Urinary NT-proBNP Research Articles

Urinary NT-proBNP compared head-to-head to plasmatic NT-proBNP in a real life collective with an ICD

AimsPlasma NT-proBNP is an established marker of heart failure. Previous studies suggested urinary NT-proBNP has potential as marker of chronic heart failure as well. The objective of this study was to compare urinary NT-proBNP to plasma NT-proBNP in a real-life collective of patients with an ICD, especially regarding ICD-therapies. Methods & ResultsNT-proBNP was assessed in plasma and fresh spot urine (the latter related to urinary creatinine) from 322 patients of our ICD outpatient clinic. 54 healthy individuals served as a control group. Follow-up regarding mortality and ICD therapies was performed after 32 months (IQR 5– 35 months). Plasma and urinary NT-proBNP was positively correlated (r=0.89, p<0,001). According to ROC analysis urinary NT-proBNP detected LV dysfunction (EF<35% vs. healthy CTRL) with very satisfying predictive values (AUC 0.95), but plasma NT-proBNP showed slightly better values (AUC 0.99). Patients who received appropriate ICD-shock-therapies showed significantly higher plasma (p<0.001) as well as urinary NT-proBNP levels (p=0.011) compared to patients without shock-therapy. In Kaplan-Meier analysis, plasma as well as urinary NT-proBNP levels > Youden-Index showed significantly higher event rates for appropriate ICD-shock therapies (p<0.001 and p=0.016) and the combined endpoint of all-cause-mortality and shock therapies (each p<0.001). Urinary and plasma NT-proBNP were independent predictors for appropriate ICD-shock-therapies and for the combined endpoint of all-cause mortality and appropriate ICD-shock-therapies (each p<0.001). ConclusionUrinary NT-proBNP as a marker for LV dysfunction and symptomatic heart failure showed promising predictive values. Associations between plasma as well as urinary NT-proBNP and ICD shock-therapies could be shown.

Utility of urinary NT-proBNP in congenital diaphragmatic hernia: a prospective pilot study.

Echocardiography is the reference standard for diagnosing pulmonary hypertension (PH) and cardiac dysfunction (CD) in congenital diaphragmatic hernia (CDH). The use of an adjunct non-invasive biomarker would be invaluable. Plasma N-terminal brain Natriuretic Peptide (NT-proBNP) has been evaluated as a biomarker in CDH. Our objective was to investigate the utility of urinary NT-proBNP as an adjunct biomarker in CDH. Prospective observational study of neonates with CDH. Urinary NT-proBNP and its ratio to urinary creatinine (UNBCR) were analyzed at 24 h of life (HOL). Spearman's correlation was used to quantify the association between the urinary NT-proBNP with corresponding plasma concentrations. Logistic regression and receiver operating characteristic (ROC) curve analyses were used to examine urinary NT-proBNP and UNBCR's association with need for ECMO. The Kruskal-Wallis test was used to compare urinary NT-proBNP concentrations with echocardiography parameters of PH and CD. Urinary NT-proBNP and UNBCR positively correlated with plasma concentrations. Patients with high right ventricular (RV) pressures had higher urinary NT-proBNP concentrations. Both urinary NT-proBNP and UNBCR concentrations increased with worsening left and right ventricular dysfunction on first postnatal echocardiogram. We report the feasibility of urinary NT-proBNP as a non-invasive biomarker to assess PH and CD in CDH. Non-invasive biomarkers are an important area of research in neonates as they have the potential to decrease the need for blood sampling, which may cause pain, stress, and induce iatrogenic anemia. Use of non-invasive biomarkers could be especially useful in congenital diaphragmatic hernia (CDH) who may need Extra-Corporeal Life Support (ECLS) for their management. We evaluated the potential utility of the urinary NT-proBNP in CDH. Plasma NT-proBNP has been studied in neonates with CDH; however, urinary NT-proBNP has not been explored, making this the first study to examine its potential as a biomarker.

Plasmatic NT-proBNP is strongly associated with atrial fibrillation in patients with Implantable cardioverter defibrillator

