Value of N-terminal brain natriuretic peptide as a prognostic marker in patients with CKD: results from the CREATE study

Curr Med Res Opin. 2010 Nov;26(11):2543-52. doi: 10.1185/03007995.2010.516237. Epub 2010 Sep 17.


Background and objectives: This study assessed plasma N-terminal prohormone brain natriuretic peptide (NT-proBNP) as a prognostic marker of cardiovascular risk in patients with chronic kidney disease stages 3-4 and anaemia treated with epoetin beta to two haemoglobin target ranges.

Design, setting, participants & measurements: Of 603 patients enrolled in the Cardiovascular Risk Reduction by Early Anaemia Treatment with Epoetin Beta (CREATE) trial (baseline creatinine clearance 15-35 mL/min; haemoglobin 11.0-12.5 g/dL), 291 were included in this sub-study. Patients received subcutaneous epoetin beta either immediately after randomisation (target 13.0-15.0 g/dL; Group 1), or after their haemoglobin levels had fallen < 10.5 g/dL (target 10.5-11.5 g/dL; Group 2). Chronic heart failure New York Heart Association class III-IV was an exclusion criterion. ( Identifier: NCT00321919)

Results: Cardiovascular event rates were higher in patients with baseline NT-proBNP > 400 vs. ≤ 400 pg/mL (39 vs. 13 events; p = 0.0002). Dialysis was initiated in 68 vs. 42 patients with NT-proBNP > 400 vs. ≤ 400 pg/mL (p = 0.0003). Amongst patients with NT-proBNP > 400 pg/mL, there was no significant difference between treatment groups in risk of cardiovascular events (HR = 0.57; p = 0.08) or time to dialysis (HR = 0.65; p = 0.08). The overall interpretation of this substudy is, however, limited by its relatively small sample size which, together with low clinical event rates, result in a lack of statistical power for some analyses and should be viewed as being hypothesis-generating in nature.

Conclusions: In chronic kidney disease patients with mild-to-moderate anaemia, elevated baseline plasma NT-proBNP levels are associated with a higher risk of cardiovascular events and an accelerated progression towards end-stage renal disease.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anemia / drug therapy
  • Anemia / physiopathology
  • Biomarkers / blood
  • Cardiovascular Diseases / etiology
  • Comorbidity
  • Erythropoietin / therapeutic use
  • Female
  • Humans
  • Male
  • Middle Aged
  • Natriuretic Agents / blood*
  • Natriuretic Peptide, Brain / blood*
  • Peptide Fragments / blood*
  • Predictive Value of Tests
  • Recombinant Proteins
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / physiopathology*
  • Risk Assessment


  • Biomarkers
  • Natriuretic Agents
  • Peptide Fragments
  • Recombinant Proteins
  • epoetin beta
  • Erythropoietin
  • Natriuretic Peptide, Brain

Associated data