Atrial natriuretic peptide for preventing and treating acute kidney injury

Acute kidney injury (AKI) is a generic term for an abrupt and sustained decrease in kidney function resulting in retention of nitrogenous (urea and creatinine) and a fall in urine output. Sepsis (infection), shock, trauma, kidney stones, kidney infection, drug toxicity or drug abuse are common causes of AKI. AKI is common in hospitalised patients, with the overall incidence of AKI estimated to be around 24-30 cases/1000 hospital discharges and 6% of those are critically ill. Sepsis, hypovolaemia, drug toxicity, major surgery and diagnostic investigations using radiocontrast dyes are some of the most common associated causes of hospital-acquired AKI. Restoration of kidney function is the goal of any treatment and can involve drug interventions or kidney dialysis. Atrial natriuretic peptide (ANP) has been shown to increase urine production and to reduce kidney inflammation. The aim of this review was to investigate the use of ANP in preventing AKI and treating established AKI. We identified 19 studies (11 prevention and 8 treatment) using low or high dose ANP, enrolling 1,861 patients. There was no difference in the number of deaths between ANP and control for studies preventing or treating AKI. The need for dialysis was significantly lower in both the low dose ANP treatment and prevention studies as well as for patients undergoing major surgery. The length of time spend in hospital and ICU was shorter for patients receiving low dose ANP. High dose ANP was associated with more hypotension and cardiac arrhythmias in patients with established AKI. ANP may be associated with improved outcomes when used in low doses for preventing AKI and in managing postsurgery AKI. There were no significant adverse events in the prevention studies, however in the high dose ANP treatment studies there were significant increases in hypotension and arrhythmias.

Authors' conclusions: 

ANP may be associated with improved outcomes when used in low doses for preventing AKI and in managing postsurgery AKI and should be further explored in these two settings. There were no significant adverse events in the prevention studies, however in the high dose ANP treatment studies there were significant increases hypotension and arrhythmias.

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Background: 

Acute kidney injury (AKI) is common in hospitalised patients and is associated with significant morbidity and mortality. Despite recent advances, outcomes have not substantially changed in the last four decades. Atrial natriuretic peptide (ANP) has shown promise in animal studies, however randomised controlled trials (RCTs) have shown inconsistent clinical benefits.

Objectives: 

To assess the benefits and harms of ANP for preventing and treating AKI.

Search strategy: 

We searched CENTRAL, MEDLINE and EMBASE and reference lists of retrieved articles.

Selection criteria: 

RCTs that investigated all forms of ANP versus any other treatment in adult hospitalised patients with or “at risk” of AKI.

Data collection and analysis: 

Results were expressed as risk ratios (RR) with 95% confidence intervals (CI) or mean difference (MD). Outcomes were analysed separately for low and high dose ANP for preventing or treating AKI.

Main results: 

Nineteen studies (11 prevention, 8 treatment; 1,861 participants) were included. There was no difference in mortality between ANP and control in either the low or high dose prevention studies. Low (but not high) dose ANP was associated with a reduced need for RRT in the prevention studies (RR 0.32, 95% CI 0.14 to 0.71). Length of hospital and ICU stay were significantly shorter in the low dose ANP group. For established AKI, there was no difference in mortality with either low or high dose ANP. Low (but not high) dose ANP was associated with a reduction in the need for RRT (RR 0.54, 95% CI 0.30 to 0.98). High dose ANP was associated with more adverse events (hypotension, arrhythmias). After major surgery there was a significant reduction in RRT requirement with ANP in the prevention studies (RR 0.56, 95% CI 0.32 to 0.99), but not in the treatment studies. There was no difference in mortality between ANP and control in either the prevention or treatment studies. There was a reduced need for RRT with low dose ANP in patients undergoing cardiovascular surgery (RR 0.35, 95% CI 0.18 to 0.70). ANP was not associated with outcome improvement in either radiocontrast nephropathy or oliguric AKI.

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