早期糖尿病肾病患者ACEI治疗后醛固酮逃逸现象及螺内酯干预的疗效研究

目的探讨早期糖尿病肾病患者长时间服用血管紧张素转化酶抑制剂（ACEI）后的醛固酮逃逸现象,及螺内酯干预醛固酮逃逸对糖尿病肾病患者的意义。方法将168例早期糖尿病肾病患者随机分为ACEI、ARB（血管紧张素Ⅱ受体拮抗剂）组,检测其长期服用依那普利和缬沙坦后血浆血管紧张素Ⅱ（AngH）、醛固酮（Ald）浓度变化;并将出现醛固酮逃逸的ACEI组患者分为螺内酯组、对照组,检测尿白蛋白排泄率（UAER）、血钾水平的变化。结果早期糖尿病肾病患者服用依那普利6个月后出现醛固酮逃逸现象,对此类现象加用螺内酯干预后患者的UAER比对照组明显降低（P〈0．05）,且没有出现明显的高钾血症。结论ACEI联合醛固酮受体拮抗剂可以更好地降低早期糖尿病肾病患者的UAER。     

糖尿病肾病的发病机制及治疗

糖尿病肾病(DN)的发病机制未完全明了,近年来发现DN的发病与炎性反应、缓激肽减少、足细胞损伤及microRNA等有关.由于DN的发病机制复杂,尚缺乏特效治疗,目前主张除控制蛋白摄入及优化血糖控制外,肾素-血管紧张素-醛固酮系统阻断剂、他汀类药物、螺内酯及霉酚酸酯也显示了一定的肾脏保护作用.     

单核细胞趋化蛋白-1与糖尿病肾病

单核细胞趋化蛋白-1(MCP-1)是一种对单核细胞具有特异趋化功能的细胞因子,参与单核/巨噬细胞的浸润,在糖尿病肾病(DN)的发生发展中起重要作用。而螺内酯、血管紧张素转换酶抑制剂或血管紧张素Ⅱ受体阻滞剂、噻唑烷二酮类、免疫调节剂麦考酚酸莫酯(MMF)、维生素E及他汀类均能使MCP-1水平下降,延缓DN的发生发展。     

螺内酯对慢性心力衰竭患者神经内分泌激素的影响

目的探讨螺内酯对慢性心力衰竭患者神经内分泌激素的影响。方法92例慢性心力衰竭患者(心功能Ⅱ~Ⅳ级),随机分为贝那普利组(对照组),贝那普利+螺内酯组(螺内酯组)。测定治疗前、治疗3个月后血浆去甲肾上腺素、肾上腺素、肾素、血管紧张素Ⅱ、醛固酮、内皮素水平的变化。结果两组治疗后血浆去甲肾上腺素、肾上腺素、内皮素水平均有明显下降(P<0.01),肾素、血管紧张素Ⅱ水平无明显变化(P>0.05)。醛固酮水平在对照组无显著变化(P>0.05),螺内酯组有显著下降(P<0.01)。结论血管紧张素转换酶抑制剂只有与螺内酯长期联合治疗才可以显著降低慢性心力衰竭患者的血浆醛固酮水平。     

依那普利对糖尿病肾病的肾保护作用

临床研究显示血管紧张素转换酶抑制剂比其它抗高血压药有较大的肾保护作用。这对胰岛素依赖型糖尿病更为有利,因为1/3糖尿病可发展为糖尿病肾病。因此,本文采用随机抽样、前瞻性方法,旨在确定血管紧张素转换酶抑制剂依那普利(enalapril)是否对糖尿病肾病有肾保护作用,并与美托洛尔(β受体阻滞剂)进行比较。     

螺内酯对扩张型心肌病心力衰竭患者某些体液因子的影响

目的:探讨螺内酯对扩张型心肌病心力衰竭患者血浆儿茶酚胺、肾素活性、血管紧张素Ⅱ及醛固酮的影响.方法:入选30例扩张型心肌病心力衰竭患者,随机分入螺内酯组与对照组,各15例,用螺内酯治疗前与治疗1个月后,用高效液相色谱法测定血浆去甲肾上腺素、肾上腺素,同时采用均相竞争放射免疫方法检测血浆肾素活性、血管紧张素Ⅱ与醛固酮.结果:治疗1个月后螺内酯组血浆去甲肾上腺素、肾上腺素、肾素活性、血管紧张素Ⅱ及醛固酮明显低于治疗前,也低于对照组治疗后,均有显著性差异(P＜0.05～0.01).结论:螺内酯可明显抑制扩张型心肌病心力衰竭患者的儿茶酚胺水平,降低肾素活性及醛固酮.     

