Kidney and Blood Pressure Research最新文献_第10页

Identification of Key Genes and Candidated Pathways in Human Autosomal Dominant Polycystic Kidney Disease by Bioinformatics Analysis 用生物信息学分析鉴定人类常染色体显性多囊肾病关键基因和候选通路

Kidney and Blood Pressure Research

Pub Date : 2019-07-22 DOI: 10.1159/000500458

Dongmei Liu, Yongbao Huo, Sixiu Chen, Dechao Xu, Bo Yang, C. Xue, Lili Fu, L. Bu, Shuwei Song, C. Mei

Background/Aims: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic form of kidney disease. High-throughput microarray analysis has been applied for elucidating key genes and pathways associated with ADPKD. Most genetic profiling data from ADPKD patients have been uploaded to public databases but not thoroughly analyzed. This study integrated 2 human microarray profile datasets to elucidate the potential pathways and protein-protein interactions (PPIs) involved in ADPKD via bioinformatics analysis in order to identify possible therapeutic targets. Methods: The kidney tissue microarray data of ADPKD patients and normal individuals were searched and obtained from NCBI Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified, and enriched pathways and central node genes were elucidated using related websites and software according to bioinformatics analysis protocols. Seven DEGs were validated between polycystic kidney disease and control kidney samples by quantitative real-time polymerase chain reaction. Results: Two original human microarray datasets, GSE7869 and GSE35831, were integrated and thoroughly analyzed. In total, 6,422 and 1,152 DEGs were extracted from GSE7869 and GSE35831, respectively, and of these, 561 DEGs were consistent between the databases (291 upregulated genes and 270 downregulated genes). From 421 nodes, 34 central node genes were obtained from a PPI network complex of DEGs. Two significant modules were selected from the PPI network complex by using Cytotype MCODE. Most of the identified genes are involved in protein binding, extracellular region or space, platelet degranulation, mitochondrion, and metabolic pathways. Conclusions: The DEGs and related enriched pathways in ADPKD identified through this integrated bioinformatics analysis provide insights into the molecular mechanisms of ADPKD and potential therapeutic strategies. Specifically, abnormal decorin expression in different stages of ADPKD may represent a new therapeutic target in ADPKD, and regulation of metabolism and mitochondrial function in ADPKD may become a focus of future research.

背景/目的:常染色体显性多囊肾病(ADPKD)是最常见的遗传性肾脏疾病。高通量微阵列分析已被用于阐明与ADPKD相关的关键基因和途径。大多数来自ADPKD患者的基因图谱数据已经上传到公共数据库，但没有进行彻底的分析。本研究整合了2个人类微阵列数据集，通过生物信息学分析阐明ADPKD的潜在途径和蛋白-蛋白相互作用(PPIs)，以确定可能的治疗靶点。方法:从NCBI Gene Expression Omnibus中检索ADPKD患者和正常人的肾组织芯片数据。根据生物信息学分析方案，利用相关网站和软件对差异表达基因(DEGs)进行鉴定，并对富集途径和中心节点基因进行了解析。通过实时定量聚合酶链反应验证了多囊肾与对照肾样品之间的7个deg。结果:对两个原始的人体微阵列数据集GSE7869和GSE35831进行了整合和深入分析。从GSE7869和GSE35831中分别提取了6,422和1,152个deg，其中561个deg在数据库中是一致的(291个上调基因和270个下调基因)。从421个节点中，从DEGs的PPI网络复合体中获得34个中心节点基因。利用Cytotype MCODE从PPI网络复合体中筛选出两个显著的模块。大多数已鉴定的基因涉及蛋白质结合、细胞外区域或空间、血小板脱粒、线粒体和代谢途径。结论:通过综合生物信息学分析，确定了ADPKD中的deg和相关富集通路，为ADPKD的分子机制和潜在的治疗策略提供了见解。具体来说，在ADPKD的不同阶段，decorin的异常表达可能代表着ADPKD新的治疗靶点，对ADPKD代谢和线粒体功能的调控可能成为未来研究的重点。

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引用次数: 14

Triglyceride Glucose Index Predicting Cardiovascular Mortality in Chinese Initiating Peritoneal Dialysis: A Cohort Study 甘油三酯葡萄糖指数预测开始腹膜透析的中国人心血管死亡率:一项队列研究

Kidney and Blood Pressure Research

Pub Date : 2019-07-17 DOI: 10.1159/000500979

Zechen Yan, Dahai Yu, Yamei Cai, J. Shang, R. Qin, Jing Xiao, Bin Zhao, Zhanzheng Zhao, D. Simmons

Background: Insulin resistance (IR) is increased among people with end-stage renal disease (ESRD). The Triglyceride glucose (TyG) index is a marker of IR and is also associated with the prognosis of cardiovascular disease among patients initiating peritoneal dialysis (PD). This study was aimed at examining the associations between TyG index and cardiovascular deaths in patients initiating PD. Methods and Results: Three thousand fifty-four patients initiating PD between 2007 and 2014 were included in a prospective cohort derived from Henan PD Registry, TyG index alongside other baseline characteristics were measured when ESRD patients initiated PD. Logistic regression adjusting for age, gender, and major cardiovascular risk factors estimated the association between TyG index and subsequent cardiovascular mortality within 2 years since the initiation of PD. Results: TyG index was positively associated with cardiovascular mortality: adjusted incidence rates ratio (95% CI) comparing the highest vs. lowest TyG index quartile was 2.32 (2.12–2.55) in all, 2.22 (2.01–2.46) in those with body mass index (BMI) <25 kg/m2, and 2.82 (2.24–3.54) in those with BMI ≥25 kg/m2, respectively. Linear dose-response relationships were revealed in all and by BMI. Conclusions: TyG index might be a prognostic factor in predicting cardiovascular mortality among patients initiating PD.

背景:终末期肾病(ESRD)患者胰岛素抵抗(IR)增加。甘油三酯葡萄糖(TyG)指数是IR的标志物，也与腹膜透析(PD)患者心血管疾病的预后相关。本研究旨在探讨初始PD患者TyG指数与心血管死亡之间的关系。方法和结果:2007年至2014年间，354名初始PD患者被纳入河南PD登记处的前瞻性队列，当ESRD患者初始PD时，测量TyG指数和其他基线特征。调整年龄、性别和主要心血管危险因素的Logistic回归估计了TyG指数与PD发病后2年内心血管死亡率之间的关系。结果:TyG指数与心血管疾病死亡率呈正相关:TyG指数最高与最低四分位数的校正发病率比(95% CI)为2.32(2.12-2.55)，体重指数(BMI) <25 kg/m2组为2.22 (2.01-2.46)，BMI≥25 kg/m2组为2.82(2.24-3.54)。所有受试者和BMI均显示线性剂量-反应关系。结论:TyG指数可能是预测PD患者心血管疾病死亡率的一个预后因素。

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引用次数: 15

The Cholinergic Anti-Inflammatory Pathway as a Conceptual Framework to Treat Inflammation-Mediated Renal Injury 胆碱能抗炎途径作为治疗炎症介导的肾损伤的概念框架

Kidney and Blood Pressure Research

Pub Date : 2019-07-15 DOI: 10.1159/000500920

J. Jarczyk, B. Yard, S. Hoeger

Background: The cholinergic anti-inflammatory pathway, positioned at the interface of the nervous and immune systems, is the efferent limb of the “inflammatory reflex” which mainly signals through the vagus nerve. As such, the brain can modulate peripheral inflammatory responses by the activation of vagal efferent fibers. Importantly, immune cells in the spleen express most cholinergic system components such as acetylcholine (ACh), choline acetyltransferase, acetylcholinesterase, and both muscarinic and nicotinic ACh receptors, making communication between both systems possible. In general, this communication down-regulates the inflammation, achieved through different mechanisms and depending on the cells involved. Summary: With the awareness that the cholinergic anti-inflammatory pathway serves to prevent or limit inflammation in peripheral organs, vagus nerve stimulation has become a promising strategy in the treatment of several inflammatory conditions. Both pharmacological and non-pharmacological methods have been used in many studies to limit organ injury as a consequence of inflammation. Key Messages: In this review, we will highlight our current knowledge of the cholinergic anti-inflammatory pathway, with emphasis on its potential clinical use in the treatment of inflammation-triggered kidney injury.

背景:胆碱能抗炎通路位于神经和免疫系统的交界面，是主要通过迷走神经发出信号的“炎症反射”的传出肢体。因此，大脑可以通过激活迷走神经传出纤维来调节外周炎症反应。重要的是，脾脏中的免疫细胞表达大多数胆碱能系统成分，如乙酰胆碱(ACh)，胆碱乙酰转移酶，乙酰胆碱酯酶，以及毒蕈碱和烟碱ACh受体，使这两个系统之间的通信成为可能。一般来说，这种交流通过不同的机制和所涉及的细胞来下调炎症。摘要:随着人们意识到胆碱能抗炎途径可以预防或限制周围器官的炎症，迷走神经刺激已成为治疗多种炎症的一种很有前途的策略。在许多研究中，药物和非药物方法都被用于限制炎症引起的器官损伤。在这篇综述中，我们将重点介绍我们目前对胆碱能抗炎途径的了解，并强调其在治疗炎症引发的肾损伤方面的潜在临床应用。

