Abstract
Background: Brain natriuretic peptide (BNP) is established biomarker for cardiovascular diseases. Recent studies have shown that unprocessed precursor proBNP circulates in the healthy individuals, and its levels in plasma are increased in severe heart failure patients. However, since current BNP immunoassay crossreacts proBNP, it is important to consider the significance of proBNP on clinical situation of BNP elevation. In addition, recent study has shown that most proBNP is glycosylated, and that NT-proBNP is also glycosylated in human plasma, and current NT-proBNP assay underestimates the glycosylated NT-proBNP. Recent developed super-flux dialyzer can remove middle-sized molecular solutes such as β2-microgloburin. In this study, we investigated the effects of hemodialysis using super-flux dialyzer on the glycosylated proBNP, glycosylated NT-proBNP, and BNP-related other peptide in patients with end-stage renal disease (ESRD). Method: Thirty-six ESRD patients with hemodialysis were studied. We measured plasma BNP (which was defined as BNP messured with current BNP assay system), proBNP, and mature BNP (which was defined as total BNP- proBNP), by our newly developed immunoassay before and after hemodialysis. Plasma glycosylated NT-proBNP and nonglycosylated NT-proBNP was measured by Elecsys II after deglycosylating enzyme treatment such as neuramoinidase and O-glycosydase. We also measured plasma ANP and cGMP by radioimmunoassay. Results: After hemodialysis, BNP (-28%), proBNP (-20%), mature BNP (-47%), glycosylated NT-proBNP (-33%), nonglycosylated NT-proBNP (-45%), ANP (-52%), and cGMP (-63%) significantly decreased. The decreasing ratio did not correlated with any indices of reduction of plasma volume; however, these peptides decreased after hemodialysis in a molecular weight dependent manner. ProBNP/total BNP ratio and glycosylated NT-proBNP/nonglycosylated NT-proBNP ratio increased after hemodialysis. ProBNP/total BNP ratio positively correlated with hemodialysis vintage and negatively correlated with left atrial dimater and systolic blood pressure, whereas glycosylated NT-proBNP/nonglycosylated positively correlated with parathyroid hormone levels. Conclusion: These results suggest that hemodialysis modulates profile of BNP and its related peptide, and it may be important to consider the effect of this modulation on the pathological conditions in ESRD patients in super-flux dialyzer era.
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