Depletion of proBNP1-108 in patients with heart failure prevents cross-reactivity with natriuretic peptides.

BACKGROUND: After synthesis by cardiomyocytes, precursor proBNP1-108 is cleaved into NT-proBNP and BNP. Recently, cross-reactivity between these assays was discussed. The aim of this study was to characterize the cross-reactivities, through a new biochemical innovative approach consisting in the total depletion of the circulating proBNP1-108 in patients with heart failure (HF). METHODS: This prospective study included 180 patients with chronic HF. BNP and NT-proBNP were dosed with commercial kits. ProBNP1-108 was determined using an ELISA research assay specific to the precursor. ProBNP1-108 depletion was performed by immunocapture with a specific antibody targeting exclusively the ProBNP1-108 hinge region. ProBNP1-108, BNP and NT-proBNP levels were determined before and after depletion using this process in HF patients. RESULTS: Mean age was 74.34 +/-12.5 y, and 69% of patients were males. NYHA classes II and III were the most frequent (32% and 45% respectively). Before depletion, ProBNP1-108, NT-proBNP and BNP levels were 316.8+/-265.9 pg/ml; 6,054.0+/-11,539 pg/ml and 684.3+/-82.1 pg/ml respectively, and were closely correlated with NHYA classes. After immuno-depletion, proBNP1-108 was decreased in mean by 96% (p<0.0001), BNP by 53% (p<0.0001) and NT-proBNP by 5%. The relationship between BNP or NT-proBNP and NHYA classes remained unchanged. CONCLUSION: Current BNP and NT-proBNP assays measured as well proBNP molecule. This cross reactivity percentage has been controversial. Thanks to the removal of circulating proBNP1-108 with our immunodepletion process, we are now able to assess the remaining "true" BNP and NT-proBNP molecules and further evaluate their clinical relevance

Bland Altman representation of the individual variations before and after depletion, reported to the start level of peptides BNP (A), NT-proBNP (B).

<div><p>A: BNP. The relationship is clearly linear, whatever the start level of BNP before the depletion procedure.</p> <p>B: pro-BNP: the relashionship is not strong.</p></div

Circulating BNP levels before and after depletion of proBNP_1-108.^.

<div><p>BNP decreased significantly by 53% (when means are compared), p<0.0001.</p> <p>A: Median and interquartile range of reduction for paired values (n=177).</p> <p>B: Statistical distributions for the 180 patients (median and interquartile range, 16 values are out of the axis limits).</p></div

Distribution according to renal function (estimated by CKD-EPI) of: BNP before depletion (A), after depletion (B) or NTproBNP before depletion (C), after depletion (D), and proBNP_1-108 before depletion (E).

<p>All of these Natriuretic peptides are strictly correlated with the renal function, with p<0.001 (specific values after Kruskal -Wallis analyses are indicated).</p

Living Lab MACVIA Maladies chroniques

International audienceÀl 'origine de 85 % de la mortalité et de plus de 70 % des dépenses de santé en France, les maladies chroniques non transmissibles (MCNT) ont des conséquences médico-économi-ques considérables. Intimement liées à l'environnement, au mode de vie et au vieillissement, elles s'associent fréquemment chez une même personne conduisant à des situations de multi-et comorbidité. Il est impératif que nos systèmes de santé s'adaptent au plus vite pour assurer un vieillissement actif en bonne santé. Le Living Lab MACVIA Maladies chroniques, intégré au réseau des Living Lab MACVIA-LR s'inscrit dans le Partenariat européen d'innovation pour un vieillissement actif et en bonne santé (European Innovation Partnership on Active and Healthy Ageing ; EIP on AHA, DG Sanco et DG CNECT) et a pour objectif de favoriser le dépistage et la prise en charge précoce et intégrativ

Correlations between BNP and NTproBNP assays before and after depletion of proBNP_1-108.

<div><p>A: BNP. Correlation between the two assays is very strong, in spite of the deep reduction of the values: n=178, r=0.97; p<0.0001.</p> <p>B: NT-proBNP. Correlation between the two assays is very strong, in spite of the mild reduction of the values N=178, r=0.99; p<0.0001.</p></div

Distribution according to NYHA classes of: BNP before depletion (A), after depletion (B) or NTproBNP before depletion (C), after depletion (D), and proBNP_1-108 before depletion (E).

<p>All of these Natriuretic peptides are strictly correlated with the functional classes, with p<0.001 (specific values after Kruskal-Wallis analyses are indicated).</p

Correlations between CRP, NYHA and BNP or NTproBNP after depletion of proBNP_1-108.

<div><p>A: CRP is correlated with NYHA. CRP levels increase significantly when the NYHA class becomes higher (P<0.0001).</p> <p>B: BNP after depletion is correlated with CRP levels. BNP levels are considered in quartiles. P=0.0003.</p> <p>C: NT-proBNP after depletion is correlated with CRP levels. BNP levels are considered in quartiles. P<0.0001.</p></div

Circulating NT-proBNP levels before and after depletion of proBNP_1-108.

<div><p>NT-proBNP decreased significantly by 5%, (when means are compared), p=0.02.</p> <p>A: Median and interquartile range of reduction for paired values (n=178).</p> <p>B: Statistical distributions for the 180 patients (median and interquartile range, 48 values are out of the axis limits).</p></div