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引用次数: 25

miR-29a Regulates the Proliferation and Migration of Human Arterial Smooth Muscle Cells in Arteriosclerosis Obliterans of the Lower Extremities. miR-29a 调控下肢动脉硬化闭塞症中人体动脉平滑肌细胞的增殖和迁移

Kidney and Blood Pressure Research

Pub Date : 2019-01-01 Epub Date: 2019-10-15 DOI: 10.1159/000502649

Kun Wang, Jian Yu, Bin Wang, Hui Wang, Zuolei Shi, Guangxin Li

Background: The molecular mechanisms underlying the contribution of human arterial smooth muscle cells (HASMCs), one of the most important components of the arterial wall, to the pathogenesis of arteriosclerosis obliterans (ASO) remain elusive.

Methods: The expression levels of miR-29a in arterial walls were analyzed via real-time-polymerase chain reaction. An ASO cell model was established to investigate the expression of miR-29a on HASMCs. The interaction between miR-29a and platelet-derived growth factor receptor B (PDGFRB) was detected by luciferase reporter assay, and the alteration of the expression of PDGFRB was determined in platelet-derived growth factor‑BB (PDGF-BB)-stimulated HASMCs transfected with miR-NC, miR-29a mimics, and miR-29a inhibitors. Further, HASMCs cell proliferation was investigated by cell counting kit-8 and EdU assays, and cell migrations were evaluated by Transwell and wound closure assays.

Results: The expression of miR-29a was remarkably downregulated in the arterial walls of ASO patients compared with normal arterial walls. Furthermore, expression of miR-29a in HASMCs under PDGF-BB stimulation was lower than vehicle control. PDGFRB was identified as a target of miR-29a in HASMCs, and miR-29a inhibited the proliferation and migration in PDGF-BB-induced HASMCs, via regulating the expression of PDGFRB.

Conclusion: This study showed that miR-29a is downregulated in the arterial wall of ASO patients, as well as in the PDGF-BB-stimulated HASMCs. This alteration of miR-29a could upregulate target genes PDGFRB and inhibits the proliferation and migration of HASMCs. These findings discovered new mechanisms of ASO pathogenesis, and the miR-29a/PDGFRB axis could serve as potential therapy target of ASO.

背景：人类动脉平滑肌细胞（HASMCs）是动脉壁最重要的组成部分之一，其对动脉硬化闭塞症（ASO）发病机制的分子机制仍未确定：方法：通过实时聚合酶链反应分析了动脉壁中 miR-29a 的表达水平。建立了一个 ASO 细胞模型，以研究 miR-29a 在 HASMCs 上的表达。通过荧光素酶报告实验检测了 miR-29a 与血小板衍生生长因子受体 B（PDGFRB）之间的相互作用，并测定了在转染了 miR-NC、miR-29a 模拟物和 miR-29a 抑制剂的血小板衍生生长因子-BB（PDGF-BB）刺激的 HASMC 中 PDGFRB 表达的变化。此外，还通过细胞计数试剂盒-8和EdU检测法研究了HASMCs的细胞增殖情况，并通过Transwell和伤口闭合检测法评估了细胞迁移情况：结果：与正常动脉壁相比，ASO 患者动脉壁中 miR-29a 的表达明显下调。此外，在 PDGF-BB 刺激下，HASMCs 中 miR-29a 的表达低于药物对照组。通过调节 PDGFRB 的表达，miR-29a 抑制了 PDGF-BB 诱导的 HASMCs 的增殖和迁移：本研究表明，在 ASO 患者的动脉壁以及 PDGF-BB 刺激的 HASMCs 中，miR-29a 被下调。这种 miR-29a 的改变可上调靶基因 PDGFRB，抑制 HASMC 的增殖和迁移。这些发现发现了ASO发病的新机制，而miR-29a/PDGFRB轴可作为ASO的潜在治疗靶点。

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引用次数: 0

Vitamin K1 Inhibition of Renal Crystal Formation through Matrix Gla Protein in the Kidney. 维生素 K1 通过肾脏中的基质 Gla 蛋白抑制肾晶体形成

Kidney and Blood Pressure Research

Pub Date : 2019-01-01 Epub Date: 2019-10-22 DOI: 10.1159/000503300

Yang Li, Xiuli Lu, Baoyu Yang, Jing Mao, Shan Jiang, Daojun Yu, Jichuan Pan, Tiange Cai, Takahiro Yasui, Bing Gao

Background and objectives: Vitamin K (VK) plays a major role in modifying the binding of calcium in bones and blood vessels. Understanding the effect of VK on crystal formation in the kidney would contribute to advancing the treatment and prevention of kidney stones.

