ckd一体化管理课件

1、CKD及其一体化管理王海燕北京大学肾脏疾病研究所北京大学第一医院肾内科Annul Increase of RRT in China64,77947,45853,02058,97074,050110,57040,02243,52011% 14% +49% +33,86037,53441,35050,63560,90080,3004,9225,4605,9246,6707,3208,1448,95013,4004,4004,2004,0005,0006,0007,1348,1209,20845,65030,700010,00020,00030,00040,00050,00060,00070,000

2、80,00090,000100,000110,00020012002200320042005200620072008HDPDTRANSPLANTATIONDate from Fresenius Medical Care (Shanghai) Co.我国大陆与香港/台湾/日本的透析病人数比较3北京全国2007年、2008年北京市城区和郊区血透治疗患者比较透析分布失衡 慢性肾脏病(CKD)?慢性肾脏病(CKD) 的定义 肾损害（肾脏结构或功能异常3个月，伴有或不伴有肾小球滤过率（GFR）的下降，表现为下列异常之一：有病理学检查异常；有肾损害的指标，如血、尿检查异常；GFR60ml/min/1.73

3、m2 3个月，有或无肾损害。 Am J Kidney Dis. 2002Kidney Int. 2005慢性肾脏病(CKD)及其诊断 分期 描述GFR (ml/min/1.73m2)1 肾损伤GFR正常或 90 2 肾损伤GFR轻度 6089 3 GFR中度 3059 4 GFR严重 1529 5 肾衰竭 189.21.7 (China）3.511.3 Shanghai2 2,596186.35.8 (MDRD)1.211.8 Guangdong3 6,311206.63.8 (China)3.212.1 Zhengzhou51,855205.781.58(China)8.1913.57Def

4、inition and classification of chronic kidney disease. KDIGO 2005 Prevalence of CKD in big cities of China From cross-sectional studies 1. Am J Kidney Dis 2008; 51:373-384 2. Nephrol Dial Transplant . 2009 24: 1205-12123. Nephrol Dial Transplant 2009;24:1202-12104 .Kidney Int 2005; 68:2837-2845 5.Chi

5、na J Nephrol 2008,24:9Prevalence of CKD in rural area of China from regional studiesDefinition and classification of chronic kidney disease. KDIGO 2005AreaNo.Age（year）Albumin -uria (%)Reduced renal function (%)Hemat-uria (%)CKD(%)Southeastern China1(Dongyang)1,0111810.4 3.0 10.4 13.5Southwestern Chi

6、na2(Dai Minority)5,566208.1 2.9 4.012.5Northwestern China3(Uygur Minority) 1,552184.5 1.4/5.41. Chinese Journal of Nephrology 2007; 23:152-1572. Chinese Journal of Nephrology 2008;24:609-6133. Chinese Journal of Nephrology to be published与罹患慢性肾脏病相关的因素肾功能下降的危险因素：年龄，服用肾毒性药物，脂代谢紊乱，高血压白蛋白尿的危险因素：女性，糖尿病，高

7、血压，脂代谢紊乱，慢性感染，Special interested factors have been screened: Chronic respiratory tract infection (-) Hepatitis B virus infection (-) Nephrotoxic medications Equation VariablesORP value1Agesex Concomitant diseases* nephrotoxic groupAge, OR=1.056/Nephrotoxic group, OR=2.8120.050.6220.1210.052Agesex Co

8、ncomitant diseases analgesic subgroup,CTM-AA subgroupAge, OR=1.055/Analgesic, OR=2.127CTM-AA, OR=3.2670.050.5850.1230.1440.053Agesex Concomitant diseases analgesic subgroupCTM-AA subgroup/ low doseCTM-AA subgroup/ high doseAge, OR=1.059/CTM-AA/high dose, OR=5.6250.050.6970.1800.1880.2890.054Agesex C

9、oncomitant diseases analgesic subgroup/low dose2.0kganalgesic subgroup/high dose2.0kgCTM-AA subgroup/ low doseCTM-AA subgroup/ high doseAge, OR=1.060/Analgesic/high dose, OR=3.848/CTM-AA/high dose, OR=5.5130.050.7830.1920.5130.0630.288 20%The incidence RRT will continue to increase in China in the f

10、ollowing decades, partly due to the progression of CKD. 108975.8%34824.2%1437100.0%VariablesAge- and Sex adjusted OR*(95% confidence interval)Multivariable adjusted OR (95% confidence interval)Age (per 5 years increase)1.42 (1.29-1.55)1.35 (1.22-1.50)Sex (female vs. male)0.84 (0.61-1.14)1.24 (0.85-1