Abstract Background and objectives Atrial fibrillation is common in patients with chronic heart failure and associated with poor outcome in these patients. Plasmatic NT-proBNP represents the gold standard biomarker for chronic heart failure. Further, recent studies showed prognostic impact of urinary NT-proBNP. Aim of the study was to assess the association of plasmatic as well as urinary NT-proBNP and atrial fibrillation in a cohort of patients with implantable cardioverter defibrillator (ICD). Methods 412 patients were included in the study. Fresh spot urine and blood samples were used to assess urinary as well as plasmatic NT-proBNP. Urinary NT-proBNP was normalized to urinary creatinine. Follow-up was performed after 45 months. Heart rhythm history was evaluated and a 12-lead electrocardiogram was performed at enrollment (sinus rhythm (SR, n = 306), atrial fibrillation (AFib, n = 79)). Results Patients suffering from atrial fibrillation showed significant higher age, reduced left ventricular ejection fraction (LVEF), higher rates of chronic kidney disease, hypertension and urinary as well as plasmatic NT-proBNP compared to patients with sinus rhythm (each p &amp;lt; 0.05). There were no differences regarding Diabetes, primary prevention ICD indication, coronary artery disease and dilatative cardiomyopathy (each p = n.s.). In ROC analysis, plasmatic NT-proBNP showed promising predictive values regarding AFib (AUC: 0.80, IQR 0.76-0.85, p &amp;lt; 0.001) as well as urinary NT-proBNP (AUC: 0.76, IQR 0.71-0.81, p &amp;lt; 0.001). There was no significant difference between plasmatic and urinary NT-proBNP according to ROC analysis (p = n.s.). Plasmatic NT-proBNP was shown as a significant predictor regarding existence of atrial fibrillation in binary logistic regression analysis, beside age (p &amp;lt; 0.05). Diabetes, hypertension, serum creatinine, LVEF, coronary artery disease and primary prevention ICD indication were no significant predictors (p = n.s.). Urinary NT-proBNP was not shown as a significant predictor regarding existence of atrial fibrillation in binary logistic regression analysis (p = n.s.). Conclusion Elevated levels of plasmatic NT-proBNP are strongly associated with the prevalence of atrial fibrillation in a cohort of ICD patients.

The potentially underestimated influence of atrial fibrillation on NT-proBNP in chest pain

Abstract Introduction/Purpose NT-proBNP is a widely used diagnostic marker in the emergency department (ED). The main objective of the current study was to determine the association of NT-proBNP in patients with chest pain presenting with sinus rhythm (SR) compared to atrial fibrillation (AFib). Hereby, a focus was the evaluation of serum NT-proBNP head-to-head to urinary NT-proBNP. Methods In this study, urinary as well as blood concentrations of NT-proBNP were measured in a total of 601 patients, who presented with acute chest pain in the ED (mean age = 61.1 y, SD = 16.9 y). In the initial ECG 68 patients suffered from AFib and 533 showed SR. The participants were categorized according to their diagnosis into acute coronary syndrome (ACS, AFib n = 28, SR n = 261), acute decompensated heart failure (ADHF, AFib n= 16, SR n = 21), non-ischemic chest pain without congestion (NICP, AFib n = 24, SR n = 96) or chest-wall syndrome (CWS, SR n = 155). Results In the overall study cohort, patients with AFib showed significantly higher concentrations of urinary as well as blood NT-proBNP compared to those in sinus rhythm (each p &amp;lt; 0.001). Additionally, among patients with acute coronary syndrome (ACS), there were significantly increased biomarker concentrations in patients presenting with AFib compared to sinus rhythm (each p &amp;lt; 0.001, AUCblood = 0.801, AUCurine = 0.701), similarly for patients categorized into NICP (each p &amp;lt; 0.001, AUCblood = 0.833, AUCurine = 0.756). The same pattern was observed among the ACS subcategories (each p &amp;lt; 0.001). Regarding ROC analysis, promising predictive values were shown for detection of AFib: STEMI (AUCblood = 0.902, AUCurine = 0.867), NSTEMI (AUCblood = 0.757, AUCurine = 0.696) and UA (AUCblood = 0.821, AUCurine = 0.681). Comparing ROC curves, significant differences were noted in UA (p &amp;lt; 0.001), opposite to STEMI as well as NSTEMI (each p = n. s.). Regarding ADHF, paradoxically higher NT-proBNP concentrations were noted among patients showing sinus rhythms compared to AFib. Furthermore, a multivariate binary regression analysis showed blood NT-proBNP and age as independent predictors of atrial fibrillation (p &amp;lt; 0.05), opposite to urinary NT-proBNP, high-sensitivity troponin T and diabetes (each p = n. s.). Conclusion Urinary and to a larger extent blood NT-proBNP showed significantly higher concentrations in AFib. In conclusion, in ED patients elevated NT-proBNP may potentially be frequently caused by a coexisting AFib. Regarding ADHF patients, the effect of AFib might be consumed by other conditions that have a greater impact on NT-proBNP.

Association of urinary bisphenol A levels with heart failure risk in U.S. adults from the NHANES (2003-2016).

