Change in the NT‐proBNP/Mature BNP Molar Ratio Precedes Worsening Renal Function in Patients With Acute Heart Failure: A Novel Predictor Candidate for Cardiorenal Syndrome

BACKGROUND: Early detection for worsening renal function (WRF) is indispensable in patients with acute decompensated heart failure (HF). We tested the hypothesis that the difference in the circulating levels of each B‐type or brain natriuretic peptide (BNP) molecular form is associated with the occurrence of WRF. METHODS AND RESULTS: Circulating levels of proBNP, the NT‐proBNP (N‐terminal proBNP), and total BNP (proBNP+mature BNP) were prospectively measured in patients with acute decompensated HF using specific and sensitive enzyme immunochemiluminescent assays. An estimated mature BNP (emBNP) concentration was calculated by subtracting proBNP levels from total BNP levels. WRF was defined as a >20% decrease in the estimated glomerular filtration rate during the hospitalization. One‐way repeated‐measures ANOVA was used to compare the changes of variables between the patients with and without WRF. In patients with acute decompensated HF (New York Heart Association class III–IV; 96%) hospitalized for HF, NT‐proBNP levels did not differ during the hospitalization between patients with and without WRF (n=42 and 140, respectively). By contrast, emBNP levels were lower in patients with WRF than in those without WRF on day 3 after admission. NT‐proBNP/emBNP molar ratios were elevated on day 3 after admission in the patients with WRF, before estimated glomerular filtration rate declined, but were unchanged in patients without WRF. On day 3 after hospital admission, NT‐proBNP/emBNP ratios were strongly associated with percentage decreases in estimated glomerular filtration rate. CONCLUSIONS: These findings suggest that elevation of NT‐proBNP/emBNP ratio precedes WRF in patients with acute HF and can be a potentially useful biomarker for risk stratification of cardiorenal syndrome.