Clerico A, Del Ry S, Giannessi D
Laboratory of Cardiovascular Endocrinology, Consiglio Nazionale delle Ricerche Institute of Clinical Physiology, University of Pisa, 56100 Pisa, Italy.
Clin Chem. 2000 Oct;46(10):1529-34.
Cardiac natriuretic hormones (CNHs) are a family of related peptides, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and other peptides derived from the N-terminal portion of the proANP and proBNP peptide chains. Assays for cardiac natriuretic peptides have been proposed to help assess clinical conditions associated with expanded fluid volume. In particular, the assays can be useful for distinguishing healthy subjects from patients in different stages of heart failure. Measurements of these hormones have also been considered for prognostic indicators of long-term survival in patients with heart failure and/or after acute myocardial infarction. The different CNHs differ in their production/secretion patterns and have different clearance rates. Furthermore, there are numerous proposed assay configurations for each of these hormones, and it is not clear which assay provides the best pathophysiological and/or clinical information.
Here we review recent studies concerning the competitive (such as RIA, enzyme immunoassay, or luminescence immunoassay) and noncompetitive immunoassays (such as two-site IRMA, ELISA, or immunoluminometric assay) for the different cardiac natriuretic peptides to compare the analytical characteristics and clinical relevance of assays for the different CNHs and the different assay formats.
Developing sensitive, precise, and accurate immunoassays for cardiac natriuretic peptides has been difficult because of their low concentrations (on average, approximately 3-6 pmol/L) in healthy subjects and because of their structural, metabolic, and physiological characteristics. Competitive assays have historically suffered from lack of sensitivity and specificity for the biologically active peptides. These usually require tedious extraction procedures prior to analysis. Recently, immunometric assays have been developed that have improved sensitivity and specificity; it appears these will be the methods of choice.
To date, there is no consensus on the best assay procedure of cardiac natriuretic peptides. To facilitate widespread propagation of determination of these hormones in routine clinical practice, it will be necessary to study the new generation of noncompetitive immunometric methods that are less time-consuming and more sensitive and specific. Although several studies suggest that BNP exhibits better clinical utility than the other CNHs, more studies examining multiple CNHs in the same cohorts of patients will be necessary.
心脏利钠肽（CNHs）是一类相关肽家族，包括心房利钠肽（ANP）、脑利钠肽（BNP）以及其他源自proANP和proBNP肽链N端部分的肽。已有人提出检测心脏利钠肽以帮助评估与体液量增加相关的临床状况。特别是，这些检测对于区分健康受试者与处于不同心力衰竭阶段的患者可能有用。这些激素的测量也被视为心力衰竭患者和/或急性心肌梗死后长期生存的预后指标。不同的CNHs在其产生/分泌模式上存在差异，清除率也不同。此外，针对每种这些激素都有众多提议的检测配置，目前尚不清楚哪种检测能提供最佳的病理生理和/或临床信息。
在此，我们回顾近期有关不同心脏利钠肽的竞争性检测（如放射免疫分析、酶免疫分析或发光免疫分析）和非竞争性免疫分析（如双位点免疫放射分析、酶联免疫吸附测定或免疫荧光测定）的研究，以比较不同CNHs检测方法和不同检测形式的分析特征及临床相关性。
由于心脏利钠肽在健康受试者中的浓度较低（平均约为3 - 6 pmol/L）及其结构、代谢和生理特性，开发灵敏、精确且准确的心脏利钠肽免疫分析方法一直颇具难度。传统的竞争性检测在对生物活性肽的敏感性和特异性方面存在不足。这些检测通常在分析前需要繁琐的提取程序。近年来，已开发出免疫比浊法，其敏感性和特异性有所提高；似乎这些将成为首选方法。
迄今为止，关于心脏利钠肽的最佳检测方法尚无共识。为便于在常规临床实践中广泛开展这些激素的检测，有必要研究新一代耗时较少、更灵敏且特异的非竞争性免疫比浊法。尽管多项研究表明BNP比其他CNHs具有更好的临床实用性，但仍需要更多在同一患者队列中检测多种CNHs的研究。
