Gantzel Rasmus Hvidbjerg, Kjær Mikkel Breinholt, Jepsen Peter, Aagaard Niels Kristian, Watson Hugh, Gluud Lise Lotte, Grønbæk Henning
Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N 8200, Denmark.
Gastroenterology Unit, Copenhagen University Hospital, Hvidovre 2650, Denmark.
World J Hepatol. 2022 Apr 27;14(4):827-845. doi: 10.4254/wjh.v14.i4.827.
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.
To examine the effects and safety of natriuretic peptides in cirrhosis patients with ascites.
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.
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 ( < 0.01). Moreover, natriuresis was significantly higher in study subgroups with mild/moderate ascites compared with moderate/severe and refractory ascites ( < 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 ( < 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.
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.
利钠肽参与肝硬化发生的一系列病理生理事件，可对抗血管收缩和抗利钠因子。利钠肽作为肝硬化腹水治疗方法的效果仅在小型研究中进行了调查，目前缺乏确切结果。
研究利钠肽对肝硬化腹水患者的疗效及安全性。
我们检索了MEDLINE、科学网、Scopus、考克兰图书馆和Embase，查找所有将任何利钠肽静脉注射用于肝硬化腹水患者的现有研究。纳入标准不受治疗持续时间、剂量或随访时间的限制。随机对照试验和非随机研究均符合纳入标准。主要结局是肾钠排泄的变化。次要结局包括安全指标以及肾水排泄、血浆醛固酮浓度和血浆肾素活性的变化。
纳入22项研究。心房利钠肽（ANP）是唯一经过深入研究的治疗药物。持续输注ANP可使钠排泄增加，与输注速率≤30 ng/kg/min相比，输注速率>30 ng/kg/min时钠排泄增加更显著（P<0.01）。此外，与中重度和难治性腹水的研究亚组相比，轻度/中度腹水的研究亚组中利钠作用显著更高（P<0.01）。ANP输注增加了肾水排泄，尽管未达到统计学上显著的剂量反应梯度。与治疗无反应者相比，在对ANP给药产生负钠平衡的研究亚组中，基线时血浆醛固酮浓度和血浆肾素活性显著更低（P<0.01）。应用ANP剂量≤30 ng/kg/min时，血压下降的发生频率较低。对ANP产生利钠反应的证据质量较低，主要原因是样本量小以及研究间存在相当大的异质性。关于其他利钠肽（B型利钠肽和尿钠素）的数据较少。
静脉输注ANP可增加肝硬化腹水患者的钠排泄。持续输注速率>30 ng/kg/min最为有效。然而，输注速率≤30 ng/kg/min时安全性更高。
