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1、肾脏疾病的诊治进展与临证经验,China-Japan Friendship Hospital,Beijing,ChinaLi Ping,肾脏疾病的新分类,急性肾脏损伤（Acute Kidney Injuries,AKI）慢性肾脏病（Chronic Kidney Disease,CKD）,AKI的诊断标准,肾功能在48小时内突然降低至少两次Scr升高绝对值0.3mg/dl（26.5umol/L）Scr较前升高50%持续6小时以上尿量0.5ml/kg/h,符合下列条件之一：,单独应用尿量的改变作为诊断标准时，需要除外尿路梗阻或其他可导致尿量减少的原因。,AKIN Organizing Commit
2、tee 2005,2005年9月阿姆斯特丹AKI的国际研讨会,AKI的RIFLE分级,反映预后,AKI合作研讨会标准,(Acute rise 0.5 mg/dl),2005年9月阿姆斯特丹AKI的国际研讨会,反映预后,AKI的改良RIFLE分级,J Himmelfarb.Kidney International(2007)71,971976.,AKI的RIFLE分期与预后,2005年bell等回顾性分析207名CRRT治疗的AKI患者首次采用RIFLE分期评价AKI的预后,Bell.Nephrol Dial Transplant(2005)20:354360,R,I,F,L+E,尿量能否界定C
3、RRT的介入时机,A Randomized Controlled study28例冠脉搭桥术后AKI患者Early group 尿量30ml/h 持续3h,14 cases Late group 尿量20ml/h 持续2h,14 cases,86%,14%,Early group,Late group,Souichi.Hemodialysis International.2004;8:320-325,RIFLE分期与CRRT介入时机,Chih-Chung Shiao.Critical Care.2009,13:R171,25%,27%,13%,Chronic kidney disease（CK
4、D）,Chronic kidney disease(CKD)is a worldwide public health problem with an increasing incidence and prevalence,poor outcomes,and high cost.Outcomes of CKD include not only kidney failure but also complications of decreased kidney function and cardiovascular disease.,Levey AS,et al.Ann Intern Med.200
5、3;139:137-147.,Kidney damage,Kidney damage is defined as pathologic abnormalities or markers of damage,including abnormalities in blood or urine tests or imaging studies.Persistent proteinuria is the principal marker of kidney damage.An albumin creatinine ratio greater than 30 mg/g in two of three s
6、pot urine specimens is usually considered abnormal.,Levey AS,et al.Kidney Int.2005;67:2089-2100.,NKF.Am J Kidney Dis.2002;39:S1-246.,GFR can be estimated from calibrated serum creatinine and estimating equations,such as the Modification of Diet in Renal Disease(MDRD)Study equation or the Cockcroft-G
7、ault formula.The MDRD formula is recommended by European and American guidelines for estimating GFR，which has not been fully validated in different populations and at different stages of CKD,NKF.Am J Kidney Dis.2002;39:S1-246.,GFR,To evaluate whether the MDRD equations could be applied accurately to
8、 Chinese patients with CKD,GFR estimated by using MDRD equation 7(7GFR),the abbreviated MDRD equation(aGFR),and the Cockcroft-Gault equation(cGFR)were compared in patients with different stages of CKD.Dual plasma sampling of technetium Tc 99m-labeled diethylene triamine pentaacetic acid plasma clear
9、ance was used as the reference standard GFR(sGFR)for comparison of 7GFRs,aGFRs,and cGFRs at different stages of CKD.The study enrolled 261 patients with CKD,including 146 men and 115 women.All patients were older than 18 years.,Zuo L,et al.Am J Kidney Dis.2005;45(3):463-72.,Comparison of 7GFR with s
10、GFR showed that 7GFR correlated significantly with sGFR,but the regression line was significantly different from the identical line,Comparison of Equation-Estimated GFRs With 99mTc-DTPA Plasma Clearance,Zuo L,et al.Am J Kidney Dis.2005;45(3):463-72.,The regression line showed that MDRD equation 7 ov
11、erestimated GFR at low levels and underestimated GFR at near-normal levels,Zuo L,et al.Am J Kidney Dis.2005;45(3):463-72.,*P 0.05 comparing estimated GFR with sGFR.P 0.001 comparing accuracies of an equation with those in CKD stages 4 to 5.,Zuo L,et al.Am J Kidney Dis.2005;45(3):463-72.,*P 0.05 comp
12、aring estimated GFR with sGFR.P 0.001 comparing accuracies of an equation with those in CKD stages 4 to 5.P 0.001 comparing accuracies of the C-G equation with those of the MDRD equations.,Zuo L,et al.Am J Kidney Dis.2005;45(3):463-72.,The MDRD equation 7 to estimate GFR(7GFR,ml/min per 1.73m2)=170
13、Pcr-0.999 age-0.176 BUN-0.170 albumin0.318 0.762(if female)1.211(if Chinese)Abbreviated MDRD equation to estimate GFR(aGFR,ml/min per 1.73m2)=186 Pcr-1.154 age-0.203 0.742(if female)1.233(if Chinese),Where Pcr is in mg/dl,BUN is in mg/dl,albumin is in g/dl,and age is in years.,Ma et al.J Am Soc Neph
14、rol 2006;17:2937,CKD,Subjects(million),Prevalence,Stage(Ccr90ml/min),Stage(Ccr：6089ml/min),Stage(Ccr：3059ml/min),19.20,11%,5.90,3.3%,5.30,3.0%,Third National Health and Nutrition Examination Survey,Stage(Ccr：1529ml/min),Stage(Ccr15ml/min),Total Subjects,7.60,4.3%,0.40,0.2%,0.30,0.2%,Coresh J,et al.A
15、m J Kidney Dis.2003;41:1-12.,Chadban SJ,et al.J Am Soc Nephrol.2003;14(7 Suppl 2):S131-8.,Approximately 16.4%have at least one indicator of kidney damage,9.7%,Renal Impairment,Proteinumia,1.1%,Hematuria,3.7%,0.1%,0.3%,0.6%,0.8%,11,247 Australians aged 25 yr or over,GFR 60 ml/min/1.73m2（11.2%）,Chen J
16、,et al.Kidney Int.2005;68(6):2837-45,The overall prevalence of CKD with GFR 60 mL/min/1.73m2 was 2.53%.,Chen J,et al.Kidney Int.2005;68(6):2837-45.,Overall,the age-standardized prevalences of GFR 60 to 89,30 to 59,and 30 mL/min/1.73m2 were 39.4%,2.4%,and 0.14%,respectively.,Subjects:2353 residents o
17、lder than 40 years.Results:Approximately 11.3%of subjects had at least one indicator of kidney damage.(1).Albuminuria(albumin/creatinine30mg/g),6.2%;(2).GFR60ml/min/1.73m2,5.2%;(3).Hematuria,0.8%;(4).Non-infective pyuria,0.09%.,Zhang L,et al.Nephrol Dial Transplant.2007;22:1093,Cases of renal biopsi
18、es performed each year,Li LS,Liu ZH.Kidney Int.2004;66(3):920-3.,*P 0.01;*P 0.001,compared with 1985.,Li LS,Liu ZH.Kidney Int.2004;66(3):920-3.,Li LS,Liu ZH.Kidney Int.2004;66(3):920-3.,Li LS,Liu ZH.Kidney Int.2004;66(3):920-3.,Li LS,Liu ZH.Kidney Int.2004;66(3):920-3.,Li LS,Liu ZH.Kidney Int.2004;6
19、6(3):920-3.,Liu G,et al.J Clin Intern Med.2004;21:834-838,The worldwide rise in the number of patients with CKD is reflected in the increasing number of people with end-stage renal disease(ESRD)treated by renal replacement therapydialysis or transplantation.Two factors related to the prevalence of E
