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Tong Chen,1,* Xuan Wang,1,* Xin Wang,1 Haishan Chen,1 Hua Xiao,1 Hongjuan Tang,1 Ling Feng,1 Zhicong Xiang,1 Hequn Zou,1,2 Xiaofei Shao1 1Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, People’s Republic of China; 2Department of Nephrology, Pinghu Hospital, Health Science Center, Shenzhen University, Shenzhen 518116, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaofei ShaoDepartment of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, People’s Republic of ChinaEmail 413151187@qq.comHequn Zou No. 1, Fuxin Road, Pinghu Street, Longgang District, Shenzhen 518116, People’s Republic of ChinaEmail Hequnzou@hotmail.comBackground: To determine the optimal cut-off values and evaluate the associations of product of triacylglycerol and glucose (TyG), lipid accumulation product (LAPI), visceral adiposity index (VAI) with chronic kidney diseases (CKD) stratified by sex.Methods: From January to April 2018, our team had conducted a large-scale cross-sectional survey that contained 2720 individuals on the southern coast of China. Logistic regression analysis and receiver operating characteristic (ROC) analyses were used to evaluate the optimal cut-off and value of TyG, LAPI, VAI for predicting CKD.Results: A multivariate logistic regression analysis found that the TyG had the better value of prediction for the presence of CKD for the highest quartile vs the lowest quartile in both males (OR: 3.65; 95% CI, 2.04– 6.52; p< 0.001) and females (OR: 3.50; 95% CI, 2.20– 5.56; p< 0.001), followed by LAPI and VAI, when further adjusted for cofounder factors, LAPI and VAI both lost their independence, and only TyG remains its significant association with CKD in both males (OR: 2.81; 95% CI, 1.25– 6.30; p< 0.001) and females (OR: 3.22; 95% CI, 1.56– 6.61; p< 0.001). ROC curve showed that TyG had the highest AUC for predicting CKD in males (AUC: 0.618). TyG (AUC: 0.670) and LAPI (AUC: 0.670) both had the highest AUC in females. United predicted models which contain TyG were conducted for predicting CKD in males (AUC: 758) and females (AUC: 0.773) and results indicated that multivariate analysis of TyG and other traditional factors can impressively improve the accuracy of predictive probability for CKD.Conclusion: TyG is a priority to the other two novel indices and may become valuable makers and have strong predictive power for predicting CKD, especially in females.Keywords: product of triacylglycerol and glucose, lipid accumulation product, visceral adiposity index, chronic kidney diseases

Ling Feng,* Haishan Chen,* Jianhui Chen, Chongxiang Xiong, Xiaofei Shao, Xin Wang, Jing Ning, Zhicong Xiang, Xuan Wang, Tong Chen, Hua Xiao, Hongjuan Tang, Xiaolin Li, Guobao Hong, Hequn Zou Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, People’s Republic of China*These authors contributed equally to this work.Correspondence: Hequn Zou; Xiaofei ShaoDepartment of Nephrology, The Third Affiliated Hospital, Southern Medical University, 183, Zhongshan West Avenue, Tianhe District, Guangzhou 510630, People’s Republic of ChinaEmail Hequnzou@hotmail.com; 413151187@qq.comObjective: To explore whether the red blood cell count multiplied by hematocrit index (RBCHct) in blood routine parameters can indicate the risk of impaired fasting blood glucose (IFG), and whether it is related to insulin resistance and inflammation.Methods: In this cross-sectional study, previous history of diabetes was excluded, and people with normal and impaired IFG were included. We use Spearman analysis to evaluate the correlation between RBCHct index and fasting plasma glucose, insulin resistance homeostasis model assessment (HOMA-IR), and hypersensitive C-reactive protein (hs-CRP). Binary logistic regression analysis was used to evaluate the RBCHct index for assessing the potential risk of IFG, and the receiver operating characteristic (ROC) curve