Xianglei Kong

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.

Effects of Urate-Lowering Therapy in Hyperuricemia on Slowing the Progression of Renal Function: A Meta-Analysis

Uric acid (UA) is generally regarded as an independent risk factor for poor prognosis of patients with kidney disease. However, urate-lowering therapy (ULT) in asymptomatic hyperuricemia is conservative. Whether the beneficial effect on renal function can be achieved by lowering UA remains uncertain. A compound search for randomized controlled trials was conducted in databases consisting of MEDLINE, EMBASE, the Cochrane Library, the Chinese Biomedical Literature Database, and Chinese Science and Technology periodical databases. Two investigators independently screened these studies, assessed the included trials, and extracted data. Eleven articles with a total number of 753 participants met the criteria and were included in our meta-analysis. The results showed that ULT was associated with a decrease in serum creatinine and an increase in eGFR. Our study further confirms that ULT may have beneficial effects on slowing the progression of renal function.

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.

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.

Serum anti-PLA2R antibody as a diagnostic biomarker of idiopathic membranous nephropathy: The optimal cut-off value for Chinese patients

BACKGROUND The M-type phospholipase A2 receptor (PLA2R) is a specific target autoantigen identified in idiopathic membranous nephropathy (IMN). The autoantibody against PLA2R (anti-PLA2R) may be used to diagnose IMN. However, the appropriate diagnosis cut-off value for Chinese patients with IMN has not been established. METHODS In total, 119 patients who underwent renal biopsy (57 patients with IMN and 62 patients with non-IMN glomerulonephritis) and 22 healthy individuals were recruited for our observation study from Qianfoshan Hospital between September 2011 and March 2016. The serum concentration of anti-PLA2R was measured using a quantitative enzyme-linked immunosorbent assay (ELISA). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and receiver operating characteristic (ROC) curve of anti-PLA2R in diagnosing IMN were analysed based on the ELISA detection. RESULTS The sensitivity, specificity, PPV, and NPV of anti-PLA2R in the diagnosis of IMN in the Chinese patients were 82.5, 75, 69.1, and 86.3% for the 2RU/ml cut-off value; 78.9, 91.7, 86.5, and 86.5% for the 2.6RU/ml cut-off value; 59.6, 95.2, 89.5, and 77.7% for the 14RU/ml cut-off value; 50.9, 96.4, 90.6, and 74.3% for the 20RU/ml cut-off value; and 47.4, 97.6, 93.1, and 73.2% for the 40RU/ml cut-off value, respectively. The area under the ROC curve was 0.879. CONCLUSIONS The cut-off value of 2.6RU/ml is recommended for the use of anti-PLA2R for the diagnosis of IMN in Chinese patients based on the ELISA.

Increasing Body Mass Index Predicts Rapid Decline in Renal Function: A 5 Year Retrospective Study

While obesity is a recognized risk factor for chronic kidney disease, it remains unclear whether change in body mass index (ΔBMI ) is independently associated with decline in renal function (evaluated by the change in estimated glomerular filtration rate, ΔeGFR) over time. Accordingly, to help clarify this we conducted a retrospective study to measure the association of ΔBMI with decline in renal function in Chinese adult population. A total of 4007 adults (aged 45.3±13.7 years, 68.6% male) without chronic kidney disease at baseline were enrolled between 2008 and 2013. Logistic regression models were applied to explore the relationships between baseline BMI and ΔBMI, and rapid decline in renal function (defined as the lowest quartile of ΔeGFR ). During 5 years of follow-up, the ΔBMI and ΔeGFR were 0.47±1.6 (kg/m2) and -3.0±8.8 (ml/min/1.73 m2), respectively. After adjusted for potential confounders, ΔBMI (per 1 kg/m2 increase) was independently associated with the rapid decline in renal function [with a fully adjusted OR of 1.12 (95% CI, 1.05 to 1.20). By contrast, the baseline BMI was not associated with rapid decline in renal function [OR=1.05 (95% CI, 0.98 to 1.13)]. The results were robust among 2948 hypertension-free and diabetes-free participants, the adjusted ORs of ΔBMI and baseline BMI were 1.14 (95% CI, 1.05 to 1.23) and 1.0 (95% CI, 0.96 to 1.04) for rapid decline in renal function, respectively. The study revealed that increasing ΔBMI predicts rapid decline in renal function.