Although heart failure (HF) has been linked to bisphenol A (BPA), few studies have investigated the cut-off values for the effects of urinary BPA levels on heart failure risk. The association between urinary BPA levels and HF prognosis has not been investigated. This study included 11,849 adults over 20 years old using information from the National Health and Nutrition Examination Survey (NHANES), which was conducted from 2003 to 2016. The relationship between urinary BPA levels and the risk of HF was determined via a multivariable logistic regression model, and restricted cubic spline (RCS) methods were used to determine the cut-off for the effect of BPA levels on HF risk. Based on the available NT-proBNP concentration data from the NHANES (2003-2004), multivariable linear regression was applied to determine the linear association between the NT-proBNP concentration and urinary BPA concentration. The results revealed a positive correlation between a urinary BPA concentration in the fourth quartile and the occurrence of heart failure [OR 1.49, 95% CI (1.09, 2.04), p = 0.012]. A one-unit increase (1 ng/mg creatinine) in the ln-transformed BPA concentration was linked to a 15% increase in the incidence of HF [OR 1.15, 95% CI (1.03, 1.29), p = 0.014]. The cut-off urinary BPA concentration for HF risk was 1.51 ng/mg creatinine. There was a positive correlation between urinary BPA and NT-proBNP concentrations [β = 0.093, 95% CI (0.014, 0.171), p = 0.02] in males, but there was no linear association [β = 0.040, 95% CI (-0.033, 0.113), p = 0.283] in females. Increased urinary BPA levels are linked to an increased risk of heart failure and poor prognosis. There is a significant increase in the risk of heart failure if the urinary concentration of BPA exceeds 1.51 ng/mg creatinine.

Urinary NT-proBNP: A Useful Biomarker for the Diagnosis of Respiratory Distress in the Neonatal Population.

To determine the diagnostic accuracy of urinary NT-proBNP levels in the detection and classification of the severity of respiratory distress in neonates after birth. We compared the urinary NT- proBNP levels between the respiratory distress (RD) group and the control group on the 1st, 3rd, and 5th day of life (DOL). The RD group (55 neonates) showed higher levels of NT-proBNP compared to the control group (63 neonates) on DOL1 (585.4 pg/ml vs 396.1 pg/ml (p=0.014)), DOL3 (805.1 pg/ml vs 271.9 pg/ml (p<0.001)) and DOL5 (409.7 pg/ml vs 94.4 pg/ml (p<0.001)). Especially, on DOL5, the area under the ROC curve was 0.884 and the NT-proBNP cut-off value (221.8 pg/ml) showed a sensitivity of 71% and specificity of 79%. The RD group was subclassified into neonates with mild (21 neonates), moderate (19 neonates), and severe (15 neonates) disease. NT-proBNP cut-off point of 668 pg/ml for DOL5 can safely differentiate neonates with severe disease from those with mild and moderate disease (combined subgroups) since the sensitivity was 80% and specificity was 77.5% for DOL5. Urinary NT-proBNP levels are a useful biomarker in detectingclinical signs of respiratory distress in neonates that are born within the first week of life; they can also detect neonates that are vulnerable to severe forms of the disease.

Urinary Terminal Probrain Natriuretic Peptide in Preterm Infants.

· POCUS is a dynamic way of assessing cardiopulmonary function.. · POCUS would be more cost-effective than urine NT-proBNP.. · Although POCUS is costly as compared with urine NT-proBNP, it is a one-time investment..

Evaluation of the Roche point of care system for determination of NT-proBNP in urine samples

IntroductionThe diagnostic potential of urine NT-pro-BNP has been studied recently and shows great promise, especially for children. Bedside serum-NT-proBNP determination with point of care testing (POCT) is established in adults. This study investigated the analytical capabilities of NT-proBNP POCT measurements for urine-samples. Furthermore, the stability of this biomarker in urine samples at room-temperature was explored. Methods104 urine samples were analysed, partly with double and triple determinations and compared to the established Elecsys system. To investigate the stability of NT-proBNP in urine, five samples were stored at room temperature and analysed 12-hourly over 96 h. Results34 % of samples lay outside the POCT range (60 pg/ml-9000 pg/ml). The 69 values within the range were correlated with those measured by Elecsys (correlation coefficient of 0.92; p < 0.001). Linear regression yields an r2 of 0.84. The stability of urine NT-proBNP was shown with correlation coefficients between 0.97 and 1 (p < 0.001). ConclusionAnalysing NT-ProBNP in urine with cobas h232 POC system is feasible, but the detection range needs to be adjusted. As urine NT-proBNP proved stable for at least 96 h even postal shipping would be possible. Adjusting this system‘s measuring range could help introduce a new, non-invasive, pain-free parameter.

