Key Laboratory of Nephrology

Guangzhou, China

Key Laboratory of Nephrology

Guangzhou, China
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Wu J.,Sun Yat Sen University | Wu J.,Key Laboratory of Nephrology | Liu X.,Sun Yat Sen University | Liu X.,Key Laboratory of Nephrology | And 13 more authors.
Toxicology | Year: 2014

Bardoxolone methyl (BARD) is an antioxidant modulator that acts through induction of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. This study aimed to investigate the role of BARD in protecting kidneys from aristolochic acid (AA)-induced acute kidney injury (AKI). Male C57BL/6 mice received intraperitoneal (i.p.) injections of aristolochic acid I (AAI) (5. mg/kg/day) for 5 days to produce acute AA nephropathy (AAN) model. BARD (10. mg/kg/day, i.p.) was applied for 7 consecutive days, starting 2 days prior to AAI administration. The mice in the AA group showed AKI as evidenced by worsening kidney function evaluated by blood urea nitrogen (BUN) and serum creatinine (SCr) levels, and severe tubulointerstitial injury marked by massive tubule necrosis in kidney tissues. BARD significantly reduced BUN and SCr levels which were elevated by AAI. Additionally, AAI-induced histopathological renal damage was ameliorated by BARD. Furthermore, the expression of Nrf2 was reduced, and its repressor Kelch-like ECH-associated protein 1 (Keap1) was increased significantly, whereas heme oxygenase-1 (HO-1) was upregulated and NAD(P)H quinone oxidoreductase-1 (NQO1) was barely increased in the cytoplasm of tubules in kidneys after treatment with AAI. BARD significantly upregulated renal Nrf2, NQO1 and HO-1 expression and downregulated Keap1 expression compared with those in the AA group. Moreover, it was found that Nrf2 was expressed both in the cytoplasm and nuclear of glomeruli and tubules, whereas NQO1 and HO-1 were localized in the cytoplasm of tubules only. In conclusion, AA-induced acute renal injury was associated with impaired Nrf2 activation and expression of its downstream target genes in renal tissues. BARD prevented renal damage induced by AAI, and this renoprotective effect may be exerted by activating the Nrf2 signaling pathway and increasing expression of the downstream target genes. © 2014 Elsevier Ireland Ltd.

Qin J.,Sun Yat Sen University | Qin J.,Key Laboratory of Nephrology | Yang Q.,Sun Yat Sen University | Yang Q.,Key Laboratory of Nephrology | And 11 more authors.
Clinical Nephrology | Year: 2013

Objective: To analyze the clinicopathological features and therapeutic response of nephrotic IgA nephropathy (IgAN) patients with minimal-change disease (MCD). Methods: 62 nephrotic IgAN patients were enrolled between January 2002 and December 2008, and divided into two groups including Group A: patients with MCD-like pathological features, and Group B with non-MCD pathologic pattern. The clinicopathological features, treatments, and responses were then analyzed. Results: 13 (21.0%) patients exhibited MCD-like pathological changes. Patients in Group A presented more prominent proteinuria, hypoalbuminemia but higher hemoglobin and no incidence of renal insufficiency compared to Group B (p< 0.05). 62 patients were treated with corticosteroid, and the complete remission rate in Group A is higher than that in Group B (84.6% vs. 34.7%, p = 0.008), but the relapse rate is much higher in Group A (53.8% vs. 20.4%, p = 0.03). 21 patients were treated combining with immunosuppressant due to unresponsiveness or relapse, which yielded a high re-remission rate in Group A (100%). After follow-up of 53.9 ± 26.9 months, the 5-year renal survival rate is higher in Group A (100%) than that in Group B (84.7%), but no significant difference was observed (p = 0.24). Conclusions: MCD-like pathological changes exist in quite a few nephrotic IgAN patients. These IgAN patients responded well to corticosteroid monotherapy but had a higher rate of relapse. Though manifesting with severe nephrotic symptoms, they tended to have a favorable clinical outcome probably due to the minimal pathological changes. Nevertheless, larger sample size and longer follow-up periods are needed for better understanding of the disease © 2013 Dustri-Verlag Dr. K. Feistle ISSN 0301-0430.

