Hemoglobin cycling in hemodialysis patients

Anemia is a well-recognized feature in patients with chronic kidney disease (CKD). Recently, two large-scale trials, CREATE and CHOIR, pointed to the complexity of maintaining stable hemoglobin (Hb) levels over time. According to these data, patients failing to achieve the target range of Hb levels between 11-12 g/dL may be at increased risk of dying. Both low and high Hb levels are associated with increased cardiovascular events and death. One reason for failure to achieve stable Hb levels within the target range is Hb cycling. Several causes may be responsible for a cyclic pattern of Hb levels: drug-related factors such as differences in pharmacokinetics and bioavailability in eryth-ropoiesis-stimulating agents (ESAs) as well as difficulties in iron supplementation may induce Hb instability in patients with CKD. Similarly, patient-related factors such as an inflammatory status or protein energy wasting are associated with this phenomenon. Further, variations in fluid balance and biocompatibility of dialyzer membranes, by differentially affecting inflammation, render the hemodialysis treatment itself a risk factor for Hb cycling. Strategies to reduce Hb cycling are necessary to obtain improved clinical outcomes. This review will describe the phenomenon of Hb cycling, highlighting potential contributing factors and discussing the pos-sible clinical conditions.