title: Effect of hemoglobin target on progression of kidney disease: a secondary analysis of the CHOIR (Correction of Hemoglobin and Outcomes in Renal Insufficiency) trial.
abstract: BACKGROUND
  Conflicting relationships have been described between anemia correction using erythropoiesis-stimulating agents and progression of chronic kidney disease (CKD). This study was undertaken to examine the impact of target hemoglobin level on progression of kidney disease in the CHOIR (Correction of Hemoglobin and Outcomes in Renal Insufficiency) trial.
  
  
  METHODS
  Secondary analysis of a randomized controlled trial.
  
  
  METHODS
  1,432 participants with CKD and anemia.
  
  
  METHODS
  Participants were randomly assigned to target hemoglobin levels of 13.5 versus 11.3 g/dL with the use of epoetin alfa.
  
  
  METHODS
  Cox regression was used to estimate HRs for progression of CKD (a composite of doubling of creatinine level, initiation of renal replacement therapy, or death). Interactions between hemoglobin target and select baseline variables (estimated glomerular filtration rate, proteinuria, diabetes, heart failure, and smoking history) also were examined.
  
  
  RESULTS
  Participants randomly assigned to higher hemoglobin targets experienced shorter time to progression of kidney disease in both univariate (HR, 1.25; 95% CI, 1.03-1.52; P = 0.02) and multivariable models (HR, 1.22; 95% CI, 1.00-1.48; P = 0.05). These differences were attributable to higher rates of renal replacement therapy and death for participants in the high hemoglobin arm. Hemoglobin target did not interact with estimated glomerular filtration rate, proteinuria, diabetes, or heart failure (P > 0.05 for all). In the multivariable model, hemoglobin target interacted with tobacco use (P = 0.04) such that the higher target had a greater risk of CKD progression for participants who currently smoked (HR, 2.50; 95% CI, 1.23-5.09; P = 0.01), which was not present for those who did not currently smoke (HR, 1.15; 95% CI, 0.93-1.41; P = 0.2).
  
  
  CONCLUSIONS
  A post hoc analysis; thus, cause and effect cannot be determined.
  
  
  CONCLUSIONS
  These results suggest that a high hemoglobin target is associated with a greater risk of progression of CKD. This risk may be augmented by concurrent smoking. Further defining the mechanism of injury may provide insight into methods to optimize outcomes in anemia management.
authors.affiliation: Renal Division, University of Texas Southwestern, Dallas, TX 75390-8523, USA. jula.inrig@utsouthwestern.edu
authors.forename: Jula K
authors.initials: JK
authors.lastname: Inrig
authors.forename: Huiman X
authors.initials: HX
authors.lastname: Barnhart
authors.forename: Donal
authors.initials: D
authors.lastname: Reddan
authors.forename: Uptal D
authors.initials: UD
authors.lastname: Patel
authors.forename: Shelly
authors.initials: S
authors.lastname: Sapp
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Singh
authors.forename: Lynda A
authors.initials: LA
authors.lastname: Szczech
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000740:Anemia / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D016001:Confidence Intervals; D018450:Disease Progression; D016503:Drug Delivery Systems; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006397:Hematinics / Q000627:therapeutic use*; D006452:Hemoglobinometry; D006454:Hemoglobins / Q000032:analysis* / Q000187:drug effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D012044:Regression Analysis; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000175:diagnosis / Q000401:mortality; D018570:Risk Assessment; D012720:Severity of Illness Index; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D006397:Hematinics; D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa