Background: Iron deficiency is common in the hemodialysis population, resulting from blood loss in the dialysis tubing and membranes, gastrointestinal bleeding, hyperstimulated erythropoeisis and reduced absorption. Iron is administered in response to lab markers suggesting iron deficiency, including a serum ferritin <200 ng/ml and transferrin saturation <20%. Clinical practice recommendations advocate administering iron only up to a serum ferritin of 500 ng/ml. However, more than half of the ESRD population has a ferritin >500 ng/ml and a recent study demonstrated hemoglobin increased and erythropoiesis-stimulating agent (ESA) decreased with administration of IV iron to patients with ferritin>500 ng/ml. Some evidence suggests iron may enhance bacterial growth, lending concern about its safety. However, current clinical practice has evolved to incorporate more use of iron in anemia care, emphasizing the need to better describe its effectiveness and safety.
Objectives: 1) To compare the effectiveness of iron dosing strategies (regular maintenance therapy versus intermittent ‘as needed’ therapy) on anemia management, and 2) To compare the effectiveness of lower versus higher cumulative IV iron doses on CV-related hospitalization and mortality, infection-related hospitalization and mortality, all cause mortality, and quality of life.
Study Design: Retrospective and prospective cohort studies
Methods: We will use two complimentary and nationally representative data sources to achieve our objective [Dialysis Clinics Inc (DCI) data, and Choices for Healthy Outcomes in Caring for ESRD (CHOICE) Study data]. Within each data source, we will perform several longitudinal analyses to assess the comparative effectiveness of prescribed antihypertensive therapeutic regimens with all cause and CVD mortality and morbidity.
For Aim 1, we will perform multivariable longitudinal models accounting for the time varying nature of iron administration as well as confounders of iron administration (e.g. use of other medications such as erythropoiesis stimulating agents), we will assess the association of iron dosing strategies with achievement of anemia management goals. Our models will account for potential confounders of this association, including inflammation. For Aim 2, we will quantify the association of cumulative dose of iron with mortality and the other clinical outcomes. Our models will account for time dependent confounding by other factors (including use of erythropoiesis stimulating agents) of observed relationships. We will also explicitly assess the concomitant effects of iron and ESA on outcomes. Inflammation is the major confounder of the relationship of the combination variable with the outcome and will be accounted for through effect modification and/or stratification.
Expected Outputs: At least two scientific reports will be generated regarding the different outcomes examined (mortality and morbidity).
Expected Date of Completion: June 2013
EHC Priority Condition: End-Stage Renal Disease (ESRD) and Cardiovascular Disease