Urinary NT-proBNP Research Articles

No relationship exists between urinary NT-proBNP and GPS technology in professional rugby union.

We investigated the level of cardiovascular stress associated with professional rugby union and whether these changes could be explained through external workload systems like GPS and video analysis. Urine samples (14 in game one and 13 in game two) were collected from professional rugby players before, immediately post- and 36h post-play in two consecutive games. Urine was analysed for NT-proBNP by ELISA. Comparison with GPS (player-load and distance covered at specific speed bands) and video analysis (total impacts) were conducted. There was a significant increase in urinary NT-proBNP during game one (31.6±5.4 to 53.5±10.8pg/mL) and game two (35.4±3.9 to 49.8±11.7pg/mL) that did not correlate with the number of impacts, total distance covered, distance covered at pre-determined speed bands or player-load. Concentrations returned to pre-game concentrations 36h post-game whilst a large inter-individual variation in NT-proBNP was observed among players (p<0.001). Professional rugby union causes a transient increase in cardiovascular stress that seems to be independent of the external workload characteristics of a player.

Urine measurement indicates the plasma brain natriuretic peptide concentration during optimization of heart failure treatment

Aim: To assess the correlation between the amino-terminal pro-hormone brain natriuretic peptide (NT-proBNP) concentration in blood and urine during a period when actively adjusting the treatment of heart failure (HF). Methods: Plasma and urine analyses of NT-proBNP were compared in 51 patients on admission to and discharge from a nurse-led outpatient clinic where HF treatment was optimized. The median time between the two measurements was 42 days. Correlations were analyzed using linear regression, where R2 is the degree of variability in the plasma NT-proBNP concentration that can be accounted for by the urinary NT-proBNP. Results: There was a statistically significant linear relationship between the urine and plasma concentrations of NT-proBNP on both occasions, but R2 varied greatly depending on how the data were presented. The correlation between the raw data showed an R2 of only 30%, and it almost doubled upon logarithm transformation, which shows that the variability (error) was concentration-dependent. Correction of the urinary NT-proBNP for urinary creatinine further increased R2 for the logarithm-transformed correlation to 68% on admission and 76% on discharge. The highest R2 (77%) was obtained when the relative changes in urinary NT-proBNP/creatinine between admission and discharge were compared with the corresponding relative changes in the plasma concentration. The sensitivity and specificity of the urine in indicating plasma concentration changes > 10% were 82% and 86%, respectively. Conclusion: Relative changes in plasma NT-proBNP could be reliably estimated from urine samples during a period of optimization of HF treatment.

Doxorubicin-induced cardiac dysfunction in unselected patients with a history of early-stage breast cancer.

Cardiomyopathy is a known complication of anthracycline-based adjuvant chemotherapy and is more commonly reported in population-based studies of breast cancer survivors than in clinical trials. This study prospectively evaluated the prevalence of elevated cardiac biomarkers in unselected patients who had been treated with doxorubicin for early-stage breast cancer and the prevalence of reduced LVEF in patients with an elevated biomarker. All participants underwent an examination, symptom inventory, medical record review, and biomarker analysis for BNP, troponin, and plasma and urine NT-proBNP. Patients who had one or more elevated biomarkers were referred for echocardiogram; systolic dysfunction was defined as LVEF less than 55 %. Multivariable logistic regression was used to determine the associations between age, BMI, cumulative dose of doxorubicin, diabetes, hypertension, and left-sided radiation therapy and the risk of reduced LVEF. Among the 269 patients who underwent lab testing (mean age 56 years, mean time since completion of doxorubicin-based chemotherapy 6 years), 192 (72 %) had one or more elevated biomarker. Among the 166 patients who completed an echocardiogram, 11.5 % had a LVEF < 55 %. After adjusting for covariates known to affect cardiac function, multivariable logistic regression revealed plasma NT-proBNP to be the only measured cardiac biomarker associated with systolic dysfunction. There is a relationship between NT-proBNP and the frequency of reduced LVEF in women treated with doxorubicin for curative intent; further study of NT-proBNP as a potential biomarker for subclinical cardiac dysfunction after exposure to anthracyclines is warranted.

Elevated urinary NT-proBNP after pharmacological closure of patent ductus arteriosus in very low birth weight infants

BackgroundHemodynamically significant patent ductus arteriosus (hsPDA) complicates the clinical course of preterm infants and contributes to increased morbidity and mortality. NT-proBNP is indicative of the effects of hsPDA on clinical and cardiac status of patients. AimsThe aim of this study was to evaluate the value of urinary NT-proBNP and NT-proBNP/creatinine ratio in follow-up of hsPDA. Study designUrinary NT-proBNP and NT-proBNP/creatinine ratio (UNBCR) were measured and correlated with the presence of hsPDA. Measurements were performed in 92 neonates on postnatal days 14 and 28 by ELISA methodology. Of 92 neonates, 22 required therapeutic interventions. ResultsInfants treated for hsPDA showed significant higher levels of urinary NT-proBNP and UNBCR on postnatal day 14 whereas similar results were determined on postnatal day 28. Cut-off level of NT-proBNP was 567pg/mL with a sensitivity of 79% and a specificity of 71%. ConclusionOur data showed that NT-proBNP and UNBCR levels as non-invasive and powerful methods in preterm infants may help clinicians to determine the effects of hsPDA on clinical and cardiac status of the patients even with first measurement on day 14.

Factores clínicos y biomarcadores asociados a lesión vascular subclínica en la infección por el virus de la inmunodeficiencia humana

Background and objectiveHIV-infected patients present accelerated cardiovascular disease (CVD) and CVD is among the most important causes of mortality in this population. We aimed to identify biomarkers and clinical factors associated with subclinical atherosclerosis in HIV-infected patients. Patients and methodsCarotid intima-media thickness (cIMT) and cardiovascular biomarkers were measured in 235 HIV-infected patients. Individuals with a cIMT≥75th percentile or plaque were classified as having subclinical atherosclerosis and compared with patients without subclinical atherosclerosis. ResultsAge was 46 (11) years old. Mean cIMT was 0.58 (0.13)mm. Sixty-five (27.8%) patients had subclinical atherosclerosis. These subjects had more frequently lipodystrophy (OR:2.7; CI95%:1.4-4.9), immunosuppression (OR:2.5; CI95%:1.1-5.8), longer time to HIV diagnosis (≥p50 [10 years], OR:1.4; CI95%:1.1-2.9), longer exposure to nucleoside analogues (≥p50 [132 months], OR:3.2; CI95%:1.7-6) and to protease inhibitors (≥p50 [24 months], OR:2.2; CI95%:1.1-3.6). They also showed higher levels of several biomarkers such as NT-proBNP (≥p75 [72.6pg/ml], OR:2.0; CI95%:1-4.1) and albumin/creatinine urine ratio (≥p50 [5mg/g], OR:3.8; CI95%:1.3-11). After the multivariate analysis, subclinical atherosclerosis was associated with age (OR:6.6; CI95%:2.2-19.5; P=.001), a longer time to HIV diagnosis (OR:3.1; CI95%:1.0-11.0; P=.044) and immunosuppression (OR:2.8; CI95%:1-8.3; P=.048). ConclusionsAmong HIV-infected patients, time to HIV diagnosis and immunosuppression were independently associated with subclinical atherosclerosis. Patients with subclinical atherosclerosis showed increased levels of vascular damage biomarkers, especially albumin/creatinine urine ratio and NT-proBNP.

Impact of glomerular filtration rate on urinary BNP and NT-proBNP levels in heart failure

