Author + information
- Received November 13, 2012
- Revision received November 30, 2012
- Accepted December 5, 2012
- Published online April 1, 2013.
- Rosita Zakeri, MB ChB∗∗ (, )
- S. Jeson Sangaralingham, PhD∗,
- Sharon M. Sandberg, BS∗,
- Denise M. Heublein, CLT∗,
- Christopher G. Scott, MS† and
- John C. Burnett Jr., MD∗
- ↵∗Reprint requests and correspondence:
Ms. Rosita Zakeri, Mayo Clinic and Mayo Clinic College of Medicine, 200 First Street S.W., Rochester, Minnesota 55905.
Objectives This study was conducted to determine whether urinary excretion of C-type natriuretic peptide (CNP) is elevated in acute decompensated heart failure (ADHF) and whether elevated levels predict adverse outcomes.
Background Urinary CNP has been detected in patients with heart failure, but its clinical significance and prognostic utility, compared to established kidney injury biomarkers, in ADHF is unknown.
Methods We measured 24-h urinary excretion and concurrent plasma concentrations of CNP22, CNP53, and NT-CNP53 in 58 ADHF patients and 20 healthy control subjects. Urinary kidney injury molecule (KIM)-1 and neutrophil gelatinase–associated lipocalin (NGAL) and plasma N-terminal pro-B type natriuretic peptide (NT-proBNP) were also measured. Mortality and all-cause rehospitalization/death were assessed over a follow-up of 1.5 ± 0.9 years.
Results ADHF patients had higher urinary excretion of all 3 CNP molecular forms than did controls. Plasma CNP22 and CNP53 were elevated in ADHF but showed limited correlation with urinary excretion, suggesting that mainly renal-derived CNP appears in urine. Plasma NT-proBNP and urinary KIM-1 were also elevated in ADHF (p < 0.0001); urinary NGAL was similar to that in controls. At 6 months, event-free survival values in ADHF patients were 86% for mortality and 59% for all-cause rehospitalization/death. On Cox regression analysis, urinary NT-CNP53 was the only predictor of mortality (hazard ratio: 1.7; 95% confidence interval: 1.1 to 2.4; p = 0.01) and all-cause rehospitalization/death (hazard ratio: 1.8; 95% confidence interval: 1.3 to 2.4; p = 0.0004), even after adjustment. Integrated discrimination analysis suggested that urinary NT-CNP53 combined with plasma NT-proBNP improved the prediction of adverse outcomes.
Conclusions The findings from this study support the clinical utility of urinary CNP molecular forms. In ADHF, urinary NT-CNP53 correlated with prognosis, better predicted outcomes than did urinary NGAL and KIM-1, and improved the prognostic value of plasma NT-proBNP.
This work was supported by the National Institutes of Health (grant nos. RO1 HL36634 and PO1 HL76611), the Mayo Clinic Center for Clinical and Translational Research (grant no. TL1RR024152) and the Mayo Foundation. Dr. Sangaralingham, Ms. Heublein, Dr. Burnett, and the Mayo Foundation have filed a patent for the use of urinary C-type natriuretic peptide. All others authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received November 13, 2012.
- Revision received November 30, 2012.
- Accepted December 5, 2012.
- American College of Cardiology Foundation