1. 颜红兵 首都医科大学附属北京安贞医院 北京市心肺血管疾病研究所 对比剂肾病 - 新证据，新指南

2. PCI 与 CIN

3. CIN Definition  New onset or exacerbation of renal dysfunction after CM administration in the absence of other causes: increase by > 25% or absolute  of > 0.5 mg/dL from baseline sCr Occurs 24 to 48 hrs post-CM exposure, with Cr peaking 5 -7 days later and normalizing within 7-10 days in most cases

4. Lack of Standard Definition Makes CIN Hard to Interpret  Rates of CIN vary between 3% and 10%, depending on definition used  Many patients with CIN still within normal range of SCr, eGFR levels  Adverse events extremely low in registry, even with CIN SCr  ≥ 0.5 mg/dl (n = 9) eGFR  ≥ 25% (n = 21) SCr  ≥ 25% (n = 28) Composite (n = 29) CIN3.3%7.6%10.2%10.5% Jabara R. AJC,2009,103:1657-1662

5. New Markers of Renal Function: Cystatin C  Non -glycosilated protein with low molecular mass  Produced at a constant rate in all nucleated cells and secreted from the cells  Removed from blood plasma by glomerular filtration in the kidneys  It is reabsorbed by the tubulus and degraded  Higher blood levels imply reduced GFR  Cystatin C is suggested to be a better marker for GFR than serum Cr  higher sensitivity to detect a reduced GFR than Cr determination

6. CIN Rates – Serum Cystatin C Solomon et al., CJASN 2009; 4:……

7. Circulation. 2010;121:2117-2122

9. In CKD pts undergoing angiography, isosmolar CM are indicated and are preferred. Chronic Kidney Disease-2007

10. J Am Coll Cardiol 2006;48:924 –30

12. J Am Coll Cardiol 2006;48:692–9

16. 终点 典比乐 370 组 (N=204) 威视派克 320 组 (N=210) P 值 * Scr 绝对升高 ≥ 0.5 mg/dL 9 (4.4%)14 (6.7%) 0.39 Scr 相对升高 ≥ 25% 20 (9.8%)26 (12.4%) 0.44 eGFR 减少 ≥ 25% 12 (5.9%)21 (10.0%) 0.15 * Fisher’s exact test 所有人群 (N=414) Circulation 2007;115:3189

17. 终点 典比乐 370 组 (N=78) 威视派克 320 组 (N=92) P 值 * Scr 绝对升高 ≥ 0.5 mg/dL 4 (5.1%)12 (13.0%) 0.12 Scr 相对升高 ≥ 25% 8 (10.3%)14 (15.2%) 0.37 eGFR 减少 ≥ 25% 5 (6.4%)12 (13.0%) 0.20 合并糖尿病的中至重度肾损害患者亚组 (N=170) * Fisher’s exact test Circulation 2007;115:3189

18. J Am Coll Cardiol Intv 2009;2:645–254

20. Nephrotoxicity of iso-osmolar iodixanol compared with nonionic LOCM: meta-analysis of randomized controlled trials.  25 trials were included  Iodixanol is not associated with a significantly reduced risk of CIN compared with the LOCM pooled together. However, in pts with intraarterial administration and renal insufficiency, iodixanol is associated with a reduced risk of CIN compared with iohexol, whereas no significant difference between iodixanol and other LOCM could be found. Radiology. 2009;250:68–86.

21.  No significantly different between the 2 CM groups (0.19±0.40 mg/dL for iodixanol and 0.21±0.34 mg/dL for iomeprol; P=0.53).  Albeit CIN rates were lower with iodixanol (22.2% compared with 27.8% for iomeprol), this difference was not statistically different (P=0.25).  Subgroup analysis suggested a favorable outcome regarding nephrotoxicity in pts who received higher CM volumes (>340 mL) in the iodixanol group (P interaction =0.016). Choice of CM in Pts With Impaired Renal Function Undergoing PCI CONTRAST Trial investigators Circulation: Cardiovasc Interven on Sept 22, 2009

22. 典比乐欧乃派克优维显威视派克 分子量 777.09821.14791.121550.20 粘滞度 (mPa.s)37 ℃ 300/320mgI/ml 4.76.15.111.8 典比乐分子量最小，粘滞度最低 常用对比剂理化性比较

23. 不同对比剂碘浓度 300 mg/ml 时的 渗透压和粘滞度 4 7 10 200300400500600700800 渗透压 (mOsm/kg H 2 O) 粘滞度 (mPa*s, 37°C) 威视派克 欧乃派克 典迈伦 优维显 典比乐

24. 对比剂肾脏安全性 渗透压 粘滞度 分子毒性 共同 共同 影响  对比剂渗透压 <800 mOsm/kg 时，粘滞度在 CIN 的发病中更 重要  典比乐不仅 CIN 发生率低，而且远期临床事件发生率显著低 于等渗对比剂碘克沙醇

25. New Data Support Change to CM Guidelines  Risk of kidney injury equivalent between iodixanol, LOCM  Iso-osmolar agent still more protective than ioxalgate, iohexol  Cost of iodixanol an issue in light of equally effective LOCM options

