Curcumin effects on age-related changes in oral immunity: an in vivo study.

The current study aimed to investigate the effects of ageing on oral immunity using ß-defensin (DEFB) 1/2 as a marker and evaluate the effects of curcumin (CUR) on these processes. The study sample included thirty male C57BL/6J mice divided into three groups based on the treatment method used. The young control (YC) and old control (OC) groups received 0·5 % methylcellulose-400 (CUR vehicle) orally for 5 days, whereas the CUR group of older mice received a CUR solution suspended in 0·5 % methylcellulose-400 (dose: 3·0 mg/kg body). DEFB1/2 and immune indicator levels were measured in the saliva and salivary glands post-treatment. The saliva volume and protein content were significantly reduced in the OC group compared with the YC group. CUR administration restored these parameters, decreased DEFB1 expression in the salivary gland and increased DEFB1/2 secretion and DEFB2 expression. These findings were supported by epigenetic gene regulation and partial cytokine activation from changes in WD40 repeat protein 5, TNF alpha and IL-1beta. CUR can partially restore age-related changes in oral immune responses and promote oral health, thereby preventing frailty in the older population through a nutritional therapeutic pathway.

Insomnia symptoms and related factors in a community-based population: The Yamagata Cohort study.

Objective/background: Insomnia is prevalent and is a risk factor for the development of lifestyle-related diseases and early death. To improve insomnia, it is necessary to identify the factors that affect it. This study investigated the associations between insomnia symptoms and mental, physical, and environmental factors in the general Japanese population. Patients/methods: The study participants were 7,873 individuals who responded to the Health and Lifestyle Survey questionnaire that included sleep-related items between December 2021 and March 2022. Insomnia symptoms were defined as a score of 6 or higher on the Athens Insomnia Scale (AIS). A multivariate logistic regression analysis was performed to identify factors independently associated with insomnia symptoms. Results: Of all subjects, 23.4% had insomnia symptoms. Factors associated with insomnia symptoms were older age, female sex, very difficult living conditions on current income, pain/discomfort, anxiety, lack of happiness, frequent nocturia, long duration from bathing time to bedtime, bedroom lighting, and short walking duration. The subgroup analysis showed stronger associations between walking time in men, higher body mass index in women, time from bathing time to bedtime, and daily walking duration in older adults. Conclusions: Insomnia symptoms were common in community-based populations and were independently associated with three different factor groups including physical, psychological, and environmental factors. Improvements in insomnia symptoms require appropriate practical support tailored to an individual's situation.

Regulation of Chloride Channels by Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor-Induced α-Defensin 5.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are used to treat non-small cell lung cancer with EGFR mutations. However, first-generation erlotinib and second-generation afatinib often cause diarrhea, which may develop because of the association between EGFR-TKIs and the chloride channel or abnormalities in the intestinal microbiota due to disruption of the intestinal immune system. As reports on the effects of EGFR-TKIs on intestinal immunity are lacking, we aimed to determine whether the intestinal immune system is involved in the molecular effects of EGFR-TKIs on chloride channels using Caco-2 cells. Initially, we evaluated the association of chloride channels with α-defensin 5 (DEFA5), a marker of intestinal immunity. Erlotinib and afatinib significantly increased the extracellularly secreted DEFA5 level and autophagy-related 16-like 1 and X-box binding protein 1 transcript levels, indicative of enhanced granule exocytosis. Conversely, intracellular DEFA5 and Toll-like receptor 4 protein expression and tumor necrosis factor-α transcript levels decreased significantly, suggesting that Toll-like receptor 4 suppression repressed DEFA5 production. Furthermore, among the chloride channels, DEFA5 was found to significantly increase the transcript levels of cystic fibrosis transmembrane conductance regulators. These results indicate that DEFA5 plays a significant role in the mechanism of chloride channel-mediated diarrhea induced by EGFR-TKIs. Therefore, we successfully elucidated the potential host action of DEFA5 in cancer therapy for the first time.