20、SRD are important.The first is the ageing of the population;The second factor is the global epidemic of type 2 diabetes mellitus.,Lysaght MJ.J Am Soc Nephrol.2002;13:37.United States Renal Data System.Am J Kidney Dis.2003;42:S37.King H,et al.Diabetes Care.1998;21:1414.,Li LS,Liu ZH.Kidney Int.2004;6
21、6(3):920-3.,Histology of Chinese chronic renal failure(Scr3mg/dl,N=607),According to the registration of dialysis and transplantation in China in 1999,41775 patients underwent maintenance dialysis;among them,89.5%was hemodialysis(HD)and 10.5%was peritoneal dialysis(PD).The first cause of CRF in HD p
22、atients was glomerulonephritis(50%),and then diabetic nephropathy(13.5%),hypertensive nephrosclerosis(8.9%).,Dialysis and Transplantation Registration Group.Chin J Nephrol.2001;17:77-78.,These data showed that the annual incidence rate of dialysis in Shanghai,China was coincident with the annual ave
23、rage incidence of ESRD in Europe.However,prevalence of dialysis has marked difference between Europe and Shanghai.The financial problem may be the most important cause of the difference formation.,Meguid El,et al.Lancet.2005;365:331-340.Shanghai dialysis and transplantation registration group.Chin J
24、 Nephrol.2001;17:83-85.,The criterion of CRF was creatinine clearance(Ccr)50 ml/min/1.73 m2.The mean serum creatinine were 594.7mol/L.The average annual cases accounted for 1.31%of the hospitalized cases with urologic-kidney diseases.The male to female ratio was 1.49:1.The mean age at the disease on
25、set was 8.18 years.The mean duration of pre-diagnosis of CRF was 2.53 years.The main primary renal diseases causing CRF were chronic glomerulonephritis and nephrotic syndrome(52.7%).One-fourth of all cases had congenital and hereditary renal diseases,and the majority was renal hypoplasia and dysplas
26、ia.,Yang JY,et al.Zhonghua Er Ke Za Zhi.2004;42:724-730.,The major outcomes of CKD include progression to kidney failure,complications of decreased kidney function,and CVD.Data from the NHANES III show the approximately 11%of the U.S.adult population have CKD.The prevalence of early stages of CKD(st
27、ages 1 to 4;10.8%)is more than 100 times greater than the prevalence of kidney failure(stage 5;0.1%).,Coresh J,et al.Am J Kidney Dis.2003;41:1-12.,104 patients of A/C accounted for 35.5%of ARF cases with renal biopsy during the same period drug-induced acute renal interstitial or tubulointerstitial
28、disease,pre-renal ARF and flare-up of lupus nephritis were the most common causes of ARF in A/C patients.occurred more commonly in older patients,Zhang L,et al.Clin Nephrol.2005;63:346-350.,2529 cases with dialysis were dead in China in 1999.Heart failure and cerebrovascular accident accounted for 3
