Renal Function, Congestive Heart Failure, and Amino-Terminal Pro-Brain Natriuretic Peptide Measurement

Harvard University, Cambridge, Massachusetts, United States
Journal of the American College of Cardiology (Impact Factor: 16.5). 01/2006; 47(1):91-7. DOI: 10.1016/j.jacc.2005.08.051
Source: PubMed


The relationship between renal insufficiency and amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels remains unclear. We examined this relationship in the context of patients who presented to the emergency department of an urban tertiary care medical center with dyspnea. Even in the presence of renal insufficiency, NT-proBNP remained a valuable tool for the diagnosis of acute congestive heart failure and it provides important prognostic information.
We sought to examine the interaction between renal function and amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels.
The effects of renal insufficiency on NT-proBNP among patients with and without acute congestive heart failure (CHF) are controversial. We examined the effects of kidney disease on NT-proBNP-based CHF diagnosis and prognosis.
A total of 599 dyspneic patients with glomerular filtration rates (GFRs) as low as 14.8 ml/min were analyzed. We used multivariate logistic regression to examine covariates associated with NT-proBNP results and linear regression analysis to analyze associations between NT-proBNP and GFR. Receiver-operating characteristic analysis determined the sensitivity and specificity of NT-proBNP for CHF diagnosis. We also assessed 60-day mortality rates as a function of NT-proBNP concentration.
Glomerular filtration rates ranged from 15 ml/min/1.73 m2 to 252 ml/min/1.73 m2. Renal insufficiency was associated with risk factors for CHF, and patients with renal insufficiency were more likely to have CHF (all p < 0.003). Worse renal function was accompanied by cardiac structural and functional abnormalities on echocardiography. We found that NT-proBNP and GFR were inversely and independently related (p < 0.001) and that NT-proBNP values of > 450 pg/ml for patients ages <50 years and >900 pg/ml for patients > or =50 years had a sensitivity of 85% and a specificity of 88% for diagnosing acute CHF among subjects with GFR > or =60 ml/min/1.73 m2. Using a cut point of 1,200 pg/ml for subjects with GFR <60 ml/min/1.73 m2, we found sensitivity and specificity to be 89% and 72%, respectively. We found that NT-proBNP was the strongest overall independent risk factor for 60-day mortality (hazard ratio 1.57; 95% confidence interval 1.2 to 2.0; p = 0.0004) and remained so even in those with GFR <60 ml/min/1.73 m2 (hazard ratio 1.61; 95% confidence interval 1.14 to 2.26; p = 0.006).
The use of NT-proBNP testing is valuable for the evaluation of the dyspneic patient with suspected CHF, irrespective of renal function.

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    • "Both BNP and NT-proBNP seem to provide an ideal tool to be utilized as blood tests to diagnose cardiac disorders in patients with high risk of heart failure, diabetes, chronic kidney disease, and coronary artery disease (Khan et al., 2006; Freestone et al., 2008; Czucz et al., 2011; Ganem et al., 2011). The BNP level is increased to almost 200 pg/ml and NT-proBNP levels reaches to approximately 1200 pg/ml in patients with reduced creatinin clearance (McCullough et al., 2003; Anwaruddin et al., 2006). "
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    ABSTRACT: Thus far, three related natriuretic peptides (NPs) and three distinct sub-types of cognate NP receptors have been identified and characterized based on the specific ligand binding affinities, guanylyl cyclase activity, and generation of intracellular cGMP. Atrial and brain natriuretic peptides (ANP and BNP) specifically bind and activate guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA), and C-type natriuretic peptide (CNP) shows specificity to activate guanylyl cyclase/natriuretic peptide receptor-B (GC-B/NPRB). All three NPs bind to natriuretic peptide receptor-C (NPRC), which is also known as clearance or silent receptor. The NPRA is considered the principal biologically active receptor of NP family; however, the molecular signaling mechanisms of NP receptors are not well understood. The activation of NPRA and NPRB produces the intracellular second messenger cGMP, which serves as the major signaling molecule of all three NPs. The activation of NPRB in response to CNP also produces the intracellular cGMP; however, at lower magnitude than that of NPRA, which is activated by ANP and BNP. In addition to enhanced accumulation of intracellular cGMP in response to all three NPs, the levels of cAMP, Ca(2+) and inositol triphosphate (IP3) have also been reported to be altered in different cells and tissue types. Interestingly, ANP has been found to lower the concentrations of cAMP, Ca(2+), and IP3; however, NPRC has been proposed to increase the levels of these metabolic signaling molecules. The mechanistic studies of decreased and/or increased levels of cAMP, Ca(2+), and IP3 in response to NPs and their receptors have not yet been clearly established. This review focuses on the signaling mechanisms of ANP/NPRA and their biological effects involving an increased level of intracellular accumulation of cGMP and a decreased level of cAMP, Ca(2+), and IP3 in different cells and tissue systems.
    Frontiers in Molecular Neuroscience 08/2014; 7:75. DOI:10.3389/fnmol.2014.00075 · 4.08 Impact Factor
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    • "In fact, BNP and NT-proBNP levels change also in response to arrhythmias, myocardial ischemia, valvular heart disease, changes of filling pressures, diastolic function, only to mention cardiac factors. Also non-cardiac factors, including age, sex, body mass index and genetic factors are important confounders, as are pulmonary hypertension, pulmonary embolism and chronic kidney disease [20]. NP levels correlate imperfectly with measured filling pressures and may remain elevated in the absence of significant congestion. "
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    ABSTRACT: There is increasing interest in guiding Heart Failure (HF) therapy with Brain Natriuretic Peptide (BNP) or N-terminal prohormone of Brain Natriuretic Peptide (NT-proBNP), with the goal of lowering concentrations of these markers (and maintaining their suppression) as part of the therapeutic approach in HF. However, recent European Society of Cardiology (ESC) and American Heart Association/ American College of Cardiology (AHA/ACC) guidelines did not recommend biomarker-guided therapy in the management of HF patients. This has likely to do with the conceptual, methodological, and practical limitations of the Natriuretic Peptides (NP)-based approach, including biological variability, slow time-course, poor specificity, cost and venipuncture, as well as to the lack of conclusive scientific evidence after 15 years of intensive scientific work and industry investment in the field. An increase in NP can be associated with accumulation of extra-vascular lung water, which is a sign of impending acute heart failure. If this is the case, an higher dose of loop diuretics will improve symptoms. However, if no lung congestion is present, diuretics will show no benefit and even harm. It is only a combined clinical, bio-humoral (for instance with evaluation of renal function) and echocardiographic assessment which may unmask the pathophysiological (and possibly therapeutic) heterogeneity underlying the same clinical and NP picture. Increase in B-lines will trigger increase of loop diuretics (or dialysis); the marked increase in mitral insufficiency (at baseline or during exercise) will lead to increase in vasodilators and to consider mitral valve repair; the presence of substantial inotropic reserve during stress will give a substantially higher chance of benefit to beta-blocker or Cardiac Resynchronization Therapy (CRT). To each patient its own therapy, not with a "blind date" with symptoms and NP and carpet bombing with drugs, but with an open-eye targeted approach on the mechanism predominant in that individual patient. A monocular, specialistic, unidimensional approach to HF can miss its pathogenetic and clinical complexity, which only can be overcome with an integrated, versatile and tailored approach.
    Cardiovascular Ultrasound 07/2014; 12(1):27. DOI:10.1186/1476-7120-12-27 · 1.34 Impact Factor
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    • "The exact mechanism of NT-proBNP elimination remains controversial [8]. However, it has been shown that impaired renal function with a decreased glomerular filtration rate (GFR) leads to accumulation of NT-proBNP and might therefore hamper its prognostic utility [10], [11]. "
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    ABSTRACT: N-terminal pro-brain natriuretic peptide (NT-proBNP) is a routinely used prognostic parameter in patients with pre-capillary pulmonary hypertension (PH). As it accumulates in the presence of impaired renal function, the clinical utility of NT-proBNP in PH patients with concomitant renal insufficiency remains unclear. In a retrospective approach, patients with pre-capillary PH (group I or IV) and concomitant renal insufficiency at time of right heart catheterization (glomerular filtration rate (GFR) ≤60 ml/min/1.73 m2) were identified out of all prevalent pre-capillary PH patients treated at a single center. Forty patients with renal insufficiency (25.8%) were identified and matched regarding hemodynamic parameters with a control group of 56 PH patients with normal renal function (GFR >60 ml/min/1.73 m2). Correlations of NT-proBNP levels with hemodynamic and prognostic parameters (time to clinical worsening and overall survival) were assessed. Overall, GFR correlated inversely with NT-proBNP and had the strongest influence on NT-proBNP levels in a stepwise multiple linear regression model including hemodynamic parameters and age (r2 = 0.167). PH patients with renal insufficiency had significant higher levels of NT-proBNP (median: 1935 ng/l vs. 573 ng/l, p = 0.001). Nevertheless, NT-proBNP correlated with invasive hemodynamic parameters in these patients. Using higher cut-off values than in patients with preserved renal function, NT-proBNP levels were significantly associated with time to clinical worsening (>1660 ng/l, p = 0.001) and survival (>2212 ng/l, p = 0.047) in patients with renal insufficiency. Multivariate Cox's proportional hazards analysis including established prognostic parameters, age and GFR confirmed NT-proBNP as an independent risk factor for clinical worsening in PH patients with renal insufficiency (hazard ratio 4.8, p = 0.007). Thus, in a retrospective analysis we showed that NT-proBNP levels correlated with hemodynamic parameters and outcome regardless of renal function. By using higher cut-off values, NT-proBNP seems to represent a valid clinical marker even in PH patients with renal insufficiency.
    PLoS ONE 04/2014; 9(4):e94263. DOI:10.1371/journal.pone.0094263 · 3.23 Impact Factor
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