Natriuretic Peptide Assays Revisited

Emdin, Michele; Passino, Claudio; Clerico, Aldo

doi:10.1016/j.jacc.2010.09.075

Cited by 18 publications

(3 citation statements)

References 18 publications

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“…NT-proBNP immunoassays may be improved by antibodies detecting glycosylated or non-glycosylated NT-proBNP and antibodies detecting NT-proBNP not affected by glycosylation ( Rosjo et al, 2015 ). In current proBNP immunoassays, glycosylated proBNP cross-reacts more than non-glycosylated proBNP with BNP and NT-proBNP ( Emdin et al, 2011 ). There are inter-individual differences in NT-proBNP and proBNP glycosylation in patients with and without HF ( Saenger et al, 2017 ).…”

Section: Analytical Issuesmentioning

confidence: 99%

Brain Natriuretic Peptide and Its Biochemical, Analytical, and Clinical Issues in Heart Failure: A Narrative Review

Ping

Zhu

et al. 2018

Front. Physiol.

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Heart failure (HF) is a primary cause of morbidity and mortality worldwide. As the most widely studied and commonly applied natriuretic peptide (NP), B-type natriuretic peptide (BNP) has the effects of diuresis, natriuresis, vasodilation, anti-hypertrophy, and anti-fibrosis and it inhibits the renin-angiotensin-aldosterone and sympathetic nervous systems to maintain cardiorenal homeostasis and counteract the effects of HF. Both BNP and N-terminal pro B-type natriuretic peptide (NT-proBNP) are applied as diagnostic, managing, and prognostic tools for HF. However, due to the complexity of BNP system, the diversity of BNP forms and the heterogeneity of HF status, there are biochemical, analytical, and clinical issues on BNP not fully understood. Current immunoassays cross-react to varying degrees with pro B-type natriuretic peptide (proBNP), NT-proBNP and various BNP forms and cannot effectively differentiate between these forms. Moreover, current immunoassays have different results and may not accurately reflect cardiac function. It is essential to design assays that can recognize specific forms of BNP, NT-proBNP, and proBNP to obtain more clinical information. Not only the processing of proBNP (corin/furin) and BNP (neprilysin), but also the effects of glycosylation on proBNP processing and BNP assays, should be targeted in future studies to enhance their diagnostic, therapeutic, and prognostic values.

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Section: Analytical Issuesmentioning

confidence: 99%

Brain Natriuretic Peptide and Its Biochemical, Analytical, and Clinical Issues in Heart Failure: A Narrative Review

Ping

Zhu

et al. 2018

Front. Physiol.

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“…ANP and BNP [23-26]. Clerico and co-workers concluded that the large differences in these results are most likely due to the specificity of monoclonal or polyclonal antibodies used, the design of immunoassay system (competitive vs. non-competitive assay), the analytical matrix (serum vs. EDTA vs. heparinized plasma) used, and the plethora of circulating forms of natriuretic peptides, as previously reported for ANP and BNP immunoassays [23,26,27]. These methodological sources of bias may also be conceivable for CNP and NT-proCNP assays and thus explain the great difference in results in the cited studies (Table 1).…”

Section: Discussionmentioning

confidence: 97%

Comparative measurement of CNP and NT-proCNP in human blood samples: a methodological evaluation

Kuehnl

Pelisek

Bruckmeier

et al. 2013

J Negat Results BioMed

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BackgroundC-type natriuretic peptide (CNP) has anti-inflammatory, anti-proliferative, and anti-migratory properties. During the past years, CNP has attained an increasing interest by many research groups, especially in the cardiovascular field. Nevertheless, still no reliable data exist on the difference of CNP concentration between serum and plasma samples. Also, the influence of delayed blood sample proceeding is unknown. The aim of this study was to investigate the difference of CNP and NT-proCNP concentrations between serum and plasma samples. In order to identify potential methodological bias, this study should also validate the stability of CNP and NT-proCNP in full blood samples stored at room temperature.FindingsTriplets (serum, plasma, full blood) of fasting blood samples from 12 healthy male individuals were collected. Analysis of CNP and NT-proCNP concentration was performed immediately following sampling, and after 30 minutes or 2 hours of storage at room temperature. Mean serum concentrations at baseline were 0.997 ± 0.379 ng/ml for CNP and 58.5 ± 28.3 pg/ml for NT-proCNP. Furthermore, NT-proCNP concentration did not change significantly during the allotted time and did not differ between serum, plasma, and full blood samples. At baseline, concentrations of CNP were significantly different between samples containing either sodium-citrate or EDTA as a clotting inhibitor (1.933 ± 0.699 ng/ml vs. 0.991 ± 0.489 ng/ml, p = 0.001).ConclusionsCNP and NT-proCNP are stable for at least two hours, even when sample processing is delayed or blood probes are stored at room temperature. NT-proCNP assay demonstrated more consistent and reliable data and should therefore be preferred for usage in clinical applications. Nevertheless, as recommended for ANP and BNP, immunoassays for CNP should also be standardized or harmonized in the future.

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“…In these patients, this combined measurement was particularly promising in patients with low levels of BNP, in which the clinicians could be falsely reassured. Clinical evaluation of combinations of highly specific assays for the assessment of BNP peptides are still needed [14] especially in patients with chronic renal failure since the half-life of the 3 peptides and/or their respective renal clearance is poorly understood [15]. …”

Section: Discussionmentioning

confidence: 99%

Depletion of proBNP1-108 in Patients with Heart Failure Prevents Cross-Reactivity with Natriuretic Peptides

et al. 2013

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BackgroundAfter 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).MethodsThis 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.ResultsMean 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.ConclusionCurrent 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.

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Natriuretic Peptide Assays Revisited

Cited by 18 publications

References 18 publications

Brain Natriuretic Peptide and Its Biochemical, Analytical, and Clinical Issues in Heart Failure: A Narrative Review

Brain Natriuretic Peptide and Its Biochemical, Analytical, and Clinical Issues in Heart Failure: A Narrative Review

Comparative measurement of CNP and NT-proCNP in human blood samples: a methodological evaluation

Depletion of proBNP1-108 in Patients with Heart Failure Prevents Cross-Reactivity with Natriuretic Peptides

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