Methods: Rats were treated with vitamin K1 (VK1) for 8 weeks. VK1 levels were detected and crystal formation were observed. HK2 cells were exposed to calcium oxalate monohydrate crystals. Apoptosis and cell viability were detected. Crystal deposition was analyzed using atomic absorption assay. The adenovirus vectors expressing matrix Gla protein (MGP) and siMGP were constructed to elucidate the effect and mechanism of VK1 on crystal formation. MGP expression in vivo and in vitro was analyzed by Western blot. The mRNA levels of monocyte chemoattractant protein-1 (MCP-1) and collagen I was measured by semiquantitative RT-PCR.

Results: The concentrations of VK1 in whole blood and kidney tissues rose under treatment with VK1. Crystal formation was inhibited from the second to the 6th week, the frequency and quality of crystal formation decreased significantly, and the location of crystal formation was limited to a greater extent in the rats treated by VK1 compared to the control group. Warfarin treatment in the crystals-exposed HK2 cells significantly increased the number of crystals adhering to cells and the number of apoptotic cells and reduced cell viability. VK1 treatment reversed warfarin's above influence. VK1 inhibited the upregulations of MCP-1 and collagen I in kidney tissues under crystal load. VK1 treatment increased MGP expression in vivo and in vitro, and MGP is necessary for VK1 to play a role in crystal deposition in cells.

Conclusions: VK1 treatment can inhibit the formation of renal crystals in vivo. VK1 increases MGP expression and functions through MGP to reduce crystal deposition in cells and provide cell protection. Our findings suggest that VK1 treatment could be a potential strategy for the treatment and prevention of nephrolithiasis.

背景和目的：维生素 K（VK）在改变骨骼和血管中钙的结合方面发挥着重要作用。了解维生素 K 对肾脏中晶体形成的影响将有助于推进肾结石的治疗和预防：方法：用维生素 K1（VK1）治疗大鼠 8 周。方法：用维生素 K1（VK1）治疗大鼠 8 周，检测 VK1 水平并观察晶体形成。HK2 细胞暴露于一水草酸钙晶体。检测细胞凋亡和细胞活力。用原子吸收法分析晶体沉积。为了阐明 VK1 对晶体形成的影响和机制，构建了表达基质 Gla 蛋白（MGP）和 siMGP 的腺病毒载体。通过 Western 印迹分析了 MGP 在体内和体外的表达。半定量 RT-PCR 检测了单核细胞趋化蛋白-1（MCP-1）和胶原蛋白 I 的 mRNA 水平：结果：使用 VK1 治疗后，全血和肾组织中的 VK1 浓度上升。结果：与对照组相比，VK1治疗组大鼠全血和肾组织中的VK1浓度升高，晶体形成在第2周至第6周受到抑制，晶体形成的频率和质量明显降低，晶体形成的位置受到更大程度的限制。暴露于晶体的 HK2 细胞经华法林处理后，粘附在细胞上的晶体数量和凋亡细胞数量明显增加，细胞活力降低。VK1 治疗逆转了华法林的上述影响。VK1 可抑制晶体负荷下肾组织中 MCP-1 和胶原 I 的上调。VK1 处理可增加体内和体外 MGP 的表达，而 MGP 是 VK1 在细胞内晶体沉积过程中发挥作用的必要条件：结论：VK1治疗可抑制体内肾晶体的形成。结论：VK1 治疗可抑制体内肾晶体的形成。VK1 可增加 MGP 的表达，并通过 MGP 发挥减少晶体在细胞内沉积的作用，从而为细胞提供保护。我们的研究结果表明，VK1 治疗可能是治疗和预防肾炎的一种潜在策略。