B-type natriuretic peptide (BNP) and its inactive amino-terminal fragment (NT-proBNP) are diagnostic tools for heart failure (HF), but less is understood regarding the effects of renal function on their urinary concentrations. The objective was to analyze the influence of renal function, as estimated glomerular filtration rate (eGFR), on BNP and NT-proBNP concentrations in 90 HF outpatients (65±12 years; 73% men), grouped according to eGFR below or above 60mL/min. Patients with worse eGFR had higher serum NT-proBNP (p<0.01) and BNP (p<0.01) than patients with higher eGFR: NT-proBNP, but urinary levels did not reach statistical differences. In addition, a direct significant correlation between filtered load of serum NT-proBNP or BNP with their concentrations in urine was found in patients with eGFR above 60mL/min (r=0.66, p<0.001 and r=0.338, p<0.05) and below 60mL/min (r=0.63, p<0.001 and r=0.406, p<0.01). However, after normalizing urinary natriuretic peptide concentrations by their filtered load, we obtained a significant inverse and exponential relation in patients with worse renal function for NT-proBNP and BNP (r=−0.87, p=0.001; and r=−0.71, p<0.001, respectively) and in patients with eGFR>60mL/min (r=−0.84, p<0.001; and r=−0.72, p<0.001, respectively). In conclusion, similar urinary NT-proBNP and BNP excretion was obtained in patients with high or low eGFR. Furthermore, despite the direct correlation between filtered load of serum natriuretic peptides with their urinary levels, an inverse an exponential relationship was obtained after normalizing urinary concentrations. Therefore, glomerular filtration does not seem to be the major determinant of both urinary peptide concentrations.

Urinary NT-proBNP, NGAL, and H-FABP May Predict Hemodynamic Relevance of Patent Ductus Arteriosus in Very Low Birth Weight Infants

Background: Hemodynamically significant patent ductus arteriosus (hsPDA) is the most common functional cardiovascular disease in preterm infants. The necessity to treat hsPDA can neither be derived solely from clinical nor from echocardiographic criteria. Objective: The aim of this study was to establish non-invasive parameters which can differentiate hsPDA from non-hsPDA. Methods: Urinary protein levels of NT-proBNP, NGAL, and H-FABP were measured and correlated with the necessity of therapy for PDA. In 37 neonates (<1,500 g), urinary protein concentrations were tested on days 0, 2, and 7 by ELISA methodology. Of 37 infants, 12 required therapeutic interventions according to current treatment standards. Results: Infants receiving an intervention for PDA showed significantly higher levels of pro-BNP, NGAL, and H-FABP at all time points except for NT-proBNP on day 0. Infants requiring a second or third course of ibuprofen had significantly higher levels of H-FABP and NGAL. In all samples, the concentration of the three proteins correlated positively with each other. Conclusions: The present study shows that measurement of urinary proteins is a powerful and non-invasive method to quantify the effect of PDA on systemic perfusion in preterm infants. Furthermore, NGAL and H-FABP may be used to indicate the necessity of pharmacological or surgical treatment of PDA.

Improvement of Sodium Status to Optimize the Efficacy of Renin-Angiotensin System Blockade

Blockade of the renin-angiotensin-aldosterone system (RAAS) offers superior renoprotection in the treatment of patients with hypertension, but the efficacy of RAAS inhibition strongly depends on sodium status, presumably in relation to extracellular volume status. Because assessing volume status by physical examination is challenging, 24-hour urine collection and NT-proBNP levels are useful tools for guiding volume management and achieving sodium status targets.

Comparative Prognostic Value of Plasma and Urinary N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Acute Destabilized Heart Failure

Introduction and objectives Urinary concentrations of amino-terminal pro-B type natriuretic peptide (NT-proBNP) may be prognostically meaningful; however, direct comparison to plasma concentrations of this marker have not been performed in patients with acutely decompensated heart failure (ADHF). The aims of this study were to compare the prognostic value of plasma versus urinary NT-proBNP concentration for the risk stratification of patients with ADHF. Methods Consecutive hospitalized patients with ADHF were prospectively studied. Blood and urine samples were simultaneously collected on hospital arrival to determine NT-proBNP concentrations. Clinical follow-up was obtained, and the occurrence of mortality and heart failure hospitalization was registered. Results The study included 138 patients (median, 74 years [interquartile range, 67-80]; 54% men). During a median follow-up period of 387 days [interquartile range, 161-559], 65 patients (47%) suffered adverse clinical events. Plasma NT-proBNP concentration was higher among patients who presented adverse events (4561 pg/mL [2191-8631] vs 2906 pg/mL [1643-5823]; P = .03), whereas urinary NT-proBNP was similar in both groups ( P = .62). After multivariable Cox regression analyses, plasma NT-proBNP concentration was associated with a higher risk of adverse events, whether considered continuously (per 100 pg/mL; hazard ratio [HR] = 1.004; 95% confidence interval [CI], 1.001-1.007; P = .003) or categorically (≥3345 pg/mL; HR = 2.35; 95% CI, 1.41-3.93; P = .001). In contrast, urinary NT-proBNP concentration was not associated with adverse outcomes. Conclusions Plasma NT-proBNP concentration is superior to urinary NT-proBNP concentration for the prediction of adverse clinical outcomes among unselected patients with ADHF.

