Atrial natriuretic peptide for preventing and treating acute kidney injury: Cochrane systematic review
Assessed as up to date: 2009/08/06
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.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.
Nigwekar Sagar U, Navaneethan Sankar D, Parikh Chirag R, Hix John K
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.
Implications for practice
There are a limited number of high quality studies to make any consensus statement about the role of ANP in the management of AKI. Current evidence suggests that the use of ANP may have beneficial clinical effects when administered in patients undergoing major surgery such as cardiovascular surgery. It appears to be safe when used in low doses.
Implications for research
Based on our results, we suggest that future clinical studies should consider assessing the safety and efficacy of ANP in the cardiovascular surgical setting and should analyse the efficacy by outcomes such as the standard AKI definition suggested by the Acute Kidney Injury Network. Investigators should also consider prospectively classifying the study patients into different stages of AKI to evaluate the differential effects of ANP. Mortality and RRT can be competing outcomes in the critically ill population with or “at risk” of AKI, and it is possible that some patients with AKI did not survive to require RRT. Hence, a composite outcome such as dialysis-free survival may be more meaningful and should be considered in future studies. Researchers should, instead of proceeding with more small-scale studies, form the collaborative networks needed for a definitive large study and should also consider studying a population that is at a higher risk of postsurgery AKI such as those with pre-existing CKD. Novel biomarkers such as NGAL, IL-18 and others may help in earlier identification of established AKI compared to SCr and these biomarkers may be used as enrolment criteria for future clinical studies.Get full text at The Cochrane Library
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