血管紧张素转化酶抑制剂与血管紧张素受体拮抗剂在慢性肾脏疾病治疗中的应用

本文介绍了血管紧张素转化酶抑制剂与血管紧张素受体拮抗剂在慢性肾脏疾病治疗中的应用情况，并对两类药物作用机制、临床疗效、安全性进行综述。     

血管紧张素转化酶抑制剂与血管紧张素受体拮抗剂在慢性肾脏疾病治疗中的应用

本文介绍了血管紧张素转化酶抑制剂与血管紧张素受体拮抗剂在慢性肾脏疾病治疗中的应用情况 ,并对两类药物作用机制、临床疗效、安全性进行综述     

血管紧张素转换酶抑制剂联合血管紧张素Ⅱ受体拮抗剂治疗慢性肾脏疾病

肾素-血管紧张素-醛固酮系统在慢性肾脏疾病(CKD)的进展中起着重要作用。Ang II对肾脏具有多重的非血流动力学的病理生理学作用,包括促炎症反应和促纤维化的作用。已经鉴定出不同的Ang II产生系统,其中包括特定的局部组织肾素血管紧张素系统(RAS)。而血管紧张素转换酶抑制剂(ACE I)和血管紧张素Ⅱ受体拮抗剂(ARB)能阻断RAS途径从而起到控制血压、保护肾脏的作用。尽管这些药物成功地用于减少尿蛋白、提高肾的生存率,但仍有众多患者持续进展至终末期肾衰。因此提示单剂量ACE I或ARB并不能完全阻断RAS途径,需要联合应用来治疗慢性肾脏疾病。因此,本文从病理生理、机制和适应证等方面就ACE I和ARB联合治疗是否能够终止慢性肾脏疾病的进展加以综述。     

血管紧张素受体拮抗剂和血管紧张素转换酶抑制剂与肾脏病关系

血管紧张素 (Angiotensin)及其受体 (AT R)改肾脏损害中的作用以及血管紧张素受体拮抗剂和血管紧张素转换酶抑制剂在肾脏疾病中的保护作用一直倍受人们重视 ,本文就血管紧张素、血管紧张素受体、血管紧张素受体拮抗剂和血管紧张素转换酶抑制剂在肾脏疾病中的作用作一综述     

醛固酮及其受体拮抗剂与肾脏疾病

肾素-血管紧张素-醛固酮系统（renin-angiotensin-aldosteronesystem,RAAS）是肾脏疾病发生、发展的主要因素之一,其中血管紧张素Ⅱ（AngⅡ）是导致肾脏损害的主要物质。研究表明,醛固酮（Ald）是中小动脉损伤和肾脏疾病发生的独立风险因素,它在肾脏疾病的发生、发展中具有重要的作用。     

阻断血管紧张素Ⅱ与肾脏保护

在进行性肾脏损害过程中血管紧张素Ⅱ升高是重要致病因素之一，血管紧张素转换酶抑制剂和血管紧张素Ⅱ的Ⅰ型受体拮抗剂在不同水平抑制血管紧张素Ⅱ的作用。本文对比了二者肾脏保护作用机制的异同及已有的动物实验和临床研究     

血管紧张素转换酶抑制剂和血管紧张素受体拮抗剂在IgA肾病中的应用

血管紧张素转换酶抑制剂(ACEI)和血管紧张素受体拮抗剂(ARB)的问世和在临床上广泛应用，是肾脏病治疗领域的一个重大进展。目前ACEI和ARB正在IgA肾病(IgAN)的治疗中发挥越来越重要的作用。     

血管紧张素Ⅱ受体拮抗剂对糖尿病肾病的治疗作用

糖尿病肾病(diabetic nephropathy,DN)是糖尿病的三大微血管并发症之一,是导致糖尿病患者过早死亡和生存质量下降的主要原因.糖尿病患者一旦发生肾脏损害,出现持续尿蛋白则病情不可逆转,往往发展至终末期肾衰竭.到目前为止,尚无有效的方法阻止其发生发展.糖尿病肾病是导致发达国家终末期肾衰竭的主要原因,随着我国人民生活水平的提高,糖尿病患者越来越多,在一些血透中心DN导致的肾衰竭具有增高的趋势.由于早期症状不明显,DN患者在出现蛋白尿后进行治疗往往效果很不理想,因此,早期防治DN,并延缓其发展具有重要的临床意义.     