Yu X.-Q.,Sun Yat Sen University | Yu X.-Q.,Key Laboratory of Nephrology | Li M.,Sun Yat Sen University | Li M.,Key Laboratory of Nephrology | And 32 more authors.
Nature Genetics | Year: 2012

We performed a two-stage genome-wide association study of IgA nephropathy (IgAN) in Han Chinese, with 1,434 affected individuals (cases) and 4,270 controls in the discovery phase and follow-up of the top 61 SNPs in an additional 2,703 cases and 3,464 controls. We identified associations at 17p13 (rs3803800, P = 9.40 × 10 -11, OR = 1.21; rs4227, P = 4.31 × 10 -10, OR = 1.23) and 8p23 (rs2738048, P = 3.18 × 10 -14, OR = 0.79) that implicated the genes encoding tumor necrosis factor (TNFSF13) and α-defensin (DEFA) as susceptibility genes. In addition, we found multiple associations in the major histocompatibility complex (MHC) region (rs660895, P = 4.13 × 10-20, OR = 1.34; rs1794275, P = 3.43 × 10 -13, OR = 1.30; rs2523946, P = 1.74 × 10 -11, OR = 1.21) and confirmed a previously reported association at 22q12 (rs12537, P = 1.17 × 10 -11, OR = 0.78). We also found that rs660895 was associated with clinical subtypes of IgAN (P = 0.003), proteinuria (P = 0.025) and IgA levels (P = 0.047). Our findings show that IgAN is associated with variants near genes involved in innate immunity and inflammation. © 2012 Nature America, Inc. All rights reserved.

Wang W.,Sun Yat Sen University | Wang W.,Key Laboratory of Nephrology | Wang W.,Sichuan Provincial Peoples Hospital | Sun Y.,Sun Yat Sen University | And 5 more authors.
Journal of Human Genetics | Year: 2013

IgA nephropathy is one of the most common glomerulonephritis throughout the world, which is thought to be the multifactorial complex diseases, with genetic and environmental factors contributing to this disease. The failure of replicating the single genes in previous association studies may be of that the gene-gene interaction might have more influence on the susceptibility of the complex diseases. In all, 31 single-nucleotide polymorphisms (SNPs) in 24 candidate genes (which were involved in the pathways implicated in the development or progression of IgAN) were selected to conduct a large case-control association study in 527 IgAN patients and 543 healthy controls. Traditional linear logistic regression analyses were used to detect single-locus associations in dominant, recessive and additive genetic models. Bonferroni correction was used to adjust the P-values for multiple testing. The gene-gene interaction effects of multiple SNPs were detected by multifactor-dimensionality reduction (MDR) method. After Bonferroni correction, no significant single-locus associations was observed between IgAN patients and controls (Pc>0.05). The MDR analysis showed a potential interaction of C1GALT1-330G/T (rs1008898) and IL5RA31+197A/G (rs340833) on the susceptibility of IgAN (P<0.001). Gene-gene interaction may have some influence on the susceptibility to IgA nephropathy. This finding proposed a potential gene-gene interactive model for future studies. © 2013 The Japan Society of Human Genetics. All rights reserved.

Xia X.,Key Laboratory of Nephrology | Luo Q.,Key Laboratory of Nephrology | Li B.,Key Laboratory of Nephrology | Lin Z.,Key Laboratory of Nephrology | And 2 more authors.
Metabolism: Clinical and Experimental | Year: 2016

