Klotho exerts protection in chronic kidney disease associated with regulating inflammatory response and lipid metabolism.

BACKGROUND: The anti-aging protein Klotho plays a protective role in kidney disease, but its potential as a biomarker for chronic kidney disease (CKD) is controversial. Additionally, the main pathways through which Klotho exerts its effects on CKD remain unclear. Therefore, we used bioinformatics and clinical data analysis to determine its role in CKD. RESULTS: We analyzed the transcriptomic and clinical data from the Nephroseq v5 database and found that the Klotho gene was mainly expressed in the tubulointerstitium, and its expression was significantly positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with blood urea nitrogen (BUN) in CKD. We further found that Klotho gene expression was mainly negatively associated with inflammatory response and positively associated with lipid metabolism in CKD tubulointerstitium by analyzing two large sample-size CKD tubulointerstitial transcriptome datasets. By analyzing 10-year clinical data from the National Health and Nutrition Examination Survey (NHANES) 2007-2016, we also found that Klotho negatively correlated with inflammatory biomarkers and triglyceride and positively correlated with eGFR in the CKD population. Mediation analysis showed that Klotho could improve renal function in the general population by modulating the inflammatory response and lipid metabolism, while in the CKD population, it primarily manifested by mediating the inflammatory response. Restricted cubic spline (RCS) analysis showed that the optimal concentration range for Klotho to exert its biological function was around 1000 pg/ml. Kaplan-Meier curves showed that lower cumulative hazards of all-cause mortality in participants with higher levels of Klotho. We also demonstrated that Klotho could reduce cellular inflammatory response and improve cellular lipid metabolism by establishing an in vitro model similar to CKD. CONCLUSIONS: Our results suggest that Klotho exerts protection in CKD, which may be mainly related to the regulation of inflammatory response and lipid metabolism, and it can serve as a potential biomarker for CKD.

Identification of influence factors in overweight population through an interpretable risk model based on machine learning: a large retrospective cohort.

BACKGROUND: The identification of associated overweight risk factors is crucial to future health risk predictions and behavioral interventions. Several consensus problems remain in machine learning, such as cross-validation, and the resulting model may suffer from overfitting or poor interpretability. METHODS: This study employed nine commonly used machine learning methods to construct overweight risk models. The general community are the target of this study, and a total of 10,905 Chinese subjects from Ningde City in Fujian province, southeast China, participated. The best model was selected through appropriate verification and validation and was suitably explained. RESULTS: The overweight risk models employing machine learning exhibited good performance. It was concluded that CatBoost, which is used in the construction of clinical risk models, may surpass previous machine learning methods. The visual display of the Shapley additive explanation value for the machine model variables accurately represented the influence of each variable in the model. CONCLUSIONS: The construction of an overweight risk model using machine learning may currently be the best approach. Moreover, CatBoost may be the best machine learning method. Furthermore, combining Shapley's additive explanation and machine learning methods can be effective in identifying disease risk factors for prevention and control.

Development of a Risk Model for Predicting Microalbuminuria in the Chinese Population Using Machine Learning Algorithms.

OBJECTIVE: Microalbuminuria (MAU) occurs due to universal endothelial damage, which is strongly associated with kidney disease, stroke, myocardial infarction, and coronary artery disease. Screening patients at high risk for MAU may aid in the early identification of individuals with an increased risk of cardiovascular events and mortality. Hence, the present study aimed to establish a risk model for MAU by applying machine learning algorithms. METHODS: This cross-sectional study included 3,294 participants ranging in age from 16 to 93 years. R software was used to analyze missing values and to perform multiple imputation. The observed population was divided into a training set and a validation set according to a ratio of 7:3. The first risk model was constructed using the prepared data, following which variables with P <0.1 were extracted to build the second risk model. The second-stage model was then analyzed using a chi-square test, in which a P ≥ 0.05 was considered to indicate no difference in the fit of the models. Variables with P <0.05 in the second-stage model were considered important features related to the prevalence of MAU. A confusion matrix and calibration curve were used to evaluate the validity and reliability of the model. A series of risk prediction scores were established based on machine learning algorithms. RESULTS: Systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), triglyceride (TG) levels, sex, age, and smoking were identified as predictors of MAU prevalence. Verification using a chi-square test, confusion matrix, and calibration curve indicated that the risk of MAU could be predicted based on the risk score. CONCLUSION: Based on the ability of our machine learning algorithm to establish an effective risk score, we propose that comprehensive assessments of SBP, DBP, FBG, TG, gender, age, and smoking should be included in the screening process for MAU.

Dietary inflammatory index and cardiorenal function in women with diabetes and prediabetes.

