对比剂肾病研究新前沿

1、欧洲泌尿生殖放射协会（ESUR）对比剂指南（6.0版）Marenzietal.JACC2004;44:780-5TheinnerstripeoftheoutermedullaistheareaatriskforCIN单 体双 体（碘克沙醇）注射非离子等渗对比剂后肾小管的压力变化高粘滞度的CM滤过在小管系统浓缩水化阻力（特别是在集合小管）小管压力GFR肾髓质血流（）通常情况下，由于超滤液中很少含蛋白，因此肾小管液的粘滞度较血浆低预防性水化可以降低CM在肾脏集合管浓缩的浓度，从而有效预防CIN的发生应用对比剂后，特别是双聚体等渗对比剂后，显著增加小管液的粘滞度而使肾小管流体阻力增加因此，肾间质压力

2、增加50mmHg，肾髓质血流显著减少，GFR显著下降。American Journal of Kidney Diseases 2002; 39(2) Suppl 1: S46American Journal of Kidney Diseases 2002; 39(2) Suppl 1: S46American Journal of Kidney Diseases 2002; 39(2) Suppl 1LyndaDuncanelat.ScreeningforrenaldiseaseusingserumcreatinineNephrolDialTransplant2001,16:1042-1046

3、1086420Serum Creatinine (mg/dL)Cinulin mL/min/1.73m2020406080100120140160180Serum creatinine may remain in the normal range despite a decrease in glomerular filtrationCIN发生率为：0.7%vs2.0%Trivedietal.Nephron2003;93:C29Briguori et al. Eur Heart J 2004; 25: 206 600 mgTwice daily 1200 mgTwice dailyAll Pat

4、ients 140 mLcontrastP0.05P=N.S.P0.05 NACDoseCIN% SCr measurement GFR or CrCl calculationPatients with eGFR or CrCl 60 mL/minScreeningDay -7 to -2 Blood sample taken before hydration SCr measurement GFR or CrCl calculationBaselineDay -1Agent BAgent ADay 0Randomization SCr measurement GFR or CrCl calc

5、ulation Monitoring of adverse eventsPost-Dose ControlPost-Dose ControlDay +2 to+7CIN的临床研究设计流程的临床研究设计流程 Blood withdrawal (before hydration?) SCr measurement CrCl calculationBaselineDay -1OmnipaqueVisipaqueDay 0Randomization SCr measurement Monitoring of adverse eventsPost-Dose ControlPost-Dose Contro

6、lDay 2, 3 and 7Aspelin et al., NEJM 2007; 2003: 348: 491-499入组筛选步骤缺失！Aspelin et al., NEJM 2007; 2003: 348: 491-499024681012141618发生发生CIN的患者例数的患者例数263欧乃派克碘克沙醇0.5mg/dl1.0mg/dlJo et al., J Am Coll Cardiol 2006;48:924 930) Blood withdrawal before hydration SCr measurement CrCl calculationBaselineDay -1碘

7、克沙醇碘克沙醇 320海赛显海赛显 320Day 0Randomization SCr measurement Monitoring of adverse eventsPost-Dose ControlPost-Dose ControlDay 1 and 2Jo et al., J Am Coll Cardiol 2006;48:924 930)入组筛选步骤缺失！Jo et al., J Am Coll Cardiol 2006;48:924 930)Solomon et al., Circulation 2007;115;3189-3196威视派克-320Day -7 to -2 Day -

8、1Day 0Day +2 to +5入组/筛选482例基线典比乐-370给药后给药后SCr 测定GFR or CrCl 计算水化前采集血 液样本SCr测定GFR or CrCl 计算SCr 测定GFR or CrCl 计算半胱氨酸蛋白酶抑制剂C测定不良反应监测随机分配414例Solomon et al., Circulation 2007;115;3189-3196T-test for continuous variables; Fishers exact test for categorical variables Solomon et al., Circulation 2007;115;3

9、189-3196Solomon et al., Circulation 2007;115;3189-3196Solomon et al., Circulation 2007;115;3189-3196终点终点典比乐典比乐-370 (N=204)碘克沙醇碘克沙醇-320 (N=210)P value*Serum creatinine 绝对绝对升高升高 0.5 mg/dL9 (4.4%)14 (6.7%)0.39Serum creatinine 相对升高相对升高 25%20 (9.8%)26 (12.4%)0.44Estimated GFR 降低降低 25%12 (5.9%)21 (10.0%)0

10、.15* Fishers exact testTotal CIN Population (N=414)Solomon et al., Circulation 2007;115;3189-3196终点终点典比乐典比乐370 (N=204)碘克沙醇碘克沙醇-320 (N=210)Serum creatinine 升高升高 0.5 mg/dL9 (4.4%)14 (6.7%)Serum creatinine 升高升高 0.5 mg/dLTotal CIN Rate CARE Study, 25 Centers, North America (Circulation 2007;115;3189-319

11、6) Endpoint典比乐典比乐 370 (N=204)碘克沙醇碘克沙醇- -320 Group (N=210)SCr 绝对升高绝对升高 0.5 mg/dL and/or SCr 相相对升高对升高 25%21 (10.3%)27 (12.9%)SCr 绝对升高绝对升高 0.5 mg/dL and/or SCr 相相对升高对升高 25%CIN Rate Using Multiple EndpointsCARE Study, 25 Centers, North America (Circulation 2007;115;3189-3196) Endpoint典比乐典比乐370 (N=78)碘克沙

12、醇碘克沙醇-320 (N=92)P value*Serum creatinine绝对升高绝对升高 0.5 mg/dL4 (5.1%)12 (13.0%)0.12Serum creatinine 相对升高相对升高 25%8 (10.3%)14 (15.2%)0.37Estimated GFR 降低降低 25%5 (6.4%)12 (13.0%)0.20* Fishers exact testPatients with Diabetes and Moderate-to-Severe Renal Impairment (N=170)Solomon et al., Circulation 2007;1

13、15;3189-3196终点终点典比乐典比乐370 (N=78)碘克沙醇碘克沙醇-320 (N=92)SCr绝对升高绝对升高 0.5 mg/dL4 (5.1%)12 (13.0%)CIN Rate in Patients with Diabetes and Renal ImpairmentCARE Study, 25 Centers, North America (Circulation 2007;115;3189-3196) Endpoint典比乐典比乐370 Group (N=78)碘克沙醇碘克沙醇-320 Group (N=92)Serum creatinine 升高升高 0.5 mg/

14、dL4 (5.1%)12 (13.0%)碘克沙醇碘克沙醇CIN Rate in Patients with Diabetes and Renal ImpairmentCARE Study, 25 Centers, North America (Circulation 2007;115;3189-3196) Endpoint典比乐典比乐370 Group (N=204)碘克沙醇碘克沙醇- -320 Group (N=210)SCr绝对绝对升高升高 0.5 mg/dL and/or SCr相对相对升高升高 25%21 (10.3%)27 (12.9%)典比乐典比乐370 组组 (N=652)碘克沙醇碘克沙醇-320 Group (N=569)SCr 绝对绝对升高升高