Greater epoetin alfa responsiveness is associated with improved survival in hemodialysis patients.
OBJECTIVE
Among hemodialysis patients, achieved hemoglobin is associated with Epoetin alfa dose and erythropoietin responsiveness. A prospective erythropoietin responsiveness measure was developed and its association with mortality evaluated.


METHODS
Data from 321 participants were used and randomized to the hematocrit normalization arm of the Normal Hematocrit Cardiac Trial. Subjects were to receive a 50% Epoetin alfa dose increase at randomization. The prospective erythropoietin responsiveness measure was defined as the ratio of weekly hematocrit change (over the 3 wk after randomization) per Epoetin alfa dose increase (1000 IU/wk) corresponding to the mandated 50% dose increase at randomization. The distribution of responsiveness was divided into quartiles. Over a 1-yr follow-up, Cox proportional hazard modeling evaluated associations between this responsiveness measure and mortality.


RESULTS
Erythropoietin responsiveness values ranged from -2.1% to 2.4% per week per 1000 IU. Although subjects were similar across response quartiles, mortality ranged between 14% and 34% among subjects in the highest and lowest response quartiles (P = 0.0004), respectively. After adjusting for baseline prognostic indicators, highest versus lowest responsiveness was associated with a hazard ratio of 0.41 (95% confidence interval, 0.20 to 0.87).


CONCLUSIONS
Lower erythropoietin responsiveness is a strong, independent predictor of mortality risk and should be considered when evaluating associations between clinical outcomes and potential prognostic indicators, such as Epoetin alfa dose and achieved hemoglobin values.
Kilpatrick
Ryan D
RD
Department of Biostatistics & Epidemiology, Amgen Inc, One Amgen Center Drive, MS 24-2-A, Thousand Oaks, CA 91320, USA. rkilpatr@amgen.com
Critchlow
Cathy W
CW
Fishbane
Steven
S
Besarab
Anatole
A
Stehman-Breen
Catherine
C
Krishnan
Mahesh
M
Bradbury
Brian D
BD
D000328:Adult; D000368:Aged; D000740:Anemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D006397:Hematinics / Q000008:administration & dosage*; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007674:Kidney Diseases / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011994:Recombinant Proteins; D006435:Renal Dialysis; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome
D006397:Hematinics; D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa