Impact of Nesiritide on Renal Function and Mortality in Patients Suffering from Heart Failure

Dontas, Ioannis D.; Xanthos, T.; Dontas, Ismene; Lelovas, Pavlos; Papadimitriou, Lila

doi:10.1007/s10557-009-6167-6

Cited by 17 publications

(15 citation statements)

References 41 publications

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“…Nesiritide is used to treat acute decompensated heart failure. Of note, a meta-analysis of Sackner-Bernstein et al [28] showed an increased mortality in patients treated with Nesiritide; however, mortality was not increased in other studies with short Nesiritide application [7]. Prolonged treatment of Nesiritide has not been studied so far.…”

Section: Discussionmentioning

confidence: 99%

BNP controls early load-dependent regulation of SERCA through calcineurin

et al. 2010

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Heart failure is characterised by reduced expression of sarcoplasmic reticulum calcium-ATPase (SERCA) and increased expression of B-type natriuretic peptide (BNP). The present study was performed to investigate causality of this inverse relationship under in vivo conditions in the transversal aortic constriction mouse model (TAC). Left ventricular SERCA-mRNA expression was significantly upregulated in TAC by 32% after 6 h, but not different from sham after 24 h. Serum proANP and BNP levels were increased in TAC after 24 h (BNP +274%, p < 0.01; proANP +60%, p < 0.05), but only proANP levels were increased after 6 h (+182%, p < 0.01). cGMP levels were only increased 24 h after TAC (+307%, p < 0.01), but not 6 h after TAC. BNP infusion inhibited the increase in SERCA expression 6 h after TAC. In BNP-receptor-knockout animals (GC-A), the expression of SERCA was still significantly increased 24 h after TAC at the mRNA level by 35% (p < 0.05), as well as at the protein level by 25% (p < 0.05). MCIP expression as an indicator of calcineurin activity was regulated in parallel to SERCA after 6 and 24 h. MCIP-mRNA was increased by 333% 6 h after TAC, but not significantly different from sham after 24 h. In the GC-A-KO mice, MCIP-mRNA was significantly increased in TAC compared to WT after 24 h. In mice with BNP infusion, MCIP was significantly lower 6 h after TAC compared to control animals. In conclusion, mechanical load leads to an upregulation of SERCA expression. This is followed by upregulation of natriuretic peptides with subsequent suppression of SERCA upregulation. Elevated natriuretic peptides may suppress SERCA expression by inhibition of calcineurin activity via activation of GC-A.

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Section: Discussionmentioning

confidence: 99%

BNP controls early load-dependent regulation of SERCA through calcineurin

et al. 2010

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“…In patients who are truly refractory to diuretics, intravenous nitroglycerine or ultrafiltration can be helpful (Class IIa) 8. Though nesiritide is another Class IIa alternative to inotropes, there have been concerns about its negative effects on renal function 13. In patients whose renal function declines in response to any of the above therapies (worsening cardiorenal syndrome), inotropes may be required transiently to allow reduction in right atrial and renal venous pressure to achieve effective diuresis and symptom relief.…”

Section: Case 1 – Decompensated Heart Failure With Oliguriamentioning

confidence: 99%

Role of Inotropic Agents in the Treatment of Heart Failure

Goldhaber

Hamilton

2010

Circulation

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“…To that end, nesiritide, or recombinant human B‐type natriuretic peptide, has been studied as a therapeutic modality in left‐sided systolic HF. Identical to the endogenous hormone produced by the ventricles in response to increased wall tension, nesiritide has vasodilatory, natriuretic, and diuretic effects that were proposed to have beneficial effects in patients with HF 3–5 …”

mentioning

confidence: 99%

The Effect of Nesiritide on Renal Function and Other Clinical Parameters in Patients With Decompensated Heart Failure and Preserved Ejection Fraction

Kelesidis

Mazurek

Khullar

et al. 2011

Congestive Heart Failure

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The role of nesiritide in patients with decompensated heart failure with preserved ejection fraction (dHFpEF) has not been previously studied. In this investigation, the authors retrospectively analyzed the effect of nesiritide on renal function and clinical outcomes in patients admitted with dHFpEF. Of the 658 patients included, 328 were treated with nesiritide while 330 patients were treated with standard diuretic therapy. In both the nesiritide and no nesiritide groups, there was a significant change in mean glomerular filtration rate (GFR) and creatinine at 72 hours as well as at day of discharge (P<.001). This trend did not progress at 1 month in the nesiritide group, although it did in the no nesiritide group. At 1 month after therapy, however, there was a significant difference between the two groups in the mean change of GFR and creatinine (P<.001). There was no significant difference in >25% decrease of GFR anytime through day 30 (25% vs 29.69%, P=.236) between the two groups. On multivariate analysis, nesiritide was an important predictor of renal function at 1 month (P<.05). Thus, nesiritide can be administered safely without negatively impacting long-term renal function in patients admitted with dHFpEF.

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Impact of Nesiritide on Renal Function and Mortality in Patients Suffering from Heart Failure

Abstract: Extreme caution is required when using nesiritide in patients with both heart failure and concurrent morbidities such as renal dysfunction.

Cited by 17 publications

References 41 publications

BNP controls early load-dependent regulation of SERCA through calcineurin

BNP controls early load-dependent regulation of SERCA through calcineurin

Role of Inotropic Agents in the Treatment of Heart Failure

The Effect of Nesiritide on Renal Function and Other Clinical Parameters in Patients With Decompensated Heart Failure and Preserved Ejection Fraction

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