29、2%and 19%,respectively.Besides,16%patients died of dialysis interruption automatically,which might be related to the financial problem.In another report,CVD is the single most important cause of death among dialysis patients,accounting for 51%of overall mortality.,Dialysis and Transplantation Regist
30、ration Group.Chin J Nephrol.2001;17:77-78.,The most prevalent pathological form of CVD was left ventricular hypertrophy(LVH),accounting for 58.5%of total patients.,Hou FF,et al.Zhonghua Yi Xue Za Zhi.2005;85:458-463.,CHF,CAD,CVA,Prevalence of CVD(%),27.7,16.5,5.6,C reactive proteinFemale and anemiaC
31、alcium phosphate productHypoalbuminemiaDiabetesAgeHypertension,Hou FF,et al.Natl Med J China,2005;85:753-759,Yuan FH,et al.Ren Fail.2005;27:149-153.,Hypertension,diabetes,hyperlipidaemia,obesity,and smoking as risk factors or markers in the general population for the development of CKD.Most notable
32、among the modifiable progression factors is systemic hypertension.Proteinuria is a reliable marker of the severity of CKD and a powerful and independent predictor of its progression.Non-modifiable factors include genetics,race,age,and sex.,Klag MJ,et al.JAMA.1997;277:12931298.Klahr S,et al.N Engl J
33、Med.1994;330:877884.Jafar TH,et al.Ann Intern Med.2003;139:244252.,Li YJ,et al.Family-based association study showing that immunoglobulin A nephropathy is associated with the polymorphisms 2093C and 2180T in the 3 untranslated region of the Megsin gene.J Am Soc Nephrol.2004;15:1739-1743.Li G,et al.T
34、andem repeats polymorphism of MUC20 is an independent factor for the progression of immunoglobulin A nephropathy.Am J Nephrol.2006;26:43-49.Lu JC,et al.Uteroglobin G38A polymorphism is associated with the progression of IgA nephropathy in Chinese patients.Zhonghua Nei Ke Za Zhi.2004;43:37-40.Chen X,
35、et al.Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with the clinico-pathological manifestations in immunoglobulin A nephropathy patients.Chin Med J(Engl).1997;110:526-529.,Megsin 基因与IgA肾病的发病有关MUC20，Uteroglobin，ACE 基因与IgA肾病的进展有关,impaired renal function,severe prot
36、einuria,hypertension,glomerulosclerosis,interstitial fibrosis,DAmico G.Am J Kidney Dis.2000;36:227237.,Yang NS,et al.Chin J Intern Med.2005;l44:597-600.,Characteristics,P-value,Scr 115 umol/LUP 1.0g/24hGlomerulosclerosis 2 Crescent formationInterstitial injury 2,Multivarite analysis of influercing f
37、actors for hypertension in 540 patients with IgAN,Zhuang Y,Chen X,et al.Chin J Intern Med.2000;39:371-375.,The prevalence of hypertension in IgAN was 39.6%(214/540)at the time of renal biopsy.,Characteristics of tubulointerstitial lesions(TIL)in 609 patients with IgAN,Degree and percent of TIL:mild
38、TIL 47.1%,moderate TIL 21.7%,severe TIL 16.6%,Non-TIL 14.6%.Related factors with severity of TIL:hypertension,the level of proteinuria,the scores of vascular lesion,total glomerular lesion,hypercellularity,glomerulosclerosis,Zhang Y,Chen X,et al.Chin J Intern Med.2001;40:613-617.,Prevention of CKD,P
