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N-acetylcysteine for preventing acute kidney injury in cardiac surgery patients with pre-existing moderate renal insufficiency

[Recours à la N-acétylcystéine pour prévenir une atteinte rénale aiguë chez les patients de chirurgie cardiaque souffrant d’une insuffisance rénale modérée préexistante]

Duminda N. Wijeysundera, MD^*, W. Scott Beattie, MD PhD^*, Vivek Rao, MD PhD, John T. Granton, MD and Christopher T. Chan, MD

^* From the Department of Anesthesia;
the Division of Cardiac Surgery;
the Division of Respirology and Critical Care Medicine, and the
Division of Nephrology; Toronto General Hospital and University of Toronto, Toronto, Ontario, Canada.

Address correspondence to: Dr. Duminda N. Wijeysundera, Department of Anesthesia, Toronto General Hospital & University of Toronto, EN 3-450, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada. Phone: 416-340-4800, ext. 8981; Fax: 416-340-3698; E-mail: duminda.wijeysundera{at}uhn.on.ca

Purpose: N-acetylcysteine may prevent acute kidney injury after cardiac surgery. To determine if N-acetylcysteine warrants definitive evaluation in a large multicentre trial, we evaluated its effects on a surrogate outcome, estimated glomerular filtration rate (eGFR), in a randomized trial.

Methods: One-hundred-seventy-seven cardiac surgery patients with moderate pre-existing renal insufficiency (eGFR 60 mL·min^–1) were recruited in a blinded (patients, clinicians, data-collectors) placebo-controlled randomized trial. Eighty-nine were randomized to N-acetylcysteine (100 mg·kg^–1 iv bolus, 20 mg·kg^–1·hr^–1 infusion until four hours after cardiopulmonary bypass), and 88 to placebo. The primary outcome was the percent change in eGFR during the first 72 postoperative hours. Secondary outcomes included renal replacement therapy, mortality, atrial fibrillation, vasoactive medications, and adverse effects. A future multicentre trial was deemed to be warranted if N-acetylcysteine was associated with a percent change in eGFR that was 3.8 better (small benefit), and with an upper 95% confidence interval including 9.5 (moderate benefit).

Results: The median percent change in eGFR was 5.2% better (absolute difference) in the N-acetylcysteine arm (95% confidence interval 2.4% worse to 12.1% better; P = 0.22). With regard to secondary outcomes, all-cause mortality was lower in the N-acetylcysteine arm (0% vs 8%; P = 0.007).

Conclusion: N-acetylcysteine did not cause a statistically significant improvement in postoperative eGFR in this single-centre study. Nonetheless, its treatment effect was consistent with a plausible small-to-moderate benefit. Given this finding, N-acetylcysteine should be definitively evaluated in a large randomized trial.