1、CKD及其一體化管理王海燕北京大學腎臟疾病研究所北京大學第一醫院腎內科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.我國大陸與香港/臺灣/日本的透析病人數比較3北京全國2007年、2008年北京市城區和郊區血透治療患者比較透析分布失衡 慢性腎臟病(CKD)?慢性腎臟病(CKD) 的定義 腎損害（腎臟結構或功能異常3個月，伴有或不伴有腎小球濾過率（GFR）的下降，表現為下列異常之一：有病理學檢查異常；有腎損害的指標，如血、尿檢查異常；GFR60ml/min/1.73

3、m2 3個月，有或無腎損害。 Am J Kidney Dis. 2002Kidney Int. 2005慢性腎臟病(CKD)及其診斷 分期 描述GFR (ml/min/1.73m2)1 腎損傷GFR正常或 90 2 腎損傷GFR輕度 6089 3 GFR中度 3059 4 GFR嚴重 1529 5 腎衰竭 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與罹患慢性腎臟病相關的因素腎功能下降的危險因素：年齡，服用腎毒性藥物，脂代謝紊亂，高血壓白蛋白尿的危險因素：女性，糖尿病，高

7、血壓，脂代謝紊亂，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.開始透析病人： 心衰1/3 心絞痛1/4 心梗10% USRDS 1999125例透析前病人65.5%出現心血管合并癥需要緊急透析的病人72%為急性左心衰楊莉，等。中國實用內科雜志 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妊娠與CKD: CKD各期均影響妊娠91 CKD 病人；267 正常對照 早產 (44% versus 5%) Statistical significance across stages RR = 3.32 (1.09 to 10.13). 剖腹產 (44% versus 25%); 新生兒ICU (26% versus 1%). 1期 CKD (61 例) versus

24、controls 早產= 33% 剖腹產= 57% 新生兒ICU = 18% 病人蛋白尿與高血壓和預后有關。 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; 爭 議1. 2. 分期及其界定值3. eGFR公式的可靠性 特別是在老年人群和健康人群 蛋白尿測定的可靠性4. 是否將疾病前期(高危人群)也包涵在CKD中？ 5. 是否過高地估計了CKD人群的數量？ 對防治措施和策略以及預后的影響如何鑒定CKD的定義與分期 應基于病人的預后，而非醫生的愿望!應基于循證醫學證據，而非個人的觀點! Prognosis Matters復雜的統計學策略： 由2個

26、獨立的統計學小組進行 eGFR與終點事件的關系 (白)蛋白尿與終點事件的關系 eGFR+(白)蛋白尿與終點事件的關系 所有分析經多因素校正 eGFR和(白) 蛋白尿分別以連續變量和等級變量表示 進行年齡65歲的分組分析Analytical team Johns Hopkins UniversityUniversity Hospital Groningen 樣本來自全球,數量很大. 有基線eGFR和蛋白尿資料,隊列人群樣本量1000人,終點事件50例 共有21個研究1,234,182 例 由2個獨立的統計學小組進行數據清理,薈萃分析, 追蹤時間長,平均隨訪7.9年，5 million perso

27、n-years以硬終點事件為判斷指標,終點事件：全因死亡與心血管死亡分析討論包括不同觀點專家. -質量高 結論客觀eGFR對預后的影響全因死亡心血管死亡ESRDAKI CKD進展eGFR對預后的影響ACR對預后的影響eGFR 和(白)蛋白尿對預后的影響ACR:300 mg/g30-299 30 ,試紙法: +, +, -/全因死亡心血管死亡eGFR 和(白)蛋白尿對預后的影響不同年齡組來自數據的信息（一）eGFR與(白)蛋白尿是死亡的獨立危險因素 eGFR10mg/g 現行eGFR30mg/g是CKD預后指標。CKD1-2期患者死亡風險增加。 支持CKD1-2期是疾病。CKD3期患者在eGFR

