More than 575,000 Americans have end-stage renal disease, which is typically complicated by anemia, and most of these patients receive maintenance dialysis treatment. The proposed work will compare the effectiveness and safety of darbepoetin alfa, a novel injectible drug for the treatment of anemia, with its established cousin, epoetin alfa. Similarly, ferumoxytol, a new intravenous iron supplement for the treatment of anemia will be compared with an established iron supplement, iron sucrose. Both drugs were approved using information from randomized studies that evaluated their efficacy on reducing anemia. Very limited information, however, is available for either drug regarding their longer-term efficacy and safety. We are proposing to study the effectiveness and safety of these two medications when compared to their established cousins. Events of scientific interest include short-term outcomes (anaphylaxis, laboratory parameters including hemoglobin, iron saturation, ferritin) and longer- term outcomes including infection, cardiovascular events, cancer, and mortality. We will use already collected data from Medicare billing claims and electronic medical records of dialysis providers to address these research questions. Since facilities choose among these treatment options based on what is available in their formulary, and not necessarily based on patient characteristics, we can exploit natural experiments that occur when facilities switch their ESA or iron agent for their entire patient population. We will apply modern epidemiological techniques to eliminate bias and aspire to provide valid estimates of relative benefits and risks. Findings from the proposed work have the potential to immediately impact and improve the care that patients with end-stage renal disease receive. Our results may improve the quality of care received and, thus, the outcomes of this vulnerable patient population.
The aims and scope of work are in full congruence with the mission of the National Institutes of Diabetes and Digestive and Kidney Diseases, and more specifically the Division of Kidney, Urologic, and Hematologic Diseases, which will consider this application for funding.

Public Health Relevance

The kidneys of more than 500,000 Americans have irreversibly stopped working, which renders these patients dependent on receiving regular kidney dialysis. Anemia is widespread in this population and newer treatments for it have recently become available. We propose to study the long-term benefits and risks of two of these new drugs, darbepoetin and ferumoxytol, which will provide important new information that is necessary information to optimize safe and effective heath care of these patients.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Study Section
Kidney, Nutrition, Obesity and Diabetes (KNOD)
Program Officer
Eggers, Paul Wayne
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Stanford University
Internal Medicine/Medicine
Schools of Medicine
United States
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Winkelmayer, Wolfgang C; Goldstein, Benjamin A; Mitani, Aya A et al. (2017) Safety of Intravenous Iron in Hemodialysis: Longer-term Comparisons of Iron Sucrose Versus Sodium Ferric Gluconate Complex. Am J Kidney Dis 69:771-779
Brookhart, M Alan; Freburger, Janet K; Ellis, Alan R et al. (2016) Comparative Short-term Safety of Sodium Ferric Gluconate Versus Iron Sucrose in Hemodialysis Patients. Am J Kidney Dis 67:119-27
Freburger, Janet K; Ellis, Alan R; Wang, Lily et al. (2016) Comparative Effectiveness of Iron and Erythropoiesis-Stimulating Agent Dosing on Health-Related Quality of Life in Patients Receiving Hemodialysis. Am J Kidney Dis 67:271-82
Airy, Medha; Mandayam, Sreedhar; Mitani, Aya A et al. (2015) Comparative outcomes of predominant facility-level use of ferumoxytol versus other intravenous iron formulations in incident hemodialysis patients. Nephrol Dial Transplant 30:2068-75
Goldstein, Benjamin A; Chang, Tara I; Winkelmayer, Wolfgang C (2015) Classifying individuals based on a densely captured sequence of vital signs: An example using repeated blood pressure measurements during hemodialysis treatment. J Biomed Inform 57:219-24
Goldstein, Benjamin A; Assimes, Themistocles; Winkelmayer, Wolfgang C et al. (2015) Detecting clinically meaningful biomarkers with repeated measurements: An illustration with electronic health records. Biometrics 71:478-86
Rhee, Jinnie J; Ding, Victoria Y; Rehkopf, David H et al. (2015) Correlates of poor glycemic control among patients with diabetes initiating hemodialysis for end-stage renal disease. BMC Nephrol 16:204
Wilhelm-Leen, Emilee R; Winkelmayer, Wolfgang C (2015) Mortality risk of darbepoetin alfa versus epoetin alfa in patients with CKD: systematic review and meta-analysis. Am J Kidney Dis 66:69-74
Winkelmayer, Wolfgang C; Chang, Tara I; Mitani, Aya A et al. (2015) Longer-term outcomes of darbepoetin alfa versus epoetin alfa in patients with ESRD initiating hemodialysis: a quasi-experimental cohort study. Am J Kidney Dis 66:106-13
Shilane, D; Hlatky, M A; Winkelmayer, W C et al. (2015) Coronary artery bypass graft type and outcomes in maintenance dialysis. J Cardiovasc Surg (Torino) 56:463-71

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