血管紧张素(1-7)对心血管保护作用的研究进展

血管紧张素(1-7)是血管紧张素家族中一个新成员,它通过血管紧张素转换酶Ⅱ/血管紧张素(1-7)/Mas受体轴发挥作用。血管紧张素(1-7)作为血管紧张素Ⅰ的主要活性产物,对调节血管紧张素Ⅱ水平,尤其是组织血管紧张素Ⅱ的水平起着一定的作用。它通过激肽、一氧化氮、前列腺素产生与血管紧张素Ⅱ完全不同的作用。这些提示血管紧张素(1-7)可能是肾素-血管紧张素系统调节自身活性的重要物质。近期研究发现血管紧张素(1-7)具有保护心室心肌功能,降低缺血再灌注损伤和氧化应激,调节神经压力反射,降低血压和舒张血管,抗增殖、抗纤维化和抗炎症反应,以及调节血脂、脂肪细胞代谢、保护糖尿病所致心肌损害等心血管保护作用,现就这些保护作用的新进展做一综述。     

血管紧张素转化酶抑制剂和血管紧张素Ⅱ受体拮抗剂联合应用治疗高血压病的研究进展

血管紧张素转化酶抑制剂(ACEI)和血管紧张素Ⅱ受体拮抗剂(ARB)联合用药治疗心衰的安全性及疗效已在CHARM及VALIANT研究等大型临床试验中得到证实;数项研究证明了ACEI和ARB联合用药对糖尿病患者可显著降低蛋白尿以及延缓糖尿病肾病进展.ACEI和ARB均为一线抗高血压药物,具有良好的降压效果和靶器官保护作用,本文拟就ACEI和ARB联合用药治疗高血压的进展作一综述.     

福辛普利联合氯沙坦治疗糖尿病肾病92例

糖尿病肾病(DN)是糖尿病(DM)常见的微血管并发症之一,其引发的肾衰竭是DM患者主要死亡原因之一.近年来临床研究证明血管紧张素转换酶抑制剂( ACEI)和血管紧张素Ⅱ受体拮抗剂(ARB)均能降低血压、减少蛋白尿,对肾脏有良好的保护作用,延缓DN进展[1].本研究观察并比较单用氯沙坦和福辛普利及两药联合应用治疗DN的疗效和安全性.     

血管紧张素转换酶抑制剂及螺内酯对扩张型心肌病心肌纤维化及心功能的影响

目的评价血管紧张素转换酶抑制剂培多普利(商品名:雅思达)及螺内酯逆转原发性扩张型心肌病(DCM)心肌纤维化及改善心功能的作用.方法采用放射免疫方法测定24例正常对照者及原发性DCM应用培多普利及螺内酯治疗前后心肌纤维化指标:血清Ⅲ型前胶原(PCⅢ)、层粘连蛋白(LN)、透明质酸(HA),同时测定血浆血管紧张素Ⅱ(AngⅡ)、醛固酮(ALD)浓度,采用超声方法测定左室射血分数(LVEF).结果原发生DCM PCⅢ、LN、HA明显升高,血浆AngⅡ、ALD活性增强,使用培多普利和螺内酯治疗6个月后PCⅢ、LN、HA显著下降,AngⅡ、ALD活性减低,心功能明显改善.结论原发性DCM存在不同程度心肌纤维化.血管紧张素换酶抑制剂及螺内脂通过抑制AngⅡ、ALD逆转心肌纤维化,明显改善心功能.     