was used to evaluate the RBCHct index for diagnosing insulin resistance and chronic low-grade inflammatory efficacy among those with IFG.Results: Correlation analysis showed that the RBCHct index and fasting plasma glucose (r=0.088, P=0.003); HOMA-IR (r=0.199, P< 0.001); and hs-CRP (r=0.097, P=0.001) were positively correlated. After adjusting for confounding factors, the risk of IFG in the third and fourth quartiles of the RBCHct index increased to 1.889 and 3.048 times. The area under the ROC curve of the RBCHct index for diagnosis of insulin resistance state (HOMA-IR) was 0.695 (p< 0.001), and the area under the ROC curve of the RBCHct index for the diagnosis of chronic low-inflammatory state (hs-CRP) was 0.641 (P=0.010).Conclusion: The RBCHct index may be a potential indicator for assessing the risk of prediabetes and is closely related to whether the body is in a state of insulin resistance and inflammation under IFG.Keywords: diabetes mellitus, erythrocyte, RBCHct index, insulin resistance, inflammation

Jing Ning, Zhicong Xiang, Chongxiang Xiong, Qin Zhou, Xin Wang, Hequn Zou Department of Nephropathy, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, People’s Republic of ChinaCorrespondence: Hequn ZouDepartment of Nephropathy, The Third Affiliated Hospital of Southern Medical University, 183 Zhongshan West Avenue, Tianhe District, Guangzhou 510630, People’s Republic of ChinaTel +86 20 6278 4391Email hequnzou@hotmail.comPurpose: Diabetic kidney disease (DKD), which is related to inflammation and immune response, is the primary vascular complication of diabetes mellitus and also the leading etiology of end-stage renal disease. Urinary extracellular vesicles (UEVs) are an attractive source for biomarker detection as they involve molecular constituents derived from their parental sections of the nephron. In this study, we aimed to search for a potential biomarker in UEVs for the early diagnosis and prediction of DKD, especially before the emergence of microalbuminuria.Patients and Methods: UEVs were isolated from the urine of healthy subjects, pre-diabetic, and diabetic patients with varying degrees of kidney damage by ultracentrifugation, and the extracted UEVs were used to measure alpha1-antitrypsin (α 1-AT) by Western blot. To explore the function of α 1-AT in the inflammatory process leading to DKD, we silenced the expression of α 1-AT in renal tubular epithelial cells using cell transfection techniques to assess the differential expression of the inflammatory factors such as MCP-1 and TNF-α using qRT-PCR.Results: There was no expression of α 1-AT in the UEVs of either healthy or pre-diabetic subjects. Its expression was significantly increased in the UEVs of diabetic patients with normoalbuminuria (prior to microalbuminuria), which was more sensitive and more stable than other renal indexes to predict DKD. Additionally, the expression of α 1-AT in UEVs was gradually upregulated with the aggravation of DKD and the decline of renal function. In vitro, the mRNA expression of MCP-1 and TNF-α was significantly decreased when the generation of α 1-AT in tubular epithelial cells was inhibited under high glucose stimulation.Conclusion: Our results suggest that α 1-AT derived from UEVs, especially in diabetic patients with normoalbuminuria, might serve as a potential noninvasive biomarker for diagnosis of DKD early in the development of the disease and may predict the future decline of renal function.Keywords: diabetic kidney disease, urinary extracellular vesicles, biomarker, alpha1-antitrypsin, inflammation, tubular epithelial cell