28、 45-60及30-45ml/min/1.73m2 預后不同。 CKD3期進一步區分為CKD3a和CKD3b。來自數據的信息（二）即使相同的eGFR分期，預后隨(白)蛋白尿而不同 CKD分期應同時考慮(白)蛋白水平。年齡65歲及65歲患者雖然死亡風險有不同，但風險曲線形式相似。 證據不支持按年齡區分CKD的定義或分期。 Lancet 2010;published online May 18.CKD評定、分級指導意見工作組第一次會議2010 101-3 日第二次會議20110218-20日第三次會議2011078-9 日Work Group ofthe KDIGO Clinical Practi

29、ce Guideline for Chronic Kidney Disease:Evaluation, Classification, and Stratification.討論問題CKD定義、分期對CKD病人的評估eGRF蛋白尿的評定高危人群CKD進展的定義CKD進展的因素CKD與糖尿病CKD與心血管疾病CKD合并癥的處理影響病人安全性的因素對應用的推薦目前CKD尚存在的問題測定方法 CKD 患病率受測定方法不準確的影響老齡的影響 白蛋白尿存在的問題點尿測定 可行，方法穩定（ACR）性別、年齡的“正常值”微量蛋白尿的巨大變異 eGFR 存在的問題方法標準化 金標準？ 肌酐測定標準化公式適應人

30、群高eGFR人群老年人人種隨意尿ACR與晨尿ACR相關性r0.92，p250 mg/g for men 355 mg/g for women指南的建議如果尿試紙檢測陽性，應在三月內用定量的方法（蛋白肌酐比值或白蛋白肌酐比值）確定是否有蛋白尿。二次或二次以上定量試驗陽性，診斷為持續性蛋白尿。NKF-K/DOQIeGFR 存在的問題方法標準化 金標準？ 肌酐測定標準化公式適應人群高eGFR人群老年人人種白蛋白尿存在的問題點尿測定 可行，方法穩定（ACR）性別、年齡的“正常值”微量蛋白尿的巨大變異 腎小球濾過率的評價Scr不能單獨用作GFR的評價方法Ccr在一般情況下不必要用作GFR的評價方法估算G

31、FR（Estimates of GFR，eGFR）是當前評價腎功能的最好方法慢性腎臟病及透析的(K/DOQ)臨床實踐指南，2003MDRD公式存在的問題準確度 （ 80.6% ）于健康人群,低估其GFR值 CKD假陽性（平均r GFR39.8 21.2 ml/min/1.73m2 ）? 人群、種族差異改良的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) 中華腎臟病雜志 2006 ，23：589-

32、595JASN 2006，17：2937-2944總的偏差和準確性比較 MDRDC-a GFR 偏差中位數(25%, 75% 百分位數) (ml/min/1.73m2) -7.8 (-21.5,-1.8) -0.8* (-9.1,6.3) 準確性 66.1% 79.6%* P0.05, 改良前后簡化MDRD方程偏差和準確性的比較 中華腎臟病雜志 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. 血尿的檢測試紙條法：血紅蛋白觸媒法 尿中來自食物的不耐熱酶具有的過氧化物酶樣作用導致的假陽性 尿中含有的維C等物質 尿中紅細胞的變形裂解 假陽性率可達56.1尿沉渣鏡檢 491例患者進行復查， 持續性血尿 20.9% 目前CKD尚存在的問題測定方法老齡的影響 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遺傳因素代謝因素（血糖、尿酸、高血脂、肥胖)藥物、毒物高血壓 感染、炎癥不健康生活方式吸煙 CKDCardio-Kidney-Damage血管老化內皮功能紊亂 動脈粥樣硬化 動脈僵硬CKD 在中國及全球 都是常見病、知曉率很低。CKD是預后嚴重的慢性病。CKD 是可防、可治的。 -臨床有關CKD診斷的要點：對eGFR、尿蛋白及血尿的重復驗證對CKD原發疾病的診斷CKD病人的一體化管理治療原發疾病（嚴格控制血糖，）嚴格控制血壓RAAS抑制劑 糾正貧血治療礦物質代謝紊亂及甲旁亢控制血脂慢性腎臟病(CKD)及其分期 分期