Diagnostic and prognostic property of NT-proBNP in patients with renal dysfunction
2013; Elsevier BV; Volume: 61; Issue: 6 Linguagem: Inglês
10.1016/j.jjcc.2013.01.013
ISSN1876-4738
Autores Tópico(s)Potassium and Related Disorders
ResumoB-type natriuretic peptide (BNP) was first identified in porcine brain in 1988 and originally was termed brain natriuretic peptide. Subsequently, it was detected in ventricular cardiomyocytes and the ventricular myocardium was later recognized as the major source of circulating BNP. The main stimulus for increased BNP synthesis and secretion is wall stress and BNP is synthesized as a proBNP comprising 108 amino acids. Upon release into the circulation, it is cleaved in equal proportion into the biologically active 32 acid BNP and the biologically inactive 76 amino acid N-terminal fragment, NT-proBNP. BNP relaxes vascular smooth muscle, dilates arteries and veins, lowers blood pressure and ventricular preload, and inhibits sympathetic activity and the renin–angiotensin–aldosterone system. It also increases glomerular filtration and inhibits sodium reabsorption by the kidney, promoting natriuresis and diuresis [1Daniels L.B. Maisel A.S. Natriuretic peptides.J Am Coll Cardiol. 2007; 50: 2357-2368Abstract Full Text Full Text PDF PubMed Scopus (843) Google Scholar, 2Martinez-Rumayor A. Richards A.M. Burnett J.C. Januzzi Jr., J.L. Biology of the natriuretic peptides.Am J Cardiol. 2008; 101: 3A-8AAbstract Full Text Full Text PDF PubMed Scopus (189) Google Scholar]. BNP is mainly cleared from plasma by binding to the natriuretic peptide receptor type C (NPR-C) and through proteolysis by neutral endopeptidases. In contrast, NT-proBNP is cleared by renal clearance. This finding led to the incorrect hypothesis that NT-proBNP is dependent on renal function whereas BNP is not dependent on renal function. However, studies have shown correlation coefficients between BNP and estimated glomerular filtration rate (eGFR) [3Masson S. Latini R. Anand I.S. Vago T. Angelici L. Barlera S. Missov E.D. Clerico A. Tognoni G. Cohn J.N. Val-HeFT InvestigatorsDirect comparison of B-type natriuretic peptide (BNP) and amino-terminal proBNP in a large population of patients with chronic and symptomatic heart failure: the Valsartan Heart Failure (Val-HeFT) data.Clin Chem. 2006; 52: 1528-1538Crossref PubMed Scopus (307) Google Scholar, 4Tsutamoto T. Wada A. Sakai H. Ishikawa C. Tanaka T. Hayashi M. Fujii M. Yamamoto T. Dohke T. Ohnishi M. Takashima H. Kinoshita M. Horie M. Relationship between renal function and plasma brain natriuretic peptide in patients with heart failure.J Am Coll Cardiol. 2006; 47: 582-586Abstract Full Text Full Text PDF PubMed Scopus (164) Google Scholar]. BNP and NT-proBNP are mostly used as diagnostic biomarkers of acute heart failure (HF). The contributions of blood BNP or NT-proBNP measurements in the initial evaluation of patients presenting with acute HF have been confirmed. In the multicenter Breathing-Not-Properly Study, the use of a 100 pg/ml BNP (Triage, Biosite, San Diego, CA, USA) concentration as a diagnostic "cut-off", identified HF as the cause of acute dyspnea with a 90% sensitivity, 76% specificity, and an 83% diagnostic accuracy, in 1586 patients presenting to the emergency department, which was superior to a clinical assessment alone [[5]Maisel A.S. Krishnaswamy P. Nowak R.M. McCord J. Hollander J.E. Duc P. Omland T. Storrow A.B. Abraham W.T. Wu A.H. Clopton P. Steg P.G. Westheim A. Knudsen C.W. Perez A. et al.Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure.N Engl J Med. 2002; 347: 161-167Crossref PubMed Scopus (2823) Google Scholar]. The similar contributions made by the measurements of NT-proBNP were confirmed in the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) Study, in 600 patients presenting with acute dyspnea. NT-proBNP concentrations >450 pg/ml at 900 pg/ml at ≥50 years of age, were highly sensitive and specific for the diagnosis of acute HF, while <300 pg/ml was optimal to exclude acute HF, with a negative predictive value of 99% [[6]Januzzi Jr., J.L. Camargo C.A. Anwaruddin S. Baggish A.L. Chen A.A. Krauser D.G. Tung R. Cameron R. Nagurney J.T. Chae C.U. Lloyd-Jones D.M. Brown D.F. Foran-Melanson S. Sluss P.M. Lee-Lewandrowski E. et al.The N-terminal Pro-BNP investigation of dyspnea in the emergency department (PRIDE) study.Am J Cardiol. 2005; 95: 948-954Abstract Full Text Full Text PDF PubMed Scopus (978) Google Scholar]. From these observations, the National Academy of Clinical Biochemistry (NACB) laboratory medicine practice guidelines stated that "the use of BNP or NT-proBNP testing in an acute setting to rule out or to confirm the diagnosis of heart failure among patients with ambiguous signs and symptoms", and was assigned a class I, level of evidence A [[7]Tang W.H. Francis G.S. Morrow D.A. Newby L.K. Cannon C.P. Jesse R.L. Storrow A.B. Christenson R.H. Apple F.S. Ravkilde J. Wu A.H. National Academy of Clinical Biochemistry Laboratory MedicineNational Academy of Clinical Biochemistry Laboratory Medicine practice guidelines: clinical utilization of cardiac biomarker testing in heart failure.Circulation. 2007; 116: e99-e109Crossref PubMed Scopus (245) Google Scholar]. From the PRIDE study, the use of NT-proBNP is valuable for the evaluation of the dyspneic patient, irrespective of renal function. With receiver-operating characteristic (ROC) curves, the performance of NT-proBNP for the diagnosis of acute HF in breathless subjects with normal-to-mild renal insufficiency (glomerular filtration rate [GFR] ≥ 60 ml/min/1.73 m2, n = 393) versus moderate-to-severely impaired renal function (GFR < 60 ml/min/1.73 m2, n = 206) were compared and the difference between the two curves was not statistically significant (p = 0.34) (Fig. 1) [[8]Anwaruddin S. Lloyd-Jones D.M. Baggish A. Chen A. Krauser D. Tung R. Chae C. Januzzi Jr., J.L. Renal function, congestive heart failure, and amino-terminal pro-brain natriuretic peptide measurement: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) Study.J Am Coll Cardiol. 2006; 47: 91-97Abstract Full Text Full Text PDF PubMed Scopus (334) Google Scholar]. BNP and NT-proBNP are also used as prognostic markers in patients with HF. It is particularly noteworthy that, by multiple variable analysis, in the Valsartan Heart Failure Trial (Val-HeFT), norepinephrine, BNP, aldosterone, plasma renin activity, big endothelin (ET)-1, and ET-1 were assayed at baseline in 4300 patients. By multiple variable analysis, BNP was most closely correlated with mortality [[9]Latini R. Masson S. Anand I. Salio M. Hester A. Judd D. Barlera S. Maggioni A.P. Tognoni G. Cohn J.N. For the Val-HeFT InvestigatorsThe comparative prognostic value of plasma neurohormones at baseline in patients with heart failure enrolled in Val-HeFT.Eur Heart J. 2004; 25: 292-299Crossref PubMed Scopus (318) Google Scholar]. A substudy of the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) examined the prognostic value of NT-proBNP in a large population of patients presenting with severe chronic HF [[10]Hartmann F. Packer M. Coats A.J. Fowler M.B. Krum H. Mohacsi P. Rouleau J.L. Tendera M. Castaigne A. Anker S.D. Amann-Zalan I. Hoersch S. Katus H.A. Prognostic impact of plasma N-terminal pro-brain natriuretic peptide in severe chronic congestive heart failure. A substudy of the carvedilol prospective randomized cumulative survival (COPERNICUS) trial.Circulation. 2004; 110: 1780-1786Crossref PubMed Scopus (283) Google Scholar]. Therefore, NACB laboratory medicine practice guidelines state that "Blood BNP or NT-proBNP testing can provide a useful addition to clinical assessment in selected situations when additional risk stratification is required" and assigned it a class IIa, Evidence level A [[7]Tang W.H. Francis G.S. Morrow D.A. Newby L.K. Cannon C.P. Jesse R.L. Storrow A.B. Christenson R.H. Apple F.S. Ravkilde J. Wu A.H. National Academy of Clinical Biochemistry Laboratory MedicineNational Academy of Clinical Biochemistry Laboratory Medicine practice guidelines: clinical utilization of cardiac biomarker testing in heart failure.Circulation. 