Urinary N-terminal pro-B-type natriuretic peptide as a biomarker for cardiovascular events in a general Japanese population: the Hisayama Study.

BACKGROUND: Epidemiological evidence has shown that serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations, a diagnostic biomarker for heart failure, are positively associated with cardiovascular risk. Since NT-proBNP in serum is excreted in urine, it is hypothesized that urinary NT-proBNP concentrations are correlated with serum concentrations and linked with cardiovascular risk in the general population. METHODS: A total of 3060 community-dwelling residents aged ≥ 40 years without history of cardiovascular disease (CVD) were followed up for a median of 8.3 years (2007-2015). Serum and urinary concentrations of NT-proBNP at baseline were compared. The hazard ratios (HRs) and their 95% confidence intervals (CIs) for the association between NT-proBNP concentrations and the risk of developing CVD were computed using the Cox proportional hazards model. RESULTS: The median values (interquartile ranges) of serum and urinary NT-proBNP concentrations at baseline were 56 (32-104) pg/mL and 20 (18-25) pg/mL, respectively. There was a strong quadratic correlation between the serum and urinary concentrations of NT-proBNP (coefficient of determination [R2] = 0.72): urinary concentrations of 20, 27, and 43 pg/mL were equivalent to serum concentrations of 55, 125, and 300 pg/mL, respectively. During the follow-up period, 170 subjects developed CVD. The age- and sex-adjusted risk of CVD increased significantly with higher urinary NT-proBNP levels (P for trend < 0.001). This association remained significant after adjustment for traditional cardiovascular risk factors (P for trend = 0.009). The multivariable-adjusted risk of developing CVD almost doubled in subjects with urinary NT-proBNP of ≥ 43 pg/mL as compared to those with urinary NT-proBNP of ≤ 19 pg/mL (HR 2.07, 95% CI 1.20-3.56). CONCLUSIONS: The present study demonstrated that urinary NT-proBNP concentrations were well-correlated with serum concentrations and were positively associated with cardiovascular risk. Given that urine sampling is noninvasive and does not require specially trained personnel, urinary NT-proBNP concentrations have the potential to be an easy and useful biomarker for detecting people at higher cardiovascular risk.

Urinary N-terminal pro-B-type natriuretic peptide as a biomarker for cardiovascular events in a general Japanese population: the Hisayama Study

BACKGROUND@#Epidemiological evidence has shown that serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations, a diagnostic biomarker for heart failure, are positively associated with cardiovascular risk. Since NT-proBNP in serum is excreted in urine, it is hypothesized that urinary NT-proBNP concentrations are correlated with serum concentrations and linked with cardiovascular risk in the general population.@*METHODS@#A total of 3060 community-dwelling residents aged ≥ 40 years without history of cardiovascular disease (CVD) were followed up for a median of 8.3 years (2007-2015). Serum and urinary concentrations of NT-proBNP at baseline were compared. The hazard ratios (HRs) and their 95% confidence intervals (CIs) for the association between NT-proBNP concentrations and the risk of developing CVD were computed using the Cox proportional hazards model.@*RESULTS@#The median values (interquartile ranges) of serum and urinary NT-proBNP concentrations at baseline were 56 (32-104) pg/mL and 20 (18-25) pg/mL, respectively. There was a strong quadratic correlation between the serum and urinary concentrations of NT-proBNP (coefficient of determination [R@*CONCLUSIONS@#The present study demonstrated that urinary NT-proBNP concentrations were well-correlated with serum concentrations and were positively associated with cardiovascular risk. Given that urine sampling is noninvasive and does not require specially trained personnel, urinary NT-proBNP concentrations have the potential to be an easy and useful biomarker for detecting people at higher cardiovascular risk.

Time Course Changes in Urinary Angiotensinogen and Circulating N-Terminal Pro-B-Type Natriuretic Peptide in Patients Hospitalized with Acute Heart Failure.

Objective Home care is important in patients with heart failure (HF) in order to maintain their quality of life. A biomarker that can be measured noninvasively is needed to optimize the home care of patients with HF. Urinary angiotensinogen (uAGT) is an indicator of the intrarenal renin-angiotensin system activity, which may be augmented in HF. We hypothesized that uAGT might be a urinary biomarker in HF. Methods We measured uAGT by an enzyme-linked immunosorbent assay and uAGT normalized by urinary creatinine (uCr)-designated uAGT/uCr-at admission and discharge in 45 patients hospitalized for HF. Results We found that both uAGT/uCr [median (interquartile range): 65.5 (17.1-127.7) µg/g Cr at admission; 12.1 (6.0-37.0) µg/g Cr at discharge; p<0.01] and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels [5,422 (2,280-9,907) pg/mL at admission; 903 (510-1,729) pg/mL at discharge; p<0.01] significantly decreased between admission and discharge along with an improvement in patient's clinical status [New York Heart Association scores: 3 (3-4) at admission; 1 (1-1) at discharge; p<0.01]. The generalized least squares model revealed that the time course changes in uAGT/uCr also correlated with those in NT-proBNP levels between admission and readmission in five patients readmitted for HF. Conclusion The results indicated that the time course changes in uAGT/uCr correlated with those in the NT-proBNP levels in patients with HF who showed a clinical improvement. Further investigation and development of a kit for the rapid measurement of uAGT are needed to evaluate the clinical utility of uAGT as a biomarker in HF.

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

OBJECTIVE: This pilot study aimed to determine the feasibility of urinary NT-proBNP (NT-proBNP) as a potential noninvasive screening marker for pulmonary hypertension (PH). STUDY DESIGN: 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. RESULTS: 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). CONCLUSION: Urinary NT-proBNP measurement is feasible in preterm infants and appears to be a good noninvasive screening tool for PH.

Postmortem urine concentration of N-terminal pro-brain natriuretic peptide in relation to the cause of death.

The utility of biochemical marker analysis in forensic autopsy cases is still uncertain due to the postmortem changes which they undergo. Thus, research is required to elucidate alternative samples and biochemical markers which are less affected by postmortem changes. Levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are known to be elevated in congestive heart failure (CHF), acute myocardial infarction (AMI), and sepsis patients. Although NT-proBNP is reportedly excreted into the urine, no study has previously evaluated the diagnostic efficacy of urinary concentrations in a forensic setting. The aim of this study was to evaluate the diagnostic efficacy of NT-proBNP concentration in urine obtained postmortem in a series of forensic autopsy cases. METHODS: Urinary NT-proBNP was measured in 36 AMI, 10 CHF, and 19 sepsis cases, and in 124 control cases (all with postmortem interval [PMI]<72h). RESULTS: Urinary NT-proBNP was significantly higher in AMI, CHF, and sepsis cases than in control cases. Cut-off values for diagnosing AMI, CHF, and sepsis-related fatalities were 98 (sensitivity, 55.6 %; specificity, 73.4 %), 1050 (sensitivity, 80.0 %; specificity, 94.4 %), and 363pg/mL (sensitivity, 84.2 %; specificity, 85.5 %), respectively. Furthermore, we subdivided the control cases according to the death process as either acute death (87 cases) or prolonged death cases (37 cases). Although urine NT-proBNP of CHF and sepsis cases were significantly higher compared with both cases, the concentration in the AMI cases were significantly high only when compared with the acute death cases. CONCLUSION: This study is the first to elucidate the diagnostic utility of NT-proBNP measurement in urine obtained postmortem in a series of causes of death. This study suggests the diagnostic efficacy for AMI, CHF, and sepsis-related fatality in cases in which the PMI was within 72h.

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

AIM: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Urinary NT-proBNP levels and echocardiographic parameters for patent ductus arteriosus.

