According to our results, the current study did not find evidence to support an effect of RIPC on MAKE (mortality, need for renal replacement therapy, and persistent renal dysfunction) evaluated at 90 days postoperatively(P = 0.061). We found that in patients who developed AKI after surgery, RIPC significantly reduced MAKE within 90 days postoperatively(P = 0.046). In contrast, our previous randomized, sham-controlled study found evidence of a reduction in AKI with RIPC within 7 days postoperatively (P = 0.028), epically RIPC significantly reduced serious AKI (stage II–III) (P = 0.001).
This inconsistency may be due to several causes. First of all, patients in our study were relatively young (RIPC: