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Published on: July 14, 2017
Characterization of NT-proBNP in human urine
Suetonia C Palmer1, Zoltan H Endre, A Mark Richards
1Christchurch Cardioendocrine Research Group, University of Otago Christchurch, New Zealand.
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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