To the Editor:
In a follow-up study for their previous RenalRIP trial, Zarbock et al.1 show that remote ischemic preconditioning significantly decreases the 3-month incidence of a composite endpoint for major adverse kidney events including mortality, the need for renal replacement therapy, and persistent renal dysfunction in high-risk patients undergoing cardiac surgery. It must be pointed out, however, that the risk of long-term adverse kidney outcomes following cardiac surgery is mainly associated with incidence, severity, and duration of acute kidney injury (AKI) in the early postoperative period. Specifically, nonrecovery from AKI is more common in patients with more severe AKI and is significantly attributable to long-term adverse kidney outcomes.2 The potentially causal relationship between postoperative AKI and long-term adverse kidney outcomes may partly explain the long-term mortality associations observed in patients with AKI after cardiac surgery.
Although the RenalRIP trial has abundant strengths, there are several significant limitations. First, when using the Kidney Disease Improving Global Outcomes criteria to define and grade the postoperative AKI, Zarbock et al.3 used a 72-h time window to include the patients with serum creatinine increases of 0.3 mg/dl or more from baseline, rather than a 48-h time window, as specified by the Kidney Disease Improving Global Outcomes criteria. It was also unclear whether the serum creatinine concentrations used for definition and staging of postoperative AKI had been corrected according to perioperative fluid balance. The available evidence shows that not adjusting serum creatinine concentrations for fluid balance may underestimate incidence of AKI following cardiac surgery, given that a positive perioperative fluid balance may dilute serum creatinine.4 Second, as routinely observed variables, perioperative hemoglobin and serum albumin levels were not provided in patient data. It has been shown that preoperative anemia is independently associated with AKI after cardiac surgery, and anemic patients undergoing cardiac surgery are more susceptible to transfusion-related AKI than nonanemic patients.5 Furthermore, robust evidence exists indicating that hypoalbuminemia may causally result in the development of AKI following cardiac surgery.6 Third, the RenalRIP trial design did not include the occurrence of intraoperative hypotension, a known causative factor of postoperative AKI.7 Fourth, with the exception of myocardial infarction and major bleeding, the RenalRIP trial did not collect postoperative adverse events and complications. It has been found that low cardiac output syndrome, arrhythmia, hypoalbuminemia, blood transfusion, and pulmonary and gastrointestinal complications in the early postoperative period are the independent risk factors for AKI and are significantly associated with the short- and long-term outcomes following cardiac surgery.8 Thus, we argue that the above factors in their RenalRIP trial would have confounded the true influence of the remote ischemic preconditioning on the development of AKI in the early postoperative period, resulting in a spurious protective effect of remote ischemic preconditioning on the long-term adverse kidney outcomes in this follow-up study.
Finally, most patients who experience AKI after cardiac surgery can actually recover their kidney function at hospital discharge, and a less severe episode of AKI has only limited implications for long-term outcomes.2 To assess the effects of remote ischemic preconditioning on long-term adverse kidney outcomes, it is best to provide the duration of postoperative AKI and persistent renal dysfunction at hospital discharge, which are the main known determinants of long-term adverse kidney outcomes in patients undergoing cardiac surgery.
The authors declare no competing interests.