Meiyu Cui

Inhibition of the Expression of TGF-β1 and CTGF in Human Mesangial Cells by Exendin-4, a Glucagon-like Peptide-1 Receptor Agonist

Background: Despite the presence of glucagon-like peptide-1 receptor (GLP-1R) in kidney tissues, its direct effect on diabetic nephropathy remains unclear. The transforming growth factor-β1 (TGF-β1) and the connective tissue growth factor (CTGF) both induce extracellular matrix accumulation and persistent fibrosis in the glomerular mesangium of patients with diabetic nephropathy. Objective: Herein, we demonstrate that a GLP-1R agonist, exendin-4, exerts renoprotective effects through its influence on TGF-β1 and CTGF in human mesangial cells (HMCs), cultured in a high glucose medium. Method: HMCs, cultured in a high glucose medium, were used for the current study. The direct effect of exendin-4 on TGF-β1 and CTGF expression was confirmed in HMCs. MDL-12330A (a specific adenylate cyclase inhibitor) and PKI14-22 (a protein kinase A inhibitor) were used to examine the role of the cAMP signaling pathway in exendin’s anti-fibrosis action. Results: The findings showed that exendin-4 inhibited the proliferation of HMCs, and upregulated the expression of TGF-β1 and CTGF, induced by high glucose. The effect of exendin-4 is largely dependent on the activation of adenylate cyclase. Conclusion: This study provides new evidence that GLP-1 acts as an antifibrotic agent in HMCs.

Association between microalbuminuria and subclinical atherosclerosis evaluated by carotid artery intima-media in elderly patients with normal renal function

BackgroundModerate to severe renal insufficiency and albuminuria have been shown to be independent risk factors for atherosclerosis. However, little is known about the direct association between subclinical atherosclerosis evaluated by carotid artery intima-media thickness (IMT) and microalbuminuria in elderly patients with normal renal function.MethodsSubjects were 272 elderly patients (age  ≥ 60 years) with normoalbuminuria (n = 238) and microalbuminuria (n = 34). Carotid IMT was measured by means of high-resolution B-mode ultrasonography. Estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m2 was defined as normal renal function. Those who had macroalbuminuria and atherosclerotic vascular disease were not included.ResultsCompared to subjects with normoalbuminuria, subjects with microalbuminuria had higher mean carotid IMT (1.02 ± 0.38 vs. 0.85 ± 0.28 mm; P < 0.01) and maximal IMT (1.86 ± 0.86 vs. 1.60 ± 0.73 mm; P = 0.06). By a multiple linear regression, microalbuminuria positively correlated with mean carotid IMT after adjusting for traditional cardiovascular disease risk factors including age, sex, hypertension, diabetes, smoking, total cholesterol, pulse pressure, waist circumference, serum uric acid. As a categorical outcome, the prevalence of the highest mean cariotid IMT quartile (increased IMT ≥ 1.05 mm) was compared with the lower three quartiles. After adjusted for potential confounders, microalbuminuria was associated with increased carotid IMT, with an odds ratio of 2.95 [95 % confidence interval, 1.22 – 7.10]. eGFR was not significantly associated with mean carotid IMT in our analysis.ConclusionsA slight elevation of albuminuria is a significant determinant of carotid IMT independent of traditional cardiovascular risk factors in our patients. Our study further confirms the importance of intensive examinations for the early detection of atherosclerosis when microalbuminuria is found in elderly patients, although with normal renal function.

Long-Term Outcomes of Total Parathyroidectomy With or Without Autoimplantation for Hyperparathyroidism in Chronic Kidney Disease: A Meta-Analysis

The aim of the present study was to compare total parathyroidectomy without autotransplantation (TPTX) versus total parathyroidectomy with autotransplantation (TPTX + AT) for renal hyperparathyroidism (RHPT) with respect to long‐term outcomes. A literature search was undertaken using Medline and EMBASE from inception to December 2013. Data were analyzed using Review Manager version 5.0. A total of seven cohort studies comprising 931 patients were identified. Compared with TPTX + AT, patients in the TPTX group have lower “recurrence” (odds ratio (OR) 0.08, confidence interval (CI) 0.03 to 0.21; P < 0.00001), lower “recurrence or persistence”(OR 0.11, 95% CI 0.05 to 0.25; P < 0.00001), lower “requiring reoperation because of recurrence or persistence” (OR 0.17, CI 0.06 to 0.54; P = 0.002), and higher “hypoparathyroidism” (OR 2.97, CI 1.09 to 8.08; P = 0.03). None of the patients in these seven studies were recorded as having severe hypocalcemia or adynamic bone disease. Compared with TPTX + AT, TPTX is associated with lower “requiring reoperation because of recurrence or persistence” and without severe hypocalcemia or adynamic bone disease.

