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

Abstract

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. (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.

Trial registration: ClinicalTrials.gov identifier: NCT00321919.

Key words::

• Chronic kidney disease
• CREATE
• Haemoglobin
• NT-proBNP
• Prognostic marker

Transparency

Declaration of funding

F. Hoffmann-La Roche Ltd. provided funding for the clinical study.

Declaration of financial/other relationships

F.L. has disclosed that he is a member of advisory boards for Amgen, Dompé, F. Hoffmann-La Roche, Shire and Affymax. K.-U.E. has disclosed that he has received honoraria and lecture fees from Ortho Biotech, Amgen, F. Hoffmann-La Roche, Affymax and Shire. I.C.M. has disclosed that he has received honoraria, lecture fees and research grants from Ortho Biotech, Amgen, F. Hoffmann-La Roche, Affymax and Shire. D.T. and N.C. have disclosed that they received honoraria from F. Hoffmann-La Roche as members of the Steering Committee. T.D. has disclosed that he has received honoraria as a consultant from F. Hoffmann-La Roche and grant support and honoraria as a consultant and speaker from Amgen. H.-U.B. and A.S. have disclosed that are employees of F. Hoffmann-La Roche.

Acknowledgements

The authors thank Ms Regine Schrumpf for the operational leadership of the study; Ms Rachel Hosie for the data management; Mr Viktor Nendel and Ms Susan Gries for their support of statistical analyses; and they acknowledge the assistance of Dr Sarah Baldock and Michel Zaug in drafting the manuscript. They also thank all clinical monitors of the sub-study for their continuous commitment without which this study would not have been possible.

Notes

* NeoRecormon is a registered trade name of F. Hoffmann-La Roche Ltd, Basel, Switzerland.

† Reco–Pen is a registered trade name of Roche Pharmaceuticals, Basel, Switzerland.

‡ Elecsys is a registered trade name of Roche Diagnostics, Mannheim, Germany.