2 CKD の意義 ステートメント 1 腎機能低下と末期腎不全 1 進行した腎機能の低下 (CKD ステージ ) 1, 2) は末期腎不全の危険因子である 3-7). 2 日本人の GFR の低下速度は平均 0.36 ml/ 分 /1.73 m 2 / 年であり,40~69 歳では 50 ml/ 分 / 1.73 m 2 以下,70~79 歳では 40 ml/ 分 /1.73 m 2 以下の腎機能の場合, 腎機能低下速度が有意 に速まる 8). 2 蛋白尿と末期腎不全 1 蛋白尿およびアルブミン尿は末期腎不全の危険因子である. 蛋白尿, アルブミン尿の程度が増 すごとにリスクが高くなる 9-16). 2 治療介入による, 蛋白尿, アルブミン尿の減少の程度は, 腎機能悪化抑制と相関がある. 3 血尿と末期腎不全 血尿 ( 試験紙法 ) は, 男性において末期腎不全の危険因子であるが, その関与度は蛋白尿に比べ ると弱い. また, 尿潜血と尿蛋白の両方が陽性の場合, 末期腎不全のリスクが高い 10) 4 CKD と心血管病 (CVD) 1 腎機能の低下は心血管病 (CVD) の危険因子である 3, 17-34). 2 蛋白尿およびアルブミン尿は CVD の危険因子である. 蛋白尿, アルブミン尿の程度が増すご とに CVD のリスクが高くなる 17-20, 22, 24, 28, 30-34). 3 治療介入による, 蛋白尿 アルブミン尿の減少の程度は,CVD 発症の抑制と相関があ る 35-37). 5 日本における CKD の頻度 日本人成人における CKD 患者の頻度はステージ 1 が 0.6%, ステージ 2 が 1.7%, ステージ 3 が 10.4%, ステージ 4 + 5 が 0.2% である. ステージ 3 ~ 5 の推計患者数は約 1,097 万人にのぼり, 総合的な CKD 対策が求められている. 17
エビデンスに基づく CKD 診療ガイドライン 2009 解説 1 CKD は末期腎不全の危険因子である 1. 腎機能低下は末期腎不全の危険因子である CKD 4, 5 CKD 17 CKD 3 CKD 4 5 1 CKD 3 8, 38 2 GFR 1 Iseki 18 107,192 10 Cr 1.4 mgdl 1.2 mgdl Cr 2.0 mg dl 64 39 10 2 egfr 6069 ml1.73 m 2 2 GFR 4069 50 ml1.73 m 2 7079 40 ml1.73 m 2 8 2. 蛋白尿は末期腎不全の危険因子である. CKD 1 3 8, 10 1115 11 1,860 Cr Cr 2 1 1 g 5.56 16 CKD 1 2 ACEI 3. 血尿と末期腎不全 18
2.CKD の意義 10 2 CKD は CVD の危険因子である 1.CKD は CVD の危険因子であるという新しい考え CVD 17, 18 2002 National Kidney FoundationKidney Disease Outcomes Quality InitiativeKDOQIwork group CKD CVD 19 2003 American Heart AssociationAHA Kidney Disease as a Risk Factor for Development of Cardiovascular Disease Scientific Statement 20 2004 Kidney DiseaseImproving Global OutcomesKDIGO cardiorenal association CKD risk equivalent CKD 3 CVD CKD CVD 2. 腎機能低下は CVD の危険因子である KDOQI 19 AHA Scientific Statement 20 CVD KDOQI 19 GFR CVD CVD 1, 1926 21, 23, 25 23, 25 1, 23, 24 2123, 26 24, 27 CVD 28 2224, 27, 28 3.アルブミン尿, 蛋白尿は CVD の危険因子である CVD 18 1997 11 2,138 6.4 2 30 KDOQI 19 CVD CVD CVD 2 CVD 19, 20, 24, 2934 34 32 32 31 CVD 18, 22, 30 22, 31, 32, 34 CVD 17, 19, 20, 33 CVD 17, 22, 28 17, 22 4. 治療介入によるアルブミン尿 蛋白尿の減少は CVD 発症の抑制を示唆する CKD CVD LDL HDL CKD CVD PREVENDIntervention Trial 35 RENAAL 19
エビデンスに基づく CKD 診療ガイドライン 2009 study 36 LIFE study 37 ACEI ARB CVD 5.Traditional risk factor と non-traditional risk factor について CKD CVD CKD CVD CVD CKD CKD CVD traditional CVD risk factor CVD LDL HDL CVD CKD CKD CVD CKDrelated nontraditional CVD risk factor CKD CVD CKD GFR PCa ADMA asymmetric dimethylargininefetuina 3 日本人における CKD の頻度 1. 腎機能低下に基づいた日本人における CKD の頻度 CKD NHANES egfr60 ml1.73 m 2 19992004 8.4%2039 0.8%4059 4.4%60 27.7% 7.2% 9.4% 40 CKD GFR GFR GFR egfr60 ml 1.73 m 2 10.4% 10 2 40 egfr 0.36 ml1.73 m 2 4049 0.355059 0.316069 0.377079 0.42 ml1.73 m 2 4049 0.415059 0.31 6069 0.327079 0.39 ml1.73 m 2 9 egfr 50 106 mmhg 96 mmhg 1.2 egfr 2 9 2. 本邦における検尿システムと検尿異常者の割合 CKD CKD b 20
2.CKD の意義 3 49 1 40 CKD 2.7% 2.0% 0.6% 0.1% 6.8% 4.5% 2.0% 0.4% 4.9% 2.7% 1.8% 0.3% 7.31% b, c 6.3% 3.9% 1.7% 0.6% 18.4% 16.0% 1.4% 0.9% b 9.1% 0.6%0.9% 0.9%0.9% 6.2%1.1% b Takahata 2,321 13.7% 3 CKD 668 17.8% 41 50,501 6.35 1983 1996 9.5% 40 42 d 2 31.6%95% CI 30.632.610.5% 95% CI 9.9 11.1 43 1 e 21
エビデンスに基づく CKD 診療ガイドライン 2009 アブストラクトテーブル 論文コード対象方法結果 1.Drey N, Am J Kidney Dis 2003 405,000 CKD Cr 1.7 mgdl 5.5 Cr 5.5 4% 69% Cr 3.57 mgdl 21% Cr 5.7 mgdl 46% 2.Kovesdy CP, Adv Chronic Kidney Dis CKD 35 861 2.1 GFR MDRD GFR 20 ml 1.73 m 2 GFR4160 ml1.73 m 2 GFR 10 ml1.73 m 2 1.28 1,000 egfr 20 ml1.73 m 2 214.1 20 30 ml1.73 m 2 63.6 3140 ml 1.73 m 2 33.8 4160 ml1.73 m 2 25.3 3.Keith DS, Arch Intern Med 2004 egfr 90 ml1.73 m 2 27,998 5 GFR MDRD 5 CKD 2 1.1% 3 1.3% 4 19.9% 2 19.5% 3 24.3% 4 45.7% 4 2 3 2 11 2 10 4.Patel UD, Am J Kidney Dis 7 12,570 3 GFR MDRD 3 egfr 60 ml1.73 m 2 0.0 egfr60 ml1.73 m 2 0.2 egfr 4559 ml 1.73 m 2 0.3 egfr 3044 ml1.73 m 2 1.7 egfr 1529 ml 1.73 m 2 14.2 egfr 15 ml 1.73 m 2 29.8 5.Evans M, Am J Kidney Dis 18 74 920 Cr 3.4 mgdl 2.8 mgdl 5579 GFR MDRD 80% 739 10% GFR 45 65 6.Serrano A, Adv Chronic Kidney Dis 2007 CKD CKD 4 5 82 2 3 1 GFR GFR MDRD 82 35 27 1 7 egfr 15 ml 1.73 m 2 egfr15 ml1.73 m 2 GFR 1 ml1.73 m 2 21.2% 22
2.CKD の意義 論文コード対象方法結果 7.Norris KC, J Am Soc Nephrol GFR2065 ml 1.73 m 2 1,094 36.4 GFR 50% 25 ml 1.73 m 2 GFR 125iothalamate clearance GFR GFR 40 ml1.73 m 2 GFR 5 ml1.73 m 2 HR 1.71 8.Imai E, Hypertens Res 2008 患者対照研究 10 2 120,727 egfr MDRD egfr 0.36 ml1.73 m 2 egfr 6069 ml1.73 m 2 2 GFR 4069 50 ml 1.73 m 2 7079 40 ml1.73 m 2 9.Ishani A, J Am Soc Nephrol 12,866 MRFIT 25 egfr MDRD 1 3.1 2 15.7eGFR 60 ml 1.73 m 2 75 ml1.73 m 2 2.4 