Iron, inflammation, dialysis adequacy, nutritional status, and hyperparathyroidism modify erythropoietic response.
OBJECTIVE
The erythropoietic response in hemodialysis patients depends on several physiologic factors. Most epidemiologic studies include the effect of these factors by representing them as confounders. This study tested the hypothesis that iron stores, inflammation, dialysis adequacy, nutritional status, and hyperparathyroidism act as nonlinear effect modifiers of the erythropoietic response and quantified the magnitude of those effects over clinically relevant ranges.


METHODS
The following retrospective data from 209 hemodialysis patients receiving Epoetin alfa (Epo) were collected: monthly: predialysis hemoglobin (Hgb), transferrin saturation, serum albumin, dialysis adequacy (Kt/V); quarterly: predialysis serum ferritin and intact parathyroid hormone over a period of 13 to 69 months. The study analyzed the dynamic relationship between hemoglobin and Epo, considering nonlinear effect modification by ferritin, transferrin saturation, Kt/V, albumin, and parathyroid hormone individually.


RESULTS
Maximum Hgb response to Epo was achieved for serum ferritin between 350 and 500 ng/ml, transferrin saturation greater than 30%, Kt/V greater than 1.4, and albumin greater than 3.8 g/dl. Hgb sensitivity to Epo decreases by about 30% as parathyroid hormone increases from 0 through 1000 pg/ml.


CONCLUSIONS
Serum ferritin, transferrin saturation, Kt/V, serum albumin, and intact parathyroid hormone are markers of nonlinear effect modification of the erythropoietic response in hemodialysis patients.
Gaweda
Adam E
AE
University of Louisville, Department of Medicine, Division of Nephrology, 615 South Preston Street, Louisville, KY 40202, USA. adam.gaweda@louisville.edu
Goldsmith
Linda J
LJ
Brier
Michael E
ME
Aronoff
George R
GR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D015415:Biomarkers / Q000097:blood; D015986:Confounding Factors, Epidemiologic; D004305:Dose-Response Relationship, Drug; D000068817:Epoetin Alfa; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000008:administration & dosage*; D005260:Female; D005293:Ferritins / Q000097:blood; D006397:Hematinics / Q000008:administration & dosage*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D006961:Hyperparathyroidism / Q000097:blood / Q000209:etiology*; D007249:Inflammation / Q000097:blood / Q000209:etiology*; D007501:Iron / Q000097:blood*; D007674:Kidney Diseases / Q000097:blood / Q000150:complications / Q000628:therapy*; D016013:Likelihood Functions; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D017711:Nonlinear Dynamics; D009752:Nutritional Status; D010281:Parathyroid Hormone / Q000097:blood; D011994:Recombinant Proteins; D006435:Renal Dialysis; D012189:Retrospective Studies; D012709:Serum Albumin / Q000378:metabolism; D013997:Time Factors; D014168:Transferrin / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult
D015415:Biomarkers; D006397:Hematinics; D006454:Hemoglobins; C470125:PTH protein, human; D010281:Parathyroid Hormone; D011994:Recombinant Proteins; D012709:Serum Albumin; D014168:Transferrin; D004921:Erythropoietin; D000068817:Epoetin Alfa; D005293:Ferritins; D007501:Iron