Xin Wang,1,* Jin Deng,2,* Chongxiang Xiong,1 Haishan Chen,1 Qin Zhou,1 Yue Xia,1 Xiaofei Shao,1 Hequn Zou1 1Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Nephrology, The First Affiliated Hospital of University of South China, Hengyang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hequn Zou Tel +86 020-62784391Email zhq1962@smu.edu.cnPurpose: Hyperuricemia is an independent risk factor for renal damage and can promote the progression of chronic kidney disease (CKD). In the present study, we employ a rat model to investigate the effects of rosiglitazone (RGTZ), a peroxisome proliferator-activated receptor-gamma agonist, on the development of hyperuricemic nephropathy (HN), and we elucidate the mechanisms involved.Methods: An HN rat model was established by oral administration of a mixture of adenine and potassium oxonate daily for 3 weeks. Twenty-four rats were divided into 4 groups: sham treatment, sham treatment plus RGTZ, HN, and HN treated with RGTZ.Results: Administration of RGTZ effectively preserved renal function, decreased urine microalbumin, and inhibited interstitial fibrosis and macrophage infiltration in a rat HN model. RGTZ treatment also inhibited TGF-β and NF-κB pathway activation, decreased expression of fibronectin, collagen I, α-SMA, vimentin, MCP-1, RANTES, TNF-α, and IL-1β, and increased E-cadherin expression in the kidneys of HN rats. Furthermore, RGTZ treatment preserved expression of OAT1 and OAT3 in the kidney of HN rats.Conclusion: RGTZ attenuates the progression of HN through inhibiting TGF-β signaling, suppressing epithelial-to-mesenchymal transition, reducing inflammation, and lowering serum uric acid levels by preserving expression of urate transporters.Keywords: hyperuricemic nephropathy, peroxisome proliferator-activated receptor-gamma, rosiglitazone, renal fibrosis, epithelial-to-mesenchymal transition, inflammation &nbsp

Xin Wang,* Haishan Chen,* Xiaofei Shao, Chongxiang Xiong, Guobao Hong, Jianhui Chen, Xiaolin Li, Xu You, Peichun Gao, Yunying Chen, Ziliang Zou, Jing Ning, Hua Xiao, Hequn Zou, Lixin Wei Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hequn ZouDepartment of Nephrology, The Third Affiliated Hospital, Southern Medical University, 183, Zhongshan West Avenue, Tianhe District, Guangzhou 510630, People’s Republic of ChinaEmail Hequnzou@hotmail.comLixin WeiDepartment of Nephrology, Fujian Medical University Union Hospital, No. 29 Xinquan Road, Fuzhou, Fujian 350001, People’s Republic of ChinaEmail lixinwei66@126.comObjective: To investigate which plasma lipid parameters are useful for detecting chronic kidney disease (CKD) in a Chinese population without known CKD or renal impairment.Methods: This was a prospective study. In southern Chinese cities from 2012 to 2013, a total of 1037 subjects aged ≥ 18 years old received a survey. Logistic regression and multiple linear regression analyses were performed. The lipid parameters studied included total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (nHDL-C), TG/HDL-C ratio, TC/HDL-C ratio and nHDL-C/HDL-C ratio.Results: After adjusting for confounding factors, the fourth percentile of logTG/HDL-C was observed to be an independent risk factor for CKD (OR = 2.453, P < 0.001), and the highest quantile of the logTG/HDL-C ratio was associated with a higher prevalence of CKD (P < 0.05). This risk was reduced when the model was adjusted with Insulin resistance (IR) (OR = 2.034, P < 0.05). In the group of women, glucose metabolism disorders, high uric acid, and obesity, this risk was increased. Multiple regression models showed that log TG and nonHDL-C/HDL-C were negatively correlated with eGFR (P < 0.05), while log TG and TC were positively correlated with logACR (P < 0.05). The area under the curve (ROC) of lgTG/HDL was 0.623 (p < 0.001).Conclusion: The serum logTG/HDL-C ratio is the only suitable predictor of CKD, and IR may be the mechanism. This risk needs to be controlled in a specific population. Log TG and nonHDL-C/HDL-C were negatively correlated with eGFR, while log TG and TC were positively correlated with logACR.Keywords: lipid, chronic kidney disease, CKD, urinary albumin to creatinine ratio, ACR, estimated glomerular filtration rate, eGFR