IgA肾病诊治相关的生物标志物

IgA肾病（IgAN）是目前世界范围内最常见的原发性肾小球疾病,是终末期肾衰竭的主要原因。多见于青壮年, 目前机制尚不明确,临床和病理改变多样,尚缺乏特效治疗手段。目前确诊仍有赖于肾活检,治疗上需要临床结合病 理改变进行个体化治疗。因此,寻找敏感、特异有效、无创的生物标志物用于诊断和预后评估是迫切需要的。文章将 从IgAN诊断、疾病进展和预后评估及治疗相关的血和尿生物标志物重点进行阐述。     

CD44在IgA肾病中的表达及临床意义

目的研究CD44在IgA肾病各病变阶段肾组织中的表达及其与临床指标之间的关系,探讨CD44在IgA肾病发病机理中的生物学意义.方法应用免疫组织化学S-P法检测34例IgA肾病肾组织、6例正常肾组织中的CD44的表达情况,同时测定IgA肾病患者的24小时尿蛋白定量、血压、血肌酐(Cr)、肌酐清除率(Ccr)等.分析不同临床分组、病理分级、有无高血压、蛋白尿程度、血Cr水平等对CD44表达的影响.结果 CD44主要于系膜增生、新月体、小管间质炎性细胞浸润的部位表达,于细胞性新月体表达最强.整个球性硬化时,CD44表达近消失.CD44表达与蛋白尿程度正相关(P＜0.05);与血cr水平无明显相关性(P＞0.05);有高血压者CD44表达阳性率92%(23/25),无高血压者为33.3%(3/9),两者比较有显著性差异(P＜0.01).CD44在肾组织中的表达与IgA肾病患者的年龄、性别无相关性.结论 CD44与IgA肾病的活动性进展有关,CD44可作为判定IgA肾病早期进展的可靠指标.     

IgA肾病的近况

IgA 肾病在亚太地区是肾小球肾炎的最常见类型,易误诊为外科性血尿而进行不必要的检查。为此,本文重点对 IgA 肾病的流行病学、临床表现、经过、预后及治疗作一综合性介绍。     

IgA肾病

ＩｇＡ肾病曾彩虹陈惠萍关键词ＩｇＡ肾病临床病理治疗预后１９６８年Ｂｅｒｇｅｒ和Ｈｉｎｇｌａｉｓ首次提出一种在全球范围内最常见的原发性肾小球疾病，即ＩｇＡ肾病（ＩｇＡＮｅｐｈｒｏｐａｔｈｙ，ＩｇＡＮ）。初期，人们认为ＩｇＡＮ预后良好，近来研究发现ＩｇＡ...     

IgA肾病研究近况

IAA肾病的流行病学一、IgA肾病流行区域：IgA肾病（lgANephropathylgAN）是世界范围内最常见、分布最广泛的肾小球疾病。但其发病率有着很大的地域差异。以亚洲为例．日本和新加坡，IgAN占原发性肾小球疾病的SO％。在中国，据统计约占26／～34／，而一些南亚国家如印度、泰国等只占原发疾病的4％～7％。同样在欧洲，法国的发病率很高，英国则较低。在美国，有些地区的发病率不到2／，但西南部印第安人的发病率竟高达35％以上。二、lgAN与基因型：据调查．黑种人lgAN的发病率远没有其它肾小球疾病那样常见。这种情况被认为与IgA的结…     

糖尿病肾病合并IgA肾病

病史摘要 病史患者男性,40岁,因“口干、多饮、多尿半年,尿检异常2月余”入院。患者入院前半年自觉口干、多饮、多尿,夜尿2～3次／夜,无视物模糊、手足麻木等不适,未治。     

肾病范围蛋白尿在判断IgA肾病预后中的意义

目的：研究ＩｇＡ肾病进展为慢性肾功能不全（ＣＲＩ）的临床危险因素。方法：对８４５例经肾活检确诊的ＩｇＡ肾病患者进行追踪观察。用病例对照研究方法研究血肌酐水平、高血压、肾病范围蛋白尿、年龄、性别与ＩｇＡ肾病预后的关系。结果：血肌酐≥１２０μｍｏｌ／Ｌ、高血压、男性、年龄＞４０岁、肾病范围蛋白尿的比值比（ＯＲ）分别为１１４，４７，２８，２１，１９８。比较发病时血肌酐＜１２０μｍｏｌ／Ｌ，５年后发展为ＣＲＩ及５年后肾功能仍正常的病例，发现肾病范围蛋白尿的ＯＲ值为１８（Ｐ＜００１）。结论：血肌酐≥１２０μｍｏｌ／Ｌ、高血压、肾病范围蛋白尿、年龄＞４０岁、男性均为ＩｇＡ肾病进展为ＣＲＩ的临床危险因素。其中肾病范围蛋白尿判断预后的意义更大。     

