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1 02 慢性腎臟病流行病學 診斷及惡化因子

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3 02 D A CKD GFR albuminuria) CKD C GFR C GFR cystatin C ,24 26 Chronic Kidney Disease CKD Kidney Disease Outcome Quality Initiative KDOQI CKD GFR 60 ml/min /1.73m 2 CKD GFR 2005 Kidney Disease Improving Global Outcome KDIGO CKD 2,3 KDIGO KDIGO CKD KDIGO CKD GFR CKD 5-8 KDIGO GFR<60 ml/ min/1.73m 2 ACR 30 mg/g 053

4 Taiwan Chronic Kidney Disease Clinical Guidelines CKD AER 30 mg/24 ACR 30 mg/g 3 mg/mmol GFR GFR<60 ml/min/1.73m 2 GFR G3a G KDOQI CKD GFR CKD CKD CKD CKD GFR GFR 5-8 KDIGO 2011 GFR CKD KDIGO GFR CGA CKD CKD GFR 3 GFR ml/min/1.73m 2 G3a ml/min/1.73m 2 G3b ml/min/1.73m 2 CKD CKD GFR GFR GFR ml/min/1.73m 2 G

5 02 CKD GFR G * G3a G3b G G5 <15 CKD GFR * egfr egfr<60 3~5 CKD G1 G2 CKD AER mg/24 h CKD ACR mg/mmol mg/g A1 <30 <3 <30 A * A3 >300 >30 >300 ** AER ACR - CKD * ** >2200 mg/24h [ACR>2220 mg/g >220 mg/mmol] GFR CKD CKD CKD GFR CKD GFR CKD 055

6 Taiwan Chronic Kidney Disease Clinical Guidelines GFR albuminuria CKD 2012KDIGO A1 A2 A3 <30 mg/g mg/g >300 mg/g <3 mg/mmol 3-30 mg/mmol >30 mg/mmol G1 >=90 G GFR ( ml/min/1.73m 2 ) G3a G3b G G5 <=15 GFR<60 ml/min/1.73m 2 GFR G3a-G5 CKD CKD CKD CKD CKD inulin clearance GFR GFR 125 I-iothalamate 99m Tc- DTPA GFR 10,11 99m Tc-DTPA renal dynamic imaging 20 GFR GFR MDRD GFR

7 % cystatin C 13.3 K cysteine 酶 Cystatin C GFR 13 GFR Cystatin C GFR ml/min/m 2 GFR cystatin C GFR 24 GFR Ccr ml/min = Ucr x V / Scr x 1440 min Ucr mg/ dl Scr mg/dl V 24 ml GFR CKD trimethoprim cimetidine GFR GFR 2012 KDIGO egfr MDRD CKD-EPI MDRD ,628 GFR 40 ml/min/1.73m 2 CKD 125 I-iothalamate variable MDRD abbreviated MDRD GFR 2005 Levey 057

8 Taiwan Chronic Kidney Disease Clinical Guidelines 4-variable MDRD IDMS- MDRD 15 4-variable or abbreviated MDRD 186 Cr age (0.742, if female) (1.212, if African American) IDMS-MDRD 175 Cr age (0.742, if female) (1.212, if African American) MDRD egfr>60 ml/min/1.73m 2 Levey I-iothalamate 8,254 5,504 CKD Epidemiology Collaboration CKD-EPI 2, ,896 IDMS-MDRD egfr>60 ml/min/1.73m 2 16 CKD-EPI GFR IDMS-MDRD 17 CKD-EPI MDRD CKD 18 KDIGO CKD-EPI GFR CKD-EPI MDRD CKD-EPI CKD 19, MDRD CKD-EPI MDRD x MDRD CKD CKD-EPI x CKD-EPI egfr 1.73m 2 ml/min/1.73m 2 egfr<60 ml/min/1.73m 2 Stevens 2,980 CKD cystatin C 2008 CKD-EPI cystatin C and CKD-EPI creatinine-cystatin C CKD-EPI CKD-EPI cystatin C CKD-EPI creatinine-cystatin C Inker 13 5, CKD-EPI cystatin C 2012 CKD-EPI creatinine-cystatin C 1, CKD GFR ml/min/1.73m 2 creatinine-cystatin C creatinine cystatin C 16.9% CKD-EPI 058