Total parathyroidectomy with autotransplantation versus subtotal parathyroidectomy for renal hyperparathyroidism: a systematic review and meta-analysis.

Total parathyroidectomy with autotransplantation (TPTX + AT) and subtotal parathyroidectomy (SPTX) have been recommended to patients with renal hyperparathyroidism (RHPT).But which one is the best surgical method remains controversial. The aim of the present study was to compare the two surgical procedures with respect to long‐term outcomes.

Increasing prevalence of membranous nephropathy in patients with primary glomerular diseases: a cross‐sectional study in china

Primary glomerular disease (PGD) remains the most common renal disease in China. A limited number of single centre studies show that the frequency of membranous nephropathy (MN) has increased; however, IgA nephropathy (IgAN) is still the most common PGD. To the best of our knowledge, there has been no multi‐centre study in China that has explored the changes in PGD spectrum. To further investigate the changes in renal histopathological spectrum, we performed the cross‐sectional study.

Association of clustering of major cardiovascular risk factors with chronic kidney disease in the adult population.

BACKGROUND The prevalence of chronic kidney disease (CKD) is high in China, as is the clustering of major cardiovascular (CVD) risk factors. We aimed to explore the association of clustering of CVD risk factors with CKD in the adult population. METHODS A total of 3,287 adults who visited the Health Checkup Clinic were consecutively enrolled in the study. We investigated the clustering of four CVD risk factors (defined as two or more of the following: hypertension, diabetes, dyslipidemia, and overweight) and their association with CKD. CKD was defined as decreased estimated glomerular filtration rate (eGFR < 60 mL/min/1.73 m2) or the presence of albuminuria (urinary albumin-to-creatinine >= 30 mg/g). RESULTS Among the total participants in this study, only 27.4% were free of any pre-defined CVD risk factors, and 46% of them had clustering of CVD risk factors. The prevalence of decreased eGFR, albuminuria, and the overall prevalence of CKD in the group of clustering of CVD risk factors was higher than in the group of none or in the group of single CVD risk factors, which were 4.9% vs. 1.0% and 1.8% (p < 0.001), 9.0% vs. 4.1% and 4.0% (p < 0.001), 12.8% vs. 5.1% and 5.8% (p < 0.001), respectively. After being adjusted for potential confounders, the clustering of CVD risk factors was positively associated with either albuminuria or CKD,with odds ratio of 1.93 (95% confidence interval [CI], 1.39 - 2.68) and 1.72 (95%CI, 1.29 - 2.28). CONCLUSIONS Clustering of CVD risk factors was positively associated with CKD, which further confirms the importance of modifying lifestyle to reduce the burden of CKD. *contributed equally to this work.

Arterial stiffness evaluated by carotid-femoral pulse wave velocity increases the risk of chronic kidney disease in a Chinese population-based cohort.

Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease. Although pulse wave velocity (PWV), which reflects arterial stiffness, was increased in subjects with CKD, little is known regarding whether arterial stiffness can increase the risk of CKD. To help clarify this we conducted a prospective cohort study to measure the association of arterial stiffness with CKD.

Association between metabolic syndrome and chronic kidney disease in a Chinese urban population