2007; 116: e99-e109Crossref PubMed Scopus (245) Google Scholar]. In this issue, Horii reports that the area under the receiving operating characteristic curve (AUC) of BNP and NT-proBNP for mortality and cardiovascular events were similar for chronic kidney disease (CKD) stage 1–3. However, for CKD stage 4–5, AUC of NT-proBNP was higher than AUC of BNP. It was concluded that NT-proBNP is a superior prognostic marker to BNP for CKD stage 4–5. Calculated optimal cutoff values of BNP for all-cause death were 87.0 pg/ml in patients with an eGFR ≥ 30 ml/min/1.73 m2, and 114.5 pg/ml in patients with an eGFR < 30 ml/min/1.73 m2, so the optimal cutoff values differed by 30%. However, the optimal cutoff values of NT-pro BNP for all-cause death were 258 pg/ml in patients with an eGFR ≥ 30 ml/min/1.73 m2, and 5809 pg/ml in patients with an eGFR < 30 ml/min/1.73 m2. From a clinical point of view, it was concluded that it should be noted that the optimal cutoff of NT-proBNP varied quite widely based on renal function [[11]Horii M. Prognostic value of B-type natriuretic peptide (BNP) and its amino-terminal proBNP fragment for cardiovascular events with stratification by renal function.J Cardiol. 2013; 61: 410-416Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar]. In a subanalysis of 720 patients presenting with acute decompensated HF from the International Collaborative on NT-proBNP (ICON) study, NT-proBNP level was predictive of 60-day outcome in the setting of impaired renal function. Both an eGFR < 60 ml/min per 1.73 m2 and an NT-proBNP level above the median (4647 ng/l) predicted a poor outcome. Intriguingly, these investigators identified that it was the combination of both that carried the greatest risk (Fig. 2) [[12]van Kimmenade R.R. Januzzi Jr., J.L. Baggish A.L. Lainchbury J.G. Bayes-Genis A. Richards A.M. Pinto Y.M. Amino-terminal pro-brain natriuretic peptide, renal function, and outcomes in acute heart failure: redefining the cardiorenal interaction?.J Am Coll Cardiol. 2006; 48: 1621-1627Abstract Full Text Full Text PDF PubMed Scopus (139) Google Scholar]. Another study has also compared BNP and NT-proBNP for all-cause mortality in emergency department patients presenting with dyspnea and an eGFR < 60 ml/min per 1.73 m2. NT-proBNP levels were superior predictors of 1-year mortality after adjustment for comorbidities, renal function, and diagnosis of decompensated HF [[13]deFilippi C.R. Seliger S.L. Maynard S. Christenson R.H. Impact of renal disease on natriuretic peptide testing for diagnosing decompensated heart failure and predicting mortality.Clin Chem. 2007; 53: 1511-1519Crossref PubMed Scopus (81) Google Scholar]. In conclusion, NT-proBNP is as useful as BNP for the prognostic and diagnostic evaluation of patients with HF irrespective of renal function. Particularly in patients with severe CKD, NT-proBNP is a superior prognostic marker than BNP, although the optimal cutoff of NT-proBNP varied quite widely based on renal function. Prognostic value of B-type natriuretic peptide and its amino-terminal proBNP fragment for cardiovascular events with stratification by renal functionJournal of CardiologyVol. 61Issue 6PreviewBrain natriuretic peptide (BNP) and amino-terminal proBNP (NT-proBNP) are useful biomarkers for diagnosis and prediction of prognosis. Both of these peptides are elevated in patients with chronic kidney disease (CKD), but there is no evidence as to which peptide is the more suitable biomarker in patients with severe renal dysfunction. Full-Text PDF Open Archive
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