Strengths of this study include its prospective nature, standardized biospecimen collection at two time points, multicenter design, ruling out the influence of chronic kidney disease on the RAS by requirement of documented baseline eGFR ≥ 60 mL/min/1.73 m2, careful consideration of covariates known to influence MAKE, measurement of active renin (as opposed to renin and prorenin), and broad generalizability to a range of critically ill patients. This evidence concerns the gene REN and chronic kidney disease.