Hemodynamic and renal effects of low-dose brain natriuretic peptide  infusion in humans: a randomized, placebo-controlled crossover study

Zander, Kim van der; Houben, A. J. H. M.; Hofstra, Leo; Kroon, Abraham A.; Leeuw, Peter W. de

doi:10.1152/ajpheart.00085.2003

Cited by 42 publications

(34 citation statements)

References 33 publications

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“…The study participants remained lying down and fasted throughout the study, and exhibited, in agreement with 129±12 131±11 74±8 79±10 65±13 69±16 −30 125±10 129±6 75±8 76±3 66±13 64±11 0 129±14 129±7 77±7 77±6 66±12 65±11 30 125±14 131±10 74±5 76±8 64±13 65±10 60 127±8 125±11 73±7 74±11 61±9 70±12* 90 126±12 128±11 73±7 73±9 59±6 64±6 120 121±13 124±13 73±7 73±10 60±6 62±8 150 120±10 121±12 72±8 72±9 63±6 65±8 180 123±12 121±12 72±7 71±8 61±7 68±7* 270 121±9 128±21 71±6 74±7 60±6 73±15* previous findings, no significant changes in blood pressure [24]. Heart rate was significantly higher during BNP infusion compared with placebo at time points 60, 180 and 270 min (p<0.05) ( Table 2), which might be due to a non-significant decrease in blood pressure.…”

Section: Discussionsupporting

confidence: 74%

B-type natriuretic peptide (BNP) affects the initial response to intravenous glucose: a randomised placebo-controlled cross-over study in healthy men

et al. 2011

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Aims/hypothesis B-type natriuretic peptide (BNP) is a hormone released from cardiomyocytes in response to cell stretching and elevated in heart failure. Recent observations indicate a distinct connection between chronic heart failure and diabetes mellitus. This study investigated the role of BNP on glucose metabolism. Methods Ten healthy volunteers (25±1 years; BMI 23± 1 kg/m 2 ; fasting glucose 4.6±0.1 mmol/l) were recruited to a participant-blinded investigator-open placebo-controlled cross-over study, performed at a university medical centre. They were randomly assigned (sequentially numbered opaque sealed envelopes) to receive either placebo or 3 pmol kg −1 min −1 BNP-32 intravenously during 4 h on study day 1 or 2. One hour after beginning the BNP/placebo infusion, a 3 h intravenous glucose tolerance test (0.33 g/kg glucose + 0.03 U/kg insulin at 20 min) was performed. Plasma glucose, insulin and C-peptide were frequently measured.Results Ten volunteers per group were analysed. BNP increased the initial glucose distribution volume (13±1% body weight vs 11±1%, p<0.002), leading to an overall reduction in glucose concentration (p<0.001), particularly during the initial 20 min of the test (p=0.001), accompanied by a reduction in the initial C-peptide levels (1.42± 0.13 vs 1.62±0.10 nmol/l, p=0.015). BNP had no impact on beta cell function, insulin clearance or insulin sensitivity and induced no adverse effects. Conclusions/interpretation Intravenous administration of BNP increases glucose initial distribution volume and lowers plasma glucose concentrations following a glucose load, without affecting beta cell function or insulin sensitivity. These data support the theory that BNP has no diabetogenic properties, but improves metabolic status in men, and suggest new questions regarding BNP-induced differences in glucose availability and signalling in various organs/tissues. Trial registration: ClinicalTrials.gov: NCT01324739 Funding: The study was funded by Jubilée Fonds of the Austrian National Bank (OeNB-Fonds).

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Section: Discussionsupporting

confidence: 74%

B-type natriuretic peptide (BNP) affects the initial response to intravenous glucose: a randomised placebo-controlled cross-over study in healthy men

et al. 2011

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“…Similarly, studies of BNP have come to conflicting conclusions about the effects on glomerular filtration rate (GFR) or renal plasma flow. [5][6][7] The extent of the renal effects of nesiritide when given in therapeutic doses to decompensated CHF patients is uncertain.…”

Section: See P 1514mentioning

confidence: 99%

“…5,15 Even these studies, however, have not necessarily demonstrated improved ERPF. 6 Nesiritide appears to exert hemodynamic effects in patients with both CHF and renal dysfunction (although the effects may be quantitatively different from those seen in normal individuals). 16 Clinically, CHF patients with an elevated creatinine concentration had a response similar to those with normal renal function in the Vasodilation in the Acute Management of CHF trial.…”

Section: Gfr and Erpfmentioning

confidence: 99%

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Nesiritide Does Not Improve Renal Function in Patients With Chronic Heart Failure and Worsening Serum Creatinine

et al. 2004

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Background-Nesiritide (synthetic human brain natriuretic peptide) is approved for the treatment of symptomatic heart failure. However, studies of brain natriuretic peptide in patients with heart failure have come to conflicting conclusions about effects on glomerular filtration rate (GFR), effective renal plasma flow, natriuresis, and diuresis. Methods and Results-To identify a population at high risk of renal dysfunction with conventional treatment, we selected patients with a creatinine level increased from baseline (within 6 months). We examined the effects of nesiritide on GFR (measured by iothalamate clearance), renal plasma flow (measured by para-amino hippurate clearance), urinary sodium excretion, and urine output in a double-blind, placebo-controlled, crossover study. Patients received nesiritide (2 g/kg IV bolus followed by an infusion of 0.01 g/kg per minute) or placebo for 24 hours on consecutive days. Nesiritide and placebo data were compared by repeated-measures analysis and Student t test. We studied 15 patients with a recent mean baseline creatinine of 1.5Ϯ0.4 mg/dL and serum creatinine of 1.8Ϯ0.8 mg/dL on admission to the study. There were no differences in GFR, effective renal plasma flow, urine output, or sodium excretion for any time interval or for the entire 24-hour period between the nesiritide and placebo study days. For 24 hours, urine output was 113Ϯ51 mL/h with placebo and 110Ϯ56 mL/h with nesiritide. GFR during placebo was 40.9Ϯ25.9 mL/min and with nesiritide was 40.9Ϯ25.8. Conclusions-Nesiritide did not improve renal function in patients with decompensated heart failure, mild chronic renal insufficiency, and renal function that had worsened compared with baseline. The lack of effect may be related to renal insufficiency, hemodynamic alterations, sodium balance, severity of heart failure, or drug dose. Understanding the importance of these issues will permit effective and appropriate use of nesiritide.

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“…Both compounds show natriuretic, diuretic, and vasodilating effects [17,18]. While there is good evidence of positive short-term hemodynamic effects of nesiritide in ADHF [19], there still is controversy regarding its safety risks, including renal dysfunction and long-term mortality [20], that needs to be addressed in future trials.…”

Section: Guanylate Cyclase Pathwaymentioning

confidence: 99%

Soluble Guanylate Cyclase Modulators in Heart Failure

Mitrović¹,

Lehinant²

2012

Hemodynamics - New Diagnostic and Therapeutic Approaches

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Hemodynamic and renal effects of low-dose brain natriuretic peptide infusion in humans: a randomized, placebo-controlled crossover study

Cited by 42 publications

References 33 publications

B-type natriuretic peptide (BNP) affects the initial response to intravenous glucose: a randomised placebo-controlled cross-over study in healthy men

B-type natriuretic peptide (BNP) affects the initial response to intravenous glucose: a randomised placebo-controlled cross-over study in healthy men

Nesiritide Does Not Improve Renal Function in Patients With Chronic Heart Failure and Worsening Serum Creatinine

Soluble Guanylate Cyclase Modulators in Heart Failure

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