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Association of Hemoglobin Variability and Mortality among Contemporary Incident Hemodialysis Patients

Steven M. Brunelli^*,, Katherine E. Lynch^*, Elizabeth D. Ankers, Marshall M. Joffe, Wei Yang, Ravi I. Thadhani, and Harold I. Feldman^*,

^* Renal-Electrolyte and Hypertension Division, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; and Renal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

Correspondence: Dr. Steven M. Brunelli, Center for Clinical Epidemiology and Biostatistics, 109 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104. Phone: 215-573-1830, Fax: 215-898-0189; E-mail: steven.brunelli{at}uphs.upenn.edu

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.