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


METHODS
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. (ClinicalTrials.gov 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.
Locatelli
Francesco
F
Dialysis and Renal Transplantation, Ospedale A. Manzoni, Lecco, Italy. nephrologia@ospedale.lecco.it
Eckardt
Kai-Uwe
KU
Macdougall
Iain C
IC
Tsakiris
Dimitrios
D
Clyne
Naomi
N
Burger
Hans-Ulrich
HU
Scherhag
Armin
A
Drüeke
Tilman B
TB
D000368:Aged; D000740:Anemia / Q000188:drug therapy / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000209:etiology; D015897:Comorbidity; D004921:Erythropoietin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D045283:Natriuretic Agents / Q000097:blood*; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D011994:Recombinant Proteins; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000503:physiopathology*; D018570:Risk Assessment
D015415:Biomarkers; D045283:Natriuretic Agents; D010446:Peptide Fragments; D011994:Recombinant Proteins; C103998:epoetin beta; D004921:Erythropoietin; D020097:Natriuretic Peptide, Brain