Published online Apr 27, 2022. doi: 10.4254/wjh.v14.i4.827
Peer-review started: July 5, 2021
First decision: November 11, 2021
Revised: November 22, 2021
Accepted: March 25, 2022
Article in press: March 25, 2022
Published online: April 27, 2022
Ascites formation is the most frequent event of cirrhosis decompensation with no approved non-invasive treatment for patients with refractory ascites. However, natriuretic peptides may induce beneficial effects in patients with cirrhosis and ascites, by counterbalancing vasoconstriction and anti-natriuretic factors.
Only small studies with a broad pallet of designs, have investigated the renal and systemic effects and safety of natriuretic peptides in patients with cirrhosis and ascites. We were motivated to compile results regarding natriuretic peptides as treatment for ascites to advance pharmaceutical research concerning this disease.
We aimed to systematically review the effects and safety of natriuretic peptides in patients with cirrhosis and ascites. We collected results regarding changes in renal sodium and water excretion, plasma aldosterone concentration, and plasma renin activity, and to perform meta-analyses providing overall estimates of the effects of natriuretic peptide infusions. Safety assessments, in particular blood pressure decreases, were included and descriptively summarised.
We adhered to the PRISMA guidelines and the Cochrane Handbook. A review protocol was preregistered at PROSPERO. The databases MEDLINE, Web of Science, Embase, Scopus, and Cochrane Library were searched and references reporting the renal and systemic effects of mono-therapy with atrial natriuretic peptide (ANP), B-type natriuretic peptide, urodilatin, or any synthetic equivalent in patients with cirrhosis and ascites were considered for inclusion. Treatment administration had to be intravenous, but trials were included regardless of dose, follow-up duration, and whether a continuous infusion or bolus injection was administered. The study screening and data extraction were performed independently by two reviewers. A random-effects model was applied for the meta-analysis. Reasons for heterogeneity were explored through subgroup and leave-one-out analyses.
Twenty-two studies were included and short-term ANP infusion was the only intensively studied treatment. Renal sodium and water excretion increased in response to continuous ANP infusion and was most pronounced when infusion rates > 30 ng/kg/min were applied. Furthermore, sodium excretion was higher in study subgroups with mild/moderate ascites compared with refractory ascites. The baseline plasma aldosterone concentration and renin activity were significantly lower in subgroups achieving a negative sodium balance compared with treatment non-responders, and may be relevant response predictors to include in future trials. Blood pressure decreases occurred less frequently with doses ≤ 30 ng/kg/min.
Intravenous infusions of natriuretic peptides induce meaningful sodium and water excretion in patients with cirrhotic ascites. Continuous ANP infusions > 30 ng/kg/min induce the most pronounced renal effects, but with a higher risk of blood pressure decreases than doses ≤ 30 ng/kg/min.
Future larger-scale clinical trials are justified to determine the therapeutic potential of natriuretic peptides in patients with cirrhotic ascites.