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Advanced glycation end products (AGEs), produced by the Maillard reaction between carbohydrates and proteins, may be involved in diabetes and its complications. Accurate quantification of AGEs

Although several risk factors for chronic kidney disease (CKD) have been proposed, it remains unclear whether elevated serum uric acid (SUA) is negatively association with kidney function. The aim of this study was to elucidate the association between SUA and new onset and progression of CKD in a Japanese general population. This was a population-based retrospective cohort study using annual health checkup data of residents of Iki Island. A total of 5,507 adults (979 with CKD and 4,528 without) were included. The outcomes were new onset of CKD among participants without CKD at baseline, and progression of CKD among those with CKD. A Cox proportional hazards model was used to evaluate the association between SUA and new onset and progression of CKD. During mean follow-up of 4.6 years, 757 cases of new onset of CKD and 193 with progression of CKD were observed. SUA was significantly associated with new onset of CKD (adjusted hazard ratio 1.13, [95% confidence interval 1.03–1.24] per standard deviation [SD] increase in SUA). In contrast, SUA was not significantly associated with progression of CKD (hazard ratio 1.08, [0.92–1.27] per SD increase). Similar results were obtained when classifying uric acid as categorical. SUA was significantly associated with increased risk for new onset of CKD, but not with progression of CKD among a Japanese general population.

Background The Pandemic of coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has critically impacted the spread of infection within nursing facilities. We evaluated the usefulness of genetic and serological tests conducted during a COVID-19 outbreak in a nursing facility in Japan. Methods After the first identification of SARS-CoV-2 infection, a comprehensive, facility- and/or unit-wide PCR testing from nasopharyngeal swabs was repeatedly performed in a three-unit facility including 99 residents with dementia and 53 healthcare personnel. Additionally, PCR testing was conducted separately for residents and staff with fever of ≥37.5 °C. Facility-wide serological testing, including rapid kit testing and quantitative assay, was conducted twice over 1 month apart. Results A total of 322 PCR and 257 antibody tests were performed. 37 (24.3%) of the 152 individuals (25/99 residents, 25.3%; 12/53 staff, 22.6%) were identified as PCR-positive. Seven residents died with a mortality of 7.1% (7/99). Among the 37 individuals, 10 (27.0%) were asymptomatic at the time of testing. PCR positivity was concentrated on one unit (Unit 1) (20/30 residents, 66.7%; 9/14 staff, 64.3%). The other units showed a limited spread of infection. In unit-wide and separate tests, PCR positivity detection was highly prevalent (22.9 and 44.4%, respectively) in Unit 1, compared with that in the other units. Serological testing identified two additional infected residents with a negative PCR result and showed that no staff was newly identified as infected. Conclusions Thorough PCR testing, in combination with comprehensive and separate tests, is critical for managing COVID-19 outbreaks in nursing facilities, particularly, in units considered an epicenter. Serological testing is also beneficial for tracing contacts, confirming the number of infected individuals, and authorizing the termination of the outbreak.

A 54-year-old Japanese woman developed simultaneous abdominal distension and bilateral leg edema. Her medical history and results of periodic medical check-up were unremarkable. Blood tests revealed severe hypoproteinemia and acute kidney injury, and urinalysis revealed 4+ proteinuria and 2+ hematuria. Abdominal computed tomography revealed a large intra-abdominal mass with fat tissue density. She underwent emergency tumor excision, splenectomy, and distal pancreatectomy. However, hypoproteinemia and acute kidney injury worsened. Therefore, she was transferred to the nephrology division for confirmation of diagnosis and for treatment of acute kidney injury and nephrotic syndrome. We conducted percutaneous kidney biopsy and diagnosed minimal change disease (MCD). Intravenous prednisolone was started, and heavy proteinuria and systemic edema were gradually alleviated. She achieved complete remission 2 months later, and oral prednisolone was tapered. Histopathological diagnosis of abdominal tumor was dedifferentiated liposarcoma of retroperitoneal origin. Immunohistochemical staining revealed strong expression of vascular endothelial growth factor in the tumor cells in the dedifferentiated component. Currently, her clinical course is stable without recurrence of liposarcoma and nephrotic syndrome. MCD develops in patients with Hodgkin’s lymphoma, solid organ cancers, hematological malignancies, and thymoma, whereas concurrent MCD and liposarcoma are rare. Remission of nephrotic syndrome and normalized kidney function induced by steroid therapy are important for better management of patients with malignancy.

Combined computed tomography-derived myocardial blood flow (CTP-MBF) and computed tomography angiography (CTA) has shown good diagnostic performance for detection of coronary artery disease (CAD). However, fractal analysis might provide additional insight into ischemia pathophysiology by characterizing multiscale perfusion patterns and, therefore, may be useful in diagnosing hemodynamically significant CAD.The purpose of this study was to investigate, in a multicenter setting, whether fractal analysis of perfusion improves detection of hemodynamically relevant CAD over myocardial blood flow quantification (CTP-MBF) using dynamic, 4-dimensional, dynamic stress myocardial computed tomography perfusion (CTP) imaging.In total, 7 centers participating in the prospective AMPLIFiED (Assessment of Myocardial Perfusion Linked to Infarction and Fibrosis Explored with Dual-source CT) study acquired CTP and CTA data in patients with suspected or known CAD. Hemodynamically relevant CAD was defined as ≥90% stenosis on invasive coronary angiography or fractional flow reserve 0.80. Both fractal analysis and CTP-MBF quantification were performed on CTP images and were combined with CTA results.This study population included 127 participants, among them 61 patients, or 79 vessels, with CAD as per invasive reference standard. Compared with the combination of CTP-MBF and CTA, combined fractal analysis and CTA improved sensitivity on the per-patient level from 84% (95% CI: 72%-92%) to 95% (95% CI: 86%-99%; P = 0.01) and specificity from 70% (95% CI: 57%-82%) to 89% (95% CI: 78%-96%; P = 0.02). The area under the receiver-operating characteristic curve improved from 0.83 (95% CI: 0.75-0.90) to 0.92 (95% CI: 0.86-0.98; P = 0.01).Fractal analysis constitutes a quantitative and pathophysiologically meaningful approach to myocardial perfusion analysis using dynamic stress CTP, which improved diagnostic performance over CTP-MBF when combined with anatomical information from CTA.