9 ml/min/1.73m 2 60 ml/min/1.73m 2 24 Shlipak cystatin C creatinine 11 90,750 5 CKD 2,960 CKD-EPI ml/min/1.73m 2 42% cystatin C 60 ml/min/1.73m 2 34% 80% ESRD cystatin C cystatin C creatinine egfr ESRD 25 egfr 4,26 KDIGO egfr ml/min/1.73m 2 CKD - egfr cystatin C mg/dl cystatin C cystatin C- egfr ml/min/1.73m 2 B CKD C CKD B AKI CKD ,41 B CKD ,31,36,38, 43,

10 Taiwan Chronic Kidney Disease Clinical Guidelines CKD CKD 12% GFR 48 CKD 24,492 6, % CKD 26.5% 95% CI % 49 CKD / CKD 2013 CKD HUNT II 65, % 20 CKD 3,069 egfr<60 ml/min/1.73m 2 CKD 4.7% % CI CKD 28 CKD CKD CKD CKD ( ) ,534 CKD CKD DM DM CKD Hazard Ratio HR % CI 3 10 DM HR % CI

11 , CKD 11% CKD ml/min/1.73m % 3.7% UKPDS 5,102 albuminuria DM 15 DM CKD 1% microalbuminuria HR % CI macroalbuminuria HR % CI DM HR % CI GFR 60 ml/min/1.73m 2 HR % CI ( ) ,534 CKD CKD ( 120 mmhg 80 mmhg ) CKD HR % CI HR % CI HR % CI HR % CI / HR % CI HR % CI % CI % CI % CI % CI UKPDS 5,102 DM 15 CKD 10 mmhg HR % CI HR % CI GFR 60 ml/min/1.73m 2 HR % CI HR % CI

12 Taiwan Chronic Kidney Disease Clinical Guidelines , , % CKD CKD OR ( ) 2006 UKPDS 5,102 DM 15 CKD HR % CI HR % CI ,826 CKD % CKD % Odds Ratio, OR = % CI ( ) ,365 OR=1.5 95% CI OR=1.9 95% CI OR=2.1 95% CI ESRD ESRD 33 ( ) ,728 2 mg/dl 1.8 mg/dl 0.4 mg/dl / TG CKD Rate Ratio, RR % CI HDL-C CKD RR % CI LDL-C CKD

13 02 ( ) ,620 ESRD 25,843 ESRD ESRD OR % CI ESRD OR % CI ESRD OR % CI ESRD OR % CI ( ) HR % CI , ESRD HR % CI CKD AKI ESRD HR % CI CKD AKI ESRD HR % CI ( ) , CKD 11% ml/min/1.73m 2 0.9% % >70 16% CKD >1.7 mg/dl 1, ,

14 Taiwan Chronic Kidney Disease Clinical Guidelines 2006 UKPDS 5, CKD HR %CI GFR 60 ml/ min/1.73m 2 HR % CI HR % CI ( ) , ESRD BMI>35 RR %CI , % CKD GFR 60 ml/min/1.73m 2 NCEP-ATP3 CKD OR % CI , , % CKD>26.6 kg/m 2 <22.7 kg/m 2 CKD OR % CI % CKD OR % CI UKPDS 5, CKD HR % CI HR % CI egfr 60 ml/ min/1.73m 2 HR HR= % CI , CKD OR % CI CKD

15 ,288 15% % GFR 60 ml/min/1.73m 2 CKD HR % CI ,035 HOMA 11.1% 8.99% CKD RR %CI CKD 11 30,146 CKD OR % CI CKD OR % CI OR % CI HDL-C OR % CI OR % CI OR % CI ( ) 2007 CKD 9.9% CKD OR % CI ( ) ,534 CKD CKD CKD HR % CI HR % CI , ESRD 20 CKD RR % CI UKPDS 5, CKD HR % CI GFR 60 ml/ min/1.73m 2 HR % CI

16 Taiwan Chronic Kidney Disease Clinical Guidelines ( ) , RR, RR=3.7 95% CI RR % CI CKD RR , , % CKD CKD OR 31 ( ) CKD 1 mg/dl OR % CI A proteinuria 20% Tamm-Horsfall mucoprotein immunoglobulin light chain beta2-microglobulin 066

17 proteinuria microalbuminuria 300 macroalbuminuria 1 51 KDIGO CKD 4 ACR >=30 mg/g >=3 mg/mmol 1- / ACR PCR B B ACR CKD PCR PCR ,55 C trace (+/-) Good practice point Good practice point 067

18 Taiwan Chronic Kidney Disease Clinical Guidelines Dipstick mg 60 mg/dl < 10 (+/-) (trace) > 1000 (1) ,028 8, , mg/dl (2) Okinawa 3%, 57 [-] [+/-] [1+] [2+] [>= 3+] 17 >= 3+ 16% % % +/- 0.38% 58 (3)

19 02 (4) (5) ACR 2+ GFR ml/min/1.73m 2 GFR 2.16 ml/min1.73m 2 1+ GFR ml/ min1.73m 2 GFR 0.51 ml/min1.73m 2 56 PCR (1) PCR 24 PCR likelihood ratios 0.2 PCR rule out 51 (2) PCR pre-eclampsia 55 ACR (3) PCR ACR (1) 24 ACR 24 AER ACR odds ratio 45.8 ACR (2) RR 4.8 RR (3) ACR PCR 4 (4) ACR PCR

20 Taiwan Chronic Kidney Disease Clinical Guidelines (5) ACR>=30 mg/g >=3 mg/mmol 4,63 (6) AER PER 4 (7) 1- monoclonal SIGN 2008 KDIGO 2012 CKD CKD KDIGO 2012 SIGN 2008 dipstick : KDIGO 2012 ACR PCR AER PER (mg/g) < > 300 (mg/mmol) < > 30 (mg/g) < > 500 (mg/mmol) < > 50 (mg/24h) < > 300 (mg/min) (mg/24h) < > 500 (SIGN 2008) 1+~3+ : (1) ACR PCR 1g 2 x ACR = PCR 1 g 1.3 x ACR = PCR 300 mg/day 500 mg/day (2) PCR ACR 1 mg/mmol=10 mg/g 070

21 02 Hematuria 1. 3 / ( ) 1. The National Kidney Disease Education Program NKDEP of the National Institutes of Health NIH 2. egfr 60 ml/min/1.73m 2 ACR PCR NKDEP CKD NKDEP 65 ( ) calcineurin lithium GFR NSAID GFR 63 ( ) / GFR 071

22 Taiwan Chronic Kidney Disease Clinical Guidelines ( ) NICE 2008 CKD 63 GFR (good practice points) ml/min/1.73m >= <

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24 Taiwan Chronic Kidney Disease Clinical Guidelines 12. Ma YC, Zuo L, Zhang CL, Wang M, Wang RF, Wang HY. Comparison of 99mTc-DTPA renal dynamic imaging with modified MDRD equation for glomerular filtration rate estimation in Chinese patients in different stages of chronic kidney disease. Nephrol Dial Transplant. 2007;22(2): (2-) 13. Dharnidharka VR, Kwon C, Stevens G. Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. Am J Kidney Dis. 2002;40(2): (1-) 14. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999;130(6): (2+) 15. Levey AS, Coresh J, Greene T, et al. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006;145(4): (2+) 16. Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9): (2+) 17. Earley A, Miskulin D, Lamb EJ, Levey AS, Uhlig K. Estimating equations for glomerular filtration rate in the era of creatinine standardization: a systematic review. Ann Intern Med. 2012;156(11): , w-270, w-271, w-272, w-273, w-274, w-275, w-276, w-277, w-278.(2++) 18. Matsushita K, Mahmoodi BK, Woodward M, et al. Comparison of risk prediction using the CKD-EPI equation and the MDRD study equation for estimated glomerular filtration rate. Jama. 2012;307(18): (1-) 19. Matsuo S, Imai E, Horio M, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53(6): (2-) 20. Horio M, Imai E, Yasuda Y, Watanabe T, Matsuo S. Modification of the CKD epidemiology collaboration (CKD-EPI) equation for Japanese: accuracy and use for population estimates. Am J Kidney Dis. 2010;56(1):32-38.(2-) 21. Chen LI, Guh JY, Wu KD, et al. Modification of diet in renal disease (MDRD) study and CKD epidemiology collaboration (CKD-EPI) equations for Taiwanese adults. PLoS One. 2014;9(6):e99645.(2-) 22. Stevens LA, Coresh J, Schmid CH, et al. Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3,418 individuals with CKD. Am J Kidney Dis. 2008;51(3): (2+) 074