{"title":"Vitamin K1 Inhibition of Renal Crystal Formation through Matrix Gla Protein in the Kidney.","authors":"Yang Li, Xiuli Lu, Baoyu Yang, Jing Mao, Shan Jiang, Daojun Yu, Jichuan Pan, Tiange Cai, Takahiro Yasui, Bing Gao","doi":"10.1159/000503300","DOIUrl":"10.1159/000503300","url":null,"abstract":"Background and objectives: Vitamin K (VK) plays a major role in modifying the binding of calcium in bones and blood vessels. Understanding the effect of VK on crystal formation in the kidney would contribute to advancing the treatment and prevention of kidney stones.Methods: Rats were treated with vitamin K1 (VK1) for 8 weeks. VK1 levels were detected and crystal formation were observed. HK2 cells were exposed to calcium oxalate monohydrate crystals. Apoptosis and cell viability were detected. Crystal deposition was analyzed using atomic absorption assay. The adenovirus vectors expressing matrix Gla protein (MGP) and siMGP were constructed to elucidate the effect and mechanism of VK1 on crystal formation. MGP expression in vivo and in vitro was analyzed by Western blot. The mRNA levels of monocyte chemoattractant protein-1 (MCP-1) and collagen I was measured by semiquantitative RT-PCR.Results: The concentrations of VK1 in whole blood and kidney tissues rose under treatment with VK1. Crystal formation was inhibited from the second to the 6th week, the frequency and quality of crystal formation decreased significantly, and the location of crystal formation was limited to a greater extent in the rats treated by VK1 compared to the control group. Warfarin treatment in the crystals-exposed HK2 cells significantly increased the number of crystals adhering to cells and the number of apoptotic cells and reduced cell viability. VK1 treatment reversed warfarin's above influence. VK1 inhibited the upregulations of MCP-1 and collagen I in kidney tissues under crystal load. VK1 treatment increased MGP expression in vivo and in vitro, and MGP is necessary for VK1 to play a role in crystal deposition in cells.Conclusions: VK1 treatment can inhibit the formation of renal crystals in vivo. VK1 increases MGP expression and functions through MGP to reduce crystal deposition in cells and provide cell protection. Our findings suggest that VK1 treatment could be a potential strategy for the treatment and prevention of nephrolithiasis.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000503300","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85798089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Urine Epidermal Growth Factor, Monocyte Chemoattractant Protein-1 or Their Ratio as Biomarkers for Interstitial Fibrosis and Tubular Atrophy in Primary Glomerulonephritis 尿表皮生长因子、单核细胞趋化蛋白-1或其比值作为原发性肾小球肾炎间质纤维化和小管萎缩的生物标志物

Kidney and Blood Pressure Research

Pub Date : 2016-12-01 DOI: 10.1159/000452595

S. Worawichawong, S. Worawichawong, P. Radinahamed, D. Muntham, N. Sathirapongsasuti, A. Nongnuch, M. Assanatham, C. Kitiyakara

Background/Aims: The degree of tubular atrophy and interstitial fibrosis (IFTA) is an important prognostic factor in glomerulonephritis. Imbalance between pro-inflammatory cytokines such as monocyte chemoattractant protein- 1 (MCP-1) and protective cytokines such as epidermal growth factor (EGF) likely determine IFTA severity. In separate studies, elevated MCP-1 and decreased EGF have been shown to be associated with IFTA severity. In this study, we aim to evaluate the predictive value of urinary EGF/MCP-1 ratio compared to each biomarker individually for moderate to severe IFTA in primary glomerulonephritis (GN). Methods: Urine samples were collected at biopsy from primary GN (IgA nephropathy, focal and segmental glomerulosclerosis, minimal change disease, membranous nephropathy). MCP-1 and EGF were analyzed by enzyme-linked immunosorbent assay. Results: EGF, MCP-1 and EGF/MCP-1 ratio from primary GN, all correlated with IFTA (n=58). By univariate analysis, glomerular filtration rate, EGF, and EGF/MCP-1 ratio were associated with IFTA. By multivariate analysis, only EGF/MCP-1 ratio was independently associated with IFTA. EGF/MCP-1 ratio had a sensitivity of 88% and specificity of 74 % for IFTA. EGF/MCP-1 had good discrimination for IFTA (AUC=0.85), but the improvement over EGF alone was not significant. Conclusion: EGF/MCP-1 ratio is independently associated IFTA severity in primary glomerulonephritis, but the ability of EGF/MCP-1 ratio to discriminate moderate to severe IFTA may not be much better than EGF alone.

背景/目的:小管萎缩和间质纤维化(IFTA)的程度是肾小球肾炎预后的重要因素。促炎细胞因子如单核细胞趋化蛋白-1 (MCP-1)和保护性细胞因子如表皮生长因子(EGF)之间的失衡可能决定IFTA的严重程度。在单独的研究中，MCP-1升高和EGF降低已被证明与IFTA严重程度相关。在这项研究中，我们的目的是评估尿EGF/MCP-1比值与每个生物标志物单独比较对原发性肾小球肾炎(GN)中重度IFTA的预测价值。方法:对原发性肾小球肾病(IgA肾病、局灶性和节段性肾小球硬化、微小病变、膜性肾病)患者进行活检采集尿样。酶联免疫吸附法检测MCP-1和EGF。结果:原发性GN的EGF、MCP-1和EGF/MCP-1比值均与IFTA相关(n=58)。单因素分析显示，肾小球滤过率、EGF和EGF/MCP-1比值与IFTA相关。通过多变量分析，只有EGF/MCP-1比值与IFTA独立相关。EGF/MCP-1比值对IFTA的敏感性为88%，特异性为74%。EGF/MCP-1对IFTA有很好的鉴别作用(AUC=0.85)，但与单独使用EGF相比改善不显著。结论:EGF/MCP-1比值与原发性肾小球肾炎IFTA严重程度独立相关，但EGF/MCP-1比值判别中重度IFTA的能力可能并不比单纯EGF好多少。

