The change in B-type natriuretic peptide levels over time predicts significant rejection in cardiac transplant recipients.
BACKGROUND
B-type natriuretic peptide (BNP) correlates with cardiac filling pressures and outcomes in patients with heart failure. In heart transplant recipients, we hypothesize that a within-individual change in BNP over time would be more helpful than absolute BNP in detecting International Society of Heart and Lung Transplantation (ISHLT) grade 2R or greater rejection.


METHODS
N-terminal pro-BNP (NT-proBNP) levels were measured in 146 consecutive transplant recipients undergoing routine endomyocardial biopsies. In the cross-sectional analysis, multiple observations per individual were accounted for using generalized estimation equations.


RESULTS
A cross-sectional analysis demonstrated a weak association between NT-proBNP levels and rejection, with an odds ratio (OR) of 1.01 for every 100-pg/mL increase in NT-proBNP (p = 0.02). However, with a doubling of an individual's NT-proBNP level, the OR for significant rejection was 2.9 (95% confidence interval [CI] 1.2-7.0), the OR with a 5-fold increase was 9.1 (95% CI, 2.7-31.5), and the OR with a 10-fold increase was 27.7 (95% CI, 5.9-129). A 10-fold increase in NT-proBNP offered a negative predictive value of 95% for the diagnosis of rejection. The relationship between within-individual increases in NT-proBNP and rejection persisted after adjusting for a fall in ejection fraction and a rise pulmonary capillary wedge pressure, and was a stronger predictor than changes in these parameters.


CONCLUSIONS
There is a strong, graded relationship between the within-individual increase in NT-proBNP and the odds of significant rejection independent of hemodynamic parameters. These results suggest that the change in NT-proBNP rather than absolute BNP levels may offer a non-invasive approach to detect rejection.
Kittleson
Michelle M
MM
Department of Medicine, Division of Cardiology, University of California at Los Angeles, Los Angeles, California, USA.
Skojec
Diane V
DV
Wittstein
Ilan S
IS
Champion
Hunter C
HC
Judge
Daniel P
DP
Barouch
Lili A
LA
Halushka
Marc
M
Hare
Joshua M
JM
Kasper
Edward K
EK
Russell
Stuart D
SD
D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D003430:Cross-Sectional Studies; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis; D012680:Sensitivity and Specificity
D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain