Elevated levels of each circulating B‐type or brain natriuretic peptide (BNP) molecular form precede worsening renal function (WRF) in patients with acute heart failure (HF), potentially making these levels a useful biomarker for stratifying risk in cardiorenal syndrome, according to study results published in the Journal of the American Heart Association.

In patients with acute decompensated HF, early WRF detection is indispensable. The study investigators hypothesized that the difference in circulating levels of N-terminal prohormone brain natriuretic peptide (NT-proBNP) and mature BNP vary and that their ratio is associated with WRF occurrence. In this prospective, cross-sectional study, investigators tested the hypothesis that the difference in circulating levels of proBNP, the NT‐proBNP, and total BNP (proBNP + mature BNP) is associated with WRF occurrence in this patient population.

They prospectively measured circulating BNP levels in eligible patients using sensitive and specific enzyme immunochemiluminescent assays and determined an estimated mature BNP (emBNP) concentration by subtracting proBNP levels from total BNP levels.


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Researchers classified WRF as >20% decrease in estimated glomerular filtration rate (eGFR) during hospitalization. They compared changes of variables between patients with and without WRF using one-way repeated-measures analysis of variance.

The study included 182 patients, with a median hospital stay of 22 days and a median follow-up of 18 days. In hospitalized patients with acute decompensated HF (New York Heart Association class III–IV; 96%), levels of NT‐proBNP did not differ between patients with (n=42) and without WRF (n=140), although levels of emBNP were lower in participants with WRF than in participants without by day 3 of hospitalization. By day 3, participants with WRF demonstrated elevated NT‐proBNP/emBNP molar ratios before a decline in eGFR, but participants without WRF did not experience any changes.

NT‐proBNP/emBNP ratios were significantly associated with percentage decreases in eGFR on day 3 after admission whereas NT-proBNP levels were moderately associated with eGFR decreases and emBNP levels were not associated with eGFR decreases. In participants with WRF, NT-proBNP/emBNP ratios were associated with clinical outcomes whereas in participants without WRF, NT-proBNP alone was associated with clinical outcomes.

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Limitations to the study included the limited number of patients, the single-center design, a lack of power to determine predictive parameters, the fact that some patients did not receive a blood test after day 3, and a lack of measurement of some biomarkers; however, study investigators concluded, “We demonstrated the differences in changes in NT‐proBNP and emBNP between patients with acute HF with and without WRF. NT‐proBNP/emBNP molar ratios are strongly associated with renal function during the short‐term phase of acute HF and with adverse clinical events. This ratio provides information about patients with cardiorenal syndrome that cannot be derived from measurements of total BNP or eGFR individually and also provides valuable information about pathophysiological characteristics in both the heart and kidney.”

Reference

Takahama H, Nishikimi T, Takashio S, et al. 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. J Am Heart Assoc. 2019;8(17):e011468.