Supplementary Material for: Dietary Fiber Consumption Decreases the Risks of Overweight and Hypercholesterolemia in Japanese Children

<b><i>Aims:</i></b> It remains inconclusive whether high dietary fiber intake decreases the risk of obesity, hypercholesterolemia or high blood pressure during childhood. Therefore, this study investigated the relationships of dietary fiber intake with weight status and related clinical parameters among Japanese children. <b><i>Methods:</i></b> We analyzed the data of 5,600 subjects aged 10-11 years, between 2006 and 2010. Fiber intake was assessed using the Brief-type Diet History Questionnaire. Body height and weight and blood pressure were measured. Serum levels of total cholesterol, low- and high-density lipoprotein cholesterol and triglycerides were analyzed. Fiber intake was categorized into quintiles, and multivariate models were used to adjust for lifestyle factors. <b><i>Results:</i></b> Total fiber intake decreased the risks of overweight and high total cholesterol (OR Quintile 5 vs. Quintile 1 overweight: 0.71 for boys, 0.40 for girls; total cholesterol: 0.60 for boys, 0.66 for girls). Water-soluble fiber intake was associated with a lower risk of high blood pressure, although the ORs were not significant. <b><i>Conclusions:</i></b> Increasing the dietary fiber intake in Japanese children may have favorable effects on overweight and hypercholesterolemia

Supplementary Material for: Anemia and Long-Term Renal Prognosis in Patients with Post-Renal Acute Kidney Injury of Nonmalignant Cause

<p><b><i>Background/Aims:</i></b> The renal prognosis of post-renal acute kidney injury (PoR-AKI) has not been verified so far. The objective of this study was to assess the association of baseline anemia with long-term renal prognosis in patients with PoR-AKI. <b><i>Methods:</i></b> We performed a multicenter retrospective cohort study. Consecutive adult patients from December 2006 to February 2010, who met the requirements as mentioned in the definition of PoR-AKI, were included. Patients without data on baseline renal function and at 6 months after PoR-AKI were excluded. We set baseline hemoglobin (Hb) level (g/dl) as the main exposure to be tested. The main outcome measure was long-term renal prognosis as determined by the difference between proximate estimated glomerular filtration rate (eGFR) at 6 months after diagnosis of PoR-AKI and baseline eGFR prior to the occurrence of the present PoR-AKI (ΔeGFR after 6 months) using the general linear model. <b><i>Results:</i></b> We included 136 patients with PoR-AKI. The most frequent cause of PoR-AKI was malignancy, accounting for 39.0% (n = 53) of cases. Multivariate analysis adjusted for possible confounders showed that ΔeGFR after 6 months significantly changed by -4.28 ml/min/1.73 m² for every 1 g/dl lower Hb at diagnosis (95% CI 1.86-6.69, p < 0.01). An additional multivariate analysis that was stratified by the presence or absence of malignancy as the cause of PoR-AKI yielded the same significant result only in the stratum of the nonmalignant cause of PoR-AKI. <b><i>Conclusion:</i></b> Patients with a nonmalignant cause of PoR-AKI who have baseline anemia may have poor long-term renal prognosis. In these cases, close observation of renal function after renal recovery may be required.</p

Supplementary Material for: Up-Regulation of CD74 Expression in Parietal Epithelial Cells in a Mouse Model of Focal Segmental Glomerulosclerosis

<i>Background/Aims:</i> De novo expression of CD44 is considered as a marker of parietal epithelial cell (PEC) activation. The aim of our study was to explore CD74 expression, which can form a complex with CD44, in PECs during the progression of focal segmental glomerulosclerosis (FSGS). To clarify the role of CD74 expression and of its interaction with CD44, we generated a new mouse model with enhanced PEC activation through lipopolysaccharide (LPS) application to adriamycin (ADR)-induced nephropathy mice (LPS-treated ADR mice). <i>Methods:</i> As a new model, LPS was intraperitoneally injected into the mice 3 weeks after ADR injection. The mice were divided into 3 categories: control mice, ADR mice and LPS-treated ADR mice. Renal function parameters, histologic changes and immunohistochemical expression of CD74 and other PEC activation markers were analyzed after LPS application. <i>Results:</i>After LPS stimulation, the glomeruli were characterized by enlarged epithelial cells with strong CD74 expression, followed by pseudo-crescent formation. By double staining, CD74-positive enlarged cells showed co-expression of classical PEC markers, but not of <i>Lotus tetragonolobus</i> lectin (marker of proximal tubular cells), suggesting amplification of PEC activation. Time-course analysis displayed marked upregulation of CD74 expression during rapid PEC activation compared with CD44. Additionally, the time-dependent change in ERK phosphorylation showed a similar pattern to CD74. <i>Conclusion:</i> Our results indicate that CD74 can be a marker for PEC activation in FSGS. By modifying the ADR mouse model through LPS treatment, we found that CD74 upregulation better reflects a rapid amplification of PEC activation than CD44 expression

Erratum: Intra-Operative Damage to the Pelvic Diaphragm Musculature and Difficulty in Exposure of the Urethra Are Risk Factors of Postoperative Urinary Incontinence after Laparoscopic Radical Prostatectomy: Review of Surgical Video

<i>Purpose: </i>The aim of this study was to clarify risk factors related to postoperative urinary incontinence after laparoscopic radical prostatectomy (LRP). <i>Patients and Methods: </i>Outcomes of 214 consecutive patients who underwent LRP at our institute between April 2001 and January 2009 were reviewed. Patients were divided into 2 groups, continent patients (group A: n = 172), who used one or fewer urinary pads per day 6 months after LRP, and incontinent patients (group B: n = 42), who used two or more pads per day 6 months after LRP. Patient age, prostate specific antigen before LRP, blood loss, duration of indwelling urethral catheter, and the positive margin rate between the 2 groups were compared. In addition, surgical videos were reviewed with attention paid to surgical procedures. We examined the correlation between the occurrence of urinary incontinence and the rate of patients with intra-operative damage to the pelvic diaphragm musculature and difficulty in exposure of the urethra during LRP. <i>Results: </i>There were no significant differences in patient age, prostate specific antigen before LRP, blood loss, duration of indwelling urethral catheter, positive margin rate between groups A and B. However, significant differences were found in the rate of patients with damage to the pelvic diaphragm musculature (16.3 and 73.8%, respectively) and difficulty in exposure of the urethra (20.9 and 83.3%, respectively) during LRP. <i>Conclusions: </i>Intra-operative damage to the pelvic diaphragm musculature and difficulty in exposure of the urethra during LRP are risk factors of urinary incontinence after LRP

Supplementary Material for: Evaluations of the Selectivities of the Diacylglycerol Kinase Inhibitors R59022 and R59949 Among Diacylglycerol Kinase Isozymes Using a New Non-Radioactive Assay Method

Ten mammalian diacylglycerol kinase (DGK) isozymes (a-γ) have been identified. Recent studies have revealed that DGK isozymes play pivotal roles in a wide variety of pathophysiological functions. Thus, it is important to be able to easily check DGK activity in each pathophysiological event. Moreover, the conventional DGK assay is quite laborious because it requires the use of a radioisotope and thin-layer chromatography including multiple extraction steps. In order to minimize the laborious procedures, we established a non-radioactive, single well, two-step DGK assay system. We demonstrated that, compared to the conventional method, the new assay system has comparable sensitivity and much higher efficiency, and is effective in detecting potential agents with high reliability (Z'-factor = 0.69 ± 0.12; n = 3). Using the newly developed assay, we comprehensively evaluated the DGK isozyme selectivities of commercially available DGK inhibitors, R59022 and R59949, in vitro. We found that among 10 isozymes, R59022 strongly inhibited type I DGKa and moderately attenuated type III DGKe and type V DGKθ, and that R59949 strongly inhibited type I DGK a and γ, and moderately attenuated type II DGK d and γ

Supplementary Material for: The association between high-dose allopurinol and erythropoietin hyporesponsiveness in advanced chronic kidney disease. JOINT-KD study

Introduction: To explore the association between urate-lowering agents and reduced response to erythropoietin-stimulating agents in patients suffering from chronic kidney disease G5. Methods: We conducted a cross-sectional, multicenter study in Japan between April and June 2013, enrolling patients aged 20 years or older with an estimated glomerular filtration rate of ≤15 mL/min/1.73 m2. Exclusion criteria encompassed patients with a history of hemodialysis, peritoneal dialysis, or organ transplantation. The patients were categorized into four groups based on the use of urate-lowering drugs: high-dose allopurinol (>50 mg/day), low-dose allopurinol (≤50 mg/day), febuxostat, and no-treatment groups. We used a multivariable logistic regression model, adjusted for covariates, to determine the odds ratio (OR) for erythropoietin hyporesponsiveness, defined by an erythropoietin resistance index (ERI) of ≥10, associated with urate-lowering drugs. Results: A total of 542 patients were included in the analysis, with 105, 36, 165, and 236 patients in the high-dose allopurinol, low-dose allopurinol, febuxostat, and no-treatment groups, respectively. The median and quartiles of ERIs were 6.3 (0, 12.2), 3.8 (0, 11.2), 3.4 (0, 9.8), and 4.8 (0, 11.2) in the high-dose allopurinol, low-dose allopurinol, febuxostat, and no-treatment groups, respectively. The multivariate regression model showed a statistically significant association between the high-dose allopurinol group and erythropoietin hyporesponsiveness, compared to the no-treatment group (OR=1.98, 95% confidence interval: 1.10–3.57). Conclusions: Our study suggests that the use of high-dose allopurinol exceeding the optimal dose may lead to hyporesponsiveness to erythropoiesis-stimulating agents