Urine N-terminal pro-B-type natriuretic peptide and plasma proenkephalin are promising biomarkers for early diagnosis of cardiorenal syndrome type 1 in acute decompensated heart failure: a prospective, double-center, observational study in real-world

Background Patients with acute decompensated heart failure (ADHF) show cardiorenal syndrome type 1 (CRS-1) are more likely to have a poor outcome. However, the current criteria often lead to delayed CRS-1 diagnosis. Therefore, we evaluated the predictive value of plasma proenkephalin (pPENK) and urine NT-proBNP (uNT-proBNP) for early diagnosis of CRS-1 and vulnerable-phase prognosis in ADHF patients. Methods The plasma NT-proBNP (pNT-proBNP), pPENK, and uNT-proBNP were measured in 121 ADHF patients on admission. The plasma neutrophil gelatinase-associated lipocalin (pNGAL) was chosen as the reference. Logistic regression was used to determine the predictors of CRS-1. The area under the receiver operating curves (ROCs) was calculated to assess the early diagnostic value of pNGAL, pPENK, and uNT-proBNP/uCr for CRS-1. To evaluate the prognostic risk of factors for the 90-d outcomes of all ADHF patients, the Cox regression was performed and the cumulative risk curve was plotted. Results We found that pPENK [OR 1.093 (95% CI 1.022–1.169), p = 0.010; AUROC = 0.899 (95% CI 0.831–0.946)] and uNT-proBNP/uCr ratio [OR 1.015 (95% CI 1.003–1.028), p = 0.012; AUROC = 0.934 (95% CI 0.874–0.971)] could independently predict the occurrence of CRS-1 in hospitalized patients with ADHF. The pPENK [HR 1.014 (95% CI 1.000–1.042), p = 0.044] and uNT-proBNP/uCr ration [HR 0.998 (95% CI 0.997–1.000), p = 0.045] were also independent predictors of the risk of HF readmission or all-cause death 90 d after discharge in ADHF patients. Conclusions The newly found pPENK and noninvasive test of uNT-proBNP/uCr ratio (pg/nmol) on admission may be two promising novel predictive biomarkers for early diagnosis of CRS-1 occurrence and vulnerable-phase outcomes in ADHF patients.

Impact of Aging on Urinary Natriuretic Peptides in Nocturia and Nocturnal Polyuria.

PurposeThe pathophysiology of nocturia and nocturnal polyuria (NP), conditions that become more prevalent with aging, may in part be explained by changes in hormones involved in water homeostasis. The purpose of this study was to analyze the impact of aging on urinary natriuretic peptides in nocturia and NP.MethodsPatients aged ≥18 years completed 24-hour bladder diaries for assessment of nocturia and NP. They were divided into subgroups of ≥65 years old and <65 years old. Urine samples were collected and analyzed for natriuretic peptide (NT-proANP, NT-proBNP, and NT-proCNP) levels. Peptide levels were compared between patients with and without nocturia/NP and within age subgroups; correlation to the NP index (NPi) was determined.ResultsCompared to patients without nocturia (N=15), patients with nocturia (N=36) had higher median levels of urinary NT-proANP (15.8 pmol/mmol Cr vs. 10.9 pmol/mmol Cr, P=0.016) and NT-proBNP (6.3 pmol/mmol Cr vs. 4.5 pmol/mmol Cr, P=0.021), but showed no differences in NT-proCNP (2.4 pmol/mmol Cr vs. 2.5 pmol/mmol Cr, P=0.967). Patients ≥65 years old with nocturia had higher NT-proANP (29.8 pmol/mmol Cr vs. 11.0 pmol/mmol Cr, P<0.001) and NT-proBNP (9.6 pmol/mmol Cr vs. 5.0 pmol/mmol Cr, P<0.001) than patients <65 years old. Additionally, patients with NP (N=30) showed higher urinary NT-proANP (19.6 pmol/mmol Cr vs. 10.5 pmol/mmol Cr, P<0.001) and NT-proBNP (6.7 pmol/mmol Cr vs. 4.7 pmol/mmol Cr, P=0.020) compared to patients without NP (N=21). NP patients ≥65 years had higher NT-proANP (29.8 pmol/mmol Cr vs. 12.5 pmol/mmol Cr, P<0.001) and NT-proBNP (9.6 pmol/mmol Cr vs. 4.4 pmol/mmol Cr, P=0.004) than patients <65 years old. NPi positively correlated with urinary NT-proANP (RS=0.417, P=0.002) and NT-proBNP (RS=0.303, P=0.031), but not with NT-proCNP (RS=-0.094, P=0.510).ConclusionsSince urinary NT-proANP and NT-proBNP were greater in aged patients with nocturia and NP, natriuretic peptides may contribute to the pathophysiology of these conditions and further research should aim to explore them as targets for management.