Background Studies have shown inconsistent results about the association between serum uric acid levels and mortality in patients with chronic kidney disease (CKD). Methods A systematic literature search in MEDLINE, Web of Science and bibliographies of retrieved articles was performed to identify studies investigating the association between serum uric acid and mortality in patients with CKD. Pooled hazard ratios (HR) and corresponding 95% confidence intervals (CIs) were calculated using random-effects models. Results A total of 24 studies with 25,453 patients with CKD were included. By meta-analysis, patients with the highest serum uric acid level were associated with a significantly higher risk for mortality (14 studies; HR, 1.52; 95% CI, 1.33-1.73) compared with patients with the lowest serum uric acid level. For dose-response analysis, a linear relationship (8 studies; Pfor non-linearity = 0.14) between serum uric acid levels and risk of mortality was found. Overall, an increase of 1 mg/dl in serum uric acid level was associated with an 8% increased risk of mortality (21 studies; HR, 1.08; 95% CI, 1.04-1.11). Conclusions Elevated serum uric acid levels are significantly associated with risk of mortality in patients with CKD. Further randomized controlled trials should attempt to determine whether it improves survival to target serum uric acid in patients with CKD. © 2016 Elsevier Inc.

Ruan Y.,Sun Yat Sen University | Ruan Y.,Key Laboratory of Nephrology | Chen W.,Sun Yat Sen University | Li Z.,Sun Yat Sen University | And 8 more authors.
Archives of Medical Science | Year: 2015

Introduction: The aim of the study was to analyze the role of immunosuppressive therapy and identify independent predictors of therapeutic effectiveness and outcome in IgA nephropathy (IgAN) patients with proteinuria. Material and methods: Two hundred and six IgAN patients with proteinuria (1-3.5 g/day) were included between January 2005 and December 2011, and divided into two groups: group A (n = 125), receiving renin-angiotensin system blockade therapy alone; and group B (n = 81), combining the above with immunosuppressive therapy. The clinicopathological features, response and safety were recorded. In univariate and multivariate models, the factors that influence response to therapy and renal outcome, especially pathologic features, were analyzed. Results: The patients in group B presented more severe proteinuria and hypoalbuminemia with more severe hematuria (p < 0.05) but no significant difference in the pathologic changes compared with group A. After follow-up, the response rate was higher in group B than in group A (p < 0.001). No pathologic feature or clinical parameter apart from steroid therapy (HR = 0.500, 95% CI: 0.304-0.821, p = 0.006) was strongly associated with therapeutic effectiveness. Endocapillary hypercellularity (HR = 2.849, 95% CI: 1.244-6.524, p = 0.013) seemed to be an independent predictor of poor response to steroid therapy. The renal survival rate was not significantly different between the two groups (p = 0.074). Estimated glomerular filtration rate at baseline may be an independent predictor of renal outcome. Conclusions: Steroid therapy could be an effective therapy in proteinuric IgAN patients, and endocapillary hypercellularity seemed to predict poor response to steroid. Renal function at baseline rather than treatment strategies and pathologic features may be independently associated with renal survival. Copyright © 2015 Termedia & Banach.

Zhou Q.,Sun Yat Sen University | Zhou Q.,Key Laboratory of Nephrology | Yang M.,Sun Yat Sen University | Lan H.,Chinese University of Hong Kong | And 2 more authors.
American Journal of Pathology | Year: 2013

Although epithelial-mesenchymal transition (EMT) and the subsequent development of peritoneal fibrosis are key processes leading to the peritoneal failure related to peritoneal dialysis (PD), mechanisms underlying these processes remain largely unclear. In the present study, we found that miR-30a was significantly down-regulated in peritoneal tissues, with progressive fibrosis in patients with continuous ambulatory peritoneal dialysis and in a rat model of PD. In vitro, transforming growth factor (TGF)-β1-induced EMT, identified by de novo expression of α-smooth muscle actin and a loss of E-cadherin in both human and rat peritoneal mesothelial cells, was associated with down-regulation of miR-30a but up-regulation of Snai1, suggesting a close link between miR-30a and Snai1 in TGF-β1-induced peritoneal fibrosis. It was further demonstrated in vitro that miR-30a was able to bind the 3′ untranslated region of Snai1 and overexpression of miR-30a blocked TGF-β1-induced up-regulation of Snai1 and, therefore, inhibited EMT and collagen expression. To determine the functional role of miR-30a, we overexpressed miR-30a in the peritoneal tissue in a rat model of PD and found that overexpression of miR-30a blocked both Snai1 and EMT and inhibited peritoneal fibrosis, with improvement of peritoneal dysfunction. In conclusion, miR-30a negatively regulates Snai1-mediated EMT during peritoneal fibrosis in vitro and in vivo. Blockade of peritoneal fibrosis by overexpressing miR-30a in a rat model of PD reveals a therapeutic potential of miR-30a for peritoneal fibrosis associated with PD. © 2013 American Society for Investigative Pathology.