BACKGROUND AND AIMS: Previous studies had shed a new light on the importance of multiple inflammatory mechanisms in the pathogenesis of arterial stiffness. The dietary inflammatory index (DII®) is a new tool for estimating the overall inflammatory potential of the diet. The aim of this study is to assess the association of the inflammatory potential of diet with peripheral arterial stiffness and renal function in women with diabetes and prediabetes. METHODS AND RESULTS: This is an observational cross-sectional study. A total of 2644 females aged 45-75 years were included for the study. Dietary intake in the past 12 months was assessed by a validated China National Nutrition and Health Survey 2002 (CNHS2002) food-frequency questionnaire. Energy-adjusted DII (E-DII) scores were calculated from daily dietary information. In a multivariable linear regression analysis adjusted for potential confounders, E-DII was positively associated with brachial ankle pulse wave velocity (baPWV) in participants with diabetes (ß = 12.820; 95% CI = 2.565, 23.076; P = 0.014) and prediabetes (ß = 29.025; 95% CI = 1.110, 56.940; P = 0.042), but not in females with normal glucose homeostasis. In addition, per unit increase of E-DII was significantly associated with lower eGFR (ß = -1.363; 95% CI = -2.335, -0.392; P = 0.006) in patients with diabetes. CONCLUSION: We identified a direct association between E-DII and arterial stiffness, decreasedeGFR in middle-aged and elderly women with diabetes or prediabetes. Future studies are needed to verify and clarify the role of E-DII as an intervention target for cardiorenal complications of chronic hyperglycemia.

Efficacy and safety of prenatal dexamethasone treatment in offspring at risk for congenital adrenal hyperplasia due to 21-hydroxylase deficiency: A systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy and safety of prenatal dexamethasone treatment in offspring at risk for congenital adrenal hyperplasia. METHODS: MEDLINE, EMBASE, the Cochrane Library, the clinicaltrials.gov website databases were systematically searched from inception through March 2019. WMD and SMD with 95%CIs were calculated using random or fixed effects models. RESULTS: There was a significant reduction in virilization in the DEX-treated group (WMD: -2.39, 95%CI: -3.31,-1.47). No significant differences were found in newborn physical outcomes for birth weight (WMD: 0.09, 95%CI: -0.09, 0.27) and birth length (WMD = 0.27, 95%CI: -0.68, 1.21). Concerning cognitive functions, no significant differences in the domains of psychometric intelligence (SMD: 0.05, 95%CI: -0.74, 0.83), verbal memory (SMD: -0.17, 95%CI: -0.58, 0.23), visual memory (SMD: 0.10, 95%CI: -0.14, 0.34), learning (SMD: -0.02, 95%CI: -0.27, 0.22) and verbal processing (SMD: -0.38, 95%CI: -0.93, 0.17). Regarding behavioural problems, no significant differences in the domains of internalizing problems (SMD: 0.16, 95%CI: -0.49, 0.81), externalizing problems (SMD: 0.07, 95%CI: -0.30, 0.43) and total problems (SMD: 0.14, 95%CI: -0.23, 0.51). With respect to temperament, no significant differences in the domains of emotionality (SMD: 0.13, 95%CI: -0.79, 1.05), activity (SMD: 0.04, 95%CI: -0.32, 0.39), shyness (SMD: 0.25, 95%CI: -0.70, 1.20) and sociability (SMD: -0.23, 95%CI: -0.90, 0.44). CONCLUSIONS: Prenatal DEX treatment reduced virilization with no significant differences in newborn physical outcomes, cognitive functions, behavioural problems and temperament. The results need to be interpreted cautiously due to the existence of limitations.

Approach to Cushing's syndrome in pregnancy: two cases of Cushing's syndrome in pregnancy and a review of the literature.

Cushing's syndrome (CS) rarely occurs during pregnancy. The primary aim of this article is to propose a therapeutic approach to CS in pregnancy. Here, we present two cases of CS in pregnancy and a literature review. This article proposes the early diagnostic points, especially the clinical approach to this medical condition, mainly for pregnant women without a previous diagnosis of CS. More importantly, we present therapeutic strategies for CS during pregnancy, especially glucocorticoid replacement for perioperative, postoperative, and perinatal periods in pregnant women with CS in order to minimize complications for both mother and fetus. At the same time, we also assess the anxiety status of patients. This article summarizes the approach to CS in pregnancy, not only with a physiological assessment but with a psychological assessment as well.

Is waist circumference a negative predictor of calcaneal bone mineral density in adult Chinese men with normal weight?

BACKGROUND: Our study aimed to evaluate the association between waist circumference (WC) and calcaneal bone mineral density (BMD) in adult Chinese men with normal weight. METHODS: This was a cross-sectional study. A total of 4,663 male participants aged 40 years or older residing in Ningde and Wuyishan, two cities locating in Fujian province of China, were randomly recruited between 2011 and 2012. Each participant should complete a standard questionnaire, undergo anthropometric and calcaneus quantitative ultrasound (QUS) measurements and have blood sample taken. Anthropometric, biochemical and calcaneal QUS parameters of 1,583 male participants with BMI ranging from 18.5 to 22.9 were included in the analysis. WC was divided into quartiles (Q1-Q4: <71, 71-75, 75-78, >78 cm). The relationship between WC (quartiles) and BMD was analyzed by multiple linear regression models. RESULTS: Mean age of the whole population was 54.6±9.8 years. Anthropometric and biochemical parameters were almost normal. Multiple linear regression analysis showed that BMD was negatively associated with increasing WC quartiles except for Q2 after adjusting for age and BMI, and this relationship remained negative except for Q2 when further adjustment was made for other covariates. Multiple logistic regression model also showed that the risks of osteopenia and osteoporosis increased across WC quartiles. CONCLUSIONS: The present study indicated that WC was a negative predictor of calcaneal BMD in adult Chinese men with normal weight. It suggests that, even for the normal-weight Asian males, monitoring accrual of abdominal adipose is still helpful for the purpose of preventing bone loss.

Early life exposure to famine and reproductive aging among Chinese women.

OBJECTIVE: To assess the effect of early life exposure to famine, as endured during 1959 to 1961 in China, on reproductive aging in adult women. METHODS: Between 2011 and 2012, 2,868 women born around the Chinese famine period (1956-1964) were enrolled in this study from three communities in China. Age at natural menopause was obtained retrospectively from a structured questionnaire. The associations of early life famine exposure with reproductive aging during adulthood were estimated, with adjustment of socioeconomic status, lifestyle factors, and body mass index. RESULTS: Women exposed to prenatal famine had a higher risk of early menopause (ie, natural menopause <45 years, odds ratio: 1.59, 95% confidence interval [CI]: 1.07, 2.36), and a nonsignificant trend of higher risk of premature ovarian failure (ie, natural menopause <40 y, odds ratio: 1.94, 95% CI: 0.93, 4.00), compared to unexposed women. Exposure to famine during childhood was not significantly associated with reproductive aging. In a secondary analysis focusing on the fetal exposure, prenatal famine exposure was associated with a higher risk of premature ovarian failure (odds ratio: 2.07, 95% CI: 1.08, 3.87), and a nonsignificant trend of higher risk of early menopause (odds ratio: 1.37, 95% CI: 0.98, 1.91), compared to those unexposed to prenatal famine. CONCLUSIONS: Our study showed that fetal exposure to famine was associated with an increased risk of early menopause. Such findings provided evidence in favor of the thrifty phenotype theory in reproductive aging and helped better understand the etiology of early menopause.

Association Between Bone Mineral Density and Pancreatic ß-Cell Function in Elderly Men and Postmenopausal Women.

PURPOSE: To explore the association between bone mineral density (BMD) and ß-cell function. METHODS: A cross-sectional study was performed in Fujian, China, from 2011 to 2012. The study included 572 elderly men older than age 60 years and 1558 postmenopausal women aged 45 to 86 years, excluding those with diabetes and insulin resistance. Fasting glucose and insulin concentrations were measured. Pancreatic ß-cell function was estimated by using the homeostasis model assessment (HOMA-ß). Calcaneus BMD was measured by using quantitative ultrasonography. Multiple regression analyses were applied to explore the association. RESULTS: Participants with decreased BMD had lower fasting glucose (P < 0.001 in postmenopausal women; P = 0.007 in elderly men) and greater HOMA-ß (P = 0.001 in postmenopausal women; P = 0.008 in elderly men) than those with normal BMD, whereas no statistical differences in insulin were seen among categories of BMD. After adjustment for all confounders, HOMA-ß was still significantly negatively related to BMD in both groups (all P < 0.001), and remarkable positive relationships were found between BMD and fasting glucose. Furthermore, binary logistic regression presented fully adjusted odds ratios for diabetes in those with osteoporosis vs those with normal BMD: 0.60 [95% confidence interval (CI), 0.38 to 0.94] and 0.66 (95% CI, 0.49 to 0.91) in the original selected population of elderly men (n = 1070) and postmenopausal women (n = 2825), respectively. CONCLUSIONS: BMD was independently inversely associated with HOMA-ß and positively associated with fasting glucose in both elderly men and postmenopausal women, suggesting that bone mass may be a predictor of glucose metabolism. Further research is needed to verify the associations and determine the exact mechanism underlying them.