IgA肾病治疗经验谈

IgA肾病是一个免疫病理诊断,它可以发生在各种原发性肾小球疾病病理类型基础上(膜性肾病例外),而且可呈现出各种肾小球疾病的临床表现,这就决定了该病治疗方案不能划一.现将我们对IgA肾病治疗的看法与大家作一交流.     

IgA肾病的进展状况

IgA肾病是一个免疫病理学的诊断概念,主要是指在肾小球系膜区有广泛、显著的IgA沉着的肾小球疾病。现将本病的进展状况作一概述。一、病因及发病机理多数学者认为本病属于免疫性疾病。有人发现病人分泌IgA的B细胞株增加而抑制IgA分泌的T细胞减少,辅助/抑制T细胞比例增加表示免疫系统紊乱。皮肤、肝脏中有IgA及补体C_3沉着表示为系统性疾病。肾小球沉积物中的IgA多为多聚体,     

蛋白尿在IgA肾病小管间质损害中的意义

目的探讨蛋白尿对IgA肾病（IgAN）小管间质病理变化的影响.方法对68例IgA肾病患者临床病理资料进行回顾性分析.根据24小时尿蛋白排泄量将68例患者分为A组（21例,＜1 g/24 h）、B组（33例,1.0～3.0 g/24 h）和C组（14例,＞3.0 g/24 h）.小管间质病理损害按Katafuchi R的半定量标准评分.结果蛋白尿程度增加,肾小管间质病理损害明显,组间比较有显著性差异（P＜0.05）.蛋白尿程度与尿视黄醇结合蛋白含量及血清C反应蛋白水平呈显著正相关（r=015302,P＜0102）.结论蛋白尿可能通过促进小管间质的免疫炎症反应,加重小管间质的损伤,是IgA肾病慢性进展的重要影响因子之一.对IgA肾病蛋白尿进行早期干预治疗有重要临床意义.     

Proteins induced by telomere dysfunction and DNA damage represent biomarkers of human aging and disease

Telomere dysfunction limits the proliferative capacity of human cells by activation of DNA damage responses, inducing senescence or apoptosis. In humans, telomere shortening occurs in the vast majority of tissues during aging, and telomere shortening is accelerated in chronic diseases that increase the rate of cell turnover. Yet, the functional role of telomere dysfunction and DNA damage in human aging and diseases remains under debate. Here, we identified marker proteins (i.e., CRAMP, stathmin, EF-1alpha, and chitinase) that are secreted from telomere-dysfunctional bone-marrow cells of late generation telomerase knockout mice (G4mTerc(-/-)). The expression levels of these proteins increase in blood and in various tissues of aging G4mTerc(-/-) mice but not in aging mice with long telomere reserves. Orthologs of these proteins are up-regulated in late-passage presenescent human fibroblasts and in early passage human cells in response to gamma-irradiation. The study shows that the expression level of these marker proteins increases in the blood plasma of aging humans and shows a further increase in geriatric patients with aging-associated diseases. Moreover, there was a significant increase in the expression of the biomarkers in the blood plasma of patients with chronic diseases that are associated with increased rates of cell turnover and telomere shortening, such as cirrhosis and myelodysplastic syndromes (MDS). Analysis of blinded test samples validated the effectiveness of the biomarkers to discriminate between young and old, and between disease groups (MDS, cirrhosis) and healthy controls. These results support the concept that telomere dysfunction and DNA damage are interconnected pathways that are activated during human aging and disease.     