Fractal analysis of dynamic, four-dimensional computed tomography myocardial perfusion (4D-CTP) imaging might have potential for noninvasive differentiation of microvascular ischemia and macrovascular coronary artery disease (CAD) using fractal dimension (FD) as quantitative parameter for perfusion complexity. This multi-center proof-of-concept study included 30 rigorously characterized patients from the AMPLIFiED trial with nonoverlapping and confirmed microvascular ischemia (nmicro = 10), macrovascular CAD (nmacro = 10), or normal myocardial perfusion (nnormal = 10) with invasive coronary angiography and fractional flow reserve (FFR) measurements as reference standard. Perfusion complexity was comparatively high in normal perfusion (FDnormal = 4.49, interquartile range [IQR]:4.46–4.53), moderately reduced in microvascular ischemia (FDmicro = 4.37, IQR:4.36–4.37), and strongly reduced in macrovascular CAD (FDmacro = 4.26, IQR:4.24–4.27), which allowed to differentiate both ischemia types, p

This study measured the fume particle size distribution and fume generation rate during arc welding of cast iron and estimated the generation rate of respirable dust. In addition, the generation rate of particles with a diameter of 0.3 µm or less was estimated. In this experiment, three types of filler materials (mild steel wire, stainless steel wire, and mild steel covered electrodes) with main constituents of Fe or Fe-Cr-Ni, as proposed previously by the authors, were used. The welding methods were gas metal arc welding and shielded metal arc welding. The fumes measured in this research contained 73–91% respirable dust, and the fume generation rates were in the range of 1.96–12.2 mg/s. The results of this study were as follows: (i) the welding current affects the generation rate of respirable dust, and it is highly likely that the higher the fume generation rate, the more respirable dust is generated; (ii) the generation rates of respirable dust at low and high current were highest when mild steel covered electrodes and stainless steel wire was used, respectively; and (iii) the generation rate of particles with a diameter of 0.3 µm or less was highest when stainless steel wire is used.

Background There is uncertainty surrounding the causal relationship between serum uric acid and hypertension. The aim was to investigate the association between serum uric acid and prevalence of hypertension in a general population of Japanese. Methods This was a population-based cross-sectional study using health check-up data of the residents of the Iki City, Nagasaki Prefecture, Japan. A total of 7,484 participants aged 30 years or older were included in this study. Serum uric acid was classified into four groups: group 1 (< 357 µmol/L (< 6 mg/dL)), group 2 (357 - 415 µmol/L (6 - 6.9 mg/dL)), group 3 (416 - 475 µmol/L (7 - 7.9 mg/dL)) and group 4 (≥ 476 µmol/L (≥ 8 mg/dL)). Hypertension was defined as blood pressure (BP) levels of ≥ 140/90 mm Hg or use of BP lowering medications. Results Hypertension was observed among 3,467 participants (prevalence 46.3%). The prevalence of hypertension increased with elevation of serum uric acid levels: 42.8% in group 1, 55.0% in group 2, 57.6% in group 3 and 59.8% in group 4 (P < 0.001 for trend). This association was significant even after adjustment for other risk factors including age, sex, current smoking, current alcohol intake, obesity, diabetes, dyslipidemia, estimated glomerular filtration rate and proteinuria: odds ratios (95% confidence intervals) were 1.50 (1.28 - 1.77) for group 2, 1.58 (1.25 - 1.99) for group 3 and 1.89 (1.36 - 2.64) for group 4 compared with the reference group of group 1 (P < 0.001 for trend). Conclusions Serum uric acid was clearly associated with prevalence of hypertension in a general population of Japanese.

Objective.We investigated the association of airway comorbidities with the clinical phenotypes and outcomes of myeloperoxidase (MPO)–antineutrophil cytoplasmic antibodies (ANCA)–positive ANCA-associated vasculitis (AAV).Methods.An AAV patient multicenter cohort trial was established in 13 hospitals in western Japan between 2012 and 2018. We examined 143 of the new-onset MPO-ANCA–positive AAV patients. Their clinical characteristics and comorbidities at disease onset were compared based on clinical phenotypes. Multivariate analysis was performed to identify factors predictive of remission and death.Results.Twenty-seven cases with granulomatosis with polyangiitis (GPA), 10 with eosinophilic GPA (EGPA), 81 with microscopic polyangiitis (MPA), and 25 with unclassified AAV were identified. The average age of MPO-ANCA–positive patients was 71.4 years. Comorbidity (87.4%) and airway comorbidity (70.6%) were frequently observed in these patients. Examination of the clinical phenotypes revealed that the cases of GPA were frequently accompanied by infectious airway comorbidity (upper airway disease, bronchiectasis, pulmonary infections), and most of the cases of MPA and unclassified AAV were accompanied by fibrotic interstitial lung disease (fILD) or emphysema. Among MPO-ANCA–positive patients, infectious airway comorbidity was predictive of both remission (HR 1.58, P = 0.03) and mortality (HR 2.64, P = 0.04), and fILD was predictive of mortality (HR 7.55, P = 0.008). The combination of infectious airway comorbidities and fILD caused the worst survival outcomes in patients.Conclusion.MPO-ANCA–positive AAV was frequently accompanied by airway comorbidities. In addition to fILD, infectious airway comorbidities were closely associated with those clinical phenotypes and outcomes.