MP18-01 THE EFFECT OF AGING ON URINE NATRIURETIC PEPTIDES IN NOCTURIA AND NOCTURNAL POLYURIA

You have accessJournal of UrologyCME1 May 2022MP18-01 THE EFFECT OF AGING ON URINE NATRIURETIC PEPTIDES IN NOCTURIA AND NOCTURNAL POLYURIA Lakshay Khosla, Joseph U. Boroda, Joshua Salama, Syed N. Rahman, Danielle J. Gordon, Matthew W. Moy, Yonatan Akivis, Alla Akivis, Jason M. Lazar, Jeffrey P. Weiss, and Lori A. Birder Lakshay KhoslaLakshay Khosla More articles by this author , Joseph U. BorodaJoseph U. Boroda More articles by this author , Joshua SalamaJoshua Salama More articles by this author , Syed N. RahmanSyed N. Rahman More articles by this author , Danielle J. GordonDanielle J. Gordon More articles by this author , Matthew W. MoyMatthew W. Moy More articles by this author , Yonatan AkivisYonatan Akivis More articles by this author , Alla AkivisAlla Akivis More articles by this author , Jason M. LazarJason M. Lazar More articles by this author , Jeffrey P. WeissJeffrey P. Weiss More articles by this author , and Lori A. BirderLori A. Birder More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002551.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Hormones involved in water homeostasis may impact the pathophysiology of age-related nocturia and nocturnal polyuria (NP). The purpose of this study was to analyze the effect of aging on urine natriuretic peptides in nocturia and NP. METHODS: Patients aged ≥18 years were recruited from 2019 to 2021 to complete bladder diaries for assessment of nocturia, defined as ≥2 nighttime voids, and NP, defined as nocturnal urine volume divided by 24-hour urine volume, or NP index (NPi), >0.33. Patients were excluded if they had characteristics that influence nocturia. They were divided into subgroups of <65 years old and ≥65 years old. Urine samples were analyzed for natriuretic peptide fragments (NT-proANP, NT-proBNP, and NT-proCNP). The Kruskal-Wallis H and Mann-Whitney U tests were used to compare patients stratified by status of nocturia/NP and age subgroups. Spearman’s rank order correlation was used to analyze correlations between NPi and urine natriuretic peptides. RESULTS: Compared to patients without nocturia (n=15; median ± IQR, 64.0±13.8 years), those with nocturia (n=36; 68.0±8.0 years) had significantly higher urine NT-proANP (86.0 vs 50.2 pmol/L, p=0.012) and NT-proBNP (33.1 vs 17.9 pmol/L, p=0.017), but showed no differences in NT-proCNP (11.4 vs 11.8 pmol/L, p=0.702). Patients with NP (n=30) had higher NT-proANP (96.2 vs 45.5 pmol/L, p<0.001) and NT-proBNP (34.9 vs 20.2 pmol/L, p=0.014), but showed no differences in NT-proCNP (11.8 vs 11.7, p=0.962) compared to those without NP (n=21). Compared to patients <65 years old with nocturia or NP, patients ≥65 years old with nocturia or NP had higher NT-proANP and NT-proBNP (Table 1). NPi positively correlated with NT-proANP (RS=0.416, p=0.002) and NT-proBNP (RS=0.328, p=0.019), but not with NT-proCNP (RS=-0.029, p=0.840). CONCLUSIONS: Age-related nocturia may in part be explained by natriuretic peptides, since aged patients with nocturia had greater urine NT-proANP and NT-proBNP. To understand hormonal changes in the mechanisms of age-related nocturia, future work should look to analyze these effects in controlled settings and exploit the differences to determine potential treatment pathways for nocturia management. Source of Funding: This study was supported by the Ferdinand C. Valentine Medical Student Research Grant in Urology from The New York Academy of Medicine awarded to LK © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e295 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Lakshay Khosla More articles by this author Joseph U. Boroda More articles by this author Joshua Salama More articles by this author Syed N. Rahman More articles by this author Danielle J. Gordon More articles by this author Matthew W. Moy More articles by this author Yonatan Akivis More articles by this author Alla Akivis More articles by this author Jason M. Lazar More articles by this author Jeffrey P. Weiss More articles by this author Lori A. Birder More articles by this author Expand All Advertisement PDF DownloadLoading ...

Risk factors and diagnostic value of urinary N-terminal pro-brain natriuretic peptide for verification of heart failure in human immunodeficiency virus-infected patients

