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Determination and stability of N-terminal pro-brain natriuretic peptide in saliva samples for monitoring heart failure

  • Bellagambi, Francesca G.1, 2
  • Petersen, Christina3
  • Salvo, Pietro4
  • Ghimenti, Silvia1
  • Franzini, Maria5
  • Biagini, Denise1
  • Hangouët, Marie6
  • Trivella, Maria Giovanna4
  • Di Francesco, Fabio1
  • Paolicchi, Aldo5
  • Errachid, Abdelhamid2
  • Fuoco, Roger1
  • Lomonaco, Tommaso1
  • 1 University of Pisa, Pisa, 56124, Italy , Pisa (Italy)
  • 2 University Claude Bernard Lyon 1, Lyon, 69100, France , Lyon (France)
  • 3 Fondazione Toscana Gabriele Monasterio, Pisa, 56124, Italy , Pisa (Italy)
  • 4 National Research Council, Pisa, 56124, Italy , Pisa (Italy)
  • 5 University of Pisa, Pisa, 56126, Italy , Pisa (Italy)
  • 6 French National Center for Scientific Research (CNRS), Lyon, 69100, France , Lyon (France)
Published Article
Scientific Reports
Springer Nature
Publication Date
Jun 22, 2021
DOI: 10.1038/s41598-021-92488-2
Springer Nature
  • article


Heart failure (HF) is the main cause of mortality worldwide, particularly in the elderly. N-terminal pro-brain natriuretic peptide (NT-proBNP) is the gold standard biomarker for HF diagnosis and therapy monitoring. It is determined in blood samples by the immunochemical methods generally adopted by most laboratories. Saliva analysis is a powerful tool for clinical applications, mainly due to its non-invasive and less risky sampling. This study describes a validated analytical procedure for NT-proBNP determination in saliva samples using a commercial Enzyme-Linked Immuno-Sorbent Assay. Linearity, matrix effect, sensitivity, recovery and assay-precision were evaluated. The analytical approach showed a linear behaviour of the signal throughout the concentrations tested, with a minimum detectable dose of 1 pg/mL, a satisfactory NT-proBNP recovery (95–110%), and acceptable precision (coefficient of variation ≤ 10%). Short-term (3 weeks) and long-term (5 months) stability of NT-proBNP in saliva samples under the storage conditions most frequently used in clinical laboratories (4, − 20, and − 80 °C) was also investigated and showed that the optimal storage conditions were at − 20 °C for up to 2.5 months. Finally, the method was tested for the determination of NT-proBNP in saliva samples collected from ten hospitalized acute HF patients. Preliminary results indicate a decrease in NT-proBNP in saliva from admission to discharge, thus suggesting that this procedure is an effective saliva-based point-of-care device for HF monitoring.

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