Graft biopsy is the gold standard for diagnosis of BK polyomavirus-associated nephropathy (BKPyVAN), and polymerase chain reaction is the most specific screening technique. Development of a noninvasive, cost-effective marker for BKPyVAN is important.We reviewed 492 adult kidney transplant patients. We investigated peripheral blood lymphocyte (PBL) count and urinary cytology at graft biopsy in patients with BKVPyAN (n = 21), acute T-cell-mediated rejection (n = 79), and no evidence of acute rejection (n = 149). We performed univariate and multivariate logistic regression and receiver operating characteristics analyses to compare the test performance of PBL count, urinary cytology, and their combination for diagnosis of BKPyVAN.The PBL count at biopsy was significantly lower in the BKPyVAN group than the acute T-cell-mediated rejection and no acute rejection groups (959 ± 290/μL, 1433 ± 673/μL, and 1531 ± 549/μL, respectively; P .01). The PBL count was 959 ± 290/μL at diagnosis of BKPyVAN and increased to 1123 ± 377/μL, 1238 ± 419/μL, and 1292 ± 491/μL at 1, 2, and 3 months after treatment, respectively (P .05). On univariate analysis, the area under the curve was significantly higher for the combined model than for PBL and cytology alone (0.930, 0.797, and 0.875, respectively; P .01). The improved test performance in the combined model remained significant after multivariate adjustment (0.972, 0.844, and 0.928, respectively; P .01).Decreased PBL count was found in BKPyVAN, and the predictive performance of the combination of PBL count and urinary cytology was significantly enhanced for diagnosis of BKPyVAN.

A 66-year-old-man who had undergone partial aortic arch and descending aortic graft replacement for a dissecting aortic aneurysm presented to our hospital with pain and beating swelling of his left back shoulder. Enhanced computed tomography and aortic angiography revealed graft rupture caused by one of the claws of a rib fixation strut. Furthermore, another claw had invaded a lung. We performed emergency thoracic endovascular aortic repair, and removed all of the struts 3 weeks later. Claw-type rib fixation struts have the potential to injure other organs, including prosthetic grafts. Careful follow-up is mandatory after implantation of this type of strut.

Background: We investigated whether eating speed was associated with the incidence of diabetes in a Japanese general population. Methods: A total of 4853 Japanese individuals without diabetes at baseline were analyzed. Self-reported eating speed was categorized as slow, medium, and fast on the basis of questionnaire responses. The study outcome was the incidence of diabetes. Results: After an average follow-up period of 5.1 years, 234 individuals developed diabetes. The incidence of diabetes per 1000 person-years was 4.9 in the slow eating speed group, 8.8 in the medium eating speed group, and 12.5 in the fast eating speed group, respectively (*** p &lt, 0.001 for trend). The HRs were 1.69 (95%CI 0.94–3.06) for the medium eating speed and 2.08 (95%CI 1.13–3.84) for the fast eating speed, compared to the slow eating speed (* p = 0.014 for trend) after adjustment for age, gender, smoking status, drinking, exercise, obesity, hypertension, and dyslipidemia. Conclusion: Faster eating speed increased a risk for the incidence of diabetes in a general Japanese population.

Background and Aims Diabetic nephropathy (DN) is currently a leading cause of end-stage kidney disease worldwide. Kidney biopsy is generally performed in diabetic patients to discriminate between DN and non-diabetic kidney disease (NDKD), and to provide more specific treatments. In addition to conventional predicting factors of DN, recent studies suggested the predictive value of anemia in the diagnosis of DN, however detailed pathophysiology and the significance of anemia in renal pathology are not fully understood. This study aimed to investigate the impact of anemia on renal pathology and clinical course in patients who underwent kidney biopsy. Method We reviewed 81 patients (60.4 ± 13.7 years, 54 men and 27 women) with type 2 diabetes who underwent percutaneous kidney biopsy in Fukuoka University Hospital from January 2001 through March 2020. DN was diagnosed by mesangial expansion or nodular glomerulosclerosis observed under a light microscope, and immunofluorescence assisted in differentiating NDKD from DN. Anemia was defined as hemoglobin level Results According to their pathological findings, patients were classified into two groups: isolated DN (DN group, n=30) and NDKD alone or concurrent DN (NDKD group, n=51). There were 11 types of NDKD. Of these, membranous nephropathy was the most common (23.5%), followed by IgA nephropathy (17.6%), and crescentic glomerulonephritis (13.7%). In multiple logistic regression analysis, absence of severe hematuria (odds ratio (OR) 11.66, 95% confidence interval (CI) 1.68 - 89.9) and presence of anemia (OR 11.38, 95% CI 2.51 - 51.52) were significantly related with the diagnosis of DN. Akaike’s information criterion (AIC) and net reclassification improvement (NRI) analyses revealed improved predictive performance by adding anemia to the conventional factors (AIC 100.152 to 91.844; NRI 27.0%). The tissues of patients in the DN group demonstrated more severe interstitial fibrosis and tubular atrophy (IF/TA) than the NDKD group (p Conclusion DN is associated with anemia because of severe IF/TA regardless of renal function, and anemia helps clinician discriminate clinically between isolated DN and NDKD.

Single-center studies indicated a high diagnostic accuracy of dynamic computed tomography perfusion (CTP) imaging in the diagnosis of coronary artery disease (CAD).This prospective multicenter study determined the diagnostic performance of combined coronary computed tomography angiography (CTA) and CTP for detecting hemodynamically significant CAD defined by invasive coronary angiography (ICA) with fractional flow reserve (FFR).Seven centers enrolled 174 patients with suspected or known CAD who were clinically referred for ICA. CTA and dynamic CTP were performed using dual-source CT before ICA. FFR was done as part of ICA in the case of 26% to 90% coronary diameter stenosis. Hemodynamically significant stenosis was defined as FFR of 0.8 or90% stenosis on ICA.The study protocol was completed in 157 participants, and hemodynamically significant stenosis was detected in 76 of 157 patients (48%) and 112 of 442 vessels (25%). According to receiver-operating characteristic curve analysis, adding dynamic CTP to CTA significantly increased the area under the curve from 0.65 (95% CI: 0.57-0.72) to 0.74 (95% CI: 0.66-0.81; P = 0.011) on the patient level, with decreased sensitivity (93% vs 72%; P 0.001), improved specificity (36% vs 75%; P 0.001), and improved overall accuracy (64% vs 74%; P 0.001).In this prospective multicenter study on dynamic CTP, the combination of anatomic assessment with coronary CTA and functional evaluation with dynamic CTP allowed more accurate identification of hemodynamically significant CAD compared with CTA alone. However, the clinical significance of this approach needs to be further investigated, including its usefulness in improving prognosis. (Assessment of Myocardial Perfusion Linked to Infarction and Fibrosis Explored With Dual-Source CT [AMPLIFiED]; UMIN000016353).