10.Iseki K, 2003 106,177 17 1 2.71 1.38 11.Zhang Z, J Am Soc Nephrol 2 vs. Cr 3.4 300 mgg Cr Cr 1.33.0 mg dl1,513 RE- NAAL 1 g 24 g 2.6 4 g 18.6 12.Peterson JC, Ann Intern Med 1995 CKD 840 MDRD vs. 2.2 GFR 13.Lea J, Arch Intern Med GFR vs. vs. 2065 ml1.73 m 2 3.8 1,094 AASK 2 GFR 0.54 ml1.73 m 2 14.Halbesma N, J Am Soc Nephrol 8,592 PREVEND 22 factorial design 4 CVD HR 2.6HR 3.4eGFR 2.3 ml1.73 m 2 7.2 ml1.73 m 2 15.Atkins RC, Am J Kidney Dis 1 900 mg 2 Cr 3.0 mgdl 1,715 2 Cr 2 2.04 23
エビデンスに基づく CKD 診療ガイドライン 2009 論文コード対象方法結果 16.Jafar TH, 2001 メタ解析 19771997 ACEI 11 1,860 ACEI vs. 2.2 Cr 1 1 g RR 2.94 Cr 1 1 g RR 5.56 17.Kannel WB, Am Heart J 1984 Framingham study 5,209 2 30 HR 2.995%CI2.04.2 1.795%CI 1.02.9 18.Damsgaard EM, BMJ1990 Fredericia 216 2 6283 HR 2.94 95%CI1.316.64 19.KDOQI, Am J Kidney Dis 2002 システマティックレビュー CKD CVD NKF CKD CVD 10 CKD CVD 28 CVD CKD CVD 20.Sarnak MJ, Circulation 2003 システマティックレビュー CKD CVD AHA CVD 13 CVD 21 CVD 49 CVD CKD CVD AHA 21.Ninomiya T, 2,634 19882000 Cox CKD coronary heart disease egfrml HR 2.2695%CI1.064.79ischemic stroke 1.73 m 2 60 CKD HR 1.9195%CI1.153.13 CVD coronary heart disease ischemic strokehemorrhagic stroke 22.Nakayama M, Nephrol Dial Transplant 2007 19921997 7.8 Cox 1,977 Calculated CCr ml1.73 m 2 40 40 70 70 3 CVD HR CVD HR 23.Anavekar NS, VALIANT study N Engl J Med CVD 14,527 2004 ( からの観察研究 ) Cox egfr ml1.73 m 2 45.0 45.059.960.074.975.0 4 CVD 24.7 GFRmL1.73 m 2 10 CVD HR1.10 95% CI1.081.12 24
2.CKD の意義 論文コード対象方法結果 24.Kottgen A, J Am Soc Nephrol 2007 19872002 Cox egfr 4 ml1.73 m 2 60 60 90 90 3 14,857 13.2 egfrml1.73 m 2 90 60 HR 1.9495%CI1.49 2.53 25.Brugts JJ, Arch Intern Med 19901993 Ommoord 4,484 8.6 Cox CockcroftGault MDRD 4 4 3 2 1 CockcroftGault HR 1.6495%CI1.032.591.9495%CI1.21 3.103.0695%CI1.805.19MDRD HR 1.3495%CI0.892.011.6695%CI 1.142.491.9095%CI1.252.90 26.Weiner DE, J Am Soc Nephrol 2007 27.Go AS, N Engl J Med 2004 19871989 111 2 A R I C s t u d y, CHS 20,358 19962000 Kaiser Permanent 1,120,295 Cox egfr ml 1.73 m 2 60 CKD CKD CKD HR 1.2295%CI 1.021.441.1895%CI1.141.21 CKD SBPmmHg120 120129 HR 2.51 95%CI1.304.87 J shape 2.84 Cox RR egfrml1.73 m 2 15 15293044 455960 5 CVD 28.Irie F, 96,739 19932003 Cox CVD CVD CVD CVD CVD RR 29.Manjunath G, J Am Coll Cardiol 2003 4 15,350 6.2Cox egfrml1.73 m 2 90150 egfrml1.73 m 2 CVD HR 1559608990150 3 CVD 30.Dinneen SF, Arch Intern Med 1997 メタ解析 NIDDM 11 2,138 HR 2.4 CVD CVD 95%CI1.33.1CVD CVD 6.4 2.095%CI1.42.7 31.Gerstein HC, JAMA HOPE study 55 2001 CVD ( からの観察研究 ) 5,545 CVD 3,498 32.Wachtell K, LIFE study Ann Intern Med II, III 2003 8,206 ( からの観察研究 ) 19941999, 4.5 Cox CVD 39,122 Cox Cr 10 5 CVD HR CVD1.8395%CI1.642.05 2.09 95%CI1.842.38 3.23 95%CI2.544.10 Cr 10 57%CVD 97.7% 75.2% 51% 45% 25
エビデンスに基づく CKD 診療ガイドライン 2009 論文コード対象方法結果 33.Hillege HL, Circulation 2002 Groningen 40,548 19971998 UAC CVD CVD 961 Cox UAC 4 10 mgl 1020 mgl 20200 mgl200 mgl 4 CVD CVD 34.Klausen K, Circulation 2004 19221994 The Third Copenhagen City Heart Study 2,762 CHD 1998 2001 8 Cox 4 2.1g 2.13.0g 3.04.8 g4.8g 4 CHD 4.8g HR CHD 2.095%CI1.43.0 1.9 95%CI1.52.4 35.Asselbergs FW, Circulation 2004 19981999 Groningen PREVEND 15300 mg 24 hr 864 46 22 factorial designcvd CVD 26% 40% 36.de Zeeuw D, Circulation 2004 ( からの観察研究 ) 37.Olsen MH, J Hypertens ( からの観察研究 ) RENAAL study NIDDM 0.3 g g Cr 24 0.5 g 1,513 LIFE study 1 34 6,679 Cox 6 CVD Cox 1 log Cr CVD 50% CVD 18% 27% 1 log Cr HR 1.29 per 10fold increase CVD HR 1.59, p 0.001 Framingham risk score CVD 38.Eriksen BO, Tromso CKD 3 egfr 30 59 ml1.73 m 2 3,047 10 44 GFR MDRD egfr 1.03 ml1.73 m 2 959 31%CKD 5 62 2%10 0.0410 0.51 egfr 10 ml1.73 m 2 2.50 39.Iseki K, 1997 20 Cr 95,255 7 CockcroftGault CCr 1,000 86.8 CCr 50.213.6 CCr 50.263.98.3 CCr64.079.37.9 CCr79.41.2 CCr 50.20.7 CCr50.263.90.04 CCr64.079.30.13 CCr79.4 CCr 26
2.CKD の意義 論文コード対象方法結果 40.Coresh J, JAMA 2007 National Health and Nutrition Examination Sur veynhanes 19881994 15,488 19992004 13,233 30 mgg Cr MDRD GFR CKD CKD 10.0%1988199413.1% 19992004 11.7%198819941.8%19992004 22.7%198819943.2%1999 2004 35.4%19881994, 7.7% 19992004 40.21%1988 19940.35%19992004 41.Konta T, 40 2,321 CockcroftGault CCr 1 13.7%1.7%4.4% CKD 35 668 17.8 % 2.7% 42.Yamagata K, Nephron 2002 1562 50,501 772 6.35 2 9.5% 40 43.Yokoyama H, Diabetes Care 2007 29 Japan Diabetes Clinical Data Management Study Group 2 8,897 Cr 2 31.6% 95% CI 30.632.610.5%95% CI 9.911.1 27
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