Characterization of NT-proBNP in human urine.
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.
Palmer
Suetonia C
SC
Christchurch Cardioendocrine Research Group, University of Otago Christchurch, New Zealand.
Endre
Zoltan H
ZH
Richards
A Mark
AM
Yandle
Timothy G
TG
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006331:Heart Diseases / Q000652:urine; D006801:Humans; D007118:Immunoassay; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000652:urine*; D010446:Peptide Fragments / Q000097:blood / Q000652:urine*
D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain