Abstract 13451: Renal Derived Amino-Terminal C-Type Natriuretic Peptide-53 is a Novel Urinary Biomarker Which Predicts Adverse Outcomes in Patients with Acute Decompensated Heart Failure
Introduction Renal production and processing of C-type natriuretic peptide (CNP) may be activated by humoral mechanisms or hypoxia operant in cardiorenal disease. CNP has been detected in the urine of stable heart failure patients but its clinical significance in acute decompensated heart failure (ADHF) is unknown and its prognostic utility, particularly in comparison to known kidney injury biomarkers, has not been studied. We hypothesized that urinary excretion of CNP molecular forms is elevated in ADHF patients compared to normal controls, and better predicts adverse outcomes in this population than urinary NGAL and KIM-1.
Methods We measured 24 hour urinary excretion and concurrent plasma concentrations of CNP22, CNP53, and NT-CNP53 in 58 ADHF patients (mean age 70±10 years, 59% male) and 20 normal controls. Urinary NGAL, KIM-1 and plasma NT-proBNP were also measured. Mean (SD) follow up was 1.5 (0.9) years. The primary outcome was mortality; a secondary outcome of all-cause rehospitalization/death was also studied.
Results ADHF patients had higher urinary excretion of all three CNP forms compared to controls (median CNP22: 14.0 vs. 7.2ng/gCr, p=0.0003; CNP53: 115.2 vs. 64.7ng/gCr, p=0.02; NT-CNP53: 35.8 vs. 19.4ng/gCr, p=0.002). Plasma CNP22 and CNP53 were elevated in ADHF but did not correlate with urinary excretion, suggesting mainly renal derived CNP appears in the urine. Plasma NT-proBNP and urinary KIM-1 were also elevated in ADHF compared to controls (p<0.0001); urinary NGAL was unchanged. ADHF mortality was 31% and all-cause rehospitalization/death rate 62%. Urinary CNP22, CNP53, and NT-CNP53 excretion was higher in patients who died than survivors; NGAL and KIM-1 were unchanged. Urinary NT-CNP53 was the only biomarker to significantly predict mortality (HR 1.7, 95%CI 1.1-2.4, p=0.01) and all-cause rehospitalization/death (HR 1.8, 95%CI 1.3-2.4, p=0.0004). Its predictive value persisted after adjusting for age and plasma NT-proBNP. Urinary NT-CNP53 was a stronger prognostic marker than plasma NT-proBNP.
Conclusion This is the first study to demonstrate the clinical utility of urinary CNP molecular forms. In ADHF urinary NT-CNP53 correlates with prognosis and has better predictive value than urinary NGAL, KIM-1 and plasma NT-proBNP.
- © 2012 by American Heart Association, Inc.