| Abstract: | Background and objectives: Anemia and hemoglobin (Hb) variability are associated with mortality in hemodialysis patients who are on erythropoiesis-stimulating agents (ESA). Our aim was to describe the degree of Hb variability present in nondialysis patients with chronic kidney disease (CKD), including those who were not receiving ESA, and to investigate the association between Hb variability and mortality.Design, setting, participants, & measurements: Hb variability was determined using 6 mo of “baseline” data between January 1, 2003, and October 31, 2005. A variety of definitions for Hb variability were examined to ensure consistency and robustness.Results: A total of 6165 patients from 22 centers in seven countries were followed for a mean of 34.0 ± 15.8 mo; 49% were prescribed an ESA. There was increased Hb variability with ESA use; the residual SD of Hb was 4.9 ± 4.4 g/L in patients who were not receiving an ESA, compared with 6.8 ± 4.8 g/L. Hb variability was associated with a small but significantly increased risk for death per g/L residual SD, irrespective of ESA use. Multivariate linear regression model explained only 11% of the total variance of Hb variability.Conclusions: Hb variability is increased in patients who have CKD and are receiving ESA and is associated with an increased risk for death (even in those who are not receiving ESAs). This analysis cannot determine whether Hb variability causally affects mortality. Thus, the concept of targeting Hb variability with specific agents needs to be examined within the context of factors that affect both Hb variability and mortality.Substantial numbers of epidemiologic studies have described the association of anemia with worse outcomes in all populations, including chronic kidney disease (CKD) populations. More recently, the identified phenomenon of hemoglobin (Hb) variability (the oscillations or fluctuations of an individual dialysis patient''s Hb over time) (1–5) has also been associated with adverse outcomes and has received increasing attention as a therapeutic target (4,6–9). It remains unclear what the best method is to define or measure Hb variability and whether its association with adverse outcomes is simply an epiphenomenon or a causal relationship. Furthermore, CKD studies to date have been primarily restricted almost exclusively to hemodialysis patients who were receiving erythropoiesis-stimulating agents (ESA) (1–8)Debate exists on which factors may influence the severity and frequency of Hb variability. Identification of these factors is necessary if manipulation of Hb variability in experimental or clinical settings is a goal (3,4,8,10,11,12). There are some data to suggest that physician prescribing patterns of ESA and the type of ESA affect variability; however, because both may be confounded by other factors, the specific contribution of these and other factors to Hb variability remains uncertain (3,4,10,11,12).The goal of this analysis was to assess the presence of anemia and Hb variability within a culturally diverse, nondialysis CKD population that included patients who were not receiving ESA therapy. We assessed the association of Hb variability with mortality and explored factors that are associated with Hb variability. |
