Iron Chelator in Contrast-Induced Acute Renal Failure

描述（由申请人提供）： 根据NIH工作人员的建议和评审员的评论，该修订后的申请将作为R33申请重新提交。修订后的申请现在是一个多中心试验，涉及经验丰富的研究人员詹姆斯A。Tumlin，MD（Emory），帕特里克T. Murray博士（芝加哥）和由Michael Kutner博士领导的成熟的生物统计中心。大量证据表明氧化剂和铁（可参与自由基反应）在实验性急性肾衰竭模型中的重要性。然而，铁螯合剂在预防人类ARF中的作用以前没有被检查过。我们假设去铁酮，一种口服铁螯合剂，可以预防接受放射造影研究的患者的ARF。 我们建议研究CRI患者心脏手术后放射性造影剂诱导的肾病，因为这是一种定义明确的临床情况，易于识别和监测。此外，造影剂通常用于各种诊断和治疗程序。与需要使用造影剂的非冠状动脉手术相比，我们拟定的研究选择心导管插入术，因为：1）接受心导管插入术的患者中ARF的发生率要高得多，因此需要较少的患者2）心导管插入术在大多数患者中，即使是在发生ARF的高风险患者中，而需要非心脏对比研究的类似受试者通常有其他相对安全的选择（例如，MRI）。 拟议研究的主要目的是： 1.比较接受心导管插入术的CRI患者接受长效去铁酮1800 mg口服，每日2次，与安慰剂相比，在术前1天和手术当天的ARF发生率。 2.确定去铁酮1800 mg缓释剂口服给药的安全性，每日两次，在心导管插入术前一天和当天。

DESCRIPTION (provided by applicant): This revised application is being resubmitted as an R33 application based on the recommendation of the NIH staff and the reviewers' critique. The revised application is now a multicenter trial involving experienced investigators James A. Tumlin, MD (Emory), Patrick T. Murray, MD (University of Chicago), and a well-established biostatistic center headed by Michael Kutner, PhD. There is a large body of evidence indicating the importance of oxidants and iron (which can participate in free radical reactions) in models of experimental acute renal failure. However, the effect of iron chelators in preventing ARF in humans previously has not been examined. We hypothesize that deferiprone, an oral iron chelator, can prevent ARF in patients undergoing a radiocontrast study. We propose to study radiocontrast medium-induced nephropathy after cardiac procedures in patients with CRI because this is a well-defined clinical situation that is easy to recognize and monitor. Furthermore, contrast medium is commonly used for various diagnostic and therapeutic procedures. Cardiac catheterization is selected for our proposed study as opposed to non-coronary procedures requiring contrast use because: 1) the incidence of ARF is much higher in patients undergoing cardiac catheterization and therefore fewer patients will be required 2) cardiac catheterization (when indicated) cannot be deferred in most patients, even in those who are at high risk for developing ARF, while similar subjects requiring a non-cardiac contrast study usually have other relatively safe options available (e.g., MRI). The Primary objectives of the proposed study are: 1.To compare the incidence of ARF in patients with CRI undergoing cardiac catheterization and receiving long-acting deferiprone 1800 mg orally twice a day versus placebo, one day prior to and on the day of the procedure. 2. To ascertain the safety of deferiprone 1800 mg sustained-release administered orally, twice a day, one day prior to, and on the day of cardiac catheterization.