Association between α-defensin 5 and the expression and function of P-glycoprotein in differentiated intestinal Caco-2 cells.

α-Defensin 5 is known to be secreted by Paneth cells in the small intestine and plays an important role in eliminating pathogenic microorganisms. It has been reported that a decrease in α-defensin 5 level in the human small intestine is a risk of inflammatory bowel disease (IBD). Furthermore, P-glycoprotein (P-gp), a member of the ATP-binding cassette transporter superfamily, encoded by the ABCB1/MDR1 gene, plays an important role in the front line of host defense by protecting the gastrointestinal barrier from xenobiotic accumulation and may contribute to the development and persistence of IBD. Therefore, we examined the relationship between α-defensin 5 and the expression and function of P-gp using a human gastrointestinal model cell line (Caco-2). We found that MDR1 mRNA and P-gp protein level were increased in Caco-2 cells as well as α-defensin 5 secretion corresponded with the duration of cell culture. Exposure to α-defensin 5 peptide and recombinant tumor necrosis factor-α (TNF-α) significantly increased the expression and function P-gp. The mRNA levels of interleukin (IL)-8, IL-6, TNF-α, IL-1ß, and IL-2 were also increased following exposure to TNF-α, similar to α-defensin 5 treatment. These results suggest that α-defensin 5 regulates P-gp expression and function by increasing TNF-α expression in Caco-2 cells.

Clinical significance of skin autofluorescence for diabetic macroangiopathy and comparison with conventional markers of atherosclerosis: a cross-sectional and prospective study.

Background: Skin autofluorescence (SAF) is a marker for the accumulation of advanced glycation end products (AGEs), and is associated with diabetic macroangiopathy. However, whether SAF is superior to conventional markers of atherosclerosis such as carotid intima-media thickness (IMT) and pulse wave velocity (PWV) in detecting macroangiopathy remains unclear. Methods: We recruited 845 patients with type 2 diabetes enrolled in a community diabetes cohort (ViNA cohort) who had SAF, IMT, and PWV measured at baseline. The prevalence of macroangiopathy at baseline and new cardiovascular events during the 2-year follow-up period was investigated. SAF was measured using an AGE reader. Coronary artery calcification (CAC) was measured by computed tomography in 485 patients. Peripheral artery disease (PAD) was defined as the ankle-brachial blood pressure ratio of ≤ 0.9. Results: SAF, IMT, and PWV were significantly correlated with each other, and age, diabetes duration, and estimated glomerular filtration rate were their strong confounders. SAF was associated with baseline stroke and new stroke after adjusting for confounders, but not with coronary artery disease (CAD) or PAD. The nonsignificant relationship between SAF and CAD was consistent with the relationship between SAF and CAC. Multivariate analysis showed a significant association of SAF with baseline and new stroke independent of IMT and PWV. Maximum-IMT was significantly associated with baseline CAD, PAD, and stroke, but not with a new stroke, whereas PWV was associated with a new stroke. Conclusion: Among diabetic macroangiopathies, SAF is a good stroke biomarker, but not for CAD and PAD. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-022-00608-8.

Two Cases of Acquired High-Density Lipoprotein Deficiency with Immunoglobulin G4-Related Lecithin-Cholesterol Acyltransferase Autoantibody.

Lecithin-cholesterol acyltransferase (LCAT) plays a significant role in the progression from premature to mature high-density lipoprotein (HDL) in circulation. Consequently, primary or secondary LCAT deletion or reduction naturally results in low serum HDL cholesterol levels. Recently, rare cases of acquired HDL deficiency with LCAT autoantibodies have been reported, mainly from Japan, where LCAT autoantibodies of immunoglobulin G (IgG) caused the HDL deficiency. Here to our knowledge, we report for the first time two cases of acquired HDL deficiency caused by IgG4 linked LCAT autoantibodies with or without a high serum IgG4 level. Furthermore, these cases can extend to a new concept of "IgG4 autoimmune disease" from the viewpoint of verifying the serum autoantibody and/or renal histopathology.