Valor pronóstico comparativo del pro-péptido natriurético tipo B aminoterminal urinario en pacientes con insuficiencia cardiaca aguda descompensada

Introduction and objectives Urinary concentrations of amino-terminal pro-B type natriuretic peptide (NT-proBNP) may be prognostically meaningful; however, direct comparison to plasma concentrations of this marker have not been performed in patients with acutely decompensated heart failure (ADHF). The aims of this study were to compare the prognostic value of plasma versus urinary NT-proBNP concentration for the risk stratification of patients with ADHF. Methods Consecutive hospitalized patients with ADHF were prospectively studied. Blood and urine samples were simultaneously collected on hospital arrival to determine NT-proBNP concentrations. Clinical follow-up was obtained, and the occurrence of mortality and heart failure hospitalization was registered. Results The study included 138 patients (median, 74 years [interquartile range, 67-80]; 54% men). During a median follow-up period of 387 days [interquartile range, 161-559], 65 patients (47%) suffered adverse clinical events. Plasma NT-proBNP concentration was higher among patients who presented adverse events (4561 pg/mL [2191-8631] vs 2906 pg/mL [1643-5823]; P = .03), whereas urinary NT-proBNP was similar in both groups ( P = .62). After multivariable Cox regression analyses, plasma NT-proBNP concentration was associated with a higher risk of adverse events, whether considered continuously (per 100 pg/mL; hazard ratio [HR] = 1.004; 95% confidence interval [CI], 1.001-1.007; P = .003) or categorically (≥3345 pg/mL; HR = 2.35; 95%CI, 1.41-3.93; P = .001). In contrast, urinary NT-proBNP concentration was not associated with adverse outcomes. Conclusions Plasma NT-proBNP concentration is superior to urinary NT-proBNP concentration for the prediction of adverse clinical outcomes among unselected patients with ADHF. Full English text available from: www.revespcardiol.org

Valor pronóstico a largo plazo de los valores séricos y urinarios del fragmento N-terminal del péptido natriurético tipo B y del filtrado glomerular en pacientes con insuficiencia cardíaca

The amino-terminal pro-brain natriuretic peptide (NT-proBNP) and estimated glomerular filtration rate (eGFR) values are related to short prognosis in patients with heart failure (HF). This study evaluates the prognostic power of serum and urinary NT-proBNP levels, and eGFR values, in HF patients during a 60-month follow-up. We studied 93 HF outpatients (66 males, age 65+/-12). Primary endpoint was defined as cardiovascular mortality and secondary endpoint as cardiovascular mortality or admissions. Only serum NT-proBNP levels had a significant area under the curve for the prognosis of 60-month mortality and combined events, 0.70 (p=0.004) and 0.67 (p=0.019), respectively. Urinary NT-proBNP and eGFR did not have statistical significant areas under the curve. Patients with high serum NT-proBNP had the highest risk of cardiovascular death [44 (IC 95% 38-50) vs. 56 (IC 95% 53-59) months, p=0.0006] and combined events [33 (IC 95% 28-38) vs. 42 (IC 95% 28-38) months; p=0.027]. After the integration of serum NT-proBNP and renal function, patients with high peptide levels and low eGFR had the worst survival [42 (IC 95% 33-52) months; p=0.010]. Finally, only serum NT-proBNP concentration above 933 pg/mL was a predictor of poor survival (hazard ratio=2.81, p=0.033) and NT-proBNP above 550 pg/mL for combined events (hazard ratio=1.79, p=0.049). Serum NT-proBNP levels were superior to urine NT-proBNP and eGFR values for predicting 60-month cardiovascular death and combined events in HF patients.

