The long-term goal of this project is to assess the fall in glomerular filtration rate attributable to the commonly utilized therapy of parenteral iron in patients with chronic kidney disease (CKD). We hypothesize that in subjects with mild to moderate CKD, infusion of intravenous iron (MR) when compared to oral iron, will generate oxidative stress and cause an inflammatory response that will be associated with a more rapid decline in glomerular filtration rate (GFR) compared to oral iron. Comparison of IV iron with oral iron will allow testing the hypothesis that MR is injurious to the kidney.
Specific aims : We will directly test the hypothesis that MR will generate an inflammatory response and albuminuria in the short-term, that will directly lead to a greater rate of fall in GFR, in the long-term, compared to oral iron. We hypothesize that after administration of one gram of IV iron over a course of 8 weeks, renal injury as documented by albuminuria (and fall in GFR) will be increased with IV iron sucorse therapy compared to those randomized to oral iron therapy. Methods: A randomized, parallel group, controlled trial will be performed. GFR will be measured every 6 months for two years in 200 participants by iothalamate clearances. Significance: Intravenous iron is commonly utilized and is likely a mechanism of renal injury in patients with CKD. Novelty and Health Relatedness of the Project: This proposal will provide translational data on the role of intravenous iron to progression of kidney disease in patients with CKD.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project--Cooperative Agreements (U01)
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Study Section
Pathobiology of Kidney Disease Study Section (PBKD)
Program Officer
Kusek, John W
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Indiana University-Purdue University at Indianapolis
Internal Medicine/Medicine
Schools of Medicine
United States
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Agarwal, Rajiv; Kusek, John W; Pappas, Maria K (2015) A randomized trial of intravenous and oral iron in chronic kidney disease. Kidney Int 88:905-14
Agarwal, Rajiv (2015) The Author Replies. Kidney Int 88:1446-1447
Hagan, Andrew S; Jones, David R; Agarwal, Rajiv (2013) Use of dried plasma spots for the quantification of iothalamate in clinical studies. Clin J Am Soc Nephrol 8:909-14
Agarwal, Rajiv (2010) Epidemiology of chronic kidney disease among normotensives: but what is chronic kidney disease? Hypertension 55:1097-9
Agarwal, Rajiv (2010) Individualizing decision-making--resurrecting the doctor-patient relationship in the anemia debate. Clin J Am Soc Nephrol 5:1340-6
Elliott, James; Mishler, Dennis; Agarwal, Rajiv (2009) Hyporesponsiveness to erythropoietin: causes and management. Adv Chronic Kidney Dis 16:94-100
Holden, Jocelyn E; Kelley, Ken; Agarwal, Rajiv (2008) Analyzing change: a primer on multilevel models with applications to nephrology. Am J Nephrol 28:792-801