11、.82)Body mass index (per 5 kg/m2 increase)1.26 (1.00-1.57)1.05 (0.81-1.35)History of cardiovascular disease1.05 (0.71-1.56)0.95 (0.64-1.42)Current smoking0.81 (0.53-1.24)0.86 (0.55-1.33)Diabetes 1.23 (0.88-1.72)1.21 (0.85-1.74)SBP (per 10mmHg increase)1.12 (1.03-1.23)1.09 (0.99-1.19)Plasma uric acid

12、 (per 59 mol/L increase)1.24 (1.10-1.39)1.25 (1.10-1.43)Triglycerides (per 1 mmol/L increase)1.06 (0.97-1.16)0.98 (0.88-1.10)HDL cholesterol (per 1 mmol/L increase)0.70 (0.44-1.11)0.82 (0.49-1.37)Albuminuria1.83 (1.07-3.12)1.79 (1.02-3.15)eGFR (90 eGFR 60-89 eGFR60 Ualb- Ualb+ Ualb- Ualb+ Ualb- Ualb

13、+ (N=273) (N=24) (N=616) (N=51) (N=73) (N=9)Mean IMT 0.740.27 0.840.30 0.810.28a 0.970.41c 0.940.39b 0.910.32dMaximal IMT 1.310.71 1.550.82 1.480.75e 1.750.94f 1.820.93g 1.480.44h a P90 and Ualb-, b P0.05 compared with eGFR90 and Ualb+, c P90 and Ualb-, d P90 and Ualb+, Abbreviations: IMT, intima-me

14、dia thickness; eGFR, estimated glomerular filtration rate; Ualb, albuminuria; - absent; +present;Note: To convert eGFR in ml/min/1.73m2 to mL/s/1.73m2, multiply by 0.01667Am J Kidney Dis 2007, 49:786-792.开始透析病人： 心衰1/3 心绞痛1/4 心梗10% USRDS 1999125例透析前病人65.5%出现心血管合并症需要紧急透析的病人72%为急性左心衰杨莉，等。中国实用内科杂志 2004N

15、umber of patients with CMBs according to CKD stages P = 0.0041 ( 2 test).CKD stageStage 1 or 2Stage 3Stage 4Stage 5Total numberHealthy subjectsWithout CMBs3124324012724With CMBs14921350Total number3228416116224T2*-weighted MRI of brain was performed with a 1.5-T MRI system 162 CKD patients (CKD stag

16、es 15, excluding CKD stage 5(D)24 normal subjects. N DT 2010 25(5):1554-1559 Model 1Model 2Model 3 Online ISSN 1460-2385 - Print ISSN 0931-0509Copyright 2010 European Renal Association - European Dialysis and Transplant AssocOxford Journals Oxford University Press Site Map Privacy Policy Frequently

17、Asked Questions Other Oxford University Press sites: Model 1Model 2Model 3Odds ratio95% CIPOdds ratio95% CIPOdds ratio95% CIPAge (year)1.0501.0011.1020.04661.0761.0221.1320.00511.0360.9891.0850.1331Gender (female vs male)0.3470.1310.9190.03110.3280.1270.8450.02090.3370.1310.8640.0236eGFR (ml/min)0.9

18、710.9421.0000.05280.9560.9260.9880.00670.9670.9390.9960.0274Systolic pressure (mm Hg)1.0341.0341.0140.0006Diastolic pressure (mm Hg)1.0581.0191.0990.0035Pulse pressure (mm Hg)1.0301.0081.0530.0072 Return to article Odds ratio for the presence of CMBs adjusted by variablesAssociation of CKD and Cance

19、r Risk in Older People 3654 residents aged 49 to 97 yr, during a mean follow-up of 10.1 yr 711 (19.5%) cancers occurred in 3654 participants. Men with at least stage 3 CKD had a significantly increased risk for cancer (test of interaction for gender P = 0.004). The excess risk began at an estimated

20、GFR (eGFR) of 55 ml/min per 1.73 m2 (adjusted hazard ratio HR 1.39; 95% confidence interval CI 1.00 to 1.92) Journal of the American Society of Nephrology April 30, 2009Association of CKD and Cancer Risk in Older People 3654 residents aged 49 to 97 yr, during a mean follow-up of 10.1 yr 711 (19.5%)

