Effects and safety of natriuretic peptides as treatment of cirrhotic ascites: A systematic review and meta-analysis

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  • Rasmus Hvidbjerg Gantzel
  • Mikkel Breinholt Kjær
  • Peter Jepsen
  • Niels Kristian Aagaard
  • Hugh Watson
  • Gluud, Lise Lotte
  • Henning Grønbæk

BACKGROUND Natriuretic peptides are involved in the cascade of pathophysiological events occurring in liver cirrhosis, counterbalancing vasoconstriction and anti-natriuretic factors. The effects of natriuretic peptides as treatment of cirrhotic ascites have been investigated only in small studies, and definitive results are lacking. AIM To examine the effects and safety of natriuretic peptides in cirrhosis patients with ascites. METHODS We searched MEDLINE, Web of Science, Scopus, Cochrane Library and Embase for all available studies applying intravenous administration of any natriuretic peptide to patients suffering from cirrhotic ascites. Inclusion was not limited by treatment duration or dose, or by follow-up duration. Both randomised controlled trials and non-randomised studies were eligible for inclusion. The primary outcome was change in renal sodium excretion. Secondary outcomes included safety measures and changes in renal water excretion, plasma aldosterone concentration, and plasma renin activity. RESULTS Twenty-two studies were included. Atrial natriuretic peptide (ANP) was the only intensively studied treatment. Sodium excretion increased in response to continuous ANP infusion and was more pronounced when infusion rates of > 30 ng/kg/min were administered compared with ≤ 30 ng/kg/min (P < 0.01). Moreover, natriuresis was significantly higher in study subgroups with mild/moderate ascites compared with moderate/severe and refractory ascites (P < 0.01). ANP infusions increased renal water excretion, although without reaching a statistically significant dose-response gradient. Plasma aldosterone concentration and plasma renin activity were significantly lower at baseline in study subgroups achieving a negative sodium balance in response to an ANP administration compared with treatment non-responders ( P < 0.01). Blood pressure decreases occurred less frequently when ANP doses ≤ 30 ng/kg/min were applied. The quality of evidence for a natriuretic response to ANP was low, mainly due to small sample sizes and considerable between-study heterogeneity. Data were sparse for the other natriuretic peptides; B-type natriuretic peptide and urodilatin. CONCLUSION Intravenous ANP infusions increase sodium excretion in patients with cirrhotic ascites. Continuous infusion rates > 30 ng/kg/min are the most effective. However, safety increases with infusion rates ≤ 30 ng/kg/min.

OriginalsprogEngelsk
TidsskriftWorld Journal of Hepatology
Vol/bind14
Udgave nummer4
Sider (fra-til)827-845
Antal sider19
ISSN1948-5182
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
Conflict-of-interest statement: Grønbæk H has received a research grant (No. ULA04-2019-1) from ADS AIPHIA Development Services AG (Switzerland) to investigate ularitide in patients with refractory ascites. Watson H owns stocks in Sanofi. Gantzel RH, Kjær MB, Jepsen P, and Aagaard NK have nothing to report. Financial support: Grønbæk H has received research funding from Intercept, Abbvie, NOVO Nordisk Foundation, Arla, and ADS AIPHIA Development Services AG. Grønbæk H is an advisory board member for Ipsen and speaker for Norgine. Gluud LL has received grants from Novo Nordisk, Alexion, and Gilead.

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© The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved

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