�ٴ�ָ���ж��������������Ԥ���ֵ�������

糖尿病肾病是糖尿病主要的并发症,已成为终末期肾脏病的主要病因之一。糖尿病合并肾脏损害有很大比例是非糖尿病性肾脏疾病,两者的治疗和预后明显不同,因此早期诊断对改善预后尤为重要。综合应用年龄、糖尿病病程、糖尿病视网膜病变、血压、血糖等临床指标有助于两者的鉴别诊断及判断预后,但单纯应用临床指标仍存在一定局限性,对怀有疑问的病例仍需依靠肾活检进行确诊。新型生物标志物的临床应用价值还须进一步验证。     

Effects of Different Doses of Irbesartan Combined With Spironolactone on Urinary Albumin Excretion Rate in Elderly Patients With Early Type 2 Diabetic Nephropathy

Background

There is a lack of research on the effect of low dose of angiotensin receptor blockers combined with spironolactone, and the effect of high dose of angiotensin receptor blockers alone on the urinary albumin excretion rate (UAER) in elderly patients with early type 2 diabetic nephropathy (DN).

Epidemiology of diabetic nephropathy

The epidemiology of diabetic nephropathy (DN) should be approached from two angles: a) incidence of diabetic nephropathy in patients with diabetes, and b) epidemiology of chronic renal failure (CHRF) in diabetic patients. According to data from different sources, DN affects, in all its stages, about one third of patients irrespective of the type of diabetes they suffer from, with the peak rate of incidence after 15 years of duration of the illness. It is estimated that the rate of DN prevalence is 4-8% of patients monitored in diabetes centres. In addition, a significant portion of diabetics, especially the type 2 diabetic patients, are affected by the non-diabetic type nephropathy of primarily atherosclerotic etiology. Currently, DN is the principal cause of CHRF in advanced industrial countries (Western Europe, USA,Japan). A similar trend has been recorded in the Czech Republic which has one of the highest incidences of DN among the former Eastern Block countries. Most affected patients are type 2 diabetes patients. The cause of the above increase is the growing prevalence and incidence of type 2 diabetes, and, primarily, better care for type 2 diabetes patients who live long enough to develop severe macro and microvascular complications including DN. The principal factors influencing the risk of a diabetic patient developing DN are long-term monitoring ofglycaemia, control of hypertension, genetic (ethnic) factors, age and sex. Metabolic control has an effect on the risk of diabetic nephropathy developing in type 1 and 2 diabetes, yet it is blood pressure control which is critical for the progression of chronic renal insufficiency in DN patients. In view of the high number of diabetic patients with CHRF which, in addition, associates with their high polymorbidity and extensive demands put on medical and nursing care which is not directly associated with CHRF therapy, we have to do with a serious medical and economic problem.     

尿液蛋白质组学与糖尿病肾病

蛋白质组学是系统研究细胞或组织全套蛋白质生物学信息的科学,其中尿液蛋白质组学以其独特的优点广泛应用于基础和临床研究领域.糖尿病肾病是糖尿病最常见且危害巨大的并发症之一,许多学者运用尿液蛋白质组学分析方法对糖尿病肾病进行研究,发现了一些与糖尿病肾病相关的生物学标志及可能的发生机制,展示了尿液蛋白质组学技术在糖尿病肾病早期诊断、动态监测病情及发现新的治疗靶点方面的前景.     

Insights into the Genetic Architecture of Diabetic Nephropathy

Diabetic nephropathy (DN) is a devastating complication of type 1 and type 2 diabetes and leads to increased morbidity and premature mortality. Susceptibility to DN has an inherent genetic basis as evidenced by familial aggregation and ethnic-specific prevalence rates. Progress in identifying the underlying genetic architecture has been arduous with the realization that a single locus of large effect does not exist, unlike in predisposition to non-diabetic nephropathy in individuals with African ancestry. Numerous risk variants have been identified, each with a nominal effect, and they collectively contribute to disease. These results have identified loci targeting novel pathways for disease susceptibility. With continued technological advances and development of new analytic methods, additional genetic variants and mechanisms (e.g., epigenetic variation) will be identified and help to elucidate the pathogenesis of DN. These advances will lead to early detection and development of novel therapeutic strategies to decrease the incidence of disease.     