内皮素受体阻断剂对糖尿病大鼠肾脏血管紧张素Ⅱ1型受体表达的影响

目的：观察糖尿病大鼠肾脏血管紧张素Ⅱ1型（AT1）受体的改变以及内皮素受体阻断剂bosentan对其影响。方法：将SD大鼠建成链脲佐菌素诱导的糖尿病模型,设非治疗组、bosentan治疗组和正常对照组。4周后采用免疫组织化学、Western blot及RT－PCR方法检测肾脏AT1受体基因和蛋白表达。结果：与SD对照组相比,糖尿病大鼠存在明显的蛋白尿和内生肌酐清除率升高,其肾脏AngⅡ水平明显升高,同时伴有AT1受体的mRNA和蛋白表达显著下降。bosentan能显著缓解上述异常。结论：糖尿病大鼠肾脏AngⅡ及AT1受体表达明显异常,bosentan具有治疗作用。     

Treatment of diabetic nephropathy with angiotensin II receptor antagonist

Type 2 diabetes is an ever-growing problem worldwide. Approximately 40% of the patients with type 2 diabetes will develop diabetic kidney disease. In the United States, diabetes has become the most common single cause of endstage renal disease defined by the need for dialysis or transplantation. Patients with type 2 diabetes and diabetic nephropathy have a dramatically increased cardiovascular risk. The Irbesartan Diabetic Nephropathy Trial was designed to determine whether the use of irbesartan or a calcium channel blocker would provide protection against the progression of nephropathy due to type 2 diabetes beyond that attributable to the lowering of blood pressure. In that study, 1715 hypertensive patients with nephropathy due to type 2 diabetes were randomly assigned to irbesartan 300 mg/day or amlodipine 10 mg/day, or placebo. All patients randomized in this trial had more than 900 mg of protein in their urine and serum creatinines between 1.0 mg/dl and 3.0 mg/dl. The target blood pressure was 135/85 mmHg or less in all groups. The primary outcome was time to a combined endpoint of doubling of their baseline serum creatinine concentration, the development of endstage renal disease, or death from any cause. The mean duration of follow-up was 2.6 years. Treatment with irbesartan was associated with a risk of the primary composite endpoint that was 20% lower than that in the placebo group (P = 0.02) and 23% lower than that in the amlodipine group (P = 0.006). The risk of doubling of the serum creatinine concentration was 33% lower in the irbesartan group than in the placebo group (P = 0.003) and 37% lower in the irbesartan group than in the amlodipine group (P < 0.001). Treatment with irbesartan was associated with a relative risk of endstage renal disease that was 23% lower than that in both other groups. These differences were not accounted for by differences in the blood pressures that were achieved. Proteinuria was reduced on average by 33% in the irbesartan group as compared with 6% in the amlodipine group and 10% in the placebo group. The angiotensin II receptor blocker irbesartan was shown to be effective in protecting against the progression of nephropathy due to type 2 diabetes. In a study done in patients with type 2 diabetes and early nephropathy as manifested by microalbuminuria, 590 hypertensive patients with type 2 diabetes and microalbuminuria were randomized to receive either irbesartan 150 mg/day or irbesartan 300 mg/day and followed for 2 years. The primary outcome in that trial was the time to the onset of diabetic nephropathy, defined by persistent albuminuria in overnight specimens, with a urinary albumin excretion rate that was more than 200 mg/min or at least 30% higher than the baseline level. The irbesartan 150 mg/day group demonstrated a 39% relative risk reduction versus the control group in the development of overt proteinuria. The irbesartan 300 mg/day group demonstrated a highly significant 70% risk reduction versus the control group (P < 0.001). The albumin excretion rate was reduced in the two irbesartan groups throughout the study (−11% and −38% at 24 months compared with baseline in the irbesartan 150-mg and 300-mg groups, respectively). The albumin excretion rate remained unchanged in the control group. Irbesartan was demonstrated in the above study to be renoprotective, independent of its blood pressure-lowering effect, in patients with type 2 diabetes and microalbuminuria. Thus, irbesartan, an angiotensin receptor blocker, was demonstrated to be significantly renoprotective in patients with type 2 diabetes with either early nephropathy (microalbuminuria) or late nephropathy (proteinuria). The renoprotective effects of irbesartan were above and beyond the effects irbesartan had on systemic blood pressure. Patients with type 2 diabetes and either early or late diabetic nephropathy should be treated with the angiotensin II receptor blocker irbesartan. Received: October 18, 2002 / Accepted: December 17, 2002 Correspondence to:E.J. Lewis     