Prediction of mortality risk of health checkup participants using machine learning-based models: the J-SHC study.

Early detection and treatment of diseases through health checkups are effective in improving life expectancy. In this study, we compared the predictive ability for 5-year mortality between two machine learning-based models (gradient boosting decision tree [XGBoost] and neural network) and a conventional logistic regression model in 116,749 health checkup participants. We built prediction models using a training dataset consisting of 85,361 participants in 2008 and evaluated the models using a test dataset consisting of 31,388 participants from 2009 to 2014. The predictive ability was evaluated by the values of the area under the receiver operating characteristic curve (AUC) in the test dataset. The AUC values were 0.811 for XGBoost, 0.774 for neural network, and 0.772 for logistic regression models, indicating that the predictive ability of XGBoost was the highest. The importance rating of each explanatory variable was evaluated using the SHapley Additive exPlanations (SHAP) values, which were similar among these models. This study showed that the machine learning-based model has a higher predictive ability than the conventional logistic regression model and may be useful for risk assessment and health guidance for health checkup participants.

Obesity and febrile urinary tract infection in young children.

BACKGROUND: Obesity is a risk factor for infectious diseases. However, the relationship between obesity and febrile urinary tract infection (fUTI) is controversial. This study aimed to determine the relationship between obesity and fUTI in young children. METHODS: We analyzed the medical records of children aged <2 years who were admitted to our hospital because of fever between April 2013 to March 2018. The children were categorized into three groups of non-obese, overweight, and obese according to the World Health Organization weight-for-length curves for children aged <2 years. RESULTS: A total of 600 patients were enrolled in this study, of whom 118 were diagnosed with first fUTI. Patients in the fUTI group were younger than those in the control group (patients who were diagnosed with other febrile diseases) (5 ± 5.11 vs 11 ± 6.53 months; P < 0.001). There were no significant differences in the populations of overweight and obese children between the fUTI and control groups. In the fUTI group, the duration of fever, types of pathogen, recurrent rate, the grades of vesicoureteral reflux, and renal scarring were not associated with obesity. The white blood cell count and C-reactive protein levels were not significantly different among the three weight-for-length categories. The same results were obtained when the fUTI group was compared with an age-matched control group (n = 192, 4 ± 2.55 months old; P = 0.261). CONCLUSIONS: Obesity is not a significant risk factor for fUTI in febrile hospitalized young children. Our study suggests that conducting urinalysis for febrile young children without obvious sources, irrespective of obesity, should be considered.

Metabolic Properties of Lowdensity Lipoprotein (LDL) Triglycerides in Patients with Type 2 Diabetes, Comparison with Small Dense LDL-Cholesterol.

AIMS: Abnormal compositional changes in low-density lipoprotein (LDL) particles, such as triglyceride (TG) enrichment and size reduction, are common in patients with diabetes. Several cohort studies have demonstrated that LDL-TG and sdLDL-cholesterol (C) are sensitive biomarkers for predicting atherosclerotic cardiovascular diseases beyond LDL-C. Although sdLDL has been extensively studied, little is known about the properties of LDL-TG. We investigated similarities or differences between LDL-TG and sdLDL-C. METHODS: Fasting plasma was obtained from 1,085 patients with type 2 diabetes who were enrolled in the diabetes regional cohort study (ViNA Cohort). LDL-TG and sdLDL-C concentrations were measured using a homogeneous assay established by us. In a subset of subjects, LDL-TG and sdLDL-C levels were measured postprandially or after treatment with lipid-lowering drugs. RESULTS: In a quartile analysis, higher LDL-TG quartiles were associated with higher frequency of female and fibrate users, whereas sdLDL-C quartiles were associated with frequency of men, drinking, and metabolic syndrome-related measurements. Higher quartiles of LDL-TG/LDL-C were associated with smoking, drinking, fibrate users, and statin users. LDL-TG was significantly correlated with TG, LDL-C, sdLDL-C, and apolipoprotein (apo) B, with apoB being the primary determinant. LDL-TG correlated to high sensitive C-reactive protein (CRP) independently of other lipids. Mean LDL-TG did not change with fasting/non-fasting. Statin treatment reduced LDL-TG, whereas fibrates increased it, but these drugs reduced sdLDL-C equally. CONCLUSIONS: LDL-TG levels were more tightly regulated by the number of LDL particles than plasma TG levels were. SdLDL-C was closely associated with metabolic syndrome-related factors, whereas LDL-TG was associated with low-grade systemic inflammation.

