Higher Haemoglobin Level Variation under Treatment with Erythropoitin is Associated with Mortality in Haemodialysis

Background: During recent years therapy with erythropoesis stimulating agents (ESA) in chronic kidney disease necessitating dialysis (CKD5D) has been challenged following worse study outcome in patients exceeding upper haemoglobin (Hb) target levels. Considering such difficulties to establish a certain and safe Hb target, a focus more on trends of Hb change and fluctuation might be beneficial to encase alternative parameters and hypotheses into anemia management. We conducted an analysis investigating the association of hemoglobin variation, and achievement of Hb targets with mortality in 245 hemodialysis patients from an outpatient center within 15 years follow-up.

Methods: Variation coefficients of Hb course, Hb levels, proportion of Hb within guideline targets, means of ESA dose and dose response were considered as independent variables. Further variables for population characterization and multivariate survival analysis were age, gender and laboratory surrogates.

Outcome was computed as

(¡) Overall mortality by computing OR for death and
(¡¡) Mortality difference between two Hb variation groups compared by Kaplan-Meier and multivariate survival analysis.

Results: The OR of death in the higher of two Hb variation groups was 5.01 (95% CI 2.85 to 9.11). Hb variation coefficient above 4% had a strong association with all-cause mortality (LogRank=54.1, p<0.001). Hb variation, Hb levels, Hb within targets and ESA dose response, entered overall and conditional multivariate models for survival (x2=131.3; p<0.001) with Hb variation holding the strongest place in every model.

Conclusion: This unselected population exhibited a strong, significant association of Hb variation and a weaker association of reaching Hb targets with crude mortality. Clinical pathways as well as future controlled trials should encounter these findings in algorithms for ESA therapy.