Dexamethasone for Preventing Major Adverse Kidney Events following Cardiac Surgery - Post-Hoc Analysis to Identify Subgroups

AKI is a serious and frequent complication of cardiac surgery, occurring in up to one third of patients (1). Despite years of investigation, therapies to prevent cardiac surgery-associated AKI (CSA-AKI) are lacking. Glucocorticoids have been suggested as a potential therapy to prevent CSA-AKI, because inflammation induced by cardiac surgery could contribute to AKI in this setting. The Dexamethasone for Cardiac Surgery (DECS) study tested this hypothesis in a multicenter, randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov NCT00293592) in 4494 adults undergoing cardiac surgery with cardiopulmonary bypass (CPB) (2). Patients received a single intravenous dose of dexamethasone (1 mg/kg) or placebo before initiation of CPB (additional details are reported elsewhere) (2). Although the DECS trial did not find an effect of dexamethasone on the incidence of AKI, the definition used for AKI—a tripling of serum creatinine (SCr) postoperatively—did not include the requirement for RRT. Thus, extracorporeal clearance of creatinine in patients who required RRT could have resulted in a discrepancy between actual AKI events and its protocol definition. Therefore, we previously conducted a post hoc analysis in which we defined AKI as the requirement for RRT. We found that the incidence of AKI requiring RRT was lower in dexamethasone- versus placebo-treated patients [relative risk, 0.44; 95% confidence interval (95% CI), 0.19 to 0.96]. In stratified analyses, the benefit of dexamethasone appeared greatest in patients with lower baseline eGFR (3). Since it is unknown whether factors other than kidney function might modify the effect of dexamethasone on CSA-AKI, we investigated the treatment effect of dexamethasone on AKI across various subgroups of patient- and surgical characteristics. We reasoned that detection of heterogeneity across subgroups in the efficacy of dexamethasone could allow for more precise targeting of high-risk patients in future trials of glucocorticoid prophylaxis. In the current analyses, we included 4465 (99.4%) of …