Hemoglobin level variability: associations with mortality.
OBJECTIVE
Awareness of hemoglobin level variability in dialysis patients is increasing, as is interest in its potential implications. In this retrospective, national study of associations between the degree of hemoglobin level variability in the first 6 mo of 2004 and subsequent mortality rates in the following 6 mo, 159,720 hemodialysis patients receiving epoetin therapy were studied.


METHODS
Monthly hemoglobin values were categorized as low (L; < 11 g/dl), intermediate (I; 11 to 12.5 g/dl), and high (H; >12.5 g/dl). Variability groups were classified on the basis of the lowest and highest hemoglobin categories seen during the 6-mo observation period: low-low (L-L), 1.4%; intermediate-intermediate (I-I), 6.0%; high-high (H-H), 2.3%; low-intermediate (L-I), 18.3%; intermediate-high (I-H), 31.7%, and low-high (L-H), 40.2%.


RESULTS
On multivariate analysis, adjusted hazards ratios for subsequent mortality events were as follows: I-I, 1.0 (reference category); I-H, 1.02 (95% confidence interval [CI] 0.95 to 1.11); H-H, 1.06 (95% CI 0.93 to 1.21); L-H, 1.19 (95% CI 1.10 to 1.28); L-I, 1.44 (95% CI 1.33 to 1.56), and L-L, 2.18 (95% CI 1.93 to 2.45). Persistently and transiently low hemoglobin levels and highly variable hemoglobin levels were associated with increased risk of death; transiently and persistently high hemoglobin levels were not associated with increased risk of death. Bayesian modeling indicated that > or =3 mo with hemoglobin levels <11 g/dl may be associated with of increased risk of death.


CONCLUSIONS
Number of months with hemoglobin values below the target range, rather than hemoglobin variability itself, may be the primary driver of increased risk of death. Further research is needed to distinguish cause from effect and to understand the underlying mechanisms.
Chronic Disease Research Group, Minneapolis Medical Research Foundation, 914 South 8th Street, Suite S-206, Minneapolis, MN 55404, USA. dgilbertson@cdrg.org
David T
DT
Gilbertson
James P
JP
Ebben
Robert N
RN
Foley
Eric D
ED
Weinhandl
Brian D
BD
Bradbury
Allan J
AJ
Collins
D000328:Adult; D000368:Aged; D000740:Anemia / Q000097:blood* / Q000401:mortality*; D001499:Bayes Theorem; D005260:Female; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016012:Poisson Distribution; D016016:Proportional Hazards Models; D006435:Renal Dialysis; D012189:Retrospective Studies; D012307:Risk Factors
D006454:Hemoglobins