Here, we report FSGS characteristics in a large population of affected patients., Methods: This retrospective study included 119 patients with FSGS, diagnosed using the Columbia classification; all had been referred to our hospital for genetic testing from 2016 to 2021. We conducted comprehensive gene screening of all patients using a targeted next-generation sequencing panel that included 62 podocyte-related genes. Data regarding patients' clinical characteristics and pathologic findings were obtained from referring clinicians. We analyzed the associations of histologic variants with clinical characteristics, kidney survival, and gene variant detection rates., Results: The distribution of histologic variants according to the Columbia classification was 45% ( n =53) FSGS not otherwise specified, 21% ( n =25) cellular, 15% ( n =18) perihilar, 13% ( n =16) collapsing, and 6% ( n =7) tip. The median age at end stage kidney disease onset was 37 years; there were no differences in onset age among variants. We detected monogenic disease-causing variants involving 12 of the screened podocyte-related genes in 34% (40 of 119) of patients. The most common genes were WT1 (23%), INF2 (20%), TRPC6 (20%), and ACTN4 (10%). The perihilar and tip variants had the strongest and weakest associations with detection of monogenic variants (83% and 0%, respectively; P <0.001)., Conclusions: We revealed the distributions of histologic variants of genetic FSGS and nongenetic FSGS in a large patient population. Detailed data concerning gene variants and pathologic findings are important for understanding the etiology of FSGS., Competing Interests: R. Hamada reports research funding from Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Takeda Pharmaceutical Co., and Teijin Pharma Ltd.; and honoraria from Alexion Pharmaceuticals, Inc., Asahi Kasei Pharma Corporation, Chugai Pharmaceutical Co., Ltd., and Teijin Pharma Ltd. T. Horinouchi reports research funding from Otsuka Pharmaceutical Co., Ltd. K. Iijima reports consultancy for JCR Pharmaceuticals Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Takeda Pharmaceutical Co., Ltd., and Zenyaku Kogyo Co., Ltd.; research funding from Air Water Medical, Inc., Astellas Pharma, Inc., Eisai Co., Ltd., JCR Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., Nihon Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Shionogi & Co., Ltd., and Zenyaku Kogyo Co., Ltd.; honoraria from Astellas Pharma, Inc., Chugai Pharmaceutical Co., Ltd., Integrated Development Associates Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Shionogi & Co., Ltd., and Zenyaku Kogyo Co., Ltd.; a patent application on the development of antisense nucleotides for exon skipping therapy in Alport syndrome; and an advisory or leadership role for CJASN and Pediatric Nephrology (Editorial Board). S. Ito reports consultancy for Alexion Pharma, Takeda Pharmaceutical Company, Teijin Pharma, and Zenyaku Kogyo Co Ltd.; research funding from Asahi Kasei Pharma, Chugai Pharmaceutical Co., Ltd., CSL Behring, Kyowa Hakko Kirin Co., Ltd., Maruho Pharma, Mitsubishi Tanabe Pharma, and Teijin Pharma Ltd.; honoraria from Alexion Pharma, Teijin Pharma Ltd., and Zenyaku Kogyo Co., Ltd.; an advisory or leadership role for Clinical Experimental Nephrology, JMA Journal, and the Korean Journal of Pediatrics; and participation in a speakers’ bureau for AbbVie LLC, Alexion Pharma, Asahi Kasei Pharma, Astellas Pharma, Inc., Chugai Pharmaceutical Co., Ltd., CSL Behring, Daiichi Sankyo Co., Ltd., Mitsubishi Tanabe Pharma, Novartis Pharma K.K., Pfizer Japan, Inc., Sanofi Co., Ltd., Teijin Pharma Ltd., and Zenyaku Kogyo Co., Ltd. K. Kamei reports research funding from Astellas Pharma, Inc., Chugai Pharmaceutical Co., Ltd., Public Foundation of Vaccination Research Center, Taiju Life Social Welfare Foundation, Terumo Foundation for Life Sciences and Arts, Ono Pharmaceutical Co; Otsuka Pharmaceutical Co., Ltd., Teijin Pharma Ltd; Shionogi Co., Ltd.; and honoraria from Baxter Ltd., Tanabe Mitsubishi Pharma, and Zenyaku Kogyo Co., Ltd. K. Matsuoka reports participating in a speakers’ bureau for Chugai Pharmaceutical Co., Ltd. K. Nozu reports research funding from Chugai Pharmaceutical Company, Dainippon Sumitomo Pharmaceutical Company, Kyowa Kirin Pharmaceutical Company, and Shionogi, Inc.; patents or royalties from Daiichi Sankyo Pharmaceutical Company; an advisory or leadership role for Kyowa Kirin Pharmaceutical Company and Toa Eiyo Ltd.; and receiving lecture fees from Chugai Pharmaceutical Company, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Company, Ltd., Kyowa Kirin Pharmaceutical Company, Novartis Pharma Co., Ltd., and Sumitomo Dainippon Pharma Co., Ltd. All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

