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Clinical Chemistry 0: clinchem.2008.121673v1, 2009; 10.1373/clinchem.2008.121673
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Received on November 27, 2008
Accepted on March 16, 2009

General Clinical Chemistry

Characterization of Amino-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) in Human Urine

Suetonia C. Palmer 1, Zoltan H. Endre 2, A. Mark Richards 3, Timothy G. Yandle 3*

1 Christchurch Cardioendocrine Research Group, Christchurch Kidney Research Group, and Department of Medicine, University of Otago Christchurch, New Zealand
2 Christchurch Kidney Research Group, and Department of Medicine, University of Otago Christchurch, New Zealand
3 Christchurch Cardioendocrine Research Group, and Department of Medicine, University of Otago Christchurch, New Zealand

* To whom correspondence should be addressed. E-mail: tim.yandle{at}otago.ac.nz.

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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 Eur J Heart FailHome page
S. C. Palmer, T. G. Yandle, M. G. Nicholls, C. M. Frampton, and A. M. Richards
Regional clearance of amino-terminal pro-brain natriuretic peptide from human plasma
Eur J Heart Fail, September 1, 2009; 11(9): 832 - 839.
[Abstract] [Full Text] [PDF]


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