Assessing association between duration of postoperative acute kidney injury and in-hospital mortality after noncardiac surgery

Sir,

We read with interest the recent article by Wu et al.1 assessing the association between the duration of postoperative acute kidney injury (AKI) and in-hospital mortality in critically ill patients after noncardiac surgery. They showed that duration of postoperative AKI, especially AKI duration  <7 days, predicted in-hospital mortality of patients after adjustment for the variables involving the baseline and clinical characteristics, organ scoring system, underlying disease, emergent intervention, surgical category, AKI stages, and severity of infection. Furthermore, the combination of AKI duration with AKI stage was better in predicting in-hospital mortality than AKI stage alone. Strengths of this study include a large sample of patients and use of appropriate statistical methods to adjust and reduce the influences of potential confounders on study endpoints. However, other than the limitations described in the discussion, we note other issues of this study making interpretation of their results questionable.

First, the intraoperative factors were not provided and included in the Cox proportional hazards model. Consequently, it is difficult to estimate whether intraoperative interventions might have influenced primary outcomes. Actually, intraoperative massive blood loss, hypotension, blood transfusion, total vasopressor dose administered, use of a vasopressor infusion and diuretic administration have been shown as independent predictors of postoperative AKI and short-term mortality.2^,3 Furthermore, intraoperative use of hydroxyethyl starch can impair kidney function in a dose-dependent manner.4 Thus, not taking intraoperative risk factors into account would have tampered with the inferences of the Cox proportional hazards model for adjusted postoperative in-hospital mortality.

Second, we were not provided with postoperative complications, although they can affect postoperative AKI and in-hospital mortality after noncardiac surgery. For example, postoperative anemia is strongly associated with AKI after noncardiac surgery. Compared with patients who do not have a decrease in postoperative hemoglobin, a decrement of 1.1–2.0  g/dL is associated with an adjusted hazard ratio of 1.51 (95% CI: 1.15–1.98), and a decrement of  >4.0 g/dL with an adjusted hazard ratio of 4.7 (95% CI: 3.6–6.2) for AKI.5 Furthermore, the available literature provides compelling evidence that pulmonary complications are frequent after noncardiac surgery and are associated with increased postoperative short-term mortality.6 In addition to AKI, postoperative myocardial injury, heart failure, arrhythmias, acute ischemic stroke, delirium, and deep vein thrombosis have also been shown as significantly independent predictors of increased short-term mortality after noncardiac surgery. Given that these postoperative risk factors are not included in the potential confounders, the statistical adjustment for hazard ratios of postoperative in-hospital mortality in this study would have been biased.

Therefore, we argue that as with all retrospective studies employing observational designs, the study by Wu et al.1 cannot prove whether statistical association between increased duration or stage of postoperative AKI and in-hospital mortality is a causal relationship. Considering the facts that the durations of AKI, KDIGOmax and the organ scoring systems, such as APACHE II score, MODS, SOFA score, are more severe in the patients with AKI than in the non-AKI patients, increased duration or stage of postoperative AKI in critically ill patients after noncardiac surgery may only be a marker of a more severe and complex perioperative clinical pattern; for example, the sicker patients have more severe stage of AKI or longer durations AKI, they are also likely the ones to suffer postoperative in-hospital mortality.

Declaration of Interest

The authors report no conflicts of interest.