Dyslipidemia in diabetic kidney disease classified by proteinuria and renal dysfunction: A cross-sectional study from a regional diabetes cohort.

AIMS/INTRODUCTION: Diabetic kidney disease (DKD) exacerbates dyslipidemia and increases the incidence of atherosclerotic cardiovascular disease. DKD is a concept that includes typical diabetic nephropathy and an atypical phenotype without proteinuria. We investigated dyslipidemia in different DKD phenotypes that have not been fully studied. MATERIALS AND METHODS: Fasting plasma was obtained from 1,073 diabetes patients enrolled in the regional diabetes cohort (ViNA cohort). Non-proteinuric and proteinuric DKD were defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 in the absence or presence of urinary albumin-to-creatinine ratio >300 mg/g. Novel lipid risk factors, low-density lipoprotein (LDL) triglyceride (TG) and small dense LDL cholesterol were measured using our established homologous assay. RESULTS: The proportion of atherosclerotic cardiovascular disease patients was higher in non-proteinuric DKD and even higher in proteinuric DKD than in non-DKD. Increased estimated glomerular filtration rate grade and albuminuric stage were independently correlated with higher TG, TG-rich lipoprotein cholesterol and apolipoprotein CIII. Therefore, proteinuric DKD had the highest of these levels. Small dense LDL cholesterol and LDL-TG were higher in the proteinuria without renal dysfunction group in the lipid-lowering drug-free subset. Lipoprotein(a) was higher in DKD regardless of proteinuria. CONCLUSIONS: Proteinuria was associated with an atherogenic subspecies of LDL, whereas renal dysfunction was associated with increased lipoprotein(a). Proteinuria and renal dysfunction independently exacerbated TG-rich lipoprotein-related dyslipidemia. This is in good agreement with the results of large-scale clinical studies in which proteinuria and renal dysfunction synergistically increased the risk of atherosclerotic cardiovascular disease in populations with diabetes.

Factors associated with health intentions and behaviour among health checkup participants in Japan.

Health intentions and behaviours are essential for improving the health of individuals and society. This study used cross-sectional data from 20,155 health checkup participants in the Yamagata study to identify factors associated with health intentions and behaviours. Information regarding the current level of health intentions and behaviours was collected using a baseline survey questionnaire. Participants were categorised into three groups: having no intention (no intention), having intentions to improve but not acting on them (intention), and already active (action). The associations between background factors and the presence/absence of health intentions and behaviours were assessed using logistic regression analysis. Of the participants, 35.4%, 37.7%, and 26.9% belonged to the no intention, intention, and action groups, respectively. Multivariate analysis revealed that the factors associated with health intentions were being young, being female, longer duration of education, higher body mass index and abdominal circumference, diabetes, and dyslipidaemia. The factors associated with health behaviours were being older and male, not consuming alcohol, not smoking, performing daily exercise, and having diabetes. These results indicate that health guidance considering background factors, including age, gender, education, and comorbidities, may be useful for effectively promoting health intentions and health behaviours in the Japanese population.

Leucine-rich alpha-2-glycoprotein 1 and angiotensinogen as diagnostic biomarkers for Kawasaki disease.

