title: 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.
abstract: 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.
authors.affiliation: Pediatrics, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Clara
authors.initials: C
authors.lastname: Kurishima
authors.affiliation: Pediatrics, Saitama Medical Center, Saitama Medical University, Saitama, Japan. Electronic address: masutani@saitama-med.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Masutani
authors.affiliation: Pediatrics, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Kuwata
authors.affiliation: Pediatrics, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Iwamoto
authors.affiliation: Pediatrics, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Saiki
authors.affiliation: Pediatrics, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Ishido
authors.affiliation: Pediatrics, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Tamura
authors.affiliation: Pediatrics, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Senzaki
mesh_terms: D000293:Adolescent; D015415:Biomarkers; D001830:Body Surface Area; D002648:Child; D002675:Child, Preschool; D055316:Cystatin C / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006331:Heart Diseases; D006333:Heart Failure / Q000097:blood / Q000503:physiopathology*; D006801:Humans; D007223:Infant; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D015415:Biomarkers; D055316:Cystatin C; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: Brain natriuretic peptide; Child; Heart failure; N-terminal pro-brain natriuretic peptide; Renal function