25 Inker LA, Eckfeldt J, Levey AS, et al. Expressing the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) cystatin C equations for estimating GFR with standardized serum cystatin C values. Am J Kidney Dis. 2011;58(4): (2+) 24. Inker LA, Schmid CH, Tighiouart H, et al. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med. 2012;367(1):20-29.(2+) 25. Shlipak MG, Matsushita K, Arnlov J, et al. Cystatin C versus creatinine in determining risk based on kidney function. N Engl J Med. 2013;369(10): (1+) 26. Stevens LA, Levey AS. Measured GFR as a confirmatory test for estimated GFR. J Am Soc Nephrol. 2009;20(11): (1-) 27. Wu HY, Huang JW, Peng YS, et al. Microalbuminuria screening for detecting chronic kidney disease in the general population: a systematic review. Ren Fail. 2013;35(5): (1-) 28. Hallan SI, Dahl K, Oien CM, et al. Screening strategies for chronic kidney disease in the general population: follow-up of cross sectional health survey. Bmj. 2006;333(7577):1047.(2+) 29. Haroun MK, Jaar BG, Hoffman SC, Comstock GW, Klag MJ, Coresh J. Risk factors for chronic kidney disease: a prospective study of 23,534 men and women in Washington County, Maryland. J Am Soc Nephrol. 2003;14(11): (2+) 30. Retnakaran R, Cull CA, Thorne KI, Adler AI, Holman RR. Risk factors for renal dysfunction in type 2 diabetes: U.K. Prospective Diabetes Study 74. Diabetes. 2006;55(6): (2+) 31. Gelber RP, Kurth T, Kausz AT, et al. Association between body mass index and CKD in apparently healthy men. Am J Kidney Dis. 2005;46(5): (2+) 32. Elsayed EF, Tighiouart H, Griffith J, et al. Cardiovascular disease and subsequent kidney disease. Arch Intern Med. 2007;167(11): (2+) 33. Freedman BI, Soucie JM, McClellan WM. Family history of end-stage renal disease among incident dialysis patients. J Am Soc Nephrol. 1997;8(12): (2+) 34. Lai MN, Lai JN, Chen PC, Hsieh SC, Hu FC, Wang JD. Risks of kidney failure associated with consumption of herbal products containing Mu Tong or Fangchi: a population-based case-control study. Am J Kidney Dis. 2010;55(3): (2+) 35. Muntner P, Coresh J, Smith JC, Eckfeldt J, Klag MJ. Plasma lipids and risk of developing renal dysfunction: the atherosclerosis risk in communities study. Kidney Int. 2000;58(1): (2+) 36. Stengel B, Tarver-Carr ME, Powe NR, Eberhardt MS, Brancati FL. Lifestyle factors, obesity and the risk of chronic kidney disease. Epidemiology. 2003;14(4): (2+) 075

26 Taiwan Chronic Kidney Disease Clinical Guidelines 37. Chang HY, Lee PH, Lei CC, et al. Hyperuricemia is an independent risk factor for new onset micro-albuminuria in a middle-aged and elderly population: a prospective cohort study in taiwan. PLoS One. 2013;8(4):e61450.(2+) 38. Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis. 2003;41(1):1-12.(2+) 39. Guh JY, Chen HC, Tsai JF, Chuang LY. Herbal therapy is associated with the risk of CKD in adults not using analgesics in Taiwan. Am J Kidney Dis. 2007;49(5): (2-) 40. Wu VC, Huang TM, Wu PC, et al. Preoperative proteinuria is associated with long-term progression to chronic dialysis and mortality after coronary artery bypass grafting surgery. PLoS One. 2012;7(1):e27687.(2++) 41. Wu VC, Huang TM, Lai CF, et al. Acute-on-chronic kidney injury at hospital discharge is associated with long-term dialysis and mortality. Kidney Int. 2011;80(11): (2++) 42. Thomas G, Sehgal AR, Kashyap SR, Srinivas TR, Kirwan JP, Navaneethan SD. Metabolic syndrome and kidney disease: a systematic review and meta-analysis. Clin J Am Soc Nephrol. 2011;6(10): (1+) 43. Kurella M, Lo JC, Chertow GM. Metabolic syndrome and the risk for chronic kidney disease among nondiabetic adults. J Am Soc Nephrol. 2005;16(7): (2+) 44. Cheng HT, Huang JW, Chiang CK, Yen CJ, Hung KY, Wu KD. Metabolic syndrome and insulin resistance as risk factors for development of chronic kidney disease and rapid decline in renal function in elderly. J Clin Endocrinol Metab. 2012;97(4): (2+) 45. Drey N, Roderick P, Mullee M, Rogerson M. A population-based study of the incidence and outcomes of diagnosed chronic kidney disease. Am J Kidney Dis. 2003;42(4): (2-) 46. Yang T, Chu CH, Hsu CH, et al. Impact of metabolic syndrome on the incidence of chronic kidney disease: a Chinese cohort study. Nephrology (Carlton). 2012;17(6): (2-) 47. Chen S, Chen Y, Liu X, et al. Association of insulin resistance with chronic kidney disease in non-diabetic subjects with normal weight. PLoS One. 2013;8(9):e74058.(2-) 48. Wen CP, Cheng TY, Tsai MK, et al. All-cause mortality attributable to chronic kidney disease: a prospective cohort study based on adults in Taiwan. Lancet. 2008;371(9631): (2+) 076