{"title":"Urine Epidermal Growth Factor, Monocyte Chemoattractant Protein-1 or Their Ratio as Biomarkers for Interstitial Fibrosis and Tubular Atrophy in Primary Glomerulonephritis","authors":"S. Worawichawong, S. Worawichawong, P. Radinahamed, D. Muntham, N. Sathirapongsasuti, A. Nongnuch, M. Assanatham, C. Kitiyakara","doi":"10.1159/000452595","DOIUrl":"https://doi.org/10.1159/000452595","url":null,"abstract":"Background/Aims: The degree of tubular atrophy and interstitial fibrosis (IFTA) is an important prognostic factor in glomerulonephritis. Imbalance between pro-inflammatory cytokines such as monocyte chemoattractant protein- 1 (MCP-1) and protective cytokines such as epidermal growth factor (EGF) likely determine IFTA severity. In separate studies, elevated MCP-1 and decreased EGF have been shown to be associated with IFTA severity. In this study, we aim to evaluate the predictive value of urinary EGF/MCP-1 ratio compared to each biomarker individually for moderate to severe IFTA in primary glomerulonephritis (GN). Methods: Urine samples were collected at biopsy from primary GN (IgA nephropathy, focal and segmental glomerulosclerosis, minimal change disease, membranous nephropathy). MCP-1 and EGF were analyzed by enzyme-linked immunosorbent assay. Results: EGF, MCP-1 and EGF/MCP-1 ratio from primary GN, all correlated with IFTA (n=58). By univariate analysis, glomerular filtration rate, EGF, and EGF/MCP-1 ratio were associated with IFTA. By multivariate analysis, only EGF/MCP-1 ratio was independently associated with IFTA. EGF/MCP-1 ratio had a sensitivity of 88% and specificity of 74 % for IFTA. EGF/MCP-1 had good discrimination for IFTA (AUC=0.85), but the improvement over EGF alone was not significant. Conclusion: EGF/MCP-1 ratio is independently associated IFTA severity in primary glomerulonephritis, but the ability of EGF/MCP-1 ratio to discriminate moderate to severe IFTA may not be much better than EGF alone.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87895712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 37

GSK-3beta Inhibitor Induces Expression of Nrf2/TrxR2 Signaling Pathway to Protect against Renal Ischemia/Reperfusion Injury in Diabetic Rats gsk -3 β抑制剂诱导Nrf2/TrxR2信号通路表达对糖尿病大鼠肾缺血再灌注损伤的保护作用

Kidney and Blood Pressure Research

Pub Date : 2016-12-01 DOI: 10.1159/000452598

Bo Hu, Yuhong Wu, Jie Liu, Xiaohua Shen, F. Tong, Guangtao Xu, R. Shen

Background/Aims: Diabetes mellitus (DM) can lead to renal damage and dysfunction, and exacerbate renal ischemia/reperfusion injury (RI/RI). The aim of this study was to investigate the protective effect of GSK-3β inhibitor TDZD-8 against RI/RI through Nrf2/TrxR2 signaling pathway in a rat DM model. Methods: A DM rat model was established by a single injection of streptozocin. Diabetic rats were pretreated with TDZD-8 (1 mg/kg bw) or TDZD-8+auranofin (10 nmol/L, 5ml/kg bw), and then subjected to 45-min ischemia and 24-h reperfusion. Rats were equally randomized into four groups: a Sham-operated group, a RI/RI group, a TDZD-8 group, and a TDZD-8+auranofin group. Serum levels of BUN and Scr were measured. SOD activity, MDA content, and Nrf2, TrxR2 and caspase-3 expressions in rat kidney tissues were determined. Results: Renal function was improved, oxidative stress and cell apoptosis were reduced, and the expression of Nrf2 and TrxR2 was up-regulated in TDZD-8 treated rats as compared with those in auranofin treated rats. Conclusion: TDZD-8 may exert its protective effect against RI/RI by regulating the Nrf2/TrxR2 signaling pathway in the kidney tissue in DM.