Objectives This study aimed to clarify the relationship between the white blood cell (WBC) count and hypertension in the general Japanese population. Methods We conducted a population-based retrospective cohort study using annual health check-up data of residents of Iki City, Nagasaki Prefecture, Japan. A total of 2935 participants without hypertension at baseline were included in the present analysis. WBC counts were classified as tertile 1 ( Result During an average follow-up of 4.5 years, 908 participants developed hypertension. The incidence (per 100 person-years) of hypertension increased with an elevation in the WBC count (6.3 in tertile 1, 7.0 in tertile 2, and 7.4 in tertile 3). This association was significant, even after adjustment for other risk factors, including age, sex, current smoking habits, current alcohol intake, exercise habits, obesity, elevated blood pressure, diabetes mellitus, and dyslipidemia. The hazard ratios were 1.07 for tertile 2 (95% CI 0.90–1.26) and 1.27 for tertile 3 (95% CI 1.06–1.51) compared with the reference group of tertile 1 (p = 0.009). Conclusion The WBC count was associated with future development of hypertension in the general Japanese population.

The aim of this study was to determine the relationship between eating before bed and the development of hypertension in a general Japanese population. We conducted a population-based retrospective cohort study using annual health check-up data collected from the residents of Iki City, Nagasaki Prefecture, Japan. In total, 2930 participants without hypertension at baseline (mean age 57.0 years, male 42.8%) were included in the present analysis. Eating before bed was defined as eating within 2 h of bedtime. The outcome of this study was incident hypertension (blood pressure ≥140/90 mmHg or initiation of blood pressure-lowering medications). Multivariable-adjusted hazard ratios and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. During an average follow-up of 4.5 years, 909 participants developed hypertension. The incidence (per 1000 person-years) of hypertension in the group of individuals who ate before bed was 82.8, whereas that in the group of individuals who did not eat before bed was 65.8. The association was significant even after adjusting for other risk factors, including age, sex, current smoking status, current alcohol intake, regular exercise, obesity, elevated blood pressure, diabetes mellitus, and dyslipidemia, with a hazard ratio of 1.23 (95% CI: 1.05-1.44) for the group of individuals who ate before bed compared with the group of individuals who did not eat before bed (P = 0.01 for trend). Eating before bed was correlated with a future risk of developing hypertension in the general Japanese population.

Introduction: Single-center studies indicated a high diagnostic accuracy of dynamic computed tomography perfusion (CTP) imaging in the diagnosis of hemodynamically significant coronary artery disease (CAD). However, no prospective multicenter study has assessed the performance of combined coronary computed tomography angiography (CTA) and dynamic CTP. Hypothesis: In this prospective multicenter study, we assessed the hypothesis that dynamic CTP can provide an incremental diagnostic value over CTA detecting hemodynamically significant CAD defined by invasive coronary angiography (ICA) with fractional flow reserve (FFR). Methods: Seven centers enrolled 165 patients with suspected or known CAD, who were clinically referred for ICA. CTA and dynamic CTP were performed using dual-source CT prior to ICA. FFR was done as part of ICA in case of 26-90% coronary diameter stenosis. Hemodynamically significant stenosis was defined as of FFR Results: The study protocol was completed in 157 participants and hemodynamically significant stenosis was detected in 112 of 442 vessels (25%) and 123 of 157 patients (78%). According to receiver operating characteristic curve analysis, CTA showed an area under the curve (AUC) of 0.81 (95% confidence interval [CI], 0.73-0.86) on the patient level and 0.80 (95% CI, 0.76-0.84) on the vessel level. Adding dynamic CTP to CTA significantly increased the AUC to 0.85 (95% CI, 0.78-0.90; p=0.027) on the patient level and to 0.84 (95% CI, 0.80-0.87; p=0.002) on the vessel level. In the subgroups of patients with 1-, 2- and 3-vessel disease by CTA, the addition of dynamic CTP to CTA significantly increased AUC from 0.80 to 0.84 (p=0.041) in 2-vessel disease and from 0.65 to 0.73 (p=0.022) in 3-vessel disease, but not in 1-vessel disease (from 0.84 to 0.87, p=0.265). Conclusion: In this first prospective multicenter study on dynamic CTP, the combination of anatomical assessment with coronary CTA and functional evaluation with dynamic CTP allowed more accurate detection of hemodynamically significant coronary artery stenosis. Improved diagnostic performance with dynamic CTP was mainly obtained when multivessel disease was suspected by CTA.

IgG4-related disease (IgG4-RD) is a fibroinflammatory condition that can affect various organs. The kidney is one of the organs most frequently affected and IgG4-related tubulointerstitial nephritis (TIN) is the most dominant feature.1 However, several radiologically characteristic lesions within the kidney have also been shown to be diagnostic for IgG4-RD affecting the kidney, in the setting of definitively diagnosed IgG4-related lesions in extrarenal organs.2 Therefore the term ‘IgG4-related kidney disease (IgG4-RKD)’ has been proposed as a comprehensive term for the renal lesions associated with IgG4-RD.2 3 In 2011, the IgG4-RKD working group of the Japanese Society of Nephrology proposed diagnostic criteria for IgG4-RKD.4 Recently, we validated those criteria in a Japanese kidney cohort and developed a revised version.5 On the other hand, the 2019 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for IgG4-RD (the ACR/EULAR criteria) were proposed in 2019.6 According to the latter criteria, exclusion criteria should be applied first to any potential IgG4-RD case. Then, inclusion criteria consisting of eight weighted domains are applied to any case that does not satisfy any of the exclusion criteria, and if …

Background In 2011, the IgG4-related kidney disease (IgG4-RKD) working group of the Japanese Society of Nephrology proposed diagnostic criteria for IgG4-RKD. The aim of the present study was to validate those criteria and develop a revised version. Methods Between April 2012 and May 2019, we retrospectively collected Japanese patients with kidney disease, for whom data on serum IgG4 values and/or immunohistological staining for IgG4 in renal biopsy samples were available. These patients were classified as IgG4-RKD or non-IgG4-RKD based on the diagnostic criteria for IgG4-RKD 2011, and the results were evaluated by expert opinion. Accordingly, we developed some revised versions of the criteria, and the version showing the best performance in the present cohort was proposed as the IgG4-RKD criteria for 2020. Results Of 105 included patients, the expert panel diagnosed 55 as having true IgG4-RKD and 50 as mimickers. The diagnostic criteria for IgG4-RKD 2011 had a sensitivity of 72.7% and a specificity of 90.0% in this cohort. Of the 15 patients with true IgG4-RKD who were classified as non-IgG4-RKD, all lacked biopsy-proven extra-renal lesions, although many had clinical findings highly suggestive of IgG4-RD. The revised version to which “bilateral lacrimal, submandibular or parotid swelling, imaging findings compatible with type 1 autoimmune pancreatitis or retroperitoneal fibrosis” was added as an item pertaining to extra-renal organ(s) improved the sensitivity to 90.9% while the specificity remained at 90.0%. Conclusion The revised version has considerably improved test performance after addition of the new extra-renal organ item (imaging and clinical findings).

Background and Aims Chronic kidney disease is one of the most urgent public health issue in Japan as well as other countries. Many risk factors for development and progression of CKD have been recognized, such as hypertension, diabetes, obesity. However, it is still unclear whether increase of serum uric acid has negative impact on kidney function. The aim of this study is to investigate how serum uric acid influences the new-onset and progression of CKD in Japanese general population. Method The Iki epidemiological Study of atherosclerosis And Chronic Kidney Disease (ISSA-CKD) is a population-based retrospective cohort study using annual health check-up data in the Iki Island (Nagasaki Prefecture, Japan), which has approximately 27,000 residents. A total of 7,645 residents underwent annual health check-ups from fiscal year 2008 to 2016. After excluding residents who visited only 1 health check-up and those with missing information of serum creatinine or serum uric acid, a total of 5507 adults were included in the present analysis. The outcome of the present analysis was new-onset of CKD (reduction in estimated glomerular filtration rate [eGFR] less than 60mL/min/1.73m2 or development of proteinuria among participants without CKD at baseline) and CKD progression (worsening of the stages of eGFR or proteinuria according to the KDIGO guideline among participants with CKD at baseline). Results During a mean follow-up of 4.6 years, 757 (16.7%) new-onset CKD and 193 (19.7%) progression of CKD were observed. Serum uric acid had significant relationship with new-onset CKD even after adjustment for sex, age, obese, hypertension, dyslipidemia, and diabetes mellitus: hazard ratio 1.14 per 1 mg/dL increase, 95% confidence interval 1.07-1.21, P Conclusion The findings of the present analysis show that serum uric acid was significantly associated with increased risks of new onset of CKD, but was not associated with progression of CKD in Japanese general population.

Studies regarding harmful effects of smoking on the new-onset of chronic kidney disease (CKD) have been limited. Thus, we collected and retrospectively studied 8 years of data from the annual health check-ups of the residents in Iki City (Nagasaki Prefecture, Japan). From 2008 to 2016, 4540 adults were enrolled in the study. Information on smoking habits was obtained via a self-reported questionnaire. New-onset CKD was defined as a reduction of the estimated globular filtration rate (eGFR) to less than 60 mL/min/1.73 m2 and/or new-onset proteinuria during the follow-up examinations. During an average follow-up of 4.6 years, proteinuria developed in 218 people (10.4 per 1000 person-years) and eGFR decline to less than 60 mL/min/1.73 m2 was confirmed in 594 people (28.3 per 1000 person-years) including 53 who showed both proteinuria and eGFR reduction (2.8 per 1000 person-years). In terms of proteinuria, current smokers showed a higher incidence than non-smokers (14.1 and 9.17 per 1000 person-years, respectively, p = 0.001), and a significantly high hazard ratio (HR) of 1.39 with a 95% CI of 1.01–1.92 in multivariable Cox’s proportional-hazard analyses. The tendency was more drastic among younger participants (p = 0.015 for trend): current smokers who were

Pioglitazone has superior antiatherosclerotic effects compared with other classes of antidiabetic agents, and there is substantial evidence that pioglitazone improves cardiovascular (CV) outcomes. However, there is also a potential risk of worsening heart failure (HF). Therefore, it is clinically important to determine whether pioglitazone is safe in patients with type 2 diabetes mellitus (T2DM) who require treatment for secondary prevention of CV disease, since they have an intrinsically higher risk of HF. This prospective, multicenter, open-label, randomized study investigated the effects of pioglitazone on cardiometabolic profiles and CV safety in T2DM patients undergoing elective percutaneous coronary intervention (PCI) using bare-metal stents or first-generation drug-eluting stents. A total of 94 eligible patients were randomly assigned to either a pioglitazone or conventional (control) group, and pioglitazone was started the day before PCI. Cardiometabolic profiles were evaluated before PCI and at primary follow-up coronary angiography (5–8 months). Pioglitazone treatment reduced HbA1c levels to a similar degree as conventional treatment (pioglitazone group 6.5 to 6.0%, P

