title: Epoetin therapy and hemoglobin level variability in nondialysis patients with chronic kidney disease.
abstract: OBJECTIVE
  Intrapatient variability of hemoglobin (Hb) is a newly proposed determinant of adverse outcome in chronic kidney disease (CKD). We evaluated whether intensity of epoetin therapy affects Hb variability and renal survival in nondialysis CKD.
  
  
  METHODS
  We calculated the individual therapeutic index (TI) for epoetin (EPO; difference between rates of visits that required EPO dosage change and those with effective EPO change) from 1198 visits during the first year of EPO in 137 patients. Renal death was registered in the subsequent 18.1 mo. Analysis was made by TI tertile (lower, middle, and higher; i.e., from more to less intensive therapy).
  
  
  RESULTS
  Main features and visit number were similar in tertiles. Lower Hb response to first EPO dosage was an independent predictor of higher TI (P = 0.002). The area under the curve for Hb (11.56 +/- 0.87, 11.46 +/- 1.20, and 10.95 +/- 1.48 g/dl per yr; P = 0.040) decreased from lower to higher tertile. Hb variability increased in parallel, as shown by the reduction of time with Hb at target (time in target, from 9.2 +/- 2.0 to 3.0 +/- 2.2 mo; P < 0.0001) and the wider values of within-patient Hb standard deviation (from 0.70 to 0.96; P = 0.005) and Hb fluctuations across target (P < 0.0001). In Cox analyses (hazard ratio [95% confidence interval]), risk for renal death was increased in the middle and higher tertiles (2.79 [1.36 to 5.73] and 2.94 [1.40 to 6.20]) and reduced by longer time in target (0.90 [0.83 to 0.98]).
  
  
  CONCLUSIONS
  Lack of adjustment of EPO worsens Hb variability in CKD. Hb variability may be associated with renal survival, but further studies are needed to explore the association versus causal relationship.
authors.affiliation: Nephrology Division, Second University of Naples-Santa Maria del Popolo degli Incurabili Hospital-Azienda SanitariaLocale, Solofra, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Minutolo
authors.forename: Paolo
authors.initials: P
authors.lastname: Chiodini
authors.forename: Bruno
authors.initials: B
authors.lastname: Cianciaruso
authors.forename: Andrea
authors.initials: A
authors.lastname: Pota
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bellizzi
authors.forename: Deborah
authors.initials: D
authors.lastname: Avino
authors.forename: Sara
authors.initials: S
authors.lastname: Mascia
authors.forename: Simona
authors.initials: S
authors.lastname: Laurino
authors.forename: Valerio
authors.initials: V
authors.lastname: Bertino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Conte
authors.forename: Luca
authors.initials: L
authors.lastname: De Nicola
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D000068256:Darbepoetin alfa; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D005260:Female; D006397:Hematinics / Q000627:therapeutic use*; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D007558:Italy; D007674:Kidney Diseases / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011994:Recombinant Proteins; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D006397:Hematinics; D006454:Hemoglobins; D011994:Recombinant Proteins; C103998:epoetin beta; D004921:Erythropoietin; D000068256:Darbepoetin alfa