26. Angiography in pts with CKD-2009 MODIFIED Recommendation In pts with CKD undergoing angiography and who are not on chronic dialysis, either an isosmolar CM or a low molecular weight CM other than ioxaglate or iohexol is indicated

27. J Am Coll Cardiol 2010;55:1433–1340

28. Glucose and Risk of CI-CIN

29. Glucose and CI-CIN Rates Across GFR Subgroups

31. Does Safe Dosing of CM Prevent CIN? Brown JR. Circulation: Cardiovascular Interventions. 2010 Published online before print June 29, 2010 Consecutive pts undergoing PCI were prospectively enrolled from 2000 - 2008 (n=10 065). Pts on dialysis before PCI were excluded (n=155). MACD: (5 mLxbody weight [kg])/baseline sCr [mg/dL]) Divided into categories in which 1.0 reflects the MACD limit: MACD ratios MACD (1.0 - 1.5, 1.5 - 2.0, and >2.0). CI-CIN: 0.3 (mg/dL) or 50% increase in sCr from baseline or new dialysis. Consecutive pts undergoing PCI were prospectively enrolled from 2000 - 2008 (n=10 065). Pts on dialysis before PCI were excluded (n=155). MACD: (5 mLxbody weight [kg])/baseline sCr [mg/dL]) Divided into categories in which 1.0 reflects the MACD limit: MACD ratios MACD (1.0 - 1.5, 1.5 - 2.0, and >2.0). CI-CIN: 0.3 (mg/dL) or 50% increase in sCr from baseline or new dialysis. MACD: maximum allowable contrast dose

32. Outcomes Stratified by CM Dose Level ≤ Maximum> MaximumP Value CI- CIN5.9%15.3%< 0.001 Dialysis0.2%1.5%< 0.001 Cardiac Events10.2%13.4%< 0.001 Bleeding4.1%8.4%< 0.001 Transfusion3.8%8.3%< 0.001 Length of Stay, days 2.2 ± 4.12.8 ± 4.6< 0.001 In-Hospital Death1.7%3.4%< 0.001

33. Propensity-Matched Results OR95% CIP Value CI-CIN1.751.49-2.07< 0.001 Dialysis3.131.73-5.65< 0.001 Cardiac Events1.130.97-1.320.125 Bleeding1.261.02-1.550.032 Transfusion1.301.05-1.600.016 In-Hospital Death0.980.71-1.350.904 Relationship seen between contrast volume threshold, acute kidney injury Risk of kidney damage increases by 45% for each increase in dose above safety threshold Pts with multivessel or LM disease at higher risk of excess CM Exceeding Contrast Dose Threshold Increases Risk of CIN Relationship seen between contrast volume threshold, acute kidney injury Risk of kidney damage increases by 45% for each increase in dose above safety threshold Pts with multivessel or LM disease at higher risk of excess CM Exceeding Contrast Dose Threshold Increases Risk of CIN

34. 研究比较有或无 CIN 发生的患者随访 1 年以上的临床 事件发生差异 研究比较使用典比乐 370 或威视派克 320 后发生 CIN 的 患者随访 1 年以上的临床事件发生差异 Clin J Am Soc Nephrol 4: 1162–1169, 2009

35. Incidence of Any Adverse Event within 12 Months Definition of CINPts With CINPts Without CINP Cystatin C  ≥ 15% 42%26%0.02 Cystatin C  ≥ 20% 43%27%0.03 Cystatin C  ≥ 25% 46%27%0.01 SCr  ≥ 0.3 mg/dL43%29%0.04

36. Impact of high-dose NAC vs placebo on CIN and myocardial reperfusion injury in unselected pts with STEMI undergoing PPCI: The LIPSIA-N-ACC trial Thiele H. JACC. 2010;55:2201-2209. Prospectively randomized 251 STEMI pts undergoing PPCI to either high-dose NAC (1,200 mg twice per day for 48 hrs; n = 126) or placebo (n = 125) in addition to optimal hydration with saline infusion. The groups were well matched in terms of renal function, volume of contrast medium, number of pts with high CM volume (≥ 300 ml), and other baseline demographics. Prospectively randomized 251 STEMI pts undergoing PPCI to either high-dose NAC (1,200 mg twice per day for 48 hrs; n = 126) or placebo (n = 125) in addition to optimal hydration with saline infusion. The groups were well matched in terms of renal function, volume of contrast medium, number of pts with high CM volume (≥ 300 ml), and other baseline demographics.

37. MRI Measurements NACPlaceboP Value Myocardial Salvage Index 43.5 (25.4-71.9)51.5 (29.5-75.3)0.36 Infarct Size, % LV17.4 (9.1-25.9)14.3 (8.0-26.2)0.47 LVEF, %52.1 (43.5-59.2)50.6 (41.6-58.6)0.23 NAC does not help reduce CIN, reperfusion injury, or clinical events in STEMI pts NAC does reduce markers of oxidative stress Study may be too small to draw definitive conclusions NAC does not help reduce CIN, reperfusion injury, or clinical events in STEMI pts NAC does reduce markers of oxidative stress Study may be too small to draw definitive conclusions

38. New Options May Help Prevent CIN CIN -New Evidence, New Guidelines