Aim. To determine the risk factors and diagnostic value of urinary N-terminal probrain natriuretic peptide (NT-proBNP) for verification of heart failure in human immunodeficiency virus (HIV)-infected patientsMaterial and methods. This cross-sectional screening clinical trial included 115 HIV-infected patients who were hospitalized during 24 months. The patients were divided into 2 groups, depending on the data suggestive of HF and the blood and urinary NT-proBNP concentration. So, group 1 included 69 HIV-infected patients with HF symptoms and increased blood and urinary NTproBNP, while group 2 — 46 HIV-infected patients not meeting HF criteria. NTproBNP concentration was determined on Immulite 1000 Immunoassay System (DPC, USA) in blood plasma and frozen urine using Vector Best reagents (Russia).Results. Correlation analysis revealed a significant direct moderate correlation between blood and urinary NT-proBNP in the entire cohort of studied patients (r=0,367; p&lt;0,05). Urinary NT-proBNP ≥8,6 pg/ml ml is diagnostic for HF verification in HIV-infected patients. Significant differences between the groups were obtained in the incidence of ventricular arrhythmias, viral hepatitis B and C, liver cirrhosis, infective endocarditis, other inflammatory diseases, thrombocytopenia, left ventricular (LV) diastolic dysfunction and its severity. In addition, there were differences in LV mass index, left atrial volume index, incidence of LV hypertrophy and left atrial enlargement, concentration of hemoglobin and CD4 cells &lt;200 in 1 µl. The preserved LV ejection fraction was detected significantly more often (p&lt;0,001). Conclusion. In HIV-infected patients, blood plasma and urinary NT-proBNP concentration correlates with each other. Urinary NT-proBNP ≥8,6 pg/ml is diagnostic for HF verification in HIV-infected patients. Risk factors and features of developing HF, estimated by NT-proBNP concentration in frozen urine in HIV-infected patients, are comparable to data obtained from blood plasma NTproBNP.

Performance of urinary NT-proBNP in ambulatory settings

BackgroundNT-proBNP (N-terminal prohormone of brain natriuretic peptide) has been established as a useful biomarker in plasma for children with congenital heart disease (CHD). Plasma values were shown to correlate well with urinary values. We designed a study to investigate the general utility of urinary NT-proBNP in children with and without CHD in an ambulatory setting. Material and methods202 children (mean age 93 months (1–225 months)) were included in the analysis. We investigated the performance of urinary NT-proBNP values determined from spot urine as a diagnostic tool for different forms of congenital heart disease. ResultsUrinary NT-proBNP is a good diagnostic tool for children with congenital heart disease (ROC area under the curve 0.807). Combining these values with the Ross-classification further improves the diagnostic power (ROC area under the curve 0.831) Analysis also showed significant differences between Lg10 urinary NT-proBNP values of healthy controls and those of children after corrective surgery. Furthermore, children who have completed the stages of Fontan palliation showed higher values than age matched controls. ConclusionsUrinary NT-proBNP can be used in an ambulatory setting to discriminate between relevant and nonrelevant CHD and might be valuable as a follow up parameter for children after biventricular repair or univentricular palliation. Age dependant urinary NT-proBNP normal values for children could be an easy-to-use tool for general practitioners as well as specialised clinics.

Dapagliflozin in Patients with Chronic Heart Failure: A Systematic Review and Meta-Analysis

Sodium-glucose cotransporter-2 (SGLT2) inhibitors represent newly developed oral antidiabetic drugs that are practiced for type 2 diabetes mellitus management and may decrease the risk of the first hospitalization in heart failure. The activity of SGLT2 inhibitors is not related to glucose, and the effectiveness and safety of SGLT2 inhibitors in individuals with chronic heart failure (CHF) remain unclear. We systematically retrieved PubMed, Cochrane Library, Embase, NCKI, VIP, Wanfang Data, and ClinicalTrials.gov records to identify eligible trials. The primary endpoints were cardiovascular death/hospitalization for heart failure (CV death/HHF), cardiovascular death, and hospitalization for heart failure. Secondary endpoints included hypoglycemia, volume depletion, urinary tract infection, left ventricular ejection fraction (LVEF), and NT-proBNP. Nine randomized controlled clinical trials were included. Dapagliflozin was reported to significantly decrease CV death/HHF (relative risk (RR): 0.75; 95% confidence interval (CI): 0.68–0.84), CV death (RR: 0.80; 95% CI: 0.68–0.93), and HHF (RR: 0.72; 95% CI: 0.63–0.83). There was no effect on hypoglycemia (RR: 0.69; 95% CI: 0.34–1.40), volume depletion (RR: 1.17; 95% CI: 0.97–1.41), urinary tract infection (RR: 0.82; 95% CI: 0.43–1.57), LVEF (WMD: 0.53; 95% CI: −4.04–5.09), or NT-proBNP (SMD: −0.66; 95% CI: −1.42–0.10). The risk of CV death/HHF, CV death, and HHF was lower among patients receiving dapagliflozin than patients receiving placebo.

