SGLT2 inhibitors in patients with type 2 diabetes and renal disease: overview of current evidence

Chronic kidney disease (CKD) is a frequent complication of type 2 diabetes mellitus (T2DM) and is associated with poor clinical outcomes, including an increased risk of all-cause and cardiovascular mortality, as well as adverse economic and social effects. Slowing the development and progression of CKD remains an unmet clinical need in patients with T2DM. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are widely used for the management of T2DM and have effects beyond glucose lowering that include cardiovascular benefits and potential renoprotective effects. Although the glucose-lowering efficacy of these agents is dependent on renal function, the cardiovascular and renal benefits of SGLT2 inhibition appear to be maintained to estimated glomerular filtration levels as low as 30 mL/min/1.73 m². Clinical evidence has indicated that these agents can reduce the risk of development or worsening of albuminuria, a marker of renal damage, through a range of mechanisms. These include blood pressure lowering, reduction of intraglomerular pressure and hyperfiltration, modification of inflammatory processes, reduction of ischemia-related renal injury, and increases in glucagon levels. The blood pressure-lowering effect of SGLT2 inhibitors is maintained in people with CKD and could further contribute to reduced renal burden, as well as potentially offering synergistic effects with antihypertensive therapies in these patients. Several cardiovascular outcomes trials (CVOTs) have included renal endpoints, adding to the growing evidence of the potential renoprotective effects of these agents in patients with T2DM. Several ongoing dedicated renal outcomes trials will provide further guidance on the potential clinical role of SGLT2 inhibitors in slowing the development and progression of renal impairment in individuals with T2DM.     

Reduced transcapillary escape of albumin during acute blood pressure-lowering in Type 1 (insulin-dependent) diabetic patients with nephropathy

Summary The effect of acute arterial blood pressure lowering upon albumin extravasation was studied in 10 patients with nephropathy and retinopathy due to long-standing Type 1 (insulin-dependent) diabetes. The following variables were measured: transcapillary escape rate of albumin (initial disappearance of intravenously injected ¹²⁵I-labelled human serum albumin), and urinary albumin excretion rate (radial immuno-diffusion). The study was performed twice within 2 weeks, with the patients receiving an intravenous injection of either clonidine (225 g) or saline (0.154 mmol/l). The clonidine injection induced the following changes: arterial blood pressure decreased from 134/87 to 107/73 mmHg (p<0.01), transcapillary escape rate of albumin declined from 8.1 to 6.7% of the intravascular mass of albumin/h (p<0.01), albuminuria diminished from 1434 to 815 g/min (p<0.01), and plasma volume raised slightly from 2916 to 2995ml (p<0.05). Our findings demonstrate that the enhanced albumin passage through the wall of the microvasculature characteristically found in long-term Type 1 diabetic patients with clinical microangiopathy is pressure-dependent to a large extent. This may be due to elevated hydrostatic pressure in the microcirculation.     

原发性高血压早期肾损害微量白蛋白尿的临床价值

目的 :探讨原发性高血压 (EH)早期肾损害微量白蛋白尿 (U- MAlb)的临床价值。方法 :用免疫透射比浊法对尿蛋白试纸阴性的 16 1例 EH患者测定 U- MAIb,并与 12 5例正常健康者作比较。结果 :EH组 U- MAlb排出量增加的人数占患者的 37.3% ,EH 、 级组极显著高于 级组 , 级组显著高于 级组 ,EH组 U- MAlb极显著高于正常组。结论 :EH患者有相当比例已发生 U- MAlb,高血压级越大 ,年龄越大 ,病程越长 ,发生 U- MAlb的比例越大 ,排出量也越高。定期检测 U - MAlb排出量对发现 EH早期肾损害有重要的临床价值。     

Relation of asymmetrical dimethylarginine levels with renal outcomes in hypertensive patients with and without type 2 diabetes mellitus

Aim

The aim of the study was to evaluate the association between high plasma ADMA levels, a biomarker of endothelial dysfunction, with the progression of albuminuria and chronic kidney disease (CKD) in hypertensive patients, with and without type 2 diabetes mellitus.

尿白蛋白准确定量有待解决的课题

尿中自蛋白定量是很重要的常规检验项目.尤其是近年来兴起的"尿微量白蛋白"定量在早期发现与监测肾损伤方面起着重要的作用.但最近国际权威组织认为尿白蛋白定量这一看似普通而简单的试验却仍存在许多问题.本文就一些国家发布的指南中的多处不一致,定量中存在的不少难以解决的问题,以及国际组织提出的多项改进建议和需深入研究的课题加以介绍并提出看法,包括在国内停止使用"尿微量白蛋白"一词,而仍用"尿白蛋白"定量.     

血清胱抑素C联合尿白蛋白与肌酐比值对老年2型糖尿病肾损害的早期诊断

目的探讨血清胱抑素C(Cys C)和尿中白蛋白(Alb)与肌酐(Cr)比值(UACR)对诊断老年2型糖尿病患者早期肾脏损害的临床价值。方法选择60岁以上尿蛋白阴性的2型糖尿病患者60例,其中血肌酐水平正常的30例(A组),血肌酐明显升高的30例(B组);同时纳入30例同期于我院门诊体检的60岁以上的健康人群作为对照组。采用免疫透射比浊法测定血清Cys C含量,免疫浊度法测定尿Alb含量,全自动生化分析仪同时测定血清Cr和尿Cr。结果老年糖尿病患者的血清Cys C和UACR均明显高于健康对照组,差异有统计学意义(P0.05);且联合检测的敏感性和特异性更高(相比较于单项检测,P0.05)。结论血清Cys C和UACR可以作为诊断老年2型糖尿病患者早期肾损害的敏感和特异性指标,两者联合检测对老年糖尿病患者早期肾损害的诊断有重要价值。     

