造影剂肾病的防与治

作者:万静[1] 
单位:武汉大学中南医院[1]
  随着现代诊疗技术的发展,碘造影剂的使用越来越频繁,尤其是放射科和心脏病科。碘造影剂造成的肾损害发病率逐年升高,越来越受到临床医生的关注。造影剂肾病(CIN)是在动脉或者静脉内注射碘造影剂后发生的一种医源性肾功能衰竭,不仅对患者的预后不利,而且会增加患者的医疗费用。
  造影剂肾病定义为在排除其他原因的前提下,在动脉或者静脉内注射碘造影剂后24-72小时内发生的急性肾损伤。这种肾功能损害定义为血清肌酐值≥0.5mg/dl,或者较基础值升高≥25%,或者估算的肾小球滤过率<60ml/min或更低。血清肌酐值的升高在3-5天内达到高峰,10-14天内逐渐降至基线水平。
  早期文献高估了造影剂肾病的发病率。近年来的文献显示,造影剂肾病发生于5%左右行碘注射的肾功能正常的住院患者和大约2%甚至1%的eGFR>45ml/min/1.73㎡的医院门诊病人。因此,造影剂肾病在基础肾功能正常的病人中是罕见的。事实上,造影剂肾病大多数情况下发生于基础肾功能受损的患者,尤其是糖尿病肾损害的患者。在所有导致造影剂肾病的诊疗检查中,冠状动脉造影和冠状动脉介入手术造成的造影剂肾病发病率最高。这主要取决于冠脉手术过程中大剂量碘造影剂的使用,患者合并的疾病种类,以及一些伴随疾病如长期血压波动大的高血压,糖尿病,血管疾病,基础肾功能不全等。
  Rudnick和Feldman等研究者评价了造影剂肾病与死亡率之间的因果关系以及通过采取预防措施可降低多少应用碘造影剂的患者死亡率。通过综合一些观察性研究和临床试验,研究者得出结论,造影剂肾病导致的死亡是多因素造成的,并非只与碘造影剂的使用有关,还与诸如肝脏疾病、败血症、呼吸衰竭、出血、基础肾功能不全等因素有关。造影剂肾病是使心血管疾病患者病情恶化甚至死亡的原因之一。研究者还发现,10%的基础肾功能不全的患者在行冠状动脉造影术后其肾功能会进一步下降发生严重肾功能衰竭甚至需要透析治疗。
  不同种类的碘造影剂有不同的渗透压和粘度。按照其是否能在溶液中电离出离子,分为离子型和非离子型。根据其渗透压的高低,分为高渗性、等渗性、低渗性。碘造影剂的发展经历了从离子型到非离子型、从高渗性到低渗性再到等渗性的过程。离子型高渗性造影剂的渗透压为1500-1800mOsm/Kg,相当于血浆渗透压的5-8倍。非离子型低渗性造影剂的渗透压为600-850mOsm/Kg,相当于血浆渗透压的2-3倍。非离子型等渗性造影剂的渗透压大约为290mOsm/Kg,与血浆渗透压相等。Heinrich等比较了二聚体碘造影剂和单体碘造影剂对离体肾小管上皮细胞的细胞毒性作用,结果表明,相比于低渗性或等渗性造影剂,高渗性造影剂对离体的近段肾小管具有更强的细胞毒性作用。这说明,应用低渗性或等渗性造影剂进行诊疗比较安全。
  哪些患者容易引起造影剂肾病?主要的危险因素有:1、基础肾功能不全,大多数基础肾功能不全患者发生造影剂肾病的危险增加。以估算的肾小球滤过率(eGFR)为截点,eGFR<60ml/min/1.73㎡是造影剂肾病发生的一个危险因素。血清肌酐值基线水平越高,发生造影剂肾病的危险越大。慢性肾功能不全患者缺乏抗氧化应激系统,反而增强炎症及内皮功能紊乱导致的氧化应激压力。这可能解释了基础肾功能不全成为造影剂肾病发展的一个原因。2、患者有糖尿病,糖尿病是造影剂肾病发生的另一个危险因素,尤其是伴有糖尿病肾损伤。糖尿病患者发生造影剂肾病的危险是非糖尿病患者的2倍。糖尿病患者造影剂肾病的发生率为5.7%-29.4%。一项关于糖尿病和糖尿病前期患者行冠状动脉造影发生造影剂肾病的调查研究发现,糖尿病患者为22%(RR=3.6),糖尿病前期患者为11%(RR=2.1),非糖尿病患者为5.5%。其中,糖尿病患者中3.6%需要血液透析治疗,糖尿病前期患者中0.7%需要血液透析治疗。3、其它危险因素包括脱水,充血性心力衰竭,高龄(年龄≥70岁),使用肾毒性药物等。
  预防造影剂肾病的发生,其措施包括监测血清肌酐值,尽量不用肾毒性药物,充分水化,选择肾毒性小的造影剂,尽量减少造影剂的用量,术前应用抗氧化剂等。在应用造影剂行检查前,进行充分水化是必要的。建议术前给予口服补液500ml,术后以至少1ml/min的速度给予静脉补液维持24小时。对于具有高危险因素的患者,术前6-12小时给予0.9%盐水静脉点滴,以1ml/kg/h的速度维持,一直持续到术后12-24小时,这对于心血管疾病的预后也是有利的[59,60,61]。ROS在造影剂肾病的发病过程中具有重要作用。N-乙酰半胱氨酸是一种抗氧化剂,能够增强一氧化氮的血管舒张效应。对具有高危因素的患者,可以考虑术前给予口服N-乙酰半胱氨酸每天两次,或者半小时内静脉泵入150mg/kg的剂量,或者4小时内持续静脉点滴50mg/kg的剂量。在行碘造影剂检查后,对伴有慢性肾衰竭的病人可以进行不同方式的血透,相比于低通量的血液透析和血液滤过,高通量的血液透析和血液滤过更加有效。
希望不久新型或者低毒性的碘造影剂能够开发出来并应用于临床。

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