1、 Diabetic Nephropathy Statistical Increase in DiabetesIn the past 20 years,there has been a steady increase in the proportion of all patients with ESRD who have diabetes.According to the 1997 report of the USRDS,more than 40%of all newly treated patients with ESRD have diabetes.Increasing Insulin Tr
2、eatment in NIDDMRenal Failure Cumulative Incidence.Chronic renal failure was as likely to develop at a superimposable rate in both diabetic subsets.Numbers in parentheses indicate number of patients for each line.Creatinine clearance.Further evidence of the similarity in course of diabetic nephropat
3、hy in type I(A)and type II(B)diabetes was presented in Ritz and Stefanskys study of equivalent deterioration in creatinine clearance over the course of a decade.糖尿病肾病的发病机理(1)肾内血动力学改变:肾内血流动力学改变是指肾小球高滤过及肾小球高压。动物实验,糖尿病模型建立后,即已存在肾小球的高滤过与肾小球肥大。糖尿病肾病的发病机理(1)高滤过是导致肾功能恶化的主要原因。在非糖尿病性5/6肾切除的动物模型中可见肾小球系膜基质增多,G
4、BM增厚及节段性肾小球硬化。肾小球内高压是导致肾小球硬化的另一重要因素糖尿病肾病的发病机理(2)葡萄糖的毒性效应高血糖可导致内皮细胞,系膜细胞的结构及功能的改变。高血糖促使系膜细胞合成更多的胞外基质。持续的高血糖可使血浆蛋白及组织蛋白糖基化,导致晚期糖基化终末产物的生成。糖尿病肾病的临床表现型及型糖尿病患者都有很大的可能发展为糖尿病肾病,型糖尿病患者其肾病更为显著,进展也更为迅速,当发生了明显糖尿病肾病后,两型的临床表现则无很大差别。临床上按照病理生理特点将型糖尿病肾病分为期。目前尚无糖尿病肾病的临床分期,但其发生糖尿病肾病时也大体经历高滤过,正常白蛋白尿,微量白蛋白尿,临床糖尿病肾病及慢性肾
5、功能不全等几个阶段。Stages of Nephropathy.The interrelationships between functionaland morphologic markers of the stages of diabetic nephropathy are shown.Additional pathologic studies are needed to time with precision exactly when glomerular basement membrane(GBM)thickening and glomerular mesangial expansion
6、 take place.Diabetic Nephropathy in Types I&II.Whereas microalbuminuria and glomerular hyperfiltration are subtle pathophysiologic manifestations of early DN,transformation to overt clinical DN takes place over months to many years.While not all microalbuminuric individuals progress to proteinuria a
7、nd azotemia,the majorityare at risk for ESRD due to DN.糖尿病肾病及慢性肾功能不全的预防控制血糖控制血压低蛋白饮食对AGES的治疗Clinical recognition of diabetic nephropathy.The timing of reno-protective therapy in diabetes is a subject of current inquiry.Certainly,hypertension,poor metabolic regulation,and hyperlipidemia should be add
8、ressed in every diabetic individual at discovery.Discovery of microalbuminuria is by consensus reason to start treatment with an ACEI in either type of diabetes,regardless of BP elevation.However,nearly the entire course of renal injury in diabetes is clinically silent.Medical intervention during th
9、is“silent phase,”comprising BP pressure regulation,metabolic control,dietary protein restriction,and administration of ACEI is renoprotective,as judged by slowed loss of GFR.PROGRESSION OF COMORBIDITYIN TYPE II DIABETESCOMORBIDITY INDEXHEART DISEASEComplications Initial%Subsequent%Retinopathy 50 100
10、Cardiovascular 45 90Cerebrovascular 30 70Peripheral vascular 15 50Creatinine clearance declined from 81 mL/min over 74(40119)mo.Endpoint:dialysis or death.HEART DISEASEHyperlipidemiaHypertension Volume overloadACE inhibitorErythropoietinHeart disease is the leading cause of morbidity and death in bo
11、th type I and type II diabetes.Throughout the course of DN,periodic screening for cardiac integrity is appropriate.AUTONOMIC NEUROPATHYCardiovascular(rate,QT,R-R)Orthostatic hypotensionGastroparesisCystopathyDiarrheaCLINICAL STRATEGYMain Collaborators ConsultantsOpththalmologist NeurologistPodiatris
12、t Vascular surgeonCardiologist EndocrinologistNutritionist GastroenterologistNurse educator UrologistPLANNING FOR ESRDExpose patient to treatment optionsEstablish vascular or peritoneal accessEncourage intrafamilial kidney donationMonitor creatinine,general well beingEarly dialysis startManagement w
13、ith dialysisOPTIONS IN DIABETES WITH ESRD CAPD/CCPD HD TransplantationFirst-year survival 75%75%90%Survival 10 y 5%25%Diabetic complications Progress Progress Slow progressionRehabilitation Poor Poor Fair to excellentPatient acceptance Fair Fair Good to excellentSurvival Rates of Diabetic ESRD Patie
14、nts.After a decade of treatment,the remarkable superiority of renal transplantation over dialysis(combined PD and HD,lower curve)is evident in these survival curves drawn from the 1997 report of the URDS.Fewer than 1 in 20 diabetic patients with ESRD treated with any form of dialysis will live a decade.In contrast,kidney transplantation from a LD(upper curve)or a CAD(middle curve)permits substantive cohorts to survive.FIGURE 1-58Improving one year survival with dialysis.