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Comparative analysis of membranous and other nephropathy subtypes and establishment of a diagnostic model

Hanyu Zhu, Bo Fu, Yong Wang, Jing Gao, Qiuxia Han, Wenjia Geng, Xiaoli Yang, Guangyan Cai, Xiangmei Chen, Dong Zhang

《医学前沿（英文）》 2019年 第13卷 第5期   页码 618-625 doi: 10.1007/s11684-018-0620-5

摘要： This study aimed to compare clinical features between membranous nephropathy (MN) and nonmembranous nephropathy (non-MN), to explore the clinically differential diagnosis of these two types, and to establish a diagnostic model of MN. After renal biopsy was obtained, 798 patients were divided into two groups based on their examination results: primary MN group ( = 248) and non-MN group ( = 550). Their data were statistically analyzed. Logistic regression analysis indicated that anti-PLA2R antibodies, IgG, and Cr were independently correlated with MN, and these three parameters were then used to establish the MN diagnostic model. A receiver operating characteristic (ROC) curve confirmed that our diagnostic model could distinguish between patients with and without MN, and their corresponding sensitivity, specificity, and AUC were 79.9%, 89.4%, and 0.917, respectively. The cutoff value for this combination in MN diagnosis was 0.34. The established diagnostic model that combined multiple factors shows a potential for broad clinical applications in differentiating primary MN from other kidney diseases and provides reliable evidence supporting the feasibility of noninvasive diagnosis of kidney diseases.

关键词： multiparameter analysis     diagnosis     model     membranous nephropathy    

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DQB1*060101 may contribute to susceptibility to immunoglobulin A nephropathy in southern Han Chinese

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《医学前沿（英文）》 2016年 第10卷 第4期   页码 507-516 doi: 10.1007/s11684-016-0475-6

摘要：

Immunoglobulin A nephropathy (IgAN) is a common form of chronic glomerulonephritis with unknown pathogenesis. Accumulating evidences have shown the ethnic-specific association between certain human leukocyte antigen (HLA) alleles and IgAN susceptibility. This study was designed to explore the relationship between HLA-DQB1 alleles and disease susceptibility and clinical manifestations of patients with IgAN in southern Han Chinese. A PCR sequence-based typing technique was used to detect HLA-DQB1 alleles in 217 IgAN patients and 229 healthy subjects. Clinical data were collected from each patient at the time of renal biopsy. Twenty HLA-DQB1 alleles were detected in IgAN patients and healthy subjects. High frequency of HLA-DQB1*060101 and low frequency of HLA-DQB1*030101 were observed in IgAN patients compared with healthy controls. Further stratification analysis revealed that the frequency of DQB1*060101 was significantly higher in patients with urine protein≥1.0 g/24 h than in patients with urine protein<1.0 g/24 h. In combination with our previous DRB1 results, we also analyzed the association of DRB1-DQB1 haplotypes with IgAN. We found that the frequency of haplotype DRB1*090102-DQB1*060101 was significantly higher [odds ratio (OR) = 4.409, Pc = 0.016], whereas that of HLA-DRB1*070101-DQB1*020101 was significantly lower (OR= 0.194, Pc = 0.016) compared with healthy controls. Our study indicated that HLA-DQB1*060101 alleles may be a potential predictor of high-risk IgAN susceptibility in Chinese Han population.

关键词： DQB1     human leukocyte antigen (HLA)     IgA nephropathy     haplotype     association study    

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Adenovirus-mediated antisense ERK2 gene therapy ameliorates chronic allograft nephropathy in a rat model