BACKGROUND Few studies have examined the relationships between the prevalence of chronic kidney disease (CKD) and the metabolic risk factors in a developing country such as China, where genetic and environmental backgrounds differ from those in Western countries. METHODS The subjects of this cross-sectional study were the individuals from 18 to 92y. The metabolic syndrome (MetS) was defined based on the criteria of Adult Treatment Panel Third Report (ATP III), but using body mass index (BMI) instead of waist circumference. CKD was defined as decreased estimated glomerular filtration rate (eGFR<60mL/min/1.73m2) or presence of proteinuria (urine protein≥1+) assessed using dipstick method. RESULTS A total of 26,601 subjects (average age of 48.7y) were analyzed. Among them, the prevalence of the MetS and CKD was 36.4% and 3.0%, respectively. After adjustment for age, gender, cigarette smoking and alcohol drinking, the prevalence of CKD was significantly greater in subjects with than without MetS (OR 1.99, 95% CI 1.57-2.53, p<0.001). Multivariate-adjusted odd ratios for CKD in subjects with 3, 4 or 5 MetS components were 1.82 (95% CI 1.31-2.52, p<0.001), 2.92 (95% CI 2.09-4.09, p<0.001), and 3.07 (95% CI 1.67-5.67, p<0.001), respectively. After further adjustments were made for the other components of MetS, only high fasting glucose (OR 1.52, 95% CI 1.12-2.05) were significant risk factors for reduced renal function(eGFR<60mL/min/1.73m2). High blood pressure (OR 1.81, 95% CI 1,42-2.29), high triglycerides (OR 1.34, 95% CI 1.11-1.67) and high fasting glucose (OR 2.07, 95% CI 1.62-2.66) were significant risk factors for proteinuria. CONCLUSIONS MetS was highly prevalent in the middle-aged and elderly Chinese population in the city of Jinan. There was a graded relationship between the number of MetS components and risk of CKD. High fasting blood glucose levels were the main risk factor of reduced renal function. High blood pressure, high fasting blood glucose levels and high triglycerides were main risk factors for proteinuria.

Association of hemoglobin with arterial stiffness evaluated by carotid-femoral pulse wave velocity among Chinese adults

Objective Increased hemoglobin (Hb) levels are known to be associated with increased cardiovascular events and mortalities. Therefore, we assumed that high Hb levels were associated with arterial stiffness. Pulse wave velocity (PWV) is a simple and noninvasive method for measuring arterial stiffness to assess cardiovascular disease in general populations. Accordingly, we conducted a cross-sectional study to explore the association of Hb with PWV. Methods A total of 6642 adults aged 54.5 ± 11.2 years undergoing physical examinations were enrolled, 71.7% of whom were males. Arterial stiffness was evaluated by carotid-femoral PWV (cfPWV). Multivariable regression analyses were performed to determine the relationship between Hb and increased cfPWV. Results In this study, the mean Hb (per 10 g/L increase) was 144.7 ± 13.9 g/L, and the mean cfPWV was 15.1 ± 3.1 m/s. cfPWV was significantly higher in high hemoglobin groups ≥15.4 g/L (Quartile 4) than in the lowest hemoglobin group (Quartile 1 ≤ 13.6 g/L; P < 0.001). Multiple linear regression analysis revealed that Hb positively correlated with cfPWV (β = 0.16, P < 0.01). Univariate Logistic regression analysis revealed that Hb was associated with increased cfPWV, with an odd ratio (OR) of 1.46 (95% confidence interval [CI], 1.39–1.54). After adjusting for potential confounders, Hb and the highest Hb quartile group were also independently associated with increased cfPWV, with a fully adjusted OR of 1.11 (95% CI, 1.02–1.20) and 1.45 (95% CI, 1.01–2.08), respectively. Conclusion This study demonstrated that Hb levels significantly correlate with increased cfPWV.

The serum from dialysis patients with acute coronary syndrome up-regulates the expression of TLR2 and its downstream effectors in human renal glomerular endothelial cells

Abstract Background: This study was to investigate the expression of toll-like receptor 2 and its downstream effectors in endothelial cells in response to the serum from maintenance hemodialysis (MHD) patients with acute coronary syndrome (ACS). Methods: Human renal glomerular endothelial cells (HRGEC) were treated in vitro with serum from the healthy subjects (control group), the MHD patients with stable angina pectoris (SAP group), or the MHD patients with ACS (ACS group). The cells in ACS group were cultured in the presence or absence of TLR2 signaling blockers for 18 h. The mRNA level for TLR2, nuclear factor-κB (NF-κB), interleukin-6 (IL-6) and vascular cell adhesion molecule-1 (VCAM-1) were examined by real-time qPCR, the localization of TLR2 was detected by immunocytochemistry, and the secretion of IL-6 and VCAM-1 were measured by enzyme-linked immunosorbent assay. Results: The mRNA level of TLR2, NF-κB and IL-6 were statistically higher in the ACS group when compared with those in SAP group and healthy controls (p < 0.05), but not significantly different between SAP and healthy controls. The secretion of IL-6 in ACS group was increased when compared with SAP group and control subjects (p < 0.05). When the HRGEC were cultured with the anti-TLR2 antibodies, the expression of NF-κB, IL-6 and VCAM-1 mRNA as well as the secretion of IL-6 and VCAM-1 were significantly inhibited (p < 0.05). Conclusion: This study revealed that the TLR2 signaling may mediate pro-inflammatory response in the MHD patients occurring with ACS.