39、rimary prevention of CKD will rely on controlling the obesity and associated type 2 diabetes as well as hypertension.such as weight reduction,exercise,and dietary manipulations.Secondary prevention of progression of CKD needs pharmacological approaches.,Molich M,et al.J Am Soc Nephrol.2003;14:S10310
40、7.Appel LJ.J Am Soc Nephrol.2003;14:S99102.Moser M.J Clin Hypertens.2004;6:S413.,Management of CKD,Current management options for CKD are based on the control of known risk factors such as hypertension,proteinuria,hyperlipidaemia,and smoking.Control of hypertension is the single most effective inter
41、vention.Antihypertensive approaches with inhibitors of ACE or angiotensin-2-receptor blockers have been widely advocated.Control of proteinuria and the inhibition of the rennin-angiotensin system are important factors in slowing the progression of diabetic and non-diabetic CKD.,Remuzzi G,et al.Ann I
42、ntern Med.2002;136:604615.Gaede P,et al.N Engl J Med.2003;348:383393.,我们所面对新的挑战,CVD is an epidemic,Diabetes is an epidemic,CKD is an epidemic,CVD and DM are leading causes of CKD,CKD is a risk factor for CVD,Dialysis is costly,Dialysis is life saving,中西医治疗CKD的现状分析,肾脏病的演变,肾脏病的表现,肾脏病的治疗,治疗的局限性,早期CKD1期
43、,中期CKD2-3期,中晚期CKD4期,尿毒症,单纯血尿轻度蛋白尿,合并高血压大量蛋白尿,透析肾移植,降压药糖皮质激素免疫抑制剂,西医无特殊治疗,疗效有限药副作用大,肾功能不全尿毒症前期,晚期 CKD5期,西医无特殊治疗,低蛋白饮食必需氨基酸,寻找并去除危险因素,治标不治本 器官来源不足医疗费用高,中医治疗优势,针对血尿蛋白尿治疗,降低蛋白尿减少副作用,延缓肾脏疾病进展,推迟进入透析时间,减少医疗费用,CKD中医治疗十法,滋养肝肾法 症属肝肾阴虚者，或辨证属气阴两虚以阴虚为主者，方选杞菊地黄汤、归芍地黄汤、一贯煎合二至丸、桑麻丸等加减。稍有乏力者可加太子参；有心悸怔忡者，可合用生脉饮；失眠者加
44、柏子仁或酸枣仁；口燥咽干甚者加麦冬、五味子等；兼尿频、尿急、尿热、尿痛者，可用知柏地黄汤加滑石、车前子等。,健脾益肾法,适用证属脾肾气虚者，方选七味白术散、参苓白术散加菟丝子、补骨脂；兼自汗者可合用玉屏风散；兼腰膝冷痛者加狗脊、川牛膝；兼下肢水肿者，可合用防已地黄汤或防已茯苓汤；兼有纳少腹胀者可加砂仁、寇仁；兼心悸气促者，可合用苓桂术甘汤等、葶苈大枣泻肺汤等。,益气养阴法,方选参芪地黄汤为主，兼下肢肿加车前子、冬葵子、冬瓜皮、抽葫芦、防己；兼湿热者加白花蛇舌草、石苇、；兼瘀血者加丹参、泽兰、红花；兼气滞者加广木香、槟榔、陈皮、大腹皮；气虚明显加入红参另煎兑服；阴虚明显加黄芪、石斛；兼阳虚加仙茅
45、、仙灵脾等；兼浊毒者加入生大黄，或加用大黄灌肠；有痈疽者加金银花、蒲公英、野菊花、天葵子、败酱草等；尿中有酮体加黄芩、黄连、黄柏；合并周围神经病变加当归、菊花等。,阴阳双补法,适于CKD晚期阴阳两虚者，此为气阴两虚进一步发展而来。方选桂附地黄汤等。兼水湿用济生肾气汤，贫血明显者，以红参另煎兑服，浊毒盛加生大黄。,祛风散热法,适于外感风热或风寒化热者，可用银翅散加减。阴虚者可用银翅汤，咽痛合银蒲玄麦甘桔汤（经验方，由银花、蒲公英、玄参、麦冬、桔梗、甘草等）、升降散。热毒甚者可合用五味消毒饮、黄连解毒汤。,清热利湿法,适用于兼湿热症状者。一般在扶正基础上加入清利之品。湿热重宜先清利湿热，上焦痰热可
46、用贝母瓜萎散、杏仁滑石汤；中焦湿热可用八正散去木通，或五麻散、石苇散、程氏萆解分清饮。若湿热弥漫三焦可用三仁汤、嵩芩清胆汤等以清热除湿，宣畅三焦。,渗利水湿法,适于挟水湿者。仅下肢浮肿，可于扶正方中加牛膝、车前子以渗利水湿。如水肿严重则宜先渗利水湿，脾虚明显者可用防己黄芪汤合防己茯芩汤、大橘皮汤；血瘀者可用桂枝茯芩丸、当归芍药散加减；水肿严重者，亦可前后分消，可用己椒苈黄丸、疏凿饮子；水凌心肺可用苓桂术甘汤合葶苈大枣泻肺汤。,理气开郁法,适于兼有气郁症状者。气郁的产生可与情绪波动，焦虑忧郁，或水湿、湿热、瘀血等因素导致气机受阻有关。可于扶正方中加入调理气机之品。气郁严重者宜先理气开郁，用逍遥散、柴胡疏肝散、越鞠丸、四逆散等。水湿明显者，在渗利水湿方中加入陈皮、广木香、槟榔、大腹皮、沉香等理气之品，气行水亦行，有助于水肿消退。,活血化瘀法,适用于瘀血症状明显或严重者，特别是合并其它血管病变者，常选桂枝茯苓丸、血府逐瘀汤、桃仁四物汤、桃核承气汤等方加减治疗。慢性肾脏病病程较长，正气亏虚，气机逆乱，血瘀证普遍存在，迁延难愈，因此活血化瘀法较为常用，一般可在扶正基础上加入活血化瘀之品。,泄浊解毒法,适用于终末期，浊毒弥漫，阴阳俱虚。轻者可于扶正方中加入大黄以泄浊；重则可配合大黄牡蛎方、大黄穿心莲方等煎汁灌肠或肛门点滴。,Thank you!,