OBJECTIVE: Kawasaki disease (KD) is a systemic vasculitis in childhood that can lead to coronary artery lesions (CALs). Although early diagnosis and treatment is important for preventing KD patients from development of CALs, diagnosis depends on the clinical features of KD. We studied the usefulness of leucine-rich alpha-2-glycoprotein 1 (LRG1) and angiotensinogen (AGT), previously reported as KD-related proteins, for KD diagnosis and estimation of intravenous immunoglobulin (IVIG) efficacy. METHODS: We undertook a prospective cohort study with patients having two or more KD symptoms in multiple centers in Japan, between July 2017 and February 2019. RESULTS: Two hundred forty-two patients were included. In multivariable analysis, one unit increase in LRG1 was associated with higher odds of KD diagnosis (Odds ratio [OR] 1.02 [95% confidence interval (CI) 1.001-1.03]). Double-positivity for AGT (≥ 26 µg/mL) and LRG1 (≥ 123.5 µg/mL) was an independent biomarker for KD diagnosis in both the total cohort and the subgroup of patients with two to four KD symptoms (OR 5.01 [95% CI 1.86-13.50] and 3.71 [95% CI 1.23-11.16], respectively). There was no association between LRG1/AGT and IVIG efficacy. CONCLUSION: Double-positivity for LRG1 and AGT is an biomarker for KD diagnosis, especially useful in diagnosing incomplete KD from non-KD. Future studies with larger cohorts should seek to determine whether LRG1 and AGT are valuable as definitive data referred at the diagnosis of KD and for estimating the risk of CALs.

Urinary and plasma proteomics to discover biomarkers for diagnosing between diabetic nephropathy and minimal change nephrotic syndrome or membranous nephropathy.

The choice of treatment for primary nephrotic syndrome depends on the pathologic type of the disorder. Renal biopsy is necessary for a definitive diagnosis, but it is burdensome for the patients, and can be avoided if tests could be performed using urine or plasma. In this study, we analyzed 100 urinary proteins, 141 plasma proteins, and 57 urine/plasma ratios in cases of diabetic nephropathy (DN; n = 11), minimal change nephrotic syndrome (MCNS; n = 14), and membranous nephropathy (MN; n = 23). We found that the combination of urinary retinol-binding protein 4 and SH3 domain-binding glutamic acid-rich-like protein 3 could distinguish between MCNS and DN, with an area under the curve (AUC) of 0.9740. On the other hand, a selectivity index (SI) based on serotransferrin and immunoglobulin G, which is often used in clinical practice, distinguished them with an AUC of 0.9091. Similarly, the combination of urinary afamin and complement C3 urine/plasma ratio could distinguish between MN and DN with an AUC of 0.9842, while SI distinguished them with an AUC of 0.8538. Evidently, the candidates identified in this study were superior to the SI method. Thus, the aim was to test these biomarkers for accurate diagnosis and to greatly reduce the burden on patients.

Analysis of α-Defensin 5 Secretion in Differentiated Caco-2 Cells: Comparison of Cell Bank Origin.

α-Defensin 5 has a particularly broad antibacterial spectrum; it eliminates pathogenic microorganisms and regulates intestinal flora. Although Caco-2 cells are similar to small intestinal cells, it is unclear whether they secrete α-defensin 5. Therefore, we investigated whether Caco-2 cells secrete α-defensin 5 and determined the secretion mechanism using cells from three cell banks (ATCC, DSMZ, and RIKEN). The Caco-2 cell proliferation rate increased with the number of culture days, irrespective of cell bank origin. On the other hand, the alkaline phosphatase activity, which affects cell differentiation and the mRNA levels of several cytokines, such as interleukin 8 (IL-8), IL-6, IL-1ß, tumor necrosis factor-α (TNF-α), and IL-2, in the Caco-2 cells fluctuated with the number of culture days, and differed for each cell bank. α-Defensin 5 secretion was detected in all three cell bank Caco-2 cells; particularly, the ATCC Caco-2 cells grew linearly depending on the cell culture day as well as the levels of IL-8 and TNF-α mRNA. This suggested that α-defensin 5 secretion in the ATCC Caco-2 cells was associated with fluctuations in the mRNA levels of various cytokines, such as IL-8 and TNF-α. In conclusion, Caco-2 cells may be a simple model for screening health food components and drugs that affect α-defensin 5 secretion.

