• Hiroyuki Yamada, Kent Doi, Tatsuo Tsukamoto, Hideyasu Kiyomoto, Kazuto Yamashita, Motoko Yanagita, Yoshio Terada, and Kiyoshi Mori.
• Department of Nephrology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan. hyamada@kuhp.kyoto-u.ac.jp.
• Crit Care. 2019 Feb 11; 23 (1): 41.

BackgroundTheoretically, atrial natriuretic peptide (ANP), especially low-dose ANP, is beneficial in acute kidney injury (AKI). In this study, we examined whether low-dose ANP is effective in preventing or treating AKI by conducting an updated systematic review for randomized controlled trials (RCTs).MethodWe searched the Excerpta Medica database (EMBASE), PubMed, and Cochrane CENTRAL databases for RCTs that compare the effects of low-dose ANP (≤ 50 ng/kg/min) with a placebo or conventional therapy in at-risk patients or patients with AKI. The primary outcome was the incidence of new AKI (in prevention RCTs), while the secondary outcomes were in-hospital mortality rate, renal replacement therapy (RRT) requirement, length of hospital and intensive care unit (ICU) stay, incidence of hypotension, and peak serum creatinine levels. The risk-of-bias was evaluated using the Cochrane Collaboration risk-of-bias tool. Trial sequential analysis (TSA) was used for each outcome of interest.ResultsA total of 18 RCTs (16 prevention and two treatment trials) fulfilled our inclusion criteria. In prevention RCTs, the incidence of new AKI was significantly low in the low-dose ANP group (relative risk [RR] = 0.51; 95% confidence interval [CI] = 0.36-0.72; P = 0.0001) compared to the control group. In addition, the low-dose ANP group showed a significantly reduced RRT requirement in both prevention (RR = 0.17; 95% CI = 0.04-0.64; P = 0.009) and treatment (RR = 0.43; 95% CI = 0.20-0.93; P = 0.03) RCTs. Among secondary outcomes, in some cases, low-dose ANP was associated with a reduction in ICU and in-hospital stay. The risk-of-bias assessment and TSA results indicated that the sample sizes and qualities of the RCTs were insufficient to conclude the efficacy of low-dose ANP.ConclusionLow-dose ANP might be effective in preventing or treating AKI. However, the evidence accumulated so far is not strong enough to demonstrate ANP's beneficial effects. The next step is to elucidate the effects of low-dose ANP by conducting multicenter, high-quality, large-sample RCTs.Trial RegistrationPROSPERO registry CRD42017068568 . Registered 20 June 2017.

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