糖尿病肾病新认识与防治

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,糖尿病肾病的新认识与防治,随机血糖,200mg/dl,(,11.1 mmol/l),餐后2h血糖,200mg/dl,(11.1 mmol/l),血糖,正常，,尿糖阳性,糖尿病,空腹血糖,126mg/dl,(,7.0,mmol/l),1,糖尿病,的诊断标准(ADA, 2005),糖尿病,患者受损的主要靶器官,心脏(心血管)：,冠心病，心肌病变,脑(脑血管),肾脏,眼视网膜,血管,其它：,周围神经，胃肠道，呼吸系，,骨 骼， 皮 肤，,糖尿病肾病；肾动脉粥样硬化缺血性肾病,2 糖尿病肾病定义,（diabetic nephropathy，DN）,糖尿病肾病 (DN，DKD）:,是指 糖尿病（DM）患者出现持续白蛋白尿（200g/min 或300 mg/24h）；且伴有糖尿病视网膜病变，临床及实验室检查排除肾脏或尿路其它疾病。,这一定义对1型和2型糖尿病均适用。,DNDKD，,Diabetic Kidney Disease,糖尿病肾病的诊断,（diabetic nephropathy，DN）,糖尿病肾病 (DN）,诊断依据：,糖尿病（DM）患者出现持续白蛋白尿（200g/min 或300 mg/24h）,且伴有糖尿病视网膜病变,临床及实验室检查排除肾脏或尿路其它疾病,DM+,蛋白尿,DN ！,DEVELOPMENT OF DIABETIC NEPHROPATHY,Stadium period of time features,I,hypertrophy and,hypertension,afterDM diagnosis,up to 2 years,no signs of nephropathy(B,U),increased GFR & RPF,II,histological changes,Noclinicalmanifestation, 2,years,initial morphological lesions,(,basal membrane thickness,expansion of msangium),III,starting nephropathy,10-20,years,starting,microalbuminuria,normal GFR,hypertension (50%),glomerular abnormalities,IV,clinical manifested,nephropathy,15-20,years,overt nephropathy,persistent,proteinuria,GFR, RPF,hypertension (ca. 60 %),V,end,-,stage,renal failure,20-40,years,GFR 90,有CKD危险因素,1 已有肾病GFR正常,90,2 GFR 轻度降低 6089,3 GFR 中度降低 3059,4 GFR 重度降低 1529,5 ESRD（肾衰竭） 15,*,KDOQI: Kidney diseases outcome quality initiative,3 THERAPY OF DIABETIC NEPHROPATHY,糖尿病肾病,的治疗目标,The major target in the treatment of DN is to retard the progression of nephropathy,by doing a strict,control of :,blood sugar,(strict glycemic control),控制血糖,blood pressure,控制血压,reduction of proteinuria,控制蛋白尿,reduction of overweight,控制 超重,dietary management,控制饮食,( Low Protein Diet EAA,/,KA),Management of complications (CVD),控制并发症,糖尿病肾病,的治疗目标,Target For Control,Optimal,优,Fair,良,Poor,差,Body weight Index,BMI,体重指数男性 25 27, 27,女性 24 26, 26,blood glucose,4.4- 6.1mmol/l, 7,.,0, 7,.,0,血糖,80-110 mg/dl, 126 126,HBA,1C,糖,化血红蛋白 7,.,5,blood pressure,血压,130/80,130/80,140/90,-,140/90,Blood lipid,血脂水平(下文),糖尿病肾病,的治疗目标,Target For Control,Optimal,优,Fair,良,Poor,差,Blood lipid,血脂水平(接上),胆固醇 4.5 mmol/l,6,.,0 6,.,0,(175,mg/dl,) (232,mg/dl,),甘油三酯 ,1,.,5,mmol/l, 2.2,2.2,(133,mg/dl,),(177,mg/dl,),LDL 4,.,0,(116,mg/dl,),(155,mg/dl,),HDL,1.1 mmol/l 1.1- 0.9 0.9,(42,mg/dl,),(35,mg/dl,),正常蛋白尿和病理性蛋白尿的判断标准,项 目,正常值 微量白蛋白尿 临床蛋白尿或,临床白蛋白尿,尿蛋白半定量 30 mg/dl,24小时蛋白定量 