27 Ryan TP, Sloand JA, Winters PC, Corsetti JP, Fisher SG. Chronic kidney disease prevalence and rate of diagnosis. Am J Med. 2007;120(11): (3) 50. Qaseem A, Hopkins RH, Jr., Sweet DE, Starkey M, Shekelle P. Screening, monitoring, and treatment of stage 1 to 3 chronic kidney disease: A clinical practice guideline from the American College of Physicians. Ann Intern Med. 2013;159(12): (2++) 51. Price CP, Newall RG, Boyd JC. Use of protein:creatinine ratio measurements on random urine samples for prediction of significant proteinuria: a systematic review. Clin Chem. 2005;51(9): (2++) 52. Ewald B, Attia J. Which test to detect microalbuminuria in diabetic patients? A systematic review. Aust Fam Physician. 2004;33(7): , 571.(2++) 53. Newman DJ, Mattock MB, Dawnay AB, et al. Systematic review on urine albumin testing for early detection of diabetic complications. Health Technol Assess. 2005;9(30):iii-vi, xiii-163.(2++) 54. Ruggenenti P, Gaspari F, Perna A, Remuzzi G. Cross sectional longitudinal study of spot morning urine protein:creatinine ratio, 24 hour urine protein excretion rate, glomerular filtration rate, and end stage renal failure in chronic renal disease in patients without diabetes. Bmj. 1998;316(7130): (2++) 55. Morris RK, Riley RD, Doug M, Deeks JJ, Kilby MD. Diagnostic accuracy of spot urinary protein and albumin to creatinine ratios for detection of significant proteinuria or adverse pregnancy outcome in patients with suspected pre-eclampsia: systematic review and meta-analysis. Bmj. 2012;345:e4342.(2++) 56. Turin TC, James M, Ravani P, et al. Proteinuria and rate of change in kidney function in a community-based population. J Am Soc Nephrol. 2013;24(10): (2-) 57. Iseki K, Iseki C, Ikemiya Y, Fukiyama K. Risk of developing end-stage renal disease in a cohort of mass screening. Kidney Int. 1996;49(3): (2+) 58. Iseki K, Ikemiya Y, Iseki C, Takishita S. Proteinuria and the risk of developing end-stage renal disease. Kidney Int. 2003;63(4): (2+) 59. Tonelli M, Jose P, Curhan G, Sacks F, Braunwald E, Pfeffer M. Proteinuria, impaired kidney function, and adverse outcomes in people with coronary disease: analysis of a previously conducted randomised trial. Bmj. 2006;332(7555):1426.(2+) 60. Carroll MF, Temte JL. Proteinuria in adults: a diagnostic approach. Am Fam Physician. 2000;62(6): (3) 077

28 Taiwan Chronic Kidney Disease Clinical Guidelines 61. Lin CY, Sheng CC, Chen CH, Lin CC, Chou P. The prevalence of heavy proteinuria and progression risk factors in children undergoing urinary screening. Pediatr Nephrol. 2000;14(10-11): (2+) 62. Boulware LE, Jaar BG, Tarver-Carr ME, Brancati FL, Powe NR. Screening for proteinuria in US adults: a cost-effectiveness analysis. Jama. 2003;290(23): (2++) 63. NICE clinical guideline 73: Early identification and management of chronic kidney disease in adults in primary and secondary care (4) 64. Chadban SJ, Briganti EM, Kerr PG, et al. Prevalence of kidney damage in Australian adults: The AusDiab kidney study. J Am Soc Nephrol. 2003;14(7 Suppl 2):S (2+) 65. National Kidney Disease Education Program (NKDEP). (4) 078