Does high-dose perioperative use of statins ameliorate acute kidney injury following cardiac surgery?

Abstract

Acute kidney injury (AKI) is a well-known, frequent complication in patients after cardiac surgery, occurring in 7% to 40%, depending on its definition (1). Subsequently, it is independently associated with substantial morbidity [such as need for renal replacement therapy, longer length of hospital stay and progression of chronic kidney disease (CKD)] and mortality (2). Even a minimal increase in postoperative serum creatinine is associated with an increased mortality in cardiac surgery patients (3).Due to the complex pathophysiology of AKI with multiple contributing factors, exact mechanisms are not yet fully understood and challenges remain concerning early recognition, prevention and treatment. Currently, therapy consist of supportive measures, while numerous studies and attempts on (pharmaceutical) treatment have failed to show beneficial effects in (cardiac surgery induced) AKI (4).Lipid lowering therapy with 3-hydroxy-3-methylglutarylCoA reductase inhibitors (statins) is a widely used therapy to lower cholesterol levels and prevent cardiovascular events. Its use among patients who undergo cardiac surgery is associated with a reduced incidence of perioperative mortality after coronary artery bypass graft surgery (5). Besides the lipid lowering effects of statins, established pleiotropic anti-inflammatory and endothelial stabilizing effects of statins are believed to (indirectly) contribute to this protective effect after cardiac surgery (6).As inflammatory pathways and endothelial dysfunction are also believed to play a major role in the development of AKI (7), it has been proposed that short-term use of statins could possibly improve renal outcome. Given this rationale, multiple, mostly observational, studies regarding the effect of statin use on renal outcome after cardiac surgery have been conducted and reported contradictory results. A recent meta-analysis by Wang et al., including 11 studies, showed that preoperative statin treatment reduced the incidence of post-operative AKI by 13% (8). However, the results of this meta-analysis should be interpreted with caution as the presence of supporting evidence of attenuation of AKI after cardiac surgery with preoperative statin treatment has been challenged (9). Prior studies examining specifically shortterm initiation of statins have also showed contradictory results. In a pilot randomized controlled trial (RCT) (n=100) short-term use of statins did not affect AKI incidence (10), while in a recent observational study of 17,000 patients who underwent cardiac surgery, a 22% lower relative risk for the development of AKI was observed in patients on statins in adjusted analyses (11).In this respect, Billings et al. recently tested the hypothesis that short-term high-dose perioperative use of statins would reduce AKI following cardiac surgery for both patients naïve to statin treatment and for patients already on chronic statin therapy. The primary endpoint was diagnosis of AKI according to the criteria form the acute kidney injury network (AKIN), defined by an i...