Objectives The objective was to quantify the blue-light hazard from gas metal arc welding (GMAW) of aluminum alloys. The exposure level is expected to depend on the welding conditions. Therefore, it is important to identify the blue-light hazard under various welding conditions. Methods We experimentally conducted GMAW of aluminum alloys under various welding conditions and measured the spectral radiance of the arcs. The effective blue-light radiance, which the American Conference of Governmental Industrial Hygienists has defined to quantify the exposure level of blue light, was calculated from the measured spectral radiance. The maximum acceptable exposure duration per 10000 s for this effective blue-light radiance was calculated. Results The effective blue-light radiance measured in this study was in the range of 2.9-20.0 W cm-2·sr. The corresponding maximum acceptable exposure duration per 10000 s was only 5.0-34 s, so it is hazardous to view the welding arc. The effective blue-light radiance was higher at higher welding currents than at lower welding currents, when pulsed welding currents were used rather than steady welding currents, and when magnesium was included in the welding materials. Conclusions It is very hazardous to view the arcs in GMAW of aluminum alloys. Welders and their helpers should use appropriate eye protection in arc-welding operations. They should also avoid direct light exposure when starting an arc-welding operation.

Here, we present a 67-year-old Japanese man who developed insidious-onset nephrotic syndrome. He had a history of occupational asbestos exposure for about 8 years during his 30s, and was found to have pleural effusion 3 years before his present illness. At that time, repeated cytology testing of his pleural effusion found no malignant cells, and pleural biopsy found fibrous pleuritis without evidence of malignant mesothelioma. Percutaneous kidney biopsy found massive deposits of AA-type amyloid in the glomeruli, small arteries, and medulla. Computed tomography showed a calcified mass in the right lower lung that was positive for (67)Ga uptake, but transbronchial lung biopsy and bronchoalveolar lavage found no evidence of malignancy. He was diagnosed with rounded atelectasis and diffuse pleural thickening. As these benign asbestos-related diseases have no standard treatment, we administered low-dose angiotensin II receptor blocker to preserve kidney function. Unfortunately, his nephrotic syndrome persists, with progressive chronic kidney failure. Kidney involvement in patients with asbestos-related disease is rare. To our knowledge, this is the first case to present with secondary amyloidosis. Kidney biopsy should be considered for patients with existing asbestos-related pleuropulmonary diseases who have urinary abnormalities or renal dysfunction, to clarify the incidence and pathophysiology of renal manifestations.

Objectives Ultraviolet radiation (UVR) emitted during arc welding frequently causes keratoconjunctivitis and skin erythema. The extent of the hazard of UVR varies depending on the welding process and conditions. Therefore, it is important to identify the levels of UVR present under different conditions. The purpose of this study was to investigate the degree of hazard of UVR emitted by the different types of arc welding of cast iron frequently used in industry. Methods In this study, we experimentally measured the UVR emitted during gas tungsten arc welding (GTAW), shielded metal arc welding (SMAW), and gas metal arc welding (GMAW) of cast iron. The degree of hazard of UVR was quantitatively evaluated in accordance with the guidelines of the American Conference of Governmental Industrial Hygienists. Results Effective irradiances measured in this study were in the range 0.045‐2.2 mW/cm2 at a distance of 500 mm from the welding arc. The maximum allowable exposure times corresponding to these levels were only 1.4‐67 s/day. Conclusions UVR emitted during arc welding of cast iron has the following characteristics: (a) It is more hazardous at higher welding currents. (b) The magnitude of the hazard, which depends on the welding process, increases in the order of GMAW > SMAW > GTAW. (c) It is influenced by the filler material used; that is, the components contained in the filler material affect the hazard of UVR. The effect is Fe > Ni, Cr

The aim of this study was to investigate the effects of long-term weight gain from the age of 20 on incidence of hyper-low-density-lipoprotein (LDL) cholesterolemia in the general population of Japanese people. Methods: We conducted a population-based retrospective cohort study using annual health checkup data for residents of Iki City, Nagasaki Prefecture, Japan. A total of 3179 adult (≥30 years old) men and women without hyper-LDL cholesterolemia at baseline, who underwent two or more health checkups were included in the analysis. Information on weight gain (≥10 kg) after 20 years of age was obtained using questionnaire. The outcome of this study was development of hyper-LDL cholesterolemia defined as LDL-cholesterol level ≥3.62 mmol/L and/or initiation of lipid-lowering medications. Results: During a mean follow-up period of 4.53 years, 665 of the 3179 participants developed hyper-LDL cholesterolemia (46.5/1000 person-years). The incidence of hyper-LDL cholesterolemia was higher in participants with a weight gain of ≥10 kg (55.3/1000 person-years) than among those with a weight gain of &lt, 10 kg (41.8/1000 person-years). This association remained statistically significant even after adjustment for age, sex, smoking, daily drinking, exercise, obesity, hypertension, and diabetes (multivariable hazard ratio 1.31, 95% confidence interval 1.08–1.58, p = 0.006). Conclusion: A weight gain of ≥10 after 20 years of age affected the development of hyper-LDL cholesterol regardless of age, sex, and obesity in a general population of Japanese.

Background More than 2 years have passed since the proposal of the diagnostic criteria for IgG4-related kidney disease (IgG4-RKD). The aim of this study was to estimate the number of histological diagnosis for IgG4-RKD throughout Japan and to clarify the regional distribution of the development of this disease. Methods A questionnaire was supplied to 140 research facilities registered in the Japan Renal Biopsy Registry (J-RBR). The items of the questionnaire were the total number of renal biopsies performed and the number of cases diagnosed as IgG4-RKD in 2012 and 2013 at each facility. Age, sex, and diagnosis category were also included for the IgG4-RKD cases. The geographic distribution of the disease development was evaluated using clinical case reports presented at the Eastern/Western regional meeting of the Japanese Society of Nephrology during the 15 years following 2001. Results Forty-seven facilities completed the questionnaire, resulting in a collection rate of 34 %. The total numbers of renal biopsies in 2012 and 2013 were 3387 and 3591, respectively. Forty-seven of these cases (24 in 2012 and 23 in 2013) were diagnosed as IgG4-RKD. The frequency of development of IgG4-RKD per one million over 40-year-old individuals during these 15 years varied between 0.9 and 3.1, depending on Japanese geographic region of Japan. Conclusion The results of the present survey indicate that the number of diagnosis for IgG4-RKD is approximately 130 cases per year throughout Japan, and no regional differences in disease frequency appear to exist.