OBJECTIVE: Patent ductus arteriosus (PDA) is common in preterm infants and is associated with significant morbidities. B type natriuretic peptide (BNP) is synthesized in the ventricles secondary to volume overload and excreted as urinary N-terminal pro-brain natriuretic peptide (NT-proBNP). STUDY DESIGN: We report an observational prospective study of 64 preterm infants with birth weight ⩽1000 g. Echocardiographic parameters were obtained from clinical echocardiograms performed in the first week of life. Urinary NT-proBNP/creatinine ratios (pg mg-1) were measured on the same day of the echocardiograms. RESULTS: Infants with medium to large PDA (n=39) had significantly higher NT-proBNP/creatinine levels compared with infants with small PDA (n=10) (median (IQ range): 2333 (792-6166) vs 714 (271-1632) pg mg-1, P=0.01) and compared with infants with no PDA (n=15) (2333 (792-6166) vs 390 (134-1085) pg mg-1, P=0.0003). Urinary NT-proBNP/creatinine ratios were significantly lower post treatment if PDA closed (n=17), P=0.001 or if PDA became smaller after treatment (n=9), P=0.004. Urinary NT-proBNP/creatinine levels correlated with ductal diameter (P⩽0.0001), but not with LA/Ao ratio (P=0.69) or blood flow velocity through the ductus (P=0.06). CONCLUSION: Our findings indicate that there is a positive correlation between ductal diameter and urinary NT-proBNP in preterm infants.

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.

Feasibility, safety, and tolerance of subcutaneous synthetic canine B-type natriuretic peptide (syncBNP) in healthy dogs and dogs with stage B1 mitral valve disease.

INTRODUCTION: An important aspect of heart failure is the progressive ineffectiveness of the salutary natriuretic peptide system and its secondary messenger, 3',5'-cyclic guanosine monophosphate (cGMP). In humans with acute heart failure, administration of exogenous natriuretic peptide is associated with improvement in clinical signs and reduction of cardiac filling pressures. This study aimed to determine the feasibility, tolerance, and safety of subcutaneous (SC) synthetic canine B-type natriuretic peptide (syncBNP) administration in dogs. ANIMALS: Six privately owned dogs. MATERIALS AND METHODS: Dogs were enrolled in a modified 3 + 3 phase I trial. Three dogs initially received doses of 2.5 and 5 µg/kg SC syncBNP followed by an additional three dogs dosed at 5 and 10 µg/kg. Hemodynamic monitoring was performed for 120 min after each injection. Blood and urine samples were collected at 45 and 120 min after injection of 5 µg/kg. Major adverse clinical events that would potentially halt testing were pre-defined. RESULTS: Four healthy dogs and two dogs with stage B1 mitral valve disease were recruited. Synthetic canine B-type natriuretic peptide was well tolerated at all doses. Synthetic canine B-type natriuretic peptide at 5 µg/kg significantly increased median plasma cGMP (baseline cGMP, 131.5 pmol/mL [range, 91.9-183.6 pmol/mL]; 45 min, 153.6 pmol/mL [140.3-214.3 pmol/mL]; 120 min, 192.7 pmol/mL [139.1-240.1 pmol/mL]; p=0.041). DISCUSSION AND CONCLUSIONS: We report for the first time administration of syncBNP in privately owned dogs. Administration of SC syncBNP was feasible, well tolerated, safe, and increased plasma cGMP concentration. Further studies using exogenous syncBNP for treatment of heart disease are warranted.

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

OBJECTIVES: 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. DESIGN: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Professional rugby union causes a transient increase in cardiovascular stress that seems to be independent of the external workload characteristics of a player.

Subclinical target organ damage in normotensive and prehypertensive patients.

BACKGROUND: Prehypertension is a risk factor for the development of hypertension and other cardiovascular diseases. The objective of this study was to evaluate for the evidence of subclinical target organ damage in two groups of subjects without hypertension. METHODS: This was a prospective cross-sectional study. Subjects seeking care for various clinical conditions in the hospital were invited for the survey. The subjects' were divided in to two groups according to their blood pressure: prehypertension (systolic blood pressure 120 to 139 mm Hg or diastolic blood pressure, 80 to 89 mm Hg) and normotension (systolic blood pressure, <120 mm Hg and diastolic blood pressure, <80 mm Hg). Urine albumin excretion and other biochemical analyses were performed using standard methods. RESULTS: We recruited a total of 3300 subjects, the prehypertension group included 1100 individuals and the normotension group was composed of 2200 persons. The prevalence of microalbuminuria in subjects in the prehypertension group was 6.8% and in those who are the in the optimal BP group was 3.6% (P<0.001). Subjects in the prehypertension group had a mean B-type natriuretic peptide (BNP) level of 98 (72) pg/mL compared with 43.6 (20) pg/mL found among subjects in the normotension group (<0.001). In the logistic regression model, tobacco smoking aOR 2.7 (95% CI.; 1.7-5.8), higher uric acid level aOR 2.2 (1.7-3.2), microalbuminuria 7.6 (4.9-14.7) and a higher BNP level aOR 2.5 (1.8-7.6) were significantly associated with the occurrence of prehypertension. CONCLUSIONS: Microalbuminuria, BNP level and hyperuricemia were significantly associated with prehypertension.

An oxidative stress biomarker, urinary 8-hydroxy-2'-deoxyguanosine, predicts cardiovascular-related death after steroid therapy for patients with active cardiac sarcoidosis.

BACKGROUND: We investigated whether urinary 8-hydroxy-2'-deoxyguanosine (U-8-OHdG), a marker of oxidative DNA damage, is a prognosticator of cardiovascular-related death in patients with cardiac sarcoidosis (CS). METHODS AND RESULTS: In this prospective study, 30 consecutive patients were divided into the active CS (n=20) and non-active CS (n=10) groups, based on abnormal isotope accumulation in the heart on (18)F-fluorodeoxyglucose positron-emission tomography/computed tomography ((18)F-FDG PET/CT) imaging. Nineteen patients in the active CS group underwent corticosteroid therapy. Before corticosteroid therapy initiation, U-8-OHdG, brain natriuretic peptide (BNP), other biomarkers, and indices of cardiac function were measured. Patients were followed-up for a median of 48months. The primary endpoint was the incidence of cardiovascular-related death. During the follow-up period, in the corticosteroid-treated active CS group, 7 of 19 patients experienced cardiovascular-related death. By contrast, in the non-active CS group, 1 of 10 patients died from cardiovascular-related causes. Univariate and multivariate analyses showed that U-8-OHdG and BNP were independent predictors for cardiovascular-related death. The cut-off values for predicting cardiovascular death in corticosteroid-treated patients with active CS were 19.1ng/mg·Cr and 209pg/mL for U-8-OHdG and BNP, respectively. Patients with a U-8-OHdG concentration ≥19.1ng/mg·Cr or a BNP concentration ≥209pg/mL had a significantly higher cardiovascular-related death risk, but U-8-OHdG had better predictive value compared with BNP. CONCLUSION: These findings suggested that U-8-OHdG was a powerful predictor of cardiovascular-related death in patients with CS, suggesting that active CS patients with elevated U-8-OHdG levels might be resistant to corticosteroid therapy.

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 R(2) 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 R(2) varied greatly depending on how the data were presented. The correlation between the raw data showed an R(2) 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 R(2) for the logarithm-transformed correlation to 68% on admission and 76% on discharge. The highest R(2) (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.

The impact of obstructive sleep apnea syndrome on nocturnal urine production in older men with nocturia.

OBJECTIVE: To investigate the impact of obstructive sleep apnea syndrome (OSAS) on night-time secretion of brain natriuretic peptide (BNP) and antidiuretic hormone (ADH) in older men with nocturia accompanied by nocturnal polyuria. MATERIALS AND METHODS: One hundred six men with nocturia aged ≥ 60 years underwent full-night polysomnography to determine whether they had OSAS. Blood count, standard chemistry panel, BNP, urinary ADH, urinary creatinine (u-Cre), and urinary osmolarity were measured at 6:00 AM, and a frequency volume chart was recorded on the same day that polysomnography was performed. RESULTS: We evaluated 83 patients after excluding 18 with mild OSAS and 5 with nocturnal polyuria index <0.35. Participants with OSAS had higher apnea-hypopnea index (P < .0001) than those without OSAS. Body mass index and systolic blood pressure were higher in OSAS patients than those in the control group. BNP was higher in the OSAS patients than in the control patients (48.6 ± 41.4 vs 30.7 ± 31.5; P = .0006). On urinalysis, OSAS patients showed higher urinary sodium and u-Cre secretion than controls (24.7 ± 11.3 vs 16.2 ± 5.1; P <.0001). Urine osmolarity was also higher in OSAS patients than in the control patients (616 ± 172 vs 516 ± 174; P = .0285). There was no significant difference in urinary ADH and u-Cre (6.7 ± 10.4 vs 6.8 ± 7.8; P = .3617) between the 2 groups. CONCLUSION: Our results indicated that older men with nocturnal polyuria and OSAS did not compensate their fluid imbalance presented with decreased secretion of ADH but increased BNP level.