背景/目的:糖尿病(DM)可导致肾脏损害和功能障碍，加重肾缺血/再灌注损伤(RI/RI)。本研究旨在探讨GSK-3β抑制剂TDZD-8通过Nrf2/TrxR2信号通路对大鼠DM模型中RI/RI的保护作用。方法:单次注射链脲佐菌素建立DM大鼠模型。用TDZD-8 (1 mg/kg bw)或TDZD-8+金醛脂(10 nmol/L, 5ml/kg bw)预处理糖尿病大鼠，缺血45 min，再灌注24 h。将大鼠随机分为4组:假手术组、RI/RI组、TDZD-8组和TDZD-8+金糠蛋白组。测定血清BUN和Scr水平。测定大鼠肾组织中SOD活性、MDA含量及Nrf2、TrxR2、caspase-3的表达。结果:TDZD-8处理大鼠的肾功能得到改善，氧化应激和细胞凋亡减少，Nrf2和TrxR2的表达上调。结论:TDZD-8可能通过调节DM肾组织Nrf2/TrxR2信号通路发挥对RI/RI的保护作用。

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引用次数: 49

Clinical Course of Acute Kidney Injury in Elderly Individuals Above 80 Years 80岁以上老年人急性肾损伤的临床过程分析

Kidney and Blood Pressure Research

Pub Date : 2016-12-01 DOI: 10.1159/000452599

Isabell Funk, E. Seibert, S. Markau, M. Girndt

Background/Aims: Aging is associated with renal function decline and elderly patients are more vulnerable to acute kidney injury (AKI). The causes and prognosis of AKI according to new KDIGO definition that broadened the diagnosis and included more patients without dialysis dependence have not yet been compared between younger and elderly patients. Methods: In a retrospective analysis all patients with AKI admitted to a tertiary care Nephrology department (N=424) were included. Individuals were stratified by age (≤80 years, >80 years). Primary end-point was death or dialysis dependence at hospital discharge, secondary analyses addressed the need for dialysis, creatinine at discharge, mortality, and length of stay. Results: The distribution of AKI causes was different between the age groups. Circulatory AKI was the most important cause in both groups; however, septic or toxic AKI contributed relevantly in younger patients. Nevertheless, the number of patients reaching the primary end-point was similar (younger, 20.4%; older, 18.0%; OR 1.17, 95%CI, 0.703-1.948). While mortality tended to be higher in the older population, none of the secondary analyses indicated worse outcome for the older patients. Conclusion: The prognosis of AKI in elderly patients is not necessarily worse than in middle aged individuals. Nevertheless, older patients may be particularly vulnerable to circulatory or ischemic insults of the kidneys.

背景/目的:衰老与肾功能下降有关，老年患者更容易发生急性肾损伤(AKI)。新的KDIGO定义拓宽了AKI的诊断范围，纳入了更多无透析依赖的患者，但AKI的病因和预后尚未在年轻患者和老年患者之间进行比较。方法:回顾性分析所有三级肾内科住院的AKI患者(N=424)。个体按年龄分层(≤80岁，>80岁)。主要终点是出院时的死亡或透析依赖，次要分析涉及透析需求、出院时的肌酐、死亡率和住院时间。结果:各年龄组AKI病因分布不同。循环性AKI是两组中最重要的原因;然而，感染性或毒性AKI与年轻患者相关。然而，达到主要终点的患者数量相似(年轻，20.4%;老,18.0%;或1.17,95%ci, 0.703-1.948)。虽然老年人群的死亡率往往更高，但没有一项二次分析表明老年患者的预后更差。结论:老年AKI患者的预后不一定比中年患者差。然而，老年患者可能特别容易受到肾脏循环或缺血性损伤。

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引用次数: 18

Indoxyl Sulfate Impairs Endothelial Progenitor Cells and Might Contribute to Vascular Dysfunction in Patients with Chronic Kidney Disease 硫酸吲哚酚损害内皮祖细胞并可能导致慢性肾病患者血管功能障碍

Kidney and Blood Pressure Research

Pub Date : 2016-12-01 DOI: 10.1159/000452604

Cheng-jui Lin, Chih-jen Wu, Pei-Chen Wu, C. Pan, Tuan-Jen Wang, Fang-Ju Sun, Hsuan-Liang Liu, Han-hsiang Chen, H. Yeh

Background/Aims: Indoxyl sulfate (IS) is a protein-bound uremic toxin that accumulates in patients with chronic kidney disease (CKD). We explored the effect of IS on human early endothelial progenitor cells (EPCs) and analyzed the correlation between serum IS levels and parameters of vascular function, including endothelial function in a CKD-based cohort. Methods: A cross-sectional study with 128 stable CKD patients was conducted. Flow-mediated dilation (FMD), pulse wave velocity (PWV), ankle brachial index, serum IS and other biochemical parameters were measured and analyzed. In parallel, the activity of early EPCs was also evaluated after exposure to IS. Results: In human EPCs, a concentration-dependent inhibitory effect of IS on chemotactic motility and colony formation was observed. Additionally, serum IS levels were significantly correlated with CKD stages. The total IS (T-IS) and free IS (F-IS) were strongly associated with age, hypertension, cardiovascular disease, blood pressure, PWV, blood urea nitrogen, creatine and phosphate but negatively correlated with FMD, the estimated glomerular filtration rate (eGFR), hemoglobin, hematocrit, and calcium. A multivariate linear regression analysis also showed that FMD was significantly associated with IS after adjusting for other confounding factors. Conclusions: In humans, IS impairs early EPCs and was strongly correlated with vascular dysfunction. Thus, we speculate that this adverse effect of IS may partly result from the inhibition of early EPCs.

