Cystatin C and body surface area are major determinants of the ratio of N-terminal pro-brain natriuretic peptide to brain natriuretic peptide levels in children.

BACKGROUND

Production of N-terminal pro-brain natriuretic peptide (NT) and BNP is equimolar. Although NT clearance occurs only in the kidneys, BNP clearance occurs in the kidneys and other organs. This study tested the hypothesis that NT/BNP ratio in children may be independently related to cystatin C (CysC), a glomerular filtration rate marker, when diastolic function and age/body size are taken into consideration.

METHODS

The study included 430 children (5.3±4.9 years) with heart disease who had undergone cardiac catheterization and simultaneous BNP, NT, and CysC measurements. Pulmonary capillary wedge pressure (PCWP) was used as a ventricular diastolic stretch marker. Variables showing skewed distribution were transformed into a common logarithm.

RESULTS

Univariate regression revealed that logNT/BNP was affected by PCWP (r=-0.12) and logCysC (r=0.57). When age and the log of body surface area (BSA) were added to the stepwise regression, age was not adopted because of multicollinearity to logBSA, but PCWP (β=-0.10), logCysC (β=0.22), and logBSA (β=-0.66) were independent factors of logNT/BNP.

CONCLUSIONS

Renal dysfunction independently increased NT/BNP, whereas high BSA decreased it and is the greatest determinant of NT/BNP. The observation that high PCWP decreased NT/BNP may suggest that worsening heart failure slows BNP clearance from other organs, a compensatory pathway of heart failure. These factors need to be considered when assessing BNP and NT.