外周血C反应蛋白及尿微量白蛋白在2型糖尿病合并尿路感染患者中的诊断价值

【目的】探讨外周血C反应蛋白（CRP）及尿微量白蛋白（MA）在2型糖尿病（T2DM ）合并尿路感染患者中的诊断价值。【方法】选取T2DM合并尿路感染的患者120例（观察组）,另外选取同期T2DM 非感染患者100例（对照组）,检测两组CRP和M A水平,分析其在T2DM 合并尿路感染患者中的诊断价值。【结果】观察组患者的 CPR 和 M A 水平均显著高于对照组,差异有统计学意义（ P ＜0．05）。CRP 敏感度99．17％,特异度83．00％;M A敏感度85．83％,特异度98．00％;CRP＋M A敏感度85．00％,特异度99．00％。【结论】CRP和M A在T2DM合并尿路感染患者中诊断价值高,值得临床推广。     

氯沙坦对老年高血压患者微量蛋白尿的影响

目的观察氯沙坦对老年高血压患者微量蛋白尿(MCA)的改善作用。方法采用连续样本,自身前后及分组对照方法,对32例高血压伴MCA者(EH组),观察在治疗前和每天服用氯沙坦50 mg 12周后的血压、血尿素氮(BUN)、血肌酐(Cr)2、4 h内生肌酐清除率(Ccr)、尿蛋白/肌酐(Alb/Cr)的变化,同时设12例健康老人作对照(对照组)。结果用氯沙坦治疗后,除血压有明显下降外,尿Alb/Cr亦显著性降低(P<0.01),Ccr明显升高(P<0.05)。结论氯沙坦对老年高血压患者在降压治疗的同时可降低尿蛋白的排泄,改善肾功能。     

黄芪消白颗粒治疗气虚湿淤型慢性肾小球肾炎蛋白尿随机对照研究

目的观察黄芪消白颗粒治疗慢性肾小球肾炎蛋白尿的疗效及安全性。方法采用完全随机对照方法,将2012年8月至2014年12月上海中医药大学附属曙光医院肾病科门诊慢性肾小球肾炎患者52例按就诊顺序编号随机分为2组。对照组常规治疗,肾病饮食,控制血压130~90/80~60 mm Hg之间,给予苯那普利10 mg/次,每天1次口服;治疗组给予黄芪消白颗粒(14 g/包,1包/次)每天3次口服,连续治疗随访24周。观测24 h尿蛋白定量、肾小球滤过率(estimated glomerular filtration rate,eGFR)、血红蛋白、血白蛋白、丙氨酸氨基转移酶、血钾等疗效及安全性指标,监测不良反应。结果观察24周,治疗组临床缓解2例,显效12例,有效5例,无效8例,总有效率70.37%。对照组临床缓解1例,显效3例,有效6例,无效15例,总有效率40.00%。治疗组疗效优于对照组(P0.05)。2组24 h尿蛋白定量的变化率比较,差异有统计学意义(P0.05),eGFR的变化率无统计学差异(P0.05)。黄芪消白颗粒治疗前后血红蛋白、血白蛋白、血钾等方面无统计学差异(P0.05),治疗后丙氨酸氨基转移酶较治疗前改善,差异有统计学意义(P0.05)。本研究中共发生不良反应7例,与实验方案没有关系,没有因为不良事件而退出研究。结论黄芪消白颗粒能够改善气虚湿淤型慢性肾小球肾炎蛋白尿,稳定肾功能,疗效确切,且没有明显的不良反应,具有很好的安全性。     

慢性肾脏病住院患者白蛋白尿与心血管疾病相关性研究

目的：研究慢性肾脏病（CKD）住院患者白蛋白尿与心血管疾病（CVD）的相关性,探讨白蛋白尿对非糖尿病CKD患者CVD的预测价值。方法：回顾性分析1245例非糖尿病CKD患者的一般情况、生化指标、心电图、胸部X线、心超及CVD的危险因素。结果：（1）1245例患者中CKD1、2、3、4、5期分别为304例（24.4%）、281例（22.6%）、372例（29.9%）、157例（12.6%）、131例（10.5%）;CKD1～5各期有蛋白尿者分别为208例（68.8%）、194例（69%）、269例（72.3%）、117例（74.5%）、106例（80.9%）。（2）与CKD1期患者相比,CKD2～5期患者年龄、SBP、DBP、Scr、UA明显升高,eGFR、Hb、Alb明显降低（P〈0.05）;CKD3期患者TG、LDL升高,HDL降低（P〈0.05）;CKD4、5期患者TC、LDL、HDL降低;TG升高（P〈0.05）。（3）与CKD同期非白蛋白尿组相比,白蛋白尿组CKD1～5期患者Scr、UA明显升高,Alb明显降低（P〈0.05）;CKD2～5期患者SBP、DBP明显升高,eGFR、Hb明显降低（P〈0.05）;CKD4、5期患者TC、HDL降低,TG、LDL升高（P〈0.05）。（4）CKD患者CVD发病率从CKD1～CKD5期逐步升高（P〈0.05）,白蛋白尿患者CVD发病率以及胸部X片、心电图、心超异常阳性率升高更加明显（P〈0.05）。（5）Logistic回归分析显示CVD与年龄、SBP、UA、TG、白蛋白尿呈现正相关,与GFR、Hb呈现负相关（P〈0.05）。结论：非糖尿病CKD患者CVD发病率随CKD进展而增高,与白蛋白尿密切相关,白蛋白尿是CVD患者心血管疾病危险标志。