Zhao DING, Zhishui CHEN, Xilin CHEN, Ming CAI, Hui GUO, Nianqiao GONG

《医学前沿（英文）》 2009年 第3卷 第2期   页码 204-210 doi: 10.1007/s11684-009-0039-0

摘要： To investigate the effect and underlying mechanism of adenovirus-mediated antisense ERK2 (Adanti-ERK2) gene therapy upon chronic allograft nephropathy (CAN) of rats, male Lewis (LEW, RT11) rats received male Fisher (F344, RT11v1) renal allografts. The recipients were divided into three groups: (1) empty control group; (2) vector control group; (3) gene therapy group. All recipients were sacrificed for the grafts and serum analysis at the 24th week after transplantation. Morphometric analysis was used to determine the fibrosis of grafts. Immunohistochemistry was used to detect the expression of E-Cadherin, Vimentin, TβR I and the infiltration of CD4 T lymphocyte, CD8 T lymphocyte and ED-1 monocytes. Enzyme linked immunosorbent assay (ELISA) was used to detect TGF-β1 in serum. The grafts in the control group and vector control group showed CAN. There was less E-Cadherin in renal tubular epithelial cells in the empty control group but more Vimentin and TβR I. In the gene therapy group, the fibrosis was ameliorated and fewer T lymphocytes and ED-1 monocytes infiltrated in the interstitium. There was no significant difference in the expression of E-Cadherin between the gene therapy group and normal rats. Compared with the empty control group, the expression of TGF-β1 in the gene therapy group was down-regulated. Adanti-ERK2 gene therapy protects the renal allograft and attenuates graft fibrosis, which may be correlated with a decreased renal tubular epithelial mesenchymal transition, a decreased infiltration of CD4 T lymphocyte, CD8 T lymphocytes and ED-1 monocytes in renal interstitium, and the down-regulated TGF-β1 expression.

关键词： anti-ERK2     renal transplantation     epithelial mesenchymal transition     chronic allograft nephropathy    

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Clinical characteristics and outcomes of biopsy-proven diabetic nephropathy

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《医学前沿（英文）》 2017年 第11卷 第3期   页码 386-392 doi: 10.1007/s11684-017-0574-z

摘要：

Kidney damage is common in patients with diabetes mellitus (DM). However, whether the type of kidney damage can be reliably diagnosed using clinical data alone remains unclear. Predictive factors for diabetic nephropathy (DN) outcomes are also poorly understood. In this study, the clinical manifestations of 111 cases of biopsy-proven DN were described, and the clinical and pathological parameters of patients with different DN outcomes were compared. Results showed that long DM duration (>10 years in 32.4% of patients), severe proteinuria (62.2%), and renal dysfunction (estimated glomerular filtration rate [eGFR]<60 mL/(min·1.73 m2)) (52.3%) did not accurately indicate whether the condition of these patients progressed to DN. Hematuria (48.6%) failed to specify either DN or nondiabetic renal disease. Diabetic retinopathy (78.4%) was a crucial complication in patients with DN. Kaplan–Meier analysis revealed that the renal survival of 53 patients who were diagnosed with DN and were followed up was not significantly associated with glomerular classification (P>0.05). Cox’s regression analysis demonstrated that renal survival time was significantly influenced by sex (b= 1.394, P= 0.038), hematuria (b= 0.036, P= 0.029), and eGFR (b= −0.039, P= 0.002) but was not significantly affected by age, 24 h urinary protein excretion, or glomerular classification (P>0.05). In conclusion, the clinical characteristics of DN vary, and renal biopsy is necessary to determine renal damage patterns. Sex, hematuria, and the eGFR may affect DN outcomes, whereas the glomerular classification may not.

关键词： diabetic nephropathy     clinical characteristics     renal biopsy     outcomes    

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Non-genetic mechanisms of diabetic nephropathy

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《医学前沿（英文）》 2017年 第11卷 第3期   页码 319-332 doi: 10.1007/s11684-017-0569-9

摘要：

Diabetic nephropathy (DN) is one of the most common microvascular complications in diabetes mellitus patients and is characterized by thickened glomerular basement membrane, increased extracellular matrix formation, and podocyte loss. These phenomena lead to proteinuria and altered glomerular filtration rate, that is, the rate initially increases but progressively decreases. DN has become the leading cause of end-stage renal disease. Its prevalence shows a rapid growth trend and causes heavy social and economic burden in many countries. However, this disease is multifactorial, and its mechanism is poorly understood due to the complex pathogenesis of DN. In this review, we highlight the new molecular insights about the pathogenesis of DN from the aspects of immune inflammation response, epithelial–mesenchymal transition, apoptosis and mitochondrial damage, epigenetics, and podocyte–endothelial communication. This work offers groundwork for understanding the initiation and progression of DN, as well as provides ideas for developing new prevention and treatment measures.

关键词： diabetic nephropathy     immune inflammatory response     epithelial–mesenchymal transition     apoptosis     mitochondrial damage     epigenetics     podocyte–endothelial communication    

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Preventive effect of Shenkang injection against high glucose-induced senescence of renal tubular cells

Biqiong Fu, Jie Yang, Jia Chen, Lirong Lin, Kehong Chen, Weiwei Zhang, Jianguo Zhang, Yani He

《医学前沿（英文）》 2019年 第13卷 第2期   页码 267-276 doi: 10.1007/s11684-017-0586-8

摘要： Shenkang injection (SKI) is a classic prescription composed of , rhubarb, , and . This treatment was approved by the State Food and Drug Administration of China in 1999 for treatment of chronic kidney diseases based on good efficacy and safety. This study aimed to investigate the protective effect of SKI against high glucose (HG)-induced renal tubular cell senescence and its underlying mechanism. Primary renal proximal tubule epithelial cells were cultured in (1) control medium (control group), medium containing 5 mmol/L glucose; (2) mannitol medium (mannitol group), medium containing 5 mmol/L glucose, and 25 mmol/L mannitol; (3) HG medium (HG group) containing 30 mmol/L glucose; (4) SKI treatment at high (200 mg/L), medium (100 mg/L), or low (50 mg/L) concentration in HG medium (HG+ SKI group); or (5) 200 mg/L SKI treatment in control medium (control+ SKI group) for 72 h. HG-induced senescent cells showed the emergence of senescence associated heterochromatin foci, up-regulation of P16 and cyclin D1, increased senescence-associated β-galactosidase activity, and elevated expression of membrane decoy receptor 2. SKI treatment potently prevented these changes in a dose-independent manner. SKI treatment prevented HG-induced up-regulation of pro-senescence molecule mammalian target of rapamycin and p66Shc and down-regulation of anti-senescence molecules klotho, sirt1, and peroxisome proliferator-activated receptor- in renal tubular epithelial cells. SKI may be a novel strategy for protecting against HG-induced renal tubular cell senescence in treatment of diabetic nephropathy.

关键词： Shenkang injection     senescence     renal tubular epithelial cells     diabetic nephropathy    

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标题 作者 时间 类型 操作

Comparative analysis of membranous and other nephropathy subtypes and establishment of a diagnostic model

Hanyu Zhu, Bo Fu, Yong Wang, Jing Gao, Qiuxia Han, Wenjia Geng, Xiaoli Yang, Guangyan Cai, Xiangmei Chen, Dong Zhang

期刊论文

DQB1*060101 may contribute to susceptibility to immunoglobulin A nephropathy in southern Han Chinese

null

期刊论文

Adenovirus-mediated antisense ERK2 gene therapy ameliorates chronic allograft nephropathy in a rat model

Zhao DING, Zhishui CHEN, Xilin CHEN, Ming CAI, Hui GUO, Nianqiao GONG

期刊论文

Clinical characteristics and outcomes of biopsy-proven diabetic nephropathy

null

期刊论文

Non-genetic mechanisms of diabetic nephropathy

null

期刊论文

Preventive effect of Shenkang injection against high glucose-induced senescence of renal tubular cells

Biqiong Fu, Jie Yang, Jia Chen, Lirong Lin, Kehong Chen, Weiwei Zhang, Jianguo Zhang, Yani He

期刊论文