Renin-angiotensin system blockers-SGLT2 inhibitors-mineralocorticoid receptor antagonists in diabetic kidney disease: A tale of the past two decades!

Several pharmacological agents to prevent the progression of diabetic kidney disease (DKD) have been tested in patients with type 2 diabetes mellitus (T2DM) in the past two decades. With the exception of renin-angiotensin system blockers that have shown a significant reduction in the progression of DKD in 2001, no other pharmacological agent tested in the past two decades have shown any clinically meaningful result. Recently, the sodium-glucose cotransporter-2 inhibitor (SGLT-2i), canagliflozin, has shown a significant reduction in the composite of hard renal and cardiovascular (CV) endpoints including progression of end-stage kidney disease in patients with DKD with T2DM at the top of renin-angiotensin system blocker use. Another SGLT-2i, dapagliflozin, has also shown a significant reduction in the composite of renal and CV endpoints including death in patients with chronic kidney disease (CKD), regardless of T2DM status. Similar positive findings on renal outcomes were recently reported as a top-line result of the empagliflozin trial in patients with CKD regardless of T2DM. However, the full results of this trial have not yet been published. While the use of older steroidal mineralocorticoid receptor antagonists (MRAs) such as spironolactone in DKD is associated with a significant reduction in albuminuria outcomes, a novel non-steroidal MRA finerenone has additionally shown a significant reduction in the composite of hard renal and CV endpoints in patients with DKD and T2DM, with reasonably acceptable side effects.     

血红蛋白靶目标值对慢性肾脏病患者生存影响的荟萃分析

目的 探讨血红蛋白(Hb)水平对慢性肾脏病(CKD)患者生存时间的影响,为明确CKD患者最佳Hb靶目标值提供参考依据.方法 采用荟萃分析的方法,利用Medline、Embase和Cochrane数据库检索国内外公开发表的有关Hb水平对CKD患者生存影响的临床试验,通过Cochrane协作网提供的Revman软件对检索结果进行荟萃分析.结果 纳入本次荟萃分析的文献共23篇,随访样本总量10 204例.综合分析后发现,与低Hb(Hb＜100 g/L)水平组患者相比,维持高Hb(Hb＞127 g/L)水平可增加患者死亡及发生高血压、中风及住院治疗的风险,相对危险度(RR)值分别为1.10、1.40、1.73和1.07,两组比较差异均有统计学意义(P＜ 0.05).但两组非致命性心肌梗死(RR=1.13,95％CI 0.79～1.62)及肾脏替代治疗(RR=1.00,95％CI 0.85～1.18)的发生率差异均无统计学意义.结论 在纠正CKD患者贫血过程中,维持低Hb水平可以降低患者发生高血压、中风、入院治疗和死亡的风险,但不能改善心肌梗死发生及肾脏替代治疗的风险.     

血管紧张素Ⅱ及其受体拮抗剂对肝星状细胞收缩的影响

目的观察血管紧张素Ⅱ及其受体拮抗剂对体外培养的肝星状细胞收缩的影响。方法采用HSC-T6肝星状细胞系作为活化的肝星状细胞的研究模型。将培养的肝星状细胞随机分为对照组、血管紧张素Ⅱ(1×10-9～1×10-5)mol／L组、受体拮抗剂组和血管紧张素Ⅱ+受体拮抗剂组,继续培养48 h后,比较胶原晶格收缩面积的变化,并绘制收缩的量效关系曲线和时效关系曲线。结果血管紧张素Ⅱ各浓度组,胶原晶格的收缩面积比较对照组均明显增加(P<0．05)。随着血管紧张素Ⅱ浓度的升高,胶原晶格的收缩面积逐渐增大,量效曲线呈近似直线的正相关关系;而且随着血管紧张素Ⅱ作用时间的延长,胶原晶格的收缩面积逐渐增大,在48 h之内呈时间依赖性。血管紧张素Ⅱ作用48 h后,胶原晶格面积为(379．337±37．755)mm2,同时加入受体拮抗剂,面积为(540．803±70．018)mm2,胶原晶格的收缩程度比较血管紧张素Ⅱ组明显减轻(P<0．05)。结论血管紧张素Ⅱ能够剂量依赖性和时间依赖性地促进肝星状细胞的收缩,而血管紧张素Ⅱ1型受体拮抗剂能够抑制血管紧张素Ⅱ引起的肝星状细胞的收缩。     

肾康注射液联合缬沙坦治疗糖尿病肾脏病的疗效观察

目的探讨肾康注射液联合缬沙坦对慢性肾脏病（CKD）〉3期糖尿病。肾脏病（diabetickidneydisease,DKD）患者的治疗效果。方法80例DKD患者随机分为缬沙坦组（对照组）和缬沙坦联合肾康注射液组（治疗组）,每组40例。2组均行常规治疗2个月,观察2组治疗前后的24h尿蛋白定量、血肌酐（SCr）、尿素氮（BUN）、血浆白蛋白（Alb）和体质量指数（BMI）等指标的变化。结果治疗组24h尿蛋白定量、SCr、BUN与治疗前比较均有显著改善（P〈0．01）,且显著优于对照组（P〈0．05）;2组Alb和BMI较治疗前有统计学差异（P〈0．05）,但组间比较无统计学差异（P〉0．05）。结论肾康注射液联合缬沙坦治疗CKD〉3期DKD患者能够显著改善肾功能,可以延缓或逆转早期DKD进展。     

Use of Ophiocordyceps sinensis (syn. Cordyceps sinensis) combined with angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) versus ACEI/ARB alone in the treatment of diabetic kidney disease: a meta-analysis

Abstract

Ophiocordyceps sinensis (O. sinensis; syn. Cordyceps sinensis) has been used in clinical therapy for diabetic kidney disease (DKD) for more than 15 years. O. sinensis is a household name in china and it is available even in supermarket. However, the precise role of O. sinensis has not been fully elucidated with meta-analysis. The aim of this study was to review existing evidence on the effectiveness of O. sinensis for the treatment of DKD. We identified 60 trials involving 4288 participants. Overall, O. sinensis combined with ACEI/ARB had a better effect when compared to ACEI/ARB alone on 24?h UP (MD?=??0.23?g/d, 95%?CI:???0.28 to ?0.19, p?<?0.00001), UAER (MD?=??19.71?μg/min, 95%?CI: ?22.76 to ?16.66, p?<?0.00001), MAU (MD?=??45.09?mg/d, 95%?CI: ?55.68 to ?34.50, p?<?0.00001), BUN (MD?=??0.70?mmol/L, 95%?CI: ?1.02 to ?0.39, p?<?0.0001), SCr (MD?=??8.37?μmol/L, 95%?CI: ?12.41 to ?4.32, p?<?0.0001), CRP (MD?=??1.32?mg/L; 95%?CI: ?1.78 to ?0.86; p?<?0.00001), TG (MD?=??0.51?mmol/L; 95%?CI: ?0.69 to ?0.34, p?<?0.00001), TC (MD?=??0.64?mmol/L; 95%?CI: ?0.91 to ?0.37, p?<?0.00001), and SBP (MD?=??2.01?mmHg; 95%?CI: ?3.45 to ?0.58, p?=?0.006). However, no effects were found for DBP, FBG, and HbA1C. This meta-analysis suggested that use of O. sinensis combined with ACEI/ARB may have a more beneficial effect on the proteinuria, inflammatory, dyslipidemia status as compared to ACEI/ARB alone in DKD III–IV stage patients, while there is no evidence that O. sinensis could improve the hyperglycemia status. However, with regard to low-quality and significant heterogeneity of included trials, to further verify the current results from this meta-analysis, long-term and well-designed RCTs with high-quality study are warranted to ascertain the long-term efficacy of O. sinensis.     

