Provision of Antioxidant Therapy in Hemodialysis (PATH): A... : Journal of the American Society of Nephrology (original) (raw)

Clinical Research

A Randomized Clinical Trial

Himmelfarb, Jonathan*; Ikizler, T. Alp†; Ellis, Charles†; Wu, Pingsheng‡; Shintani, Ayumi‡; Dalal, Sanjay§; Kaplan, Mark‖; Chonchol, Michel¶; Hakim, Raymond M.†

*Department of Medicine, Division of Nephrology, University of Washington, Seattle, Washington;

†Department of Medicine, Division of Nephrology, and

‡Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee;

§Department of Medicine, Western Michigan University School of Medicine, Kalamazoo, Michigan;

‖DaVita HealthCare Partners, Inc., Denver, Colorado; and

¶Department of Medicine, Division of Nephrology, University of Colorado, Denver, Colorado

Correspondence: Dr. Jonathan Himmelfarb, Harborview Medical Center, Room 10EH11, 325 9th Avenue, Seattle, WA 98104-2499. Email: [email protected]

Received May 28, 2013

Accepted September 16, 2013

Abstract

Increased markers of oxidative stress and acute-phase inflammation are prevalent in patients undergoing maintenance hemodialysis therapy (MHD), and are associated with increased mortality and hospitalization rates and decreased erythropoietin responsiveness. No adequately powered studies have examined the efficacy of antioxidant therapies on markers of inflammation and oxidative stress. We tested the hypothesis that oral antioxidant therapy over 6 months would decrease selected biomarkers of acute-phase inflammation and oxidative stress and improve erythropoietic response in prevalent MHD patients. In total, 353 patients were enrolled in a prospective, placebo-controlled, double-blind clinical trial and randomly assigned to receive a combination of mixed tocopherols (666 IU/d) plus _α_-lipoic acid (ALA; 600 mg/d) or matching placebos for 6 months (NCT00237718); 238 patients completed the study. High-sensitivity C-reactive protein (hsCRP) and IL-6 concentration were measured as biomarkers of systemic inflammation, and F2 isoprostanes and isofurans were measured as biomarkers of oxidative stress. The groups did not significantly differ at baseline. At 3 and 6 months, the treatment had no significant effect on plasma hsCRP, IL-6, F2 isoprostane, or isofuran concentrations and did not improve the erythropoietic response. No major adverse events were related to the study drug, and both groups had similar mortality and hospitalization rates during the study. In conclusion, the administration of mixed tocopherols and ALA was generally safe and well tolerated, but did not influence biomarkers of inflammation and oxidative stress or the erythropoietic response.