The comorbidity of chronic pain and mental dysfunctions such as depression and anxiety disorders has long been recognized, but the underlying mechanisms remain poorly understood. Here, using a mouse model of neuropathic pain, we demonstrated neuronal plasticity in the bed nucleus of the stria terminalis (BNST), which plays a critical role in chronic pain-induced maladaptive anxiety. Electrophysiology demonstrated that chronic pain increased inhibitory inputs to lateral hypothalamus (LH)-projecting BNST neurons. Chemogenetic manipulation revealed that sustained suppression of LH-projecting BNST neurons played a crucial role in chronic pain-induced anxiety. Furthermore, using a molecular genetic approach, we demonstrated that chronic pain elevated the excitability of a specific subpopulation of BNST neurons, which express cocaine- and amphetamine-regulated transcript (CART). The elevated excitability of CART-positive neurons caused the increased inhibitory inputs to LH-projecting BNST neurons, thereby inducing anxiety-like behavior. These findings shed light on how chronic pain induces psychiatric disorders, characterized by maladaptive anxiety.

Aim: Xanthine oxidoreductase (XOR) is known as an enzyme related to purine metabolism, catalysing the oxidation of hypoxanthine to xanthine and of xanthine to uric acid. We investigated the relationship between plasma XOR activity in stable kidney transplantation (KT) recipients and carotid artery lesions., Methods: A total of 42 KT patients visiting our outpatient clinic on regular basis were recruited. Associations between plasma XOR activity and the existence of plaque in the common carotid artery (CCA) or internal carotid artery (ICA) and maximum intima-medial thickness (IMT) of CCA (max-CIMT) > 0.9 mm were examined using univariate and multivariate analyses., Results: At blood sampling, the mean and SD patient age was 52.7 ± 13.8 years old. Plasma XOR(pmol/h/ml) activity was significantly higher in patients with CCA/ICA plaque or max-CIMT >0.9 mm than those without. [23.9 (11.8, 38.3) vs. 8.29 (6.67, 17.5), p < .01, 23.9 (16.9, 71.2) vs. 9.16 (6.67, 28.2), p = .01] Univariate and multivariate logistic regression analyses revealed age and plasma XOR activity as independent predictors of CCA/ICA plaque or max-CIMT >0.9 mm. Receiver operator characteristic curve analyses revealed that the cutoff value of plasma XOR activity for the diagnosis of CCA/ICA plaque or CCA-IMT > 0.9 mm was 16.3 pmol/h/ml., Conclusion: Plasma XOR activity is associated independently with atherosclerotic changes in the carotid artery of stable post-KT patients., (© 2021 Asian Pacific Society of Nephrology.)

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).)

Background: We have developed a simple and easy method of estimating the glomerular filtration rate (eGFR) of serum creatinine in Japanese children (eGFR Uemura ). The eGFR equation is for children aged 2-18 years. Therefore Uemura et al. developed an equation for children younger than 2 years (eGFR under 2 ). The aim of the present study was to validate this new equation., Methods: We collected the data of 13 patients from previous studies and compared the results of eGFR under 2 , eGFR Uemura , and updated eGFR developed by Schwartz (eGFR Schwartz ) with measured GFR using mean error (ME), root mean square error (RMSE), P 30 and Bland-Altman analysis., Results: The ME of eGFR under 2 , eGFR Uemura and eGFR Schwartz were 2.3 ± 15.9, 7.7 ± 14.5, and 16.0 ± 18.2 ml/min/1.73m 2 , respectively. The RMSEs were 15.5, 15.9, and 49.6, respectively. The P 30 values were 76.9%, 76.9%, and 53.8%, respectively. The graph of Bland-Altman bias analysis showed fan-shape. The eGFR under 2 equation was the most accurate in the three equations., Conclusion: The eGFR under 2 equation was useful for Japanese children younger than 2 years., (© 2021. The Author(s).)

Since the discovery of the ferroelectric perovskite-type oxide BaTiO 3 in 1943, numerous materials have been surveyed as candidates for new ferroelectrics. Perovskite-type materials have played a leading role in basic research and applications of ferroelectric materials since the last century. Experimentalists and theoreticians have developed a new materials design stream for post-perovskite materials. In this stream, we have mainly focused on the role of covalency in the evolution of ferroelectricity for displacive-type ferroelectrics in oxides. This perspective surveys the following topics: (1) crossover from quantum paraelectric to ferroelectric through a ferroelectric quantum critical point, (2) the role of cation-oxygen covalency in ferroelectricity and the crossover to quantum paraelectric in perovskite-type compounds, (3) off-center-induced ferroelectricity in perovskites, (4) second-order Jahn-Teller effect enhancement of ferroelectricity in lithium-niobate-type oxides, (5) the presence of four ferroelectric phases and structural transitions of phases of AFeO 3 with decreasing radius of A (A = La-Al), (6) tetrahedral ferroelectrics of perovskite-related Bi 2 SiO 5 and wurtzites, (7) a rare type of polarization switching system in which the coordination number of ions in κ-Al 2 O 3 systems changes between 4 and 6, and (8) lone-pair-electron-induced ferroelectrics in langasite-type compounds.

Background: The difference in outcomes of cancer surgery between patients with and without kidney failure with dialysis therapy (KFDT) remains uncertain., Methods: Using 2010-18 data in a national inpatient database in Japan, we identified patients who had undergone resection of colorectal, lung, gastric or breast cancer. We matched selected patient characteristics, type of cancer, surgical procedure and hospital of up to four patients without KFDT to each patient with KFDT. We assessed 30-day mortality and postoperative complications., Results: Through matching, we identified 2248 patients with KFDT (807 with colorectal, 579 with lung, 500 with gastric and 362 with breast cancer) and 8210 patients without KFDT (2851 with colorectal, 2216 with lung, 1756 with gastric and 1387 with breast cancer). Postoperative complications occurred in a higher proportion of patients with KFDT than of those without KFDT after colorectal {20.3% versus 14.6%; risk difference (RD): 5.7% [95% confidence interval (95% CI) 2.6%-8.8%]}, lung [18.0% versus 12.9%; RD: 5.1% (95% CI 1.6%-8.4%)], gastric [25.0% versus 13.2%; RD: 11.8% (95% CI 7.6%-16.2%)] and breast cancer surgery [7.5% versus 3.5%; RD: 3.9% (95% CI 1.1%-6.9%)]. Patients with KFDT had a higher 30-day mortality than those without KFDT after gastric cancer surgery [1.6% versus 0.3%; RD: 1.3% (95% CI 0.1%-2.3%)]. Heart failure and ischemic heart disease occurred more frequently in patients with KFDT., Conclusions: Patients with KFDT had higher rates of postoperative complications and 30-day mortality; however, RDs varied between cancer types. The higher rates of postoperative complications in patients with KFDT were mainly attributable to cardiovascular complications., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Although vaccination may precipitate relapses of nephrotic syndrome (NS) in children with idiopathic NS, no data are available regarding NS activity regarding influenza (flu) virus infections and NS relapses after receiving inactivated flu vaccines. We conducted a nationwide study of children aged 6 months to 15 years with idiopathic NS to assess the relationship between NS relapse, flu vaccination, and flu infections. We used a multivariate Poisson regression model (MPRM) to calculate the risk ratio (RR) for flu infection and for NS relapse in children with and without flu vaccination. Data of 306 children were assessed. The MPRM in all 306 children showed a significantly lower RR for flu infection (RR: 0.21, 95% confidence interval CI 0.11-0.38) and for NS relapse (RR: 0.22, 95% CI 0.14-0.35) in children receiving flu vaccination compared with unvaccinated children. In an additional MPRM only among 102 children receiving flu vaccination, they had a significantly lower risk for NS relapse during the post-vaccination period (RR: 0.31. 95% CI 017-0.56) compared with the pre-vaccination period. Although our study was observational, based on the favorable results of flu vaccinations regarding flu infections and NS relapse, the vaccine may be recommended for children with NS., (© 2021. The Author(s).)