背景/目的:硫酸吲哚酚(IS)是一种蛋白质结合的尿毒症毒素，可在慢性肾脏疾病(CKD)患者中积累。我们探讨了IS对人类早期内皮祖细胞(EPCs)的影响，并分析了血清IS水平与血管功能参数(包括ckd队列中的内皮功能)之间的相关性。方法:对128例稳定期CKD患者进行横断面研究。测量并分析血流介导舒张(FMD)、脉搏波速度(PWV)、踝肱指数、血清IS等生化指标。同时，也评估了暴露于IS后早期EPCs的活性。结果:在人EPCs中，IS对趋化运动和集落形成有浓度依赖性的抑制作用。此外，血清IS水平与CKD分期显著相关。总IS (T-IS)和游离IS (F-IS)与年龄、高血压、心血管疾病、血压、PWV、血尿素氮、肌酸和磷酸盐密切相关，但与FMD、估计肾小球滤过率(eGFR)、血红蛋白、红细胞压积和钙呈负相关。多元线性回归分析也显示，在调整其他混杂因素后，FMD与IS显著相关。结论:在人类中，IS损害早期EPCs，并与血管功能障碍密切相关。因此，我们推测IS的这种不利影响可能部分源于早期EPCs的抑制。

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引用次数: 31

Association of MYH9 Polymorphisms with Hypertension in Patients with Chronic Kidney Disease in China 中国慢性肾病患者MYH9多态性与高血压的关系

Kidney and Blood Pressure Research

Pub Date : 2016-12-01 DOI: 10.1159/000452597

Liping Liu, Caili Wang, Yan Mi, Dan Liu, Li Li, Junying Fan, L. Nan, Niya Jia, Yu Du

Background/Aims: This study explored the correlation between hypertension and non-muscle myosin heavy chain 9 (MYH9) gene polymorphisms in Chinese chronic kidney disease (CKD) patients. Methods: This case-control study included 301 patients with CKD and 293 healthy controls. The E1 haplotype single nucleotide polymorphisms (SNPs) rs3752462 and rs4821480 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The association between MYH9 polymorphisms and high systolic blood pressure (SBP ≥ 140 mmHg) susceptibility in CKD patients was analysed. Results: The cases and controls had similar genotype and allele distributions at rs3752462 and rs4821480. No GG genotype at rs4821480 was observed. Patients with SBP < 140 mmHg were more likely to have the CC genotype (17.1%) than patients with SBP ≥ 140 mmHg (4.3%) (P = 0.001). Creatinine clearance (OR = 0.99, 95% CI = 0.98-0.10, P = 0.01) was associated with SBP in patients with CKD. The risk of SBP ≥ 140 mmHg was 0.24-fold greater among patients with the CC genotype than among patients with the TT genotype (P = 0.002). Conclusion: The rs3752462 polymorphism of MYH9 is associated with SBP in patients with CKD. The T allele in the dominant model was associated with an elevated risk for high SBP.

背景/目的:本研究探讨中国慢性肾脏病(CKD)患者高血压与非肌肉肌球蛋白重链9 (MYH9)基因多态性的相关性。方法:本病例-对照研究纳入301例CKD患者和293例健康对照。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法对E1单倍型单核苷酸多态性rs3752462和rs4821480进行基因分型。分析MYH9多态性与CKD患者高收缩压(收缩压≥140 mmHg)易感性之间的关系。结果:病例与对照组rs3752462和rs4821480基因型和等位基因分布相似。rs4821480位点未见GG基因型。收缩压< 140 mmHg的患者(17.1%)比收缩压≥140 mmHg的患者(4.3%)更容易发生CC基因型(P = 0.001)。CKD患者肌酐清除率(OR = 0.99, 95% CI = 0.98-0.10, P = 0.01)与收缩压相关。CC基因型患者发生收缩压≥140 mmHg的风险是TT基因型患者的0.24倍(P = 0.002)。结论:MYH9基因rs3752462多态性与CKD患者收缩压相关。显性模型中的T等位基因与高收缩压的风险升高有关。

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引用次数: 12