Association of hemoglobin variability and mortality among contemporary incident hemodialysis patients

Abstract

Background and objectives: Evidence exists that variability in hemoglobin may be an independent risk factor for mortality among hemodialysis patients. These observations were based on a 1996 cohort, a time when anemia management differed greatly from present. Design, settings, participants and measurements: A retrospective cohort study of patients incident to Fresenius Medical Care units between 2004 and 2005 (n = 6644). Hemoglobin variability (Hgb-Var) was defined for each subject as the residual SD of a linear regression model of time on hemoglobin.

Results: The mean (SD) of Hgb-Var was 1.13 (0.55) g/dl. In the primary analysis, each g/dl increase of Hgb-Var was associated with an adjusted hazard ratio (95% confidence interval) for all-cause mortality of 1.11 (0.92 to 1.33). No significant interaction with Hgb-Var and mortality was found on the basis of age (P = 0.22), arterial disease (P = 0.45), Hgb slope (P = 0.68), or mean Hgb (P = 0.78). When Hgb-Var was defined by a regression model that included a quadratic term for time (enabling descriptions of curvilinear hemoglobin trajectories), model fit was greatly improved (P for difference <0.001). The corresponding adjusted hazard ratio (95% confidence interval) for all-cause mortality was 1.17 (0.93 to 1.49).

Conclusions: Hgb-Var was not found to be associated with all-cause mortality when examined in a contemporary incident hemodialysis population. More research is needed to determine whether differences in these findings compared with prior analyses relate to temporal trends in anemia management or from differences in the relationship between Hgb-Var and outcomes among incident versus prevalent hemodialysis patients.

Figure 1.

Flow diagram for enrollment.

Figure 2.

Survival according to Hgb parameters. (A) Kaplan-Meier survival function for all-cause mortality according to quartile of Hgb-Var. (B) Kaplan-Meier survival function for all-cause mortality according to mean Hgb level (≤11, 11–12, 12–13, >13 g/dl). The number (%) of patients with mean Hgb ≤ 11 was 829 (12.5%), mean Hgb 11 to 12 was 2198 (33.1%), mean Hgb 12 to 13 was 2752 (41.4%), and mean Hgb >13 was 865 (13.0%). (C) Kaplan-Meier survival function for all-cause mortality for subjects with Hgb slope ≤0, 0 to 0.5 g/dl per month, 0.5 to 1 g/dl per month, and >1 g/dl per month. The number (%) of patients with Hgb slope ≤ 0 was 1248 (18.8%), Hgb slope 0 to 0.5 was 2936 (44.2%), Hgb slope 0.5 to 1 was 1984 (29.9%), and Hgb slope >1 was 476 (7.2%).