Association among chronic kidney disease, airflow limitation, and mortality in a community-based population: The Yamagata (Takahata) study.

Chronic kidney disease (CKD) and chronic obstructive pulmonary disease (COPD) are known risk factors for mortality. In this study, we examined the overlap of CKD and airflow limitation (AFL) that characterises COPD and its effect on 10-year mortality in a community-based population. This study included 1,233 health check-up participants (mean age, 63.7 years; 46.7% men). We defined serum creatinine-based CKD (CKDcr) and serum cystatin C-based CKD (CKDcys) as glomerular filtration rate <60 mL/min/1.73 m2, estimated using serum creatinine or cystatin C, and/or dipstick proteinuria ≥1+. AFL was defined as forced expiratory volume in 1 s to forced vital capacity ratio <70% on spirometry. Compared with subjects without AFL, those with AFL showed a significantly higher prevalence of CKDcys but not of CKDcr. Cox proportional hazard analysis adjusted for confounders showed that the hazard ratio (95% confidence interval) for all-cause mortality was 1.45 (0.77-2.63) in subjects with CKDcys alone, 1.29 (0.60-2.54) in those with AFL alone, and 2.94 (1.33-6.12) in those with both CKDcys and AFL, with subjects without both AFL and CKD as the reference. This study showed that AFL and CKDcys are strongly associated and that their overlap is a significant risk factor for mortality in community-based populations.

An eight-year-old girl with autoimmune polyglandular syndrome type3A that developed during the course of primary Epstein-Barr virus (EBV) infection: clinical implication of EBV in autoimmune thyroid disease.

An eight-year-old girl was admitted for prolonged fever and general fatigue. Bilateral reddened and swollen tonsils covered with white fur and increased numbers of atypical lymphocytes in blood led to a diagnosis of infectious mononucleosis (IM) due to primary Epstein-Barr virus (EBV) infection, which was confirmed by a positive anti-EBV viral capsid antigen IgM antibody reaction. She had a swollen thyroid gland and glycosuria at admission, which persisted after IM resolved. Undetectable thyroid-stimulating hormone (TSH), increased thyroid hormone and elevated HbA1c levels led to a diagnosis of autoimmune polyglandular syndrome type3A, based on the presence of antibodies for TSH receptor and glutamic acid decarboxylase. The clinical significance of EBV infection in the development of autoimmune endocrine disorders has been discussed.

Gamma-Aminobutyric Acid (GABA) Attenuates Ischemia Reperfusion-Induced Alterations in Intestinal Immunity.

The aims of this study were to determine the effects of gamma-aminobutyric acid (GABA) on immunoglobulin A (IgA) secretion from Peyer's patch (PP) cells; to assess rat alpha-defensin-5 (RD-5) expression in the rat small intestine; and to determine the effect of GABA on intestinal ischemia reperfusion (I/R) injury-induced intestinal innate immunity. We found that GABA caused an increase in IgA secretion in the presence and absence of lipopolysaccharide (LPS). Moreover, GABA also significantly increased the mRNA levels of RD-5 and superoxide dismutase (Sod) 1, 3. Intestinal I/R was induced by a 30-min occlusion of the superior mesenteric artery followed by a reperfusion for 60-min. This led to a significant decrease in IgA secretion, and mRNA levels of RD-5 and Sod 1-3 in the ileum. On the other hand, administration of GABA before I/R induction had a significant protective effect against oxidative injury and attenuated the effects on intestinal immunity.