A 77-year-old man developed peritoneal dialysis-related peritonitis caused by Streptococcus oralis, a rare pathogen causing the disease. The infection, which was not controlled by one-week intraperitoneal administration of cefazolin and ceftazidime, was cured only after switching to two-week intravenous administration of cefazolin and ceftazidime. The patient had no major dental disease or recent history of dental intervention. This case suggests that S. oralis might cause peritoneal dialysis-related peritonitis with persistent systemic inflammation via an extra-oral infection route. The clinical course is discussed along with a review of the literature.

Atopic dermatitis (AD) is the most common inflammatory skin disease in children. The serum level of thymus and activation-regulated chemokine (TARC) is a useful AD index to reflect disease severity; however, it requires blood collection from young children. In comparison, urine samples are easier to collect in a pediatric clinical setting. Here, we analyzed the lipids excreted in urine to identify a diagnostic biomarker for AD. We generated a murine dermatitis model by repeated topical application of 2,4-dinitrofluorobenzene (DNFB) or tape-stripping the dorsal skin. Lipid metabolites excreted in the urine were comprehensively analyzed using liquid chromatography-tandem mass spectrometry. To corroborate our findings, we also analyzed urine samples from patients with AD. DNFB application induced AD-like skin lesions, including epidermal thickening, infiltration of eosinophils and T cells, and an increase in Th2 cytokine levels. Assessment of lipids excreted in urine showed a dominance of prostaglandins (PGs), namely, a PGF 2α metabolite (13,14-dihydro-15-keto-tetranor-PGF 1α ), a PGE 2 metabolite (13,14-dihydro-15-keto-tetranor-PGE 2 ), and a PGD 2 metabolite (13,14-dihydro-15-keto PGJ 2 ). mRNA and protein expression of PGF 2α , PGE 2 , and PGD 2 synthase was upregulated in DNFB-treated skin. The tape-stripping model also caused dermatitis but without Th2 inflammation; urine PGF 2α and PGD 2 metabolite levels remained unaffected. Finally, we confirmed that the urinary levels of the aforementioned PG metabolites, as well as PGI 2 metabolite, 6,15-diketo-13,14-dihydro-PGF 1α and arachidonic acid metabolite, 17-hydroxyeicosatetraenoic acid (17-HETE) increased in patients with AD. Our data highlights the unique urinary lipid profile in patients with AD, which may provide insight into novel urinary biomarkers for AD diagnosis., (© 2021 Federation of American Societies for Experimental Biology.)

Aim: Accurate and precise estimation of glomerular filtration rate (GFR) is essential in kidney disease. We evaluated the usefulness of the mean of creatinine clearance (C Cr ) and urea clearance (C UN ) examined over a 1-h urine collection period (1-h (C Cr  + C UN )/2) in a retrospective, cross-sectional study across two centres, as a relatively simple method for estimating GFR in children., Methods: Children aged ≤18 years who underwent inulin clearance (C In ) tests were eligible. Two clearance values were obtained during a 2-h test consisting of two periods of 1 h each. The mean clearance in two periods was defined as 1-h clearance. 1-h (C Cr  + C UN )/2, 1-h C Cr , 1-h C UN and GFR estimated by Cr-based and cystatin C (CysC)-based formulas for Japanese children were compared with C In . Bland-Altman plots were used to evaluate correlations. The primary outcome measure was the correlation between 1-h (C Cr  + C UN )/2 and C In ., Results: Fifty-three children were analysed. Their median age was 10.9 (interquartile range [IQR] 5.3-14.2) years, and median C In and 1-h (C Cr  + C UN )/2 were 77.0 (IQR: 51.5-95.1) and 81.0 (IQR: 64.1-97.7) ml/min/1.73 m 2 , respectively. Percentage difference of C In and 1-h (C Cr  + C UN )/2 in the Bland-Altman plot was -11.2% (95% confidence interval - 15.3% - -7.1%), with 95% lower and upper limits of agreement of -40.3% and 18.0%, respectively. Thus, 1-h (C Cr  + C UN )/2 was 1.12 times C In ., Conclusion: 1 h (C Cr  + C UN )/2 was almost concordant with C In . 1-h (C Cr  + C UN )/2 can estimate GFR accurately and precisely, making it a simple and speedy test for use in clinical practice., (© 2021 Asian Pacific Society of Nephrology.)