Endothelial dysfunction induced by postprandial lipemia is neutralized by addition of proteins to the fatty meal

BACKGROUND: Postprandial lipemia is known to reduce endothelium-dependent flow-mediated vasodilation (FMD). Because postprandial lipemia can be acutely mitigated when proteins are added to the fatty meal, we investigated whether this mitigation could neutralize the lipemia-induced endothelial dysfunction. DESIGN: Sixteen healthy students (aged 19-23, eight males and eight females) received three different test meals at intervals of 1 week between successive tests. Each meal contained whipping cream alone or whipping cream together with either caseinate or soy protein. The whipping cream contained 33% fat, and 3 ml (= 1 g fat) was given per kg body weight. The proteins added were either 50 g sodium caseinate or 50 g soy protein. FMD was assessed by two-dimensional ultrasonography of the brachial artery in the fasting state and 1, 2, 3, 4, 5, 6, 7, and 8h after the fatty meal. Blood was withdrawn at the same time-points from the other arm. Triglycerides, free fatty acids, and insulin were determined using routine methods, and both L-arginine and asymmetric dimethylarginine (ADMA) were determined by LC-MS. RESULTS: Postprandial lipemia reduced FMD, the reduction reaching a maximum of 58% after 3 h. This impairment of endothelial function was not observed when either of the test proteins had been added to the fatty meal (p < 0.01 for caseinate and p < 0.001 for soy protein). The effects of the protein addition were decreases in triglycerides and free fatty acids, increased insulin concentrations at all time-points, and an increased arginine/ADMA ratio between 1 and 5h after the meal, particularly in the case of the soy protein. CONCLUSION: We suggest that the neutralization of the lipemia-induced endothelial dysfunction is caused by direct and indirect effects of the proteins insulinotropy and, secondly, by an increased supply of L-arginine.     

Thyroid dysfunction induced by amiodarone

Amiodarone (2-n-butyl-3,4-diethylaminoethoxy-3',-diiodobenzoyl-benzofurone ) is a drug widely used for the treatment of cardiac arrhythmias. Due to its high iodine content and structural similarity to thyroxine it produces abnormalities in thyroid hormone metabolism and, in some cases, clinical thyroid dysfunction as well. We report 18 patients, 11 females and 7 males, whose thyroid disease developed during treatment with amiodarone (A). Age ranged from 13 to 64 years. A history of thyroid disease in a first-degree relative was present in five, and three patients had goiter prior to A therapy. Fifteen patients had atrial arrhythmias, and 3 had ventricular arrhythmias. Amiodarone was being given in doses of 200 to 800 mg daily. Thyroid function abnormalities appeared between 1 and 29 months after starting A therapy. Nine patients became clinically and chemically thyrotoxic; three patients developed diffuse thyroid enlargement and had total T4 concentration and FI4I increased with normal T3 and no signs of hyperthyroidism; and the six remaining patients became clinically hypothyroid with low values of total T4 and FTI and raised basal TSH. No relationship between dosages of A or duration of treatment and the appearance or severity of thyroid dysfunction was found. Regression of symptoms occurred in all but two patients with simple goiter between 1 and 8 months after amiodarone was discontinued and appropriate treatment was given. Our observations confirm the potential of A to induce thyroid abnormalities in patients with and without preexistent thyroid disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

氧化应激对人淋巴细胞端粒长度的影响

目的　探讨人外周血淋巴细胞遭受过氧化氢 (H2O2 )损伤时,端粒长度的变化。　方法　体外培养人外周血淋巴细胞,分为正常对照组、氧化组和抗氧化组,然后应用Southern杂交技术检测不同时间端粒长度的变化。　结果　端粒长度随着时间的变化表现为缩短;且 3组之间均有显著差异(P<0 .05)。　结论　氧化应激在一定程度上可以引起人淋巴细胞端粒长度的缩短;维生素C具有一定的抗氧化作用,它能减低过氧化损伤,从而减缓端粒缩短的速率。     

抗肿瘤治疗引发的心功能不全

常规肿瘤治疗包含了化疗、放疗和手术治疗等方式。在抗肿瘤治疗的同时，心血管毒副反应，如心肌缺血、心功能不全等日益受到重视。不同的治疗方法有着不同的机理和多种毒副反应，及时有效的监测早期心血管损害和评估心脏收缩、舒张功能，对患者的长期预后和生存显得至关重要。抗肿瘤治疗仍在不断进步中，层出不穷的治疗方式和未知的毒副反应将成为心脏病学家和肿瘤学家需要联合面对的难题。