N‐Acetylcysteine for the Prevention of Acute Kidney Injury After Cardiac Surgery

1603 2011 51 1603-1610 A kidney injury (AKI) is a serious complication after cardiac surgery and is associated with increased short-term and long-term mortality. This complication occurs in 5%-30% of patients who undergo cardiac surgery, depending on the definition used for AKI. Most of the previous studies focused on severe AKI, defined either as need for dialysis or substantial increase in serum creatinine. However, studies reporting an association between small changes in serum creatinine and adverse short-term outcome are emerging in the literature. It was reported that in 6%-20% of patients who develop AKI, dialysis is required and that 12%-64% of these patients die, compared with 1%-5% of those without AKI. The mortality risk after cardiac surgery increases with even minor elevations of creatinine from baseline and may exceed 50% in the most severe cases that require hemodialysis. Acute renal dysfunction also has an important impact on nonrenal morbidity. Indeed, patients who develop AKI after cardiac surgery have higher incidence of gastrointestinal bleeding, respiratory failure, infections, and sepsis. Several risk factors for postoperative AKI have been identified. The most consistent are preexisting chronic kidney disease (CKD), advanced age, history of heart failure, diabetes mellitus, prolonged cardiopulmonary bypass (CPB) time, and recent exposure to nephrotoxic agents, such as contrast dye. In patients with moderate and severe CKD, as defined by an estimated creatinine clearance lower than 60 mL/min, postoperative AKI occurs in almost 50% of patients and is associated with a rate of perioperative mortality that is 10 times higher, increasing to up to more than 30 times higher for patients requiring renal replacement therapy. Many factors contribute to post-cardiac surgery AKI, including exogenous toxins; hemodynamic and metabolic factors; inflammation; neurohormonal activation; release of vasoconstrictor compounds, induced by CPB; and the interactions between blood components and artificial membranes. All these mechanisms may contribute to vasoconstriction and renal ischemia and result in formation of oxygen free radicals. In particular, use of CPB during cardiac surgery, and systemic exposure to these nonbiologic surfaces, liberate oxygen free radicals from activated neutrophils, provoking an oxidative stress response that can activate systemic inflammatory processes. Moreover, CPB has been shown to increase renal vascular resistance and to release emboli. The use of CPB can also increase serum substances, including total peroxide, reactive oxidative metabolites, C reactive protein, and interleukin-6. Thus, agents with antioxidant properties may attenuate the oxidative stress and resultant inflammation observed in patients undergoing cardiac surgery and may potentially reduce postoperative complications. As high-risk patients can be easily identified before cardiac surgery, implementation of prophylactic measures represents the best opportunity to prevent AKI. Accordingly, several pharmacologic strategies, including drugs with antioxidant properties (vitamin E, vitamin C, allopurinol, N-acetylcysteine, and statins) have been used in the attempt to reduce postoperative renal dysfunction but had inconsistent results. In particular, N-acetylcysteine reduced oxygen free radical production, pump-related ischemia– reperfusion injury, and pro-inflammatory cytokine