检测2型糖尿病患者血浆同型半胱氨酸水平的临床意义探讨

目的 探讨2型糖尿病(DM)患者血浆同型半胱氨酸(HCY)水平及意义。方法 用化学发光法对55例肾功正常的2型DM患者[DM组,其中无肾病38例、早期糖尿病肾病17例(DN)例]及51例健康人(对照组)的血浆HCY水平进行测定比较,同时分析血浆HCY与DM患者年龄、病程、血压、血浆叶酸(Fol)、维生素B12、总胆固醇(CH)、肌酐(SCr)及尿白蛋白排泄率(UAER)之间的相关性。结果 DM组血浆HCY水平均较对照组明显升高(P<0.01),合并早期肾病者血浆HCY水平较无肾病者明显升高(P<0.05);DM患者血浆HCY水平与UAER及SCr呈显著正相关(P<0.05),与其他因素间无明显相关性。结论 糖尿病患者尤其是合并肾脏损害者血浆HCY明显升高,高HCY血症可能是DN发生发展的危险因素之一。     

���������Ŵ�ѧ�о���չ

??Abstract?? Susceptibility to diabetic nephropathy (DN) has an inherent genetic basis as evidenced by familial aggregation and ethnic-specific prevalence rates.DN has been widely considered as a polygenic disease.Previous ‘candidate genes’ studies selected genes with plausible physiological roles in DN.The GWAS approach allows for cost effective??unbiased surveys of the entire genome??with the hope of identifying novel genes which further elucidate the underlying biology of DN.Epigenetic regulation of gene expression may represent an important contributor to an inherited predisposition to DN.The next-generation sequencing technology is an ideal tool to search for rare variants.Genetic studies may provide valuable information regarding the pathophysiology of DN and will lead to early detection and development of novel therapeutic strategies.     

Diabetic Nephropathy: a Tangled Web to Unweave

Diabetic nephropathy (DN) is currently the leading cause of end-stage renal disease globally. Given the increasing incidence of diabetes, many experts hold the view that DN will eventually progress toward pandemic proportions. Whilst hyperglycaemia-induced vascular dysfunction is the primary initiating mechanism in DN, its progression is also driven by a heterogeneous set of pathological mechanisms, including oxidative stress, inflammation and fibrosis. Current treatment strategies for DN are targeted against the fundamental dysregulation of glycaemia and hypertension. Unfortunately, these standards of care can delay but do not prevent disease progression or the significant emotional, physical and financial costs associated with this disease. As such, there is a pressing need to develop novel therapeutics that are both effective and safe. Set against the genomic era, numerous potential target pathways in DN have been identified. However, the clinical translation of basic DN research has been met with a number of challenges. Moreover, the notion of DN as a purely vascular disease is outdated and it has become clear that DN is a multi-dimensional, multi-cellular condition. The review will highlight the current therapeutic approaches for DN and provide an insight into how the inherent complexity of DN is shaping the research pathways toward the development and clinical translation of novel therapeutic strategies.     

Does C-reactive protein to serum Albumin Ratio correlate with diabEtic nephropathy in patients with Type 2 dIabetes MEllitus? The CARE TIME study

AimsDiabetic Nephropathy (DN) is a complication of Diabetes Mellitus and is associated with chronic and low-grade inflammatory burden. Novel inflammatory predictors, such as, C-reactive protein to serum albumin ratio (CAR) has been studied various inflammatory conditions, recently. Increased inflammatory burden accompany to both type 2 Diabetes Mellitus (T2DM) and DN, hence we aimed to compare CAR levels of the T2DM subjects with DN to those of without DN.MethodsPatients with T2DM were enrolled to the study. Study population grouped into two according to the presence (group A) or absence (group B) of DN. Characteristics and laboratory data, as well as CAR levels; of the study groups were compared.ResultsMedian CAR levels of the groups A and B were 2.17% (0.02−13.2) and 0.39% (0.02−4.39), respectively (p < 0.001). CAR was found to be an independent risk factor for diabetic nephropathy (adjusted to age, BMI, fasting glucose, HbA1c, and body weight). One unit (0.1%) elevation in CAR increased the risk of nephropathy by 3.5 folds (p < 0.001, 95%CI: 2.24–5.45). CAR levels greater than 0.82% have 79% sensitivity and 78% specificity in predicting DN (AUC: 0.86 [95% CI: 0.80−0.92]; p < 0.001).ConclusionsIn conclusion, elevated CAR levels are higher in type 2 diabetic patients with diabetic nephropathy. According to the ROC curve, a level higher than 0.82% presents the best sensitivity and specificity in the association with the presence of DN.