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Atrial Natriuretic Peptide for Management of Acute Kidney Injury: A Systematic Review and Meta-analysis

Sagar U. Nigwekar^*, Sankar D. Navaneethan, Chirag R. Parikh, and John K. Hix

^* Department of Internal Medicine, Rochester General Hospital and University of Rochester School of Medicine, Rochester, New York; Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio; Section of Nephrology, Yale School of Medicine, New Haven, Connecticut; and Department of Nephrology, Rochester General Hospital and University of Rochester School of Medicine, Rochester, New York

Correspondence: Dr. Sagar U. Nigwekar, Rochester General Hospital, 1425 Portland Avenue, Rochester, NY 14621. Phone: 585-729-8636; Fax: 585-922-3987; E-mail: sagarnigs{at}hotmail.com

Background and objectives: Randomized controlled trials (RCTs) with atrial natriuretic peptide (ANP) have shown inconsistent effects for renal end-points. The authors aimed to systematically review these trials to ascertain the benefit of ANP in prevention and treatment of acute kidney injury (AKI).

Design, setting, participants, & measurements: The authors searched MEDLINE, EMBASE, and Cochrane Renal Health Library that investigated ANP in adult patients considered with or at risk for AKI. Outcomes were analyzed separately for prevention and treatment of AKI.

Results: Nineteen RCTs (11 prevention, 8 treatment) involving 1861 participants were included. Pooled analysis of prevention trials showed a trend toward reduction in renal replacement therapy in the ANP group (OR = 0.45, 95% CI, 0.21 to 0.99) and good safety profile, but no improvement in mortality. For the treatment of established AKI, ANP, particularly in high doses, was associated with a trend toward increased mortality and more adverse events. Subgroup analysis of AKI after a major surgery (14 RCTs, 817 participants) showed a significant reduction in renal replacement therapy requirement in the ANP group (OR = 0.49, 95% CI, 0.27 to 0.88). Included RCTs were mostly low- or moderate-quality, underpowered studies.

Conclusions: There are an insufficient number of high-quality studies to make any definite statement about the role of ANP in AKI. Analysis of the existing literature suggests ANP might be associated with beneficial clinical effects when administered in patients undergoing major surgery such as cardiovascular surgery. Its use, in low doses, should be explored further in this setting.