Urinary NT-proBNP: A Valuable Marker in the Assessment of Patients With Essential Hypertension

The aim was to evaluate the usefulness of urinary N-terminal fragment of B-type natriuretic peptide (NT-proBNP) measurement for predicting the presence of left ventricular hypertrophy (LVH) in 160 asymptomatic patients with essential hypertension. The urinary NT-proBNP/creatinine ratio was higher in patients with LVH than in either those without LVH (P< .0001) or control subjects (P< .0001). Multivariate linear regression analysis identified age (P=.034), left ventricular mass index (P=.026) and serum NT-proBNP level (P=.001) as predictors of the urinary peptide level. The area under the curve for the NT-proBNP/creatinine ratio was 0.71+/-0.04 (P< .0001) for identifying LVH. Logistic regression analysis showed that the NT-proBNP: creatinine ratio was a predictor of LVH (odds ratio=4.074; P=.009). In conclusion, the urinary NT-proBNP concentration is a new marker that could be useful for identifying LVH in subjects with essential hypertension.

Characterization of NT-proBNP in Human Urine

Urine amino-terminal probrain natriuretic peptide (NT-proBNP) concentrations may exclude the presence of heart failure and provide insight into renal clearance mechanisms for human NT-proBNP. We characterized the molecular forms of urine NT-proBNP detected by immunoassay. Urine from patients with heart failure was subjected to HPLC and analyzed using immunoassays specific toward different epitopes of NT-proBNP. We assessed urine NT-proBNP immunoreactivity in healthy subjects and patients with heart failure. Size-exclusion chromatography of heart failure urine identified no NT-proBNP immunoreactivity coeluting with NT-proBNP(1-76); multiple immunoreactive NT-proBNP fragments were present. The absence of intact urinary NT-proBNP was supported by reversed-phase HPLC. Urine NT-proBNP immunoreactivity was higher in patients with acute [median 192 (interquartile range 108-1445) pg/mg creatinine] and chronic [52 (15-118) pg/mg creatinine] heart failure than in healthy subjects [4.2 (2.6-5.8) pg/mg creatinine] (P < 0.001). In 40 patients with heart failure, urine NT-proBNP immunoreactivity correlated with plasma NT-proBNP (r = 0.72, P < 0.001) and inversely with left ventricular ejection fraction (r = -0.33, P = 0.04). Our findings clarify previous reported relationships of urine NT-proBNP-like immunoreactivity with plasma NT-proBNP concentrations and the diagnosis of heart failure. As urine NT-proBNP immunoreactivity is not intact NT-proBNP(1-76), but rather reflects assorted metabolites, the diagnostic performance of NT-proBNP assays in urine may be assay specific, necessitating validation of biomarker performance on an assay-by-assay basis.

The change of the urine NT-proBNP in patients With chronic heart failure

目的 探讨尿NT-proBNP在慢性心力衰竭(chroniC heart failare,CHF)中的变化规律,与心功能分级的相关性,进一步探讨尿NT-proBNP对慢性心力衰竭的诊断价值.方法 49例入院治疗的CHF患者(NYHA Ⅱ-Ⅳ级)和24例健康体检者,测定血NT-proBNP、尿NT-proBNP,超声心动图检测左室舒张末室间隔厚度、左室舒张末期内径、左室收缩末期内径、左室射血分数.结果 ①CHF组尿NT-proBNP水平和血NT-proBNP水平明显高于正常对照组,分别为(65.47±41.34)pg/ml vs(17.95±7.22)pg/ml,(3204.47±2067.34)pg/ml vs(40.60±1 5.38)pg/ml,P均<0.01.尿NT-proBNP水平与血NT-proBNP水平呈正相关(r=0.639,P<0.001).②随心功能的恶化,尿NT-proBNP水平逐渐升高.尿NT-proBNP与NYHA分级、左室舒张末期内径呈正相关(P均<0.001),与左室射血分数呈负相关(P<0.001).多元逐步回归分析显示与logNT-proBNP独立相关的变量是血NT-proBNP、左室射血分数及NYHA分级.③尿NT-proBNP、血NT-proBNP对CHF诊断价值以ROC曲线下面积表示,分别为0.837(95%可信限:0.758～0.952),0.883(95%可信限:0.809～0.963).④根据ROC曲线,以诊断CHF的敏感度与特异度之和的最高值作为截断值,尿NT-proBNP的截断值为19.01pg/ml.结论 ①在正常人和CHF患者尿中可检测到NT-proBNP.②CHF患者尿NT-proBNP水平明显高于对照组,而且尿NT-proBNP水平与血NT-proBNP水平呈正相关.③CHF患者随心功能的恶化(NYHA Ⅱ-Ⅳ级),尿NT-proBNP水平逐渐升高.尿NT-proBNP水平与LAD无相关性,与LVEDD、NYHA分级呈正相关,与LVEF呈负相关.④尿NT-proBNP在检测CHF中与血NT-proBNP具有相似的诊断价值。