Gu W.,Sun Yat Sen University | Gu W.,Key Laboratory of Nephrology | Yang X.,Sun Yat Sen University | Yang X.,Key Laboratory of Nephrology | And 3 more authors.
Clinical Nephrology | Year: 2013

Background: Metabolic syndrome (MS) is prevalent and widely proved as a predictor of cardiovascular disease (CVD) and Type 2 diabetes mellitus (T2DM) in general population. However, there was no large sample study concerning MS in patients on continuous ambulatory peritoneal dialysis (CAPD). We aimed to study the prevalence, risk factors of MS, and the relationship between CVD and MS in CAPD patients in South China. Methods: This singlecenter cross-sectional study was conducted in patients on CAPD. Demographic, clinical, and anthropometric data were collected and compared between the patients with and without MS. Logistic Regression analysis was used to identify the independent risk factors of MS. Results: A total of 511 CAPD patients were enrolled. Compared to patients without MS, patients with MS tended to be diabetic, female, and older. Fasting waist circumference, waist-to-hip ratio, visceral fat area, as well as white blood cell, platelet, globulin, and high sensitivity C reactive protein in peripheral blood were significantly higher in MS than in non-MS group. But diastolic blood pressure was significantly lower in patients with MS than in patients without MS. Logistic regression showed old age (OR: 1.50, p < 0.001), higher level of WBC (OR: 1.41, p < 0.001), and glucose load of dialysate (GLD) (OR: 1.50, p = 0.002) were independent associated factors of MS and MS was an independent associated factor of CVD (OR: 2.37, p < 0.001). Conclusions: MS was prevalent in CAPD patients in our center and an independent associated factor of CVD. Old age, higher levels of WBC, and GLD were associated with MS independently. © 2013 Dustri-Verlag Dr. K. Feistle.

Yu X.,Sun Yat Sen University | Yu X.,Key Laboratory of Nephrology | Yang X.,Sun Yat Sen University | Yang X.,Key Laboratory of Nephrology | And 2 more authors.
Peritoneal Dialysis International | Year: 2014

Managing a rapidly growing peritoneal dialysis program with more than 1000 patients involves multiple challenges, labor constraints, logistics, and excessive geographic distance. This paper describes how Sun Yat-sen University, Guangzhou, China, manages those issues, while simultaneously improving quality of the care and, subsequently, clinical outcomes. © 2014 International Society for Peritoneal Dialysis.

Yu X.,Sun Yat Sen University | Yu X.,Key Laboratory of Nephrology | Yang X.,Sun Yat Sen University | Yang X.,Key Laboratory of Nephrology
American Journal of Kidney Diseases | Year: 2014

Due to limited medical and economic resources, particularly in the countryside and remote areas, the proportion of individuals with end-stage kidney disease who are treated with dialysis in China is only about 20%. For the rest, renal replacement therapy currently is not available. Peritoneal dialysis (PD) has been developed and used for more than 30 years in China to treat patients with end-stage kidney disease. Several national PD centers of first-rate scale and quality have sprung up, but the development of PD varies widely among geographic regions across China. The Chinese government has dedicated itself to continually increasing the coverage and level of medical service for patients with end-stage kidney disease. Under the guidance of the government and because of promotion by kidney care professionals, presently there are more than 40,000 prevalent PD patients in China, representing approximately 20% of the total dialysis population. Recently, a National Dialysis Unit Training Program for countywide hospitals has been initiated. Through the efforts of programs like this, we believe that awareness of PD and advances in the underlying technology will benefit more patients with end-stage kidney disease in China. © 2014 by the National Kidney Foundation, Inc.

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