title: Erythropoiesis-stimulating agents: dose and mortality risk.
abstract: Hypo-responsiveness to erythropoiesis-stimulating agents (ESAs) has been associated with increased mortality in end-stage renal disease patients. It is not clear if this effect is related to the elevated ESAs dosage for targeting hemoglobin levels or underlying morbid conditions that lead to ESA resistance. We retrospectively evaluated from 2008 to death or December 2011, 28 consecutive incident hemodialysis patients. We identified 2 cohort of patients based on their mean annual ESAs dosage. The correlation between data was evaluated with the Spearman's rho test. Kaplan-Meier curves were generated to assess survival in subjects with high and low ESAs mean dose. Median ESAs dosage, used as a cutoff point between patients at high and low ESAs dose, was at 11.000 IU/week for epoetin alfa and beta, 55 mcg/week for darbopoietin, and 220 mcg/month for cera. Mean hemoglobin (Hb) level was 10.58 ± 0.13 g/dL. Of 28 patients, during follow-up, 6 (21,4%) died of all causes. High-dose ESA therapy was associated with increased all-cause mortality (P = .047). Moreover, there was a negative correlation between ESAs dose and Hb levels (rho = -0.825; P < .001). Higher ESAs dose for the treatment of anemia in incident hemodialysis patients was associated with higher mortality risk. ESAs and Hb serum levels were inversely correlated with mortality. Together, these findings suggest that ESAs dosage and Hb level may play a role through an independent manner or an interactive effect that adversely affects mortality.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Bellinghieri
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Italy; Unit of Nephrology and Dialysis, San Giovanni XXII Hospital, Bergamo, Italy.
authors.forename: Carmela Giuseppina
authors.initials: CG
authors.lastname: Condemi
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Saitta
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Trifirò
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Gangemi
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Savica
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Buemi
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Italy. Electronic address: santisi@hotmail.com.
authors.forename: Domenico
authors.initials: D
authors.lastname: Santoro
mesh_terms: D000740:Anemia / Q000517:prevention & control*; D005260:Female; D006397:Hematinics / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000401:mortality* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D012189:Retrospective Studies
chemical_list: D006397:Hematinics