Background It is widely accepted that tubulointerstitial injury (TII) is caused by glomerular injury (GI) in glomerular diseases. Glomerular endocapillary inflammation may result in crescent formation and exuded protein leakage, which may induce TII in antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCAGN). However, some reports have indicated a glomerulonephritis-independent mechanism of TII in ANCAGN. The aim of this study was to determine the principle cytokines correlated with TII severity and to elucidate a characteristic mechanism for TII in ANCAGN. Methods 28 myeloperoxidase-ANCA-positive ANCAGN patients were enrolled, and their kidney biopsy specimens were histologically evaluated with regard to GI and TII. The mRNA expression of various cytokines was examined in 28 specimens. Results Interleukin (IL)-1β was significantly correlated with the severity of TII. The mRNA expression of Toll-like receptor 4 (TLR4) and Nod-like receptor family pyrin domain-containing-3 (NLRP3) also correlated with TII severity. Immunohistochemical analysis demonstrated that TLR4 protein was positively stained in the tubulointerstitial infiltrating cells. NRLP3 protein was detected in macrophages in the severe infiltrating area but was absent or only very faintly expressed in the glomeruli. These results indicated that NLRP3 inflammasome-dependent processing in macrophages releases the mature active form of IL-1β, which may lead to the development and deterioration of TII. Conclusions Sterile inflammation leads to the formation of ANCA-mediated neutrophil extracellular traps (NETs), which may stimulate macrophages and dendritic cells via TLR4 and induce NF-κB-dependent mRNA expression and translation of pro-IL-1β. Simultaneously, damage-associated molecular pattern signals resulting from NETs promote NLRP3 inflammasome-dependent processing and release mature active IL-1β. Sterile inflammation utilizing the NLRP3 inflammasome might be a characteristic reaction limited to the tubulointerstitium. Thus, neutralizing IL-1β may be a promising strategy to suspend the progress of TII and improve the prognosis of chronic kidney disease resulting from ANCAGN. .

Objectives: Ultraviolet radiation (UVR) emitted during arc welding frequently causes keratoconjunctivitis and erythema in the workplace. The degree of hazard from UVR exposure depends on the welding method and conditions. Therefore, it is important to identify the UVR levels present under various conditions. Methods: We experimentally evaluated the UVR levels emitted in gas metal arc welding (GMAW) of mild steel. We used both a pulsed welding current and a non-pulsed welding current. The shielding gases were 80% Ar + 20% CO2 and 100% CO2. The effective irradiance defined in the American Conference of Governmental Industrial Hygienists guidelines was used to quantify the UVR hazard. Results: The effective irradiance measured in this study was in the range of 0.51-12.9 mW/cm2 at a distance of 500 mm from the arc. The maximum allowable exposure times at these levels are only 0.23-5.9 s/day. Conclusions: The following conclusions were made regarding the degree of hazard from UVR exposure during the GMAW of mild steel: (1) It is more hazardous at higher welding currents than at lower welding currents. (2) At higher welding currents, it is more hazardous when 80% Ar + 20% CO2 is used as a shielding gas than when 100% CO2 is used. (3) It is more hazardous for pulsed welding currents than for non-pulsed welding currents. (4) It appears to be very hazardous when metal transfer is the spray type. This study demonstrates that unprotected exposure to UVR emitted by the GMAW of mild steel is quite hazardous.

The dicarbonyl methylglyoxal reacts primarily with arginine residues to form advanced glycation end products, including Nδ-(5-hydro-5-methyl-4 -imidazolone-2-yl)-ornithine (MG-H1), which are risk factors for not only diabetic complications but also lifestyle-related disease including renal dysfunction. However, the data on serum level and clinical significance of this substance in chronic kidney disease are limited. Serum levels of MG-H1 and Ne-(carboxymethyl) lysine (CML) in 50 patients with renal dysfunction were measured by liquid chromatography/triple-quadruple mass spectrometry. The median serum MG-H1 levels in patients with estimated glomerular filtration rate (eGFR) of ≥30, 15–30, and 0.05). On the other hand, MG-H1 levels in patients with HbA1c of

Polymer synthesis was demonstrated by way of a plasma generated in bubbles in a monomer aqueous solution without a polymerization initiator reagent. Poly(N-isopropylacrylamide) (PNIPAM) was successfully synthesized by the plasma-in-liquid process. Radicals were generated by the plasma in the monomer solution, leading to the polymerization reaction. The molecular weights of PNIPAM synthesized at the discharge treatment time of 60 and 90 min were higher than those of PNIPAM synthesized at the discharge time of 10 and 30 min. The maximum m/z of PNIPAM synthesized at the discharge treatment time of 60 min was approximately 17 000. However, it decreased at the discharge treatment time of 90 min. This was attributed to the decomposition of the polymer, which occurred in the plasma-in-liquid process. Polymerization of the monomer proceeded only during the discharge process, in contrast with conventional polymerization processes. Thus, the generated radicals acted as both polymerization initiators and inhibitors.