Inflammation in diabetic kidney disease

Diabetes mellitus entails significant health problems worldwide. The pathogenesis of diabetes is multifactorial, resulting from interactions of both genetic and environmental factors that trigger a complex network of pathophysiological events, with metabolic and hemodynamic alterations. In this context, inflammation has emerged as a key pathophysiology mechanism. New pathogenic pathways will provide targets for prevention or future treatments. This review will focus on the implications of inflammation in diabetes mellitus, with special attention to inflammatory cytokines.     

血管紧张素Ⅱ受体拮抗剂抗纤维化及对Ⅰ型胶原基因表达影响的实验研究

目的　研究血管紧张素Ⅱ (angiotensinⅡ )Ⅰ型受体 (AT1)拮抗剂losartan对肝硬化大鼠Ⅰ型胶原 (TypeⅠcollagencolⅠ )基因表达的影响及抗纤维化作用。 方法　 4 1只雄性SD大鼠被随机分为 4组 :对照组 (10 )、模型组 (11)、及治疗组 (2 0 )———早期和中期各 10只 ,除对照组外所有大鼠均给予 5 0 ?l4灌胃 ,3ml/(kg·5d)一次 ,共 9周。治疗组 :早期组同时给予血管紧张素受体拮抗剂losartan灌胃 ,中期组于造模中期 (5周 )开始给药 ,用量 10mg/(kg·d)至处死前。实验结束后 ,处死取肝脏液氮冻存及福尔马林固定标本 ,分别行HE及Masson染色 ,光镜下观察组织学改变 ,图像分析系统测量胶原面积。免疫组化及RT PCR检测Ⅰ型胶原蛋白及mRNA的表达。结果　光镜下组织学检查纤维化分级、图像分析系统测量胶原面积losartan治疗组低于模型组 (P <0 0 5 )。与模型组相比 ,Losartan治疗组使Ⅰ型胶原蛋白及mRNA的表达明显降低 (P <0 0 1)。结论　Losartan对CCl4诱导的大鼠肝纤维化有良好的防治作用。     

Effects of the angiotensin II type 1 receptor antagonist candesartan,compared with angiotensin-converting enzyme inhibitors,on the urinary excretion of albumin and type IV collagen in patients with diabetic nephropathy

Background. We previously reported that the angiotensin II type 1 receptor antagonist candesartan was effective in reducing blood pressure and microalbuminuria in hypertensive patients with diabetic nephropathy after angiotensin-converting enzyme (ACE) inhibitors were replaced due to side effects. In the present study, the clinical effects of candesartan were investigated and compared with ACE inhibitors in patients with stage 2 or 3A diabetic nephropathy, mainly with respect to the effects on the urinary excretion of albumin and type IV collagen. Methods. Forty-nine patients (26 males/23 females) with diabetic nephropathy (stage 2 or 3A), including normotensive patients, were the study subjects. The patients were treated with either an ACE inhibitor (23 patients) or candesartan (26 patients) for 11 ± 3 months. The urinary excretion of albumin and urinary type IV collagen was measured. Results. Posttreatment blood pressure tended to decrease, but such a decrease did not reach a statistically significant level, nor did it show any intergroup difference. The urinary albumin excretion was positively correlated with pretreatment mean blood pressure and left ventricular mass index, but the urinary type IV collagen excretion did not show such correlations. The urinary albumin excretion decreased significantly after treatment to a similar extent in both groups, whereas the urinary type IV collagen excretion decreased significantly only in the candesartan group. Conclusion. It was revealed that ACE inhibitors and candesartan reduced urinary albumin excretion to a similar extent in patients with diabetic nephropathy. From the results of the present study, it is inferred that the renoprotective effect of candesartan in diabetic nephropathy may partially differ from that of ACE inhibitors.