Incidence of postoperative acute kidney injury is higher in men than women after colorectal surgery – PROSACC: a posthoc analysis of a global, multicenter, randomized controlled trial

ABSTRACT Postoperative acute kidney injury (AKI) is a common postoperative complication. Approximately 7% of the general, elective, non-cardiac surgical population develop AKI after surgery. The female sex was previously believed to be associated with higher incidence of AKI however more recent literature implies that men have higher risk for AKI. Estrogen has been suggested to have renoprotective properties. We therefore aimed to analyze AKI incidence after colorectal cancer resection surgery in men and women on a global, multicenter, level. In Sweden and China, a total pf 3255 patients were included in this posthoc analysis based on the CAN-trial (Cancer and Anesthesia: Survival After Radical Surgery - a Comparison Between Propofol or Sevoflurane Anesthesia). Presence of AKI was defined according to KDIGO (Kidney Disease: Improving Global Outcome) criteria for changes in plasma creatinine compared with preoperative values. After colorectal surgery, 8% of the patients had developed AKI within 10 postoperative days. Within the 4–10-day postoperative timeframe, twice as many men as women (8% vs 4%) had developed AKI and women had a significantly lower likelihood of developing AKI (OR 0.4 [0.2-0.8], p=0.009). In general, the cumulative proportion of developing AKI within 10 days postoperatively was significantly higher in men than women (p=0.037). Moreover, older patients (60+ years) had significantly higher incidence of AKI than those younger than 60 years. This trend was evident in both men and women. To our knowledge, this is the first ever global, multicenter, randomized controlled trial reporting a sex-difference in AKI incidence after colorectal surgery. Our posthoc analysis reinforces the notion that the male sex is a risk factor for postoperative AKI. Competing Interest Statement The authors have declared no competing interest. Funding Statement The study was funded by the Swedish Research Council to RF (2014-02569 and 2014-07606). Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Swedish Ethical Review Authority (Box 2110, 75002, Uppsala, Sweden) reviewed and granted the ethical approval (2021-05316-01) on November 3rd, 2021. This posthoc analysis - Propofol and Sevoflurane Anesthesia in Colorectal Cancer Surgery: Incidence of Acute Kidney Injury (PROSACC) - was published on a publicly accessible server before data were accessed (November 22, 2021; Clinical Trials NCT05585866). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes DATA AVAILABILITY STATEMENT Data cannot be shared openly due to sensitive data regulations. FUNDING The study was funded by the Swedish Research Council to RF (2014-02569 and 2014-07606). DISCLOSURES The authors declare no conflicts of interest.