Hikikomori is a Japanese term for social withdrawal, ranging from complete inability to venture outdoors to preferring to stay inside. The prevalence of hikikomori is high, up to 1.2% of the Japanese population, but only few studies have examined its emergence in adolescents. Therefore, we sought to identify environmental and psycho-behavioral characteristics related to hikikomori during adolescence. Parents of middle school students who underwent psychiatric outpatient treatment for hikikomori (n = 20) and control group parents (n = 88) completed the Child Behavior Checklist to evaluate their child's psycho-behavioral characteristics and novel scales to evaluate environmental characteristics and hikikomori severity. Scores for all eight Child Behavior Checklist subscales were significantly higher in the experimental group. Multiple regression analysis revealed that "anxious/depressed," "somatic complaints," "lack of communication between parents" and "overuse of the Internet" were significant predictors of hikikomori severity. These findings can help identify individuals who are at risk of developing hikikomori., (© 2020. The Author(s).)

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.)

Cell-free and concentrated ascites reinfusion therapy (CART) is performed by collecting the ascites from the patient, followed by filtration and concentration. Thereafter, concentrated cell-free ascites is reinfused into the patient intravenously. The new type of machine, Plasauto μ, for managing the process of CART was launched onto the market. We have evaluated the machine through postmarketing clinical study in 17 patients with malignant ascites. The amounts of original and concentrated ascites were 3673 ± 1920 g and 439 ± 228 g, respectively. Recovery rates were acceptable regarding values of total protein, albumin, and IgG that were 55.6% ± 17.3%, 60.2% ± 20.8%, and 58.2% ± 20.5%, respectively. Recovery rates were positively associated with amounts of original ascites and negatively associated with total protein concentration. No adverse events related to the machine were observed. The new type of machine showed preferable performance in processing malignant ascites., (© 2021 The Authors. Therapeutic Apheresis and Dialysis published by John Wiley & Sons Australia, Ltd on behalf of International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Although chronic heart failure is clinically associated with acute kidney injury (AKI), the precise mechanism that connects kidney and heart remains unknown. Here, we elucidate the effect of pre-existing heart failure with reduced ejection fraction (HFrEF) on kidney via sympathetic activity, using the combining models of transverse aortic constriction (TAC) and unilateral renal ischemia reperfusion (IR). The evaluation of acute (24 h) and chronic (2 weeks) phases of renal injury following IR 8 weeks after TAC in C57BL/6 mice revealed that the development of renal fibrosis in chronic phase was significantly attenuated in TAC mice, but not in non-TAC mice, whereas no impact of pre-existing heart failure was observed in acute phase of renal IR. Expression of transforming growth factor-β, monocyte chemoattractant protein-1, and macrophage infiltration were significantly reduced in TAC mice. Lastly, to investigate the effect of sympathetic nerve activity, we performed renal sympathetic denervation two days prior to renal IR, which abrogated attenuation of renal fibrosis in TAC mice. Collectively, we demonstrate the protective effect of pre-existing HFrEF on long-term renal ischemic injury. Renal sympathetic nerve may contribute to this protection; however, further studies are needed to fully clarify the comprehensive mechanisms associated with attenuated renal fibrosis and pre-existing HFrEF., (© 2021. The Author(s).)

Background: Concentric left ventricular hypertrophy (cLVH) is a common left ventricular geometric pattern in patients undergoing maintenance dialysis, including peritoneal dialysis (PD). The relationship between cLVH at PD initiation and the prognosis of patients remains unclear, however. This study aimed to investigate the impact of cLVH at PD initiation on patient survival and major adverse cardiovascular events (MACE)., Methods: The retrospective cohort study included 131 patients who underwent echocardiography during the PD initiation period. Based on echocardiographic measurements, cLVH was defined as a condition with increased LV mass index and increased relative wall thickness. The relationship between cLVH and the prognosis was assessed., Results: Concentric LVH was identified in 29 patients (22%) at PD initiation, and patient survival, MACE-free survival and PD continuation were significantly reduced in the cLVH group compared with the non-cLVH group. In the Cox regression analysis, cLVH was demonstrated as an independent risk factor of mortality (HR [95%CI]: 3.32 [1.13-9.70]) for all patients. For patients over 65 years old, cLVH was significantly associated with mortality and MACE (HR [95%CI]: 3.51 [1.06-11.58] and 2.97 [1.26-7.01], respectively). Serum albumin at PD initiation was independently correlated with cLVH., Conclusions: In our study, cLVH at PD initiation was independently associated with survival in all patients and with both survival and MACE in elderly patients. Evaluation of LV geometry at PD initiation might therefore help identify high-risk patients. Further studies involving larger numbers of patients are needed to confirm the findings from this study and clarify whether treatment interventions for factors such as nutrition status could ameliorate cLVH and improve patient outcomes.