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.