Differentiating between feline pleural effusions of cardiac and non-cardiac origin using pleural fluid NT-proBNP concentrations.

OBJECTIVE: To assess whether pleural fluid and urine amino terminal proB-type natriuretic peptide (NT-proBNP) can distinguish cardiac from non-cardiac causes of pleural effusion. METHODS: Blood, urine and pleural fluid were prospectively collected from cats presenting with pleural effusion categorised as cardiac or non-cardiac in origin. NT-ProBNP concentrations were measured using a feline-specific enzyme-linked immunosorbent assay. Groups were statistically compared and receiver operating characteristic curves constructed to determine cut-offs to distinguish cardiac from non-cardiac pleural effusion in plasma, pleural fluid and urine. RESULTS: Forty cats with pleural effusion (22 cardiac and 18 non-cardiac) were studied. NT-proBNP concentrations in plasma and pleural fluid were strongly correlated. Plasma (P<0·001) and pleural fluid (P<0·001) NT-proBNP concentrations and urinary NT-proBNT/creatinine ratios (P=0·035) were significantly higher in the cardiac group. After receiver operating characteristic curve analysis a plasma NT-proBNP cut-off of 214·3 pmol/mL was suggested [sensitivity=86·4% (95% CI: 66·7 to 95·3%), specificity=88·9% (95% CI: 67·2 to 96·9%)] and a pleural fluid NT-proBNP cut-off of 322·3 pmol/mL was suggested [sensitivity=100% (95% CI: 85·1 to 100%), specificity=94·4% (95% CI: 74·2 to 99·0%)]. No cut-off with adequate sensitivity and specificity for urinary NT-proBNP/creatinine ratios was suggested. CLINICAL SIGNIFICANCE: Measurement of NT-proBNP in pleural fluid distinguishes cardiac from non-cardiac causes of pleural effusion in cats.

Effects of nesiritide and predictors of urine output in acute decompensated heart failure: results from ASCEND-HF (acute study of clinical effectiveness of nesiritide and decompensated heart failure).

OBJECTIVES: This study sought to determine if nesiritide increases diuresis in congestive heart failure patients. BACKGROUND: In the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide and Decompensated Heart Failure), 7,141 patients hospitalized with acute decompensated heart failure (ADHF) were randomized to receive nesiritide or placebo for 24 to 168 h, in addition to standard care. There were minimal effects of nesiritide on survival, future hospitalizations, and symptoms. However, whether or not nesiritide increases diuresis in ADHF patients is unknown. METHODS: Urine output was measured in 5,864 subjects; of these, 5,320 received loop diuretics and had dose data recorded. Loop diuretics other than furosemide were converted to furosemide equivalent doses. A total of 4,881 patients had complete data. We used logistic regression models to identify the impact of nesiritide on urine output and the factors associated with high urine output. RESULTS: Median (25th, 75th percentiles) 24-h urine output was 2,280 (1,550, 3,280) ml with nesiritide and 2,200 (1,550, 3,200) ml with placebo (p = NS). Loop diuretic dose (furosemide equivalent) was 80 (40, 140) mg with both nesiritide and placebo. Diuretic dose was a strong predictor of urine output. Other independent predictors included: male sex, greater body mass index, higher diastolic blood pressure, elevated jugular venous pressure, recent weight gain, and lower blood urea nitrogen. The addition of nesiritide did not change urine output. None of the interaction terms between nesiritide and predictors affected the urine output prediction. CONCLUSIONS: Nesiritide did not increase urine output in patients with ADHF. Higher diuretic dose was a strong predictor of higher urine output, but neurohormonal activation (as evidenced by blood urea nitrogen concentration) and lower blood pressure limited diuresis.