Perioperative urinary NT-ProBNP values and their usefulness as diagnostic and prognostic markers in children with congenital heart disease

IntroductionNT-proBNP and especially the changes in values are important markers in patients with congenital heart disease (CHD). NT-proBNP values determined from a urine sample correlate well with the plasma values of NT-proBNP. This study investigated the perioperative development of plasma and urinary values, examining their diagnostic and prognostic value. Methods83 children undergoing cardiac surgery for a myriad of CHDs were included. Urine and plasma samples were collected at different points in time. Urinary values were corrected for urine creatinine concentration and transformed into Lg10-values. ResultsThe correlation between urine and plasma is weaker postoperatively (r = 0.70–0.80) in comparison to preoperatively (r = 0.87). Neonates had higher urinary values than older children. A ROC-analysis for the differentiation between complex and simple CHD showed an area under the curve of 0.854 for zlog-NT-proBNP plasma values and 0.826 for creatinine corrected urine values. A decline of NT-proBNP plasma values from the day before surgery to the time after intubation correlated with the duration of postoperative non-invasive ventilation (r = 0.9, sig. < 0.001). ConclusionUrinary NT-proBNP shows potential in discriminating between complex and simple CHD. This study is the first to show a prognostic role of NT-proBNP in establishing spontaneous respiration postoperatively in children with CHD.

1532-P: Investigating Biomarkers of the Immune Response and Tissue Remodeling in Patients with Type 2 Diabetes with Microalbuminuria

Type 2 diabetes (T2D) is a common risk factor for the development of renal fibrosis and chronic kidney disease. Owing to the nature of diabetes, an increased inflammation and an altered turnover of extracellular matrix (ECM) proteins is seen. Despite ample evidence, few studies have focused on an integrated comparison of various biomarkers of the immune response, growth factors and ECM turnover. We evaluated a comprehensive list of biomarkers including interleukin-1, 6, and 8, VCAM-1, ICAM-1, TNFα, E- and P-selectin, FGF23, YKL40, NT-proBNP, type III collagen degradation (C3M) and type VI collagen deposition (PRO-C6) in 190 patients with T2D with microalbuminuria followed for 6.1 years. Investigated endpoints included all-cause mortality (n=26), a composite of cardiovascular events (CVE; n=37), and decline in eGFR of &amp;gt;30% (deGFR, n=41). Using forward selection in Cox proportional hazard analysis we investigated which biomarkers and traditional risk factors (sex, age, systolic blood pressure, LDL-cholesterol, smoking, HbA1c, creatinine and urinary albumin excretion rate) that were retained in the final model for predicting the outcomes. Hazard ratios with 95% confidence intervals are presented per one standard deviation. For all-cause mortality, smoking (3.85 [1.68-8.83], p=0.002), PRO-C6 (1.53 [1.15-2.03], p=0.004), NT-proBNP (1.59 [1.22-2.08], p=0.0006) and ICAM-1 (1.36 [1.06-1.73], p=0.014) were retained in the final model. For CVEs, age (2.00 [1.21-3.30], p=0.007), LDL (1.37 [1.05-1.78], p=0.02), NT-proBNP (1.42 [1.11-1.81], p=0.006) and TNFα (1.35 [1.13-1.60], p=0.0007) were retained. For deGFR, urinary albumin excretion rate (1.31 [1.00-1.71], p=0.049), PRO-C6 (1.41 [1.09-1.83], p=0.009) and NT-proBNP (2.05 [1.54-2.74], p&amp;lt;0.0001) were retained. In conclusion, our investigations highlight that the best models for predicting outcome may be found by combining biomarkers of cardiac injury, ECM remodeling and the immune response. Disclosure D.G.K. Rasmussen: Employee; Self; Nordic Bioscience. T.W. Hansen: None. A. Møller: None. M. Frimodt-Møller: None. B. von Scholten: Employee; Self; Novo Nordisk A/S. P.K. Jacobsen: None. H.D. Parving: None. M.A. Karsdal: Stock/Shareholder; Self; Nordic Bioscience. P. Rossing: Advisory Panel; Self; Sanofi. Consultant; Self; Astellas Pharma Inc., AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Novo Nordisk A/S. Research Support; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; Eli Lilly and Company. Stock/Shareholder; Self; Novo Nordisk A/S. Funding Danish Research Foundation

2166-PUB: Surprisingly High Prevalence of Vitamin D Deficiency in Japanese Diabetic Patients

Vitamin D is known to regulate many cellular functions such as insulin secretion, cardiac function, immune system, skeletal muscle in addition to bone mineral metabolism. With respect to diabetes, diabetes prevention trials by vitamin D supplementation and reports showing an association between low levels of blood vitamin D and cardiovascular events, bone fractures, falls and most recently the life prognosis have been published. However, reports on Japanese diabetic patients and vitamin D is scarce. We measured serum 25 (OH) D concentration (ECLIA) in 133 patients (M/F: 85/48) with type 1 (n=15) and type 2 diabetes patients (118). Age, sex, BMI and biochemical indicators (serum Ca, P, Alb, HbA1c, LDL-C, TG, CPR and atherosclerosis indices (urinary albumin, NT-proBNP, baPWV and max IMT) were investigated. The subjects mean age was 59.1±14.0 years (mean±SD) and HbA1c9.1 ±2.6%, and BMI25.0±4.3. Serum 25 (OH) D concentration state was only 3% in sufficient group(&amp;gt;30ng/ml), 11% insufficient group and 86% was in deficiency (&amp;lt;20ng/ml). This was the same regardless of type 1 or type 2. Correlations with the aforementioned indicators including HbA1c was not observed. However, serum 25 (OH) D concentration and max IMT in HbA1c above 8% group had a weak but significant reverse correlation, which was consistent with the previous metaanalysis. The limitation of this study is a single center based, and it does not include data on dieting status, or exposure to sunlight. However, subjects have a history of medical nutritional education and they are residents of urban areas with adequate ADL, it is unlikely that they are particularly biased diabetes populations. In an aging society, it is important to prevent sarcopenia, and fractures in diabetes. The present results shed a new insight in Japanese medical nutritional therapy. For vitamin D deficiency cohort, interventions and bone salt quantification are going to be carried out and osteoporosis, fractures, and cardiovascular risk are evaluated in a prospective manner. Disclosure N. Kashima: None. K. Hamano: None.