Inhibitory Effects of Baicalein Derived from Japanese Traditional Herbal Medicine on SN-38 Glucuronidation.

PURPOSE: The chemotherapeutic agent irinotecan is hydrolyzed to its active form SN-38 by human carboxyesterases, but SN-38 is converted into the inactive form SN-38G by hepatic UDP-glucuronosyltransferases (UGTs). The aim of the present study was to evaluate the inhibitory effects of two b-glucuronidase-treated Japanese traditional herbal medicines (kampo), Hange-Shashin-To (TJ-14) and Sairei-To (TJ-114) on SN-38 glucuronidation, and the deglycosylation of baicalin (BG) and glycyrrhizic acid (GL) derived from TJ-14 and TJ-114 to form their respective aglycones, baicalein (BA) and glycyrrhetinic acid (GA). METHODS: The inhibitory effects of b-glucuronidase-treated TJ-14 and TJ-114 on SN-38 glucuronidation by human liver microsomes were examined. BA and GA, which were enzymatically converted from BG and GL present in TJ-14 and TJ-114, were examined in the same manner. Furthermore, the enzymatic activities were measured by using recombinant UGT1A1 and UGT1A9 isoforms instead of human liver microsomes. BA, GA, SN-38, and their glycosides/glucuronides were analyzed with an LC-MS system. RESULTS: As regards the linear initial reaction rate, SN-38 glucuronidation by human liver microsomes was significantly inhibited by the addition of b-glucuronidase-untreated TJ-14 and TJ-114, but was more strongly inhibited by the addition of b-glucuronidase-treated TJ-14 and TJ-114. The results of LC-MS analysis and pharmacokinetic studies suggested that BA is the main inhibitor of SN-38 glucuronidation. In the Dixon plot, BA showed competitive inhibition of SN-38 glucuronidation, and the inhibition constant was 8.70 ± 3.24 mM. Previous reports, studies of recombinant UGT isoforms indicated that SN-38 glucuronidation was mainly catalyzed by UGT1A1. CONCLUSIONS: These findings strongly suggested that SN-38 glucuronidation is inhibited by BA. BA could act as a pharmacokinetic regulating factor associated with SN-38 glucuronidation. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

The Association between Glomerular Filtration Rate Estimated Using Different Equations and Mortality in the Japanese Community-Based Population: The Yamagata (Takahata) Study.

BACKGROUND: To evaluate renal function, the indices of estimated glomerular filtration rate (eGFR) obtained using several equations, including the Japanese versions of the serum creatinine-based MDRD equation (eGFRcreat), Chronic Kidney Disease Epidemiology Collaboration equation (eGFR-EPI), and serum cystatin C-based equation (eGFRcys), are utilized. This study prospectively examined the association between these eGFR values and all-cause mortality during a 12-year observational period in a community-based population. METHODS AND RESULTS: The subjects of this study were 1312 participants undergoing a health checkup, aged ≥40 years. In the total population, the mean eGFR values (mL·min-1·1.73 m-2) were 81.5 for eGFRcreat, 78.1 for eGFR-EPI, and 76.6 for eGFRcys. There were 141 deaths during the observation period, and the area under the receiver operating characteristic curve for predicting mortality was 0.59 for eGFRcreat, 0.67 for eGFR-EPI, and 0.70 for eGFRcys (all P < 0.01). In the Cox proportional analysis adjusted for age and sex, eGFRcys, but not eGFRcreat and eGFR-EPI, showed a significant association with all-cause mortality (per 15 mL·min-1·1.73 m-2 decrease: hazard ratio 1.40, 95% confidence interval 1.18-1.67). CONCLUSIONS: This study revealed that eGFRcys showed lower values than eGFRcreat and eGFR-EPI and was significantly associated with all-cause mortality in the Japanese community-based population.