Background:The 2019 ACR/EULAR classification criteria for IgG4-RD have recently been published1). In the criteria, patients with an inclusion criteria score of >20 without exclusion criteria are classified as having IgG4-RD.Objectives:To validate the 2019 ACR/EULAR classification criteria for IgG4-RD in a Japanese kidney disease cohort.Methods:The study involved Japanese patients diagnosed as having kidney disease between April 2012 and May 2019, for whom sufficient clinical information and data on serum IgG4 values and/or immunohistological staining for IgG4 in renal biopsy samples were known. These patients were classified as having IgG4-RKD or non-IgG4-RKD (mimickers) based on the 2019 ACR/EULAR classification criteria for IgG4-RD, and the results were evaluated by expert opinion.Results:Among 105 included patients, the expert panel diagnosed 55 as having true IgG4-RKD and 50 as mimickers. The final diagnoses among the mimickers were vasculitis (n=11), idiopathic tubulointerstitial nephritis (TIN) (n=5), drug-induced TIN (n=5), Sjögren’s syndrome (n=4) and others. Among the 55 true IgG4-RKD patients, 4 had exclusion criteria, and 50 of the remaining 51 had an inclusion criteria score of ≥20 points (sensitivity 90.9%). On the other hand, 49 of the 50 mimickers were classified as having non-IgG4-RKD (specificity 98.0%) (Table 1).Table 1.General characteristics and prevalence of individual items of true IgG4-RKD and non-IgG4-RKD (mimicker)IgG4-RKD(true IgG4-RKD)(n=55)Non-IgG4-RKD(mimicker)(n=50)PAge at diagnosis,mean ±SD (years)69.9 ± 9.456.7 ± 17.4Male (%)76.4440.001Elevated serum IgG454/55 (98.2%)18/50 (36.0%)Serum IgG4 (mg/dl), mean±SD1028 ± 796226 ± 261Dense IgG4+Plasma cells (>10/hpf) in the kidney biopsy48/51 (94.1%)13/40 (32.5%)Storiform fibrosis in the kidney biopsy28/51 (54.9%)3/50 (6%)Hypocomplementemia39/55 (70.1%)7/42 (16.7%)Renal pelvis thickening/soft tissue5/55 (9%)1/50 (2%)0.20Bilateral renal cortex low-density areas29/55 (52.7%)7/50 (14.0%)Exclusion criteria present4/55 (7.3%)22/50 (44%)Total inclusion criteria points >20 without exclusion criteria50/55 (90.9%)1/50 (2%)Conclusion:The 2019 ACR/EULAR classification criteria for IgG4-RD showed good agreement with expert classification in this Japanese kidney disease cohort.References:[1] Wallace ZS, et al. The 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for IgG4-related disease. Ann Rheum Dis. 79:77-87, 2020Disclosure of Interests:None declared

The most representative kidney lesion of IgG4-related disease (IgG4-RD) is plasma cell-rich tubulointerstitial nephritis (TIN) with distinctive imaging findings including multiple low-density lesions on contrast-enhanced computed tomography. In addition, membranous glomerulonephritis is a representative glomerular lesion of this disease. Recent advances have clarified that inflammation with IgG4-positive plasma cell infiltrates is not restricted to the renal parenchyma, but can be seen in outside the renal capsule, around medium-sized arteries such as lobar arteries, around nerves, and in the renal pelvis and periureter. Hypocomplementemia is a very important feature of IgG4-TIN, and serum complement level might serve as a convenient biomarker to predict relapse. Although good responsiveness to glucocorticoid has been considered characteristic of IgG4-RD, delayed start of treatment is associated with partial scarring in the kidneys on imaging study. Therefore, steroid therapy should be immediately initiated as soon as the diagnosis of IgG4-TIN is made. Future analyses of pathogenesis will be needed to more precisely define the optimal therapeutic strategies for the various subsets of Ig4-RD patients.

This case describes a 68-year-old woman exhibiting initial proteinuria at age 55. Subsequently, at age 57, a mixed-type of amyloidosis consisting of amyloid amyloidosis (A A) and immunoglobulin (Ig) light chain amyloidosis (AL) was diagnosed by a renal biopsy examination. Monoclonal paraproteinemia was concurrently identified and diagnosed as monoclonal gammopathy of undeterminate significance (MGUS). Combined melphalan and prednisolone (MP) therapy was initiated. At age 65, anti-hypertensive drugs were administered upon finding an increased urine protein concentration and elevated blood pressure. Because there was no change in the state of MGUS detected by a bone marrow biopsy examination, MP therapy was discontinued. However, the urinary protein concentration increased, and a renal biopsy was performed again at age 66. This revealed a mixed-type amyloidosis of AA and AL, as diagnosed earlier, but AL amyloid deposition in the glomeruli had increased during the intervening period. Life-preserving treatment was continued thereafter, but nephrotic syndrome and renal dysfunction progressed rapidly. End-stage renal failure deposition is rarely seen in the same individual. Although amyloidosis is generally thought to cause a rapid decline in renal function, the patient's renal function was maintained for 13 years. This could be attributed to the following factors : l)the underlying etiology of the AA amyloidosis, which was not clear, 2)a lack of any current evidence of chronic inflammation, and 3) MGUS as the cause of AL amyloidosis. This, together with MP therapy, may have slowed down the pathological decline normally associated with AL amyloidosis.

Ultraviolet radiation (UVR) emitted during arc welding frequently causes keratoconjunctivitis and erythema. The extent of the hazard of UVR varies depending on the welding method and conditions. Therefore, it is important to identify the levels of UVR that are present under various conditions. In this study, we experimentally evaluated the hazard of UVR emitted in gas tungsten arc welding (GTAW) of aluminum alloys. The degree of hazard of UVR is measured by the effective irradiance defined in the American Conference of Governmental Industrial Hygienists guidelines. The effective irradiances measured in this study are in the range 0.10-0.91 mW/cm(2) at a distance of 500 mm from the welding arc. The maximum allowable exposure times corresponding to these levels are only 3.3-33 s/day. This demonstrates that unprotected exposure to UVR emitted by GTAW of aluminum alloys is quite hazardous in practice. In addition, we found the following properties of the hazard of UVR. (1) It is more hazardous at higher welding currents than at lower welding currents. (2) It is more hazardous when magnesium is included in the welding materials than when it is not. (3) The hazard depends on the direction of emission from the arc.