Key result
Urine NT-proBNP immunoreactivity was higher in acute (median 192 pg/mg creatinine) and chronic (52 pg/mg) heart failure than in healthy subjects (4.2 pg/mg; P<0.001).
Why the study?
What are the molecular forms of urine NT-proBNP and how do they correlate with plasma NT-proBNP in heart failure patients?
Cross-Sectional
What are the molecular forms of urine NT-proBNP and how do they correlate with plasma NT-proBNP in heart failure patients?
Absolute Event Rate: 192% vs 4.2%
p-value: p=<0.001
Urine NT-proBNP immunoreactivity reflects assorted metabolites rather than intact NT-proBNP(1-76), necessitating assay-specific validation for heart failure diagnosis.
Urine NT-proBNP may indicate HF status; leaves open assay-specific validation and prospective diagnostic studies.
BACKGROUND: Urine amino-terminal probrain natriuretic peptide (NT-proBNP) concentrations may exclude the presence of heart failure and provide insight into renal clearance mechanisms for human NT-proBNP. We characterized the molecular forms of urine NT-proBNP detected by immunoassay. METHODS: Urine from patients with heart failure was subjected to HPLC and analyzed using immunoassays specific toward different epitopes of NT-proBNP. We assessed urine NT-proBNP immunoreactivity in healthy subjects and patients with heart failure. RESULTS: Size-exclusion chromatography of heart failure urine identified no NT-proBNP immunoreactivity coeluting with NT-proBNP(1-76); multiple immunoreactive NT-proBNP fragments were present. The absence of intact urinary NT-proBNP was supported by reversed-phase HPLC. Urine NT-proBNP immunoreactivity was higher in patients with acute [median 192 (interquartile range 108-1445) pg/mg creatinine] and chronic [52 (15-118) pg/mg creatinine] heart failure than in healthy subjects [4.2 (2.6-5.8) pg/mg creatinine] (P < 0.001). In 40 patients with heart failure, urine NT-proBNP immunoreactivity correlated with plasma NT-proBNP (r = 0.72, P < 0.001) and inversely with left ventricular ejection fraction (r = -0.33, P = 0.04). CONCLUSIONS: Our findings clarify previous reported relationships of urine NT-proBNP-like immunoreactivity with plasma NT-proBNP concentrations and the diagnosis of heart failure. As urine NT-proBNP immunoreactivity is not intact NT-proBNP(1-76), but rather reflects assorted metabolites, the diagnostic performance of NT-proBNP assays in urine may be assay specific, necessitating validation of biomarker performance on an assay-by-assay basis.
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Palmer et al. (2009) conducted a cross-sectional in Heart failure. Heart failure vs. Healthy subjects was evaluated on Urine NT-proBNP immunoreactivity (p=<0.001). Urine NT-proBNP immunoreactivity was higher in acute (median 192 pg/mg creatinine) and chronic (52 pg/mg) heart failure than in healthy subjects (4.2 pg/mg; P<0.001).
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