Urinary NT-proBNP as a potential noninvasive biomarker for screening of pulmonary hypertension in preterm infants: a pilot study.

This pilot study aimed to determine the feasibility of urinary NT-proBNP (NT-proBNP) as a potential noninvasive screening marker for pulmonary hypertension (PH). A prospective cross-sectional study was conducted. Preterm infants (PI) (birthweight <1500 gm and <30 weeks gestational age (GA)) were enrolled. Serial urinary NT-proBNP measurements and echocardiograms (ECHO) were performed at 28, 32, and 36 weeks. Thirty-six patients were included in the final analysis (BPD-PH group = 6, BPD group = 20, control = 10). Urinary NT-proBNP levels were higher in the BPD-PH group compared with BPD and control groups at all study intervals. A urine NT-proBNP cutoff level of 2345 pg/ml at 28 weeks of GA had a sensitivity and specificity of 83.3% and 84.2%, respectively, for detection of BPD-PH (AUC 0.816, p = 0.022). Urinary NT-proBNP measurement is feasible in preterm infants and appears to be a good noninvasive screening tool for PH.

Retinopathy of prematurity screening at ≥30 weeks: urinary NTpro-BNP performance.

Urinary N-terminal B-type natriuretic peptide NTproBNP levels are associated with the development of retinopathy of prematurity (ROP) in infants <30 weeks of gestation. The incidence of ROP in more mature infants who meet other ROP screening criteria is very low. We therefore aimed to test whether urinary NTproBNP predicted ROP development in these infants. Prospective observational study in 151 UK infants ≥30 + 0 weeks of gestation but also <32 weeks of gestation and/or <1501 g, to test the hypothesis that urinary NTproBNP levels on day of life (DOL) 14 and 28 were able to predict ROP development. Urinary NTproBNP concentrations on day 14 and day 28 of life did not differ between infants with and without ROP (medians 144 vs 128 mcg/mL, respectively, p = 0.86 on DOL 14 and medians 117 vs 94 mcg/mL, respectively, p = 0.64 on DOL28). The association previously shown for infants <30 completed weeks between urinary NTproBNP and the development of ROP was not seen in more mature infants. Urinary NTproBNP does not appear helpful in rationalising direct ophthalmoscopic screening for ROP in more mature infants, and may suggest a difference in pathophysiology of ROP in this population.

N-terminal B-type natriuretic peptide urinary concentrations and retinopathy of prematurity.

BackgroundTo validate the findings of a single-center pilot study showing elevated urinary N-terminal B-type natriuretic peptide (NTproBNP) concentrations in preterm infants subsequently developing severe retinopathy of prematurity (ROP) in a multicenter setting across eight European and Middle East countries.MethodsProspective observational study in 967 preterm infants <30 weeks' gestational age assessing the capacity of urinary NTproBNP on days of life (DOLs) 14 and 28 to predict ROP requiring treatment.ResultsUrinary NTproBNP concentrations were markedly elevated in infants who developed ROP requiring treatment (n=94) compared with survivors without ROP treatment (n=837), at both time points (median (interquartile range) DOL14: 8,950 (1,925-23,783) vs. 3,083 (1,193-17,393) vs. 816 (290-3,078) pg/ml, P<0.001) and DOL28 (2,203 (611-4,063) vs. 1,671 (254-11,340) vs. 408 (162-1,126) pg/ml, P<0.001). C-statistic of NTproBNP for treated ROP or death was 0.731 (95% confidence interval 0.654-0.774) for DOL14 and 0.683 (0.622-0.745) for DOL28 (P<0.001). Threshold scores were calculated, potentially enabling around 20% of infants with low NTproBNP scores never to be screened with ophthalmoscopy.ConclusionThere is a strong association between early urinary NTproBNP and subsequent ROP development, which can be used to further refine subgroups of patients with high or low risk of severe ROP.