Clinical Study Effect of -Lipoic Acid on Oxidative Stress in End-Stage Renal Disease Patients Receiving Intravenous Iron Arif Showkat, 1 William R. Bastnagel, 2 and Joanna Q. Hudson 1,3 1 Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, 956 Court Avenue, Suite B224, Memphis, TN 38163, USA 2 Emergency Department, Methodist Ailiated Hospitals, Memphis, TN 38163, USA 3 Department of Clinical Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA Correspondence should be addressed to Arif Showkat; ashowkat@uthsc.edu Received 13 December 2013; Accepted 29 January 2014; Published 5 March 2014 Academic Editors: A. Arduini, E. Costa, and L. Djukanovic Copyright © 2014 Arif Showkat et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Oxidative stress is associated with increased risk of cardiovascular disease in end-stage renal disease (ESRD) patients. Intravenous (IV) iron has been shown to increase oxidative stress. he aim of the study was to evaluate changes in oxidative stress markers following administration of IV sodium ferric gluconate (SFG) to ESRD patients with and without administration of the antioxidant, -lipoic acid. his is an open-label, crossover study. 125mg of IV SFG was administered during control (C) and intervention (I) visits. During the I visit, 600 mg of -lipoic acid was given orally prior to IV SFG. Blood samples were collected at deined time periods for F 2 -isoprostane (FIP), lipid hydroperoxide (LHP), malondialdehyde (MDA), and iron indices. We recruited ten African- American ESRD subjects: 50% male; mean age 45 ± 9 years; mean hemoglobin 13 ± 1 g/dL; ferritin 449 ± 145 ng/mL; transferrin saturation 27 ± 4%. here were no signiicant diferences in iron indices between the two visits ater IV SFG. MDA, FIP, and LHP increased signiicantly for both C and I visits with a greater increase in the I group. Administration of IV SFG results in an acute rise in oxidative stress in ESRD patients. In contrast to previous studies, administration of -lipoic acid was associated with a greater increase in oxidative stress. 1. Introduction Patients with end-stage renal disease (ESRD) on hemodialysis (HD) have very high cardiovascular mortality [1]. Interest- ingly, the usual risk factors for atherosclerotic diseases in the general population fail to explain the increased car- diovascular mortality in the HD population. For example, unlike the general population, mild-to-moderate elevation of cholesterol or blood pressure does not correlate with increased atherosclerotic complications or mortality in HD patients. As a result, several nontraditional uremia-related risk factors have been considered, including elevated levels of oxidative stress [1, 2]. Intravenous (IV) iron administration has become an integral part of anemia management in ESRD patients; however, exposure to IV iron is among the factors associated with the increase in oxidative stress in the dialysis patients [3–6]. Whether chronic exposure to low maintenance doses of IV iron increases the risk of cardiovascular events has yet to be determined. he oxidative stress markers, malondialdehyde (MDA), lipid hydroperoxide (LHP), and F 2 isoprostane (FIP), rep- resent products formed by the reactive oxygen species gen- erated following administration of IV iron. MDA is an end product of peroxidation of polyunsaturated fatty acids and is a reactive aldehyde that causes toxic stress in cells [7]. MDA has been shown to increase rapidly (within 15 to 30 minutes) in patients with chronic kidney disease (CKD) and in HD patients following IV iron administration [3, 4]. Formation of LHP is indicative of lipid peroxidation, which results in oxidative damage in cell membranes, lipoproteins, and other lipid-containing structures [8]. Isoprostanes are prostaglandin-like substances produced in vivo primarily by free radical-induced peroxidation of arachidonic acid [9]. FIPs are a group of 64 compounds isomeric in structure to cyclooxygenase-derived PGF2 and serve as ideal markers Hindawi Publishing Corporation ISRN Nephrology Volume 2014, Article ID 634515, 7 pages http://dx.doi.org/10.1155/2014/634515