Within-patient variation of hemoglobin and reticulocytes: implications for evaluating ESA responsiveness in dialysis patients.
BACKGROUND
Techniques that assess percent reticulocytes (%retics) or hemoglobin (Hb) to detect erythropoiesis-stimulating agents (ESA) use in athletes may be useful in evaluating ESA responsiveness in dialysis patients. However, within-patient variation, appropriate transformation, or the relationship between the blood draw interval length and analyte variation are untested.


METHODS
In a prospective, single-arm trial, we determined Hb and %retics in 30 hemodialysis patients receiving stable ESA doses. Within-patient results were evaluated for variance homogeneity and normality with and without transformation.


RESULTS
Square-root transformation (sqrt) of %retics produced the most constant variance (lowest r-value for correlation between sqrt|normalized residuals| and fitted values: 0.018 highest P-value 0.739) compared with log transformation (r = -0.198, P < 0.001) or no transformation (r = 0.215, P < 0.001) and showed the least departure from normality (highest P-value: 0.002 vs. < 0.001 vs. < 0.001, respectively). Hb results did not improve with transformation. Within-patient variance in both %retics and Hb increased with interval length between lab draws (P < 0.001).


CONCLUSIONS
Initial assessment of anti-doping tool use in dialysis patient anemia management indicates square-root transformation of %retics and adjustment for time between lab draw intervals for both %retics and Hb will be required.
DaVita Inc., Denver, CO, USASysmex, Mundelein, IL, USAUniversity of Melbourne, Melbourne, Vic., Australia.
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DB
Van Wyck
DaVita Inc., Denver, CO, USASysmex, Mundelein, IL, USAUniversity of Melbourne, Melbourne, Vic., Australia.
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I
Giles
DaVita Inc., Denver, CO, USASysmex, Mundelein, IL, USAUniversity of Melbourne, Melbourne, Vic., Australia.
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K
Sharpe
D000740:Anemia / Q000097:blood* / Q000628:therapy*; D000068817:Epoetin Alfa / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006397:Hematinics / Q000008:administration & dosage / Q000627:therapeutic use*; D006454:Hemoglobins / Q000032:analysis*; D006801:Humans; D007501:Iron / Q000008:administration & dosage / Q000627:therapeutic use; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D006435:Renal Dialysis; D017701:Reticulocyte Count
D006397:Hematinics; D006454:Hemoglobins; D000068817:Epoetin Alfa; D007501:Iron