300 mg/24h UPE/Ucr 200 mg/g,尿白蛋白定量 300 mg/24h,UAE/Ucr 男,250 mg/g,女 355 mg/g,*UPE/Ucr：尿蛋白/尿肌酐比率， UAE/Ucr：尿白蛋白/尿肌酐比率,CKD,患者血压、血糖、,HbA,1C,的治疗目标,项 目 目 标,血,压,CKD,第,1-4,期,（,GFR,15ml/min,）,130/80,CKD,第,5,期（,GFR 15ml/min,）, 140/90,血糖（糖尿病患者，,mg/dl,）,空腹,90-130,睡前,110-150,HbA,1C,（糖尿病患者）, 7%,CKD,患者的治疗目标,蛋白尿、,GFR,或,Scr,变化,项 目 目 标,蛋,白,尿, 0.5-1.0 g/24hr,GFR,下降速度, 0.3 ml/min/mon (4 ml/min/year,）,Scr,升高速度,1),维生素：,糖尿病的饮食治疗：,energy supply,碳水化合物选择：,总量控制,血糖指数低,脂肪：,(占总热量的1/41/3),足,量的,PUFA,(PUFA/SFA,1),DN-CRF,患者,蛋白,摄入量,-,根据不同肾功水平的设计,病人分类,Ccr Scr 蛋白摄入量,(ml/min) (mg/dl) ( g/kg.d ),应用EAA/-KA,透析,病人 1.0左右,腹膜透析,一般,10,一般,植物蛋白的特点与作用,营养成分：,植物蛋白含,EAA 35%40%,左右,谷类蛋白质 含,EAA 35%,左右 豆类蛋白质 含,EAA 39-40%,动物蛋白含量（,45,%左右）,对CRF进展的作用,延缓CRF进展作用优于动物蛋白,为什么？ 何种机制?,植物蛋白的作用：临床研究,肾病类型 效 果,CGNNS:,52%大豆蛋白, X 8wk,蛋白尿减少，血脂下降,CGN,蛋白尿： 方法、结果同上,2,型,DN：,大豆蛋白1g/d,X 8wk,蛋白尿、 GFR无变化,LN： 亚麻籽15,30,45g/d,X12wk,血脂下降, Ccr升高,Pre-ESRD： 48.9g/d,大豆蛋白, X 6mo,GFR无变化，1/Scr,斜率,下降,THERAPY OF DIABETIC NEPHROPATHY,Effects of a ketodiet on the daily protein loss,UPD,VLPD + ketoacids,5.2 +/- 1.4,2.8 +/- 1.1,p 25ml/min:,LPD,可使,CRF,进展减慢10,The MDRD and other studies suggest a moderate benefit ( 10% reduction in rate of progression). Decisions about dietary therapy should depend largely on choice by informed patients.,In Patients with GFR 25ml/min:,LPD,降低,0.2,g/kg/d,可使,CRF,进展减慢,29,There is a,strong evidence,from orrelational analysis for a benefit from reduction of dietary protein,( 29%,reduction of the rate of progression for each reduction of protein by 0.2 g/kg/day).,423,例非糖尿病肾病: 血压与生存率关系,110,可能生存率,（%）,5 控制血压对慢性肾病患者GFR的影响,0,-2,-4,-6,-8,-10,-12,-14,95 98 101 104 107 110 113 116 119,r,r,=0.69;,p,0.05,130/85,140/90,Untreated,HTN,GFR (mL/min/year),平均动脉压MAP(mm Hg),未治疗的,高血压,降压治疗对血压和肾功能的影响,(Parving et al, Lancet 1983),肾小球滤过率,ml/min/1.73m,2,-24 -18 -12 -6 0 6 12 182430,1250,750,250,平均动脉压,mm Hg,100,95,85,75,65,125,115,105,95,蛋白尿,m,g/min,月,治疗开始,RENAAL首要终点,血清肌酐加倍,0,12,24,36,48,月,0,10,20,30,事件%,p=0.006,危险性下降: 25%,751,692,583,329,52,52,52,52,52,52,762,689,554,295,36,36,36,36,36,36,P,L,P (+,常规治疗,),L (+,常规治疗,),终末期肾病,0,12,24,36,48,月,事件%,0,10,20,30,762,715,610,347,42,42,42,42,42,42,751,714,625,375,69,69,69,69,69,69,p=0.002,危险性下降,: 28%,P,L,P (+,常规治疗,),L (+,常规治疗,),终末期肾病或死亡,0,12,24,36,48,月,0,10,20,30,40,50,事件%,p=0.010,危险性下降,: 20%,751,714,625,375,69,69,69,69,69,69,762,715,610,347,42,42,42,42,42,42,P,L,P (+,常规治疗,),L (+,常规治疗,),P=安慰剂 L=氯沙坦,Brenner BM et al,New Engl J Med,2001;345(12):861-869.,在 NIDDM病人中蛋白尿与各种原因死亡率间的关系,Gall et al., Diabetes 1995,.,(44):Nov.,正常白蛋白尿,微量微白蛋白尿,大量白蛋白尿,n=191,n=86,n=51,*p0.05,:,正常白蛋白尿与微量白蛋白尿,和大量白蛋白尿相比,*,6 控制DN蛋白尿,控制DM,；,控制血压,；,应用ACEI，ARB,应用PTX,治疗“非DN肾病”,其它,DM+,大量蛋白尿,（NS）,“激素治疗”,！,DN大量蛋白尿（NS）的治疗,控制DM,、,血压,；,应用ACEI，ARB；PTX,利尿，消肿,提高血浆渗透压，补充白蛋白,防止盲目补钠,营养治疗,其他,DM+,大量蛋白尿,（NS）,“激素治疗”,！,PTX对,DN蛋白尿的作用,Seventeen patients with primary glomerular diseases, a persistent spot proteinuria exceeding 1.5g/g creatinine (Cr) and a glomerular filtration rate between 24 and 115ml/min/1.73m,2,were treated with PTX 400mg twice daily for 6 months. Before and after the treatment, serum Cr, plasma renin activity and aldosterone concentrations, plasma and urinary tumor necrosis factor (TNF-,), interleukin-1,and monocyte chemoattractant protein (MCP-1 ), as well as urinary protein and Cr were measured.,Kidney International 2006; 69:14101415,PTX对,DN蛋白尿的作用,结果,PTX significantly reduced urinary protein excretion,increase of serum albumin.,PTX lowered the urinary MCP-1/Cr ratio,percent reduction of urinary protein/Cr ratio correlated directly with the precent decrease of urinary MCP-1/Cr,no significant change in blood pressure, renal function, biochemical parameters, plasma renin activity and aldosterone concentrations, or plasma TNF&MCP-1,Conclusion: PTX 800mg /d is safe & effective for reducing proteinuria in patients with proteinuric glomerular diseases. This beneficial effect occurs in close association with a reduction of urinary MCP-1 excretion.,Kidney International (2006) 69, 14101415,Additive Antiproteinuric Effect of PTX in Patients,With Type 2 Diabetes under ARB:,A Short-Term, Randomized, Controlled Trial,1200 mg,of PTF daily (,n,= 30) or to a control group (,n,= 31).,BMP-7对动物DN的作用,应用链脲霉素制作I型糖尿病的模型：,15周时小管分泌的BMP-7 及 BMP-7,mRNA,表达减少，在30周时完全消失。,随着BMP-7的减少，发生EMT。,给予外源性rHuBMP-7对该模型的作用,部分逆转肾小球滤过率下降,部分减轻蛋白尿,降低肾小球硬化的发生率（5% VS 12%）,上述作用均优于依拉普利对照组。,HIF稳定剂对动物DN的作用,给予外源性HIF稳定剂对糖尿病动物模型的作用,减轻微量白蛋白尿,减轻肾小球硬化,100,50,无症状,进展,延缓,停止进展,恢复或逆转,肾脏替代疗法,病程：年数,GFR,0,1,0,(ml/min),CKD的自然过程与干预,7 结 语,DN,的机制、诊断与防,治,DN,的,早期诊断-治疗，对延缓或逆转病情, 改善,病人预后有重要意义,。,饮食治疗能延缓早中期DN的进展。,LPD- KA/EAA,治疗具有其,独特优点,。,积极控制血糖，是控制DN的必要条件。,控制,高血压是,改善DN,患者,预后主要因素之一,。,ACEI,和,ARB,治疗,对,DN病人,具有其,独特作用。,DN,的蛋白尿处理应予以足够重视。,应用,ACEIARB, 应用 PTX, 调脂治疗，生长因子。,应积极监控CVD等并发症。,