The diagnostic value of serum and urinary NT-proBNP for heart failure

Serum B-type natriuretic peptide (BNP) and the amino-terminal cleavage product of the prohormone (NT-proBNP) have been shown to be valuable parameters for the diagnosis of heart failure (HF) in the general population. Urinary BNP and NT-proBNP have also been suggested for diagnosis of HF. The present study investigated the diagnostic value of both serum and urinary NT-proBNP in selected groups of controls and patients diagnosed with HF. Creatinine clearance and serum and urinary NT-proBNP were measured in 76 controls and in 47 patients diagnosed with HF (NYHA III and IV). Echocardiography was used to exclude cardiac dysfunction in the control population by the combined normality of left ventricular ejection fraction (LVEF), E/A ratio (echocardiographic early [E] and late, or atrial [A] phases of ventricular filling), deceleration time and LV mass index. All patients diagnosed with HF had LVEF <40%. NT-proBNP measurements in urine samples are subject to high variability. Receiver-operating characteristic area under the curve (AUC) for serum, urinary NT-proBNP and their products were 0.94, 0.72 and 0.93, respectively. Correction of urinary NT-proBNP for urinary creatinine content improved the AUC from 0.72 to 0.80. Negative predictive values for ruling out HF were 0.94, 0.67 and 0.89, respectively. Linear regression analysis revealed that creatinine clearance was more important in determining serum NT-proBNP concentrations than age. Serum NT-proBNP is the best parameter to rule out HF. The product of the serum and urinary concentrations has equal value. Urinary NT-proBNP alone performs rather poorly. Renal function influences NT-proBNP concentrations more than age in this selected population.

Urinary NT-proBNP independently predicts cardiovascular outcome in patients with chronic heart failure

Urinary NT-proBNP independently predicts cardiovascular outcome in patients with chronic heart failure

Diagnostic and prognostic value of urine NT‐proBNP levels in heart failure patients

Plasma NT-proBNP levels are sensitive markers of ventricular dysfunction. However, studies of natriuretic peptides in urine are limited. To compare urine and plasma NT-proBNP levels and to investigate the diagnostic and prognostic value of urine levels in heart failure (HF). Urinary and plasma NT-proBNP levels were measured in 96 HF patients and 20 control subjects. The patients were functionally classified according to the NYHA criteria. Urine NT-proBNP was higher in HF patients than in control subjects (94+/-31 pg/ml vs. 67+/-6 pg/ml, p<0.0001), correlating with plasma NT-proBNP levels (r=0.78, p<0.0001). Urinary levels were elevated in the more severe functional classes and diminished in obese patients. Urine NT-proBNP was a good tool for diagnosis of HF, the area under the curve (AUC) being 0.96+/-0.02 (p<0.0001), and for predicting 12-month cardiac events (p=0.011). To determine the prognostic power of urinary NT-proBNP in detecting 12-month cardiac mortality, we obtained an AUC of 0.75+/-0.10 (p=0.015). Urinary NT-proBNP, a relatively simple non-invasive test, is a new candidate marker for the diagnosis and evaluation of prognosis in HF and for the characterization of functional status in these patients.