21、cancers occurred in 3654 participants. Men with at least stage 3 CKD had a significantly increased risk for cancer (test of interaction for gender P = 0.004). The excess risk began at an estimated GFR (eGFR) of 55 ml/min per 1.73 m2 (adjusted hazard ratio HR 1.39; 95% confidence interval CI 1.00 to

22、1.92) And increased linearly as GFR declined. for every 10-ml/min decrement in eGFR, the risk for cancer increased by 29% (adjusted HR 1.29; 95% CI 1.10 to 1.53), with the greatest risk at an eGFR 40 ml/min per 1.73 m2 (adjusted HR 3.01; 95% CI 1.72 to 5.27). The risk for lung and urinary tract canc

23、ers but not prostate was higher among men with CKD Journal of the American Society of Nephrology April 30, 2009妊娠与CKD: CKD各期均影响妊娠91 CKD 病人；267 正常对照 早产 (44% versus 5%) Statistical significance across stages RR = 3.32 (1.09 to 10.13). 剖腹产 (44% versus 25%); 新生儿ICU (26% versus 1%). 1期 CKD (61 例) versus

24、controls 早产= 33% 剖腹产= 57% 新生儿ICU = 18% 病人蛋白尿与高血压和预后有关。 Clin J Am Soc Nephrol 5: 844-855, 2010Public ForumPublic Forum Top Dissecting and refining the staging of chronic kidney diseaseChristopher GWinearls & Richard JGlassockKidney Int 2009 75: 1009-1014; Abstract | Full Text Chronic kidney disease d

25、efinition and classification: no need for a rush to judgmentGarabedEknoyanKidney Int 2009 75: 1015-1018; 争 议1. 2. 分期及其界定值3. eGFR公式的可靠性 特别是在老年人群和健康人群 蛋白尿测定的可靠性4. 是否将疾病前期(高危人群)也包涵在CKD中？ 5. 是否过高地估计了CKD人群的数量？ 对防治措施和策略以及预后的影响如何鉴定CKD的定义与分期 应基于病人的预后，而非医生的愿望!应基于循证医学证据，而非个人的观点! Prognosis Matters复杂的统计学策略： 由2个

26、独立的统计学小组进行 eGFR与终点事件的关系 (白)蛋白尿与终点事件的关系 eGFR+(白)蛋白尿与终点事件的关系 所有分析经多因素校正 eGFR和(白) 蛋白尿分别以连续变量和等级变量表示 进行年龄65岁的分组分析Analytical team Johns Hopkins UniversityUniversity Hospital Groningen 样本来自全球,数量很大. 有基线eGFR和蛋白尿资料,队列人群样本量1000人,终点事件50例 共有21个研究1,234,182 例 由2个独立的统计学小组进行数据清理,荟萃分析, 追踪时间长,平均随访7.9年，5 million perso

27、n-years以硬终点事件为判断指标,终点事件：全因死亡与心血管死亡分析讨论包括不同观点专家. -质量高 结论客观eGFR对预后的影响全因死亡心血管死亡ESRDAKI CKD进展eGFR对预后的影响ACR对预后的影响eGFR 和(白)蛋白尿对预后的影响ACR:300 mg/g30-299 30 ,试纸法: +, +, -/全因死亡心血管死亡eGFR 和(白)蛋白尿对预后的影响不同年龄组来自数据的信息（一）eGFR与(白)蛋白尿是死亡的独立危险因素 eGFR10mg/g 现行eGFR30mg/g是CKD预后指标。CKD1-2期患者死亡风险增加。 支持CKD1-2期是疾病。CKD3期患者在eGFR

28、 45-60及30-45ml/min/1.73m2 预后不同。 CKD3期进一步区分为CKD3a和CKD3b。来自数据的信息（二）即使相同的eGFR分期，预后随(白)蛋白尿而不同 CKD分期应同时考虑(白)蛋白水平。年龄65岁及65岁患者虽然死亡风险有不同，但风险曲线形式相似。 证据不支持按年龄区分CKD的定义或分期。 Lancet 2010;published online May 18.CKD评定、分级指导意见工作组第一次会议2010 101-3 日第二次会议20110218-20日第三次会议2011078-9 日Work Group ofthe KDIGO Clinical Practi

29、ce Guideline for Chronic Kidney Disease:Evaluation, Classification, and Stratification.讨论问题CKD定义、分期对CKD病人的评估eGRF蛋白尿的评定高危人群CKD进展的定义CKD进展的因素CKD与糖尿病CKD与心血管疾病CKD合并症的处理影响病人安全性的因素对应用的推荐目前CKD尚存在的问题测定方法 CKD 患病率受测定方法不准确的影响老龄的影响 白蛋白尿存在的问题点尿测定 可行，方法稳定（ACR）性别、年龄的“正常值”微量蛋白尿的巨大变异 eGFR 存在的问题方法标准化 金标准？ 肌酐测定标准化公式适应人

30、群高eGFR人群老年人人种随意尿ACR与晨尿ACR相关性r0.92，p250 mg/g for men 355 mg/g for women指南的建议如果尿试纸检测阳性，应在三月内用定量的方法（蛋白肌酐比值或白蛋白肌酐比值）确定是否有蛋白尿。二次或二次以上定量试验阳性，诊断为持续性蛋白尿。NKF-K/DOQIeGFR 存在的问题方法标准化 金标准？ 肌酐测定标准化公式适应人群高eGFR人群老年人人种白蛋白尿存在的问题点尿测定 可行，方法稳定（ACR）性别、年龄的“正常值”微量蛋白尿的巨大变异 肾小球滤过率的评价Scr不能单独用作GFR的评价方法Ccr在一般情况下不必要用作GFR的评价方法估算G

31、FR（Estimates of GFR，eGFR）是当前评价肾功能的最好方法慢性肾脏病及透析的(K/DOQ)临床实践指南，2003MDRD公式存在的问题准确度 （ 80.6% ）于健康人群,低估其GFR值 CKD假阳性（平均r GFR39.8 21.2 ml/min/1.73m2 ）? 人群、种族差异改良的MDRD方程MDRD 7 (ml/min/1.73m2) =186 Pcr-1.154 Age-0.203 (女性 0.742)C - aGFR (ml/min/1.73m2) =206 Pcr-1.234 Age -0.227 (女性0.803) 中华肾脏病杂志 2006 ，23：589-

32、595JASN 2006，17：2937-2944总的偏差和准确性比较 MDRDC-a GFR 偏差中位数(25%, 75% 百分位数) (ml/min/1.73m2) -7.8 (-21.5,-1.8) -0.8* (-9.1,6.3) 准确性 66.1% 79.6%* P0.05, 改良前后简化MDRD方程偏差和准确性的比较 中华肾脏病杂志 2006 ，23：589-595 JASN 2006，17：2937-2944CKD-EPI eGFR equation Ann Interal Med 2009,May 5 8,254 participants in 10 studies (equa

33、tion development data set) 3,896 participants in 16 studies (validation data set). 16,032 participants in NHANES in prevalence estimatesLess bias (median difference between measured and estimated GFR,) 2.5 5.5 mL/min per1.73 m2Improved precision (interquartile range IQR of the differences) 16.6 18.3

34、 mL/min per1.73 m2Greater accuracy (percentage of estimated GFR within 30% of measured GFR) 84.1% 80.6%The prevalence of chronic kidney disease 11.5% 13.1% (95% CI, 10.6% to 12.4%) (CI, 12.1% to 14.0%). CKD-EPIMDRDLimitation: The sample contained a limited number of elderly people and racial and eth

35、nic minorities with measured GFR. CKD EPI Equation for Estimating GFR on the Natural Scale Expressed for Race, Sex and Range of Serum Creatinine. 血尿的检测试纸条法：血红蛋白触媒法 尿中来自食物的不耐热酶具有的过氧化物酶样作用导致的假阳性 尿中含有的维C等物质 尿中红细胞的变形裂解 假阳性率可达56.1尿沉渣镜检 491例患者进行复查， 持续性血尿 20.9% 目前CKD尚存在的问题测定方法老龄的影响 P0.05 compared with thos

36、e of the age less than 50A natural decrease in GFR with the elderly Analysis of 99mTc-DTPA plasma clearance Prevalence of CKD stages by age groups in the Beijing studyFrom L. Stevens, etal .AJKD 2008; 51:353-357遗传因素代谢因素（血糖、尿酸、高血脂、肥胖)药物、毒物高血压 感染、炎症不健康生活方式吸烟 CKDCardio-Kidney-Damage血管老化内皮功能紊乱 动脉粥样硬化 动脉僵硬CKD 在中国及全球 都是常见病、知晓率很低。CKD是预后严重的慢性病。CKD 是可防、可治的。 -临床有关CKD诊断的要点：对eGFR、尿蛋白及血尿的重复验证对CKD原发疾病的诊断CKD病人的一体化管理治疗原发疾病（严格控制血糖，）严格控制血压RAAS抑制剂 纠正贫血治疗矿物质代谢紊乱及甲旁亢控制血脂慢性肾脏病(CKD)及其分期 分期