In a secondary analysis of the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT), patients with a poor response to darbepoet in alfa had an increased risk of cardiovascular outcomes.10 However, it is difficult to ascertain whether this increased risk was due to the preexisting characteristics of the patients, an increased dose of erythropoiesis-stimulating agents (ESAs), or both. We recently found that volume overload is strongly associated with both traditional and nontraditional risk factors for CKD progression and cardiovascular disease (CVD) in ND-CKD patients.9 Because ESA treatment further increases the blood volume,the benefits of anemia correction by ESA may have been masked by the negative effects of increased fluid retention. Therefore, testing for an interaction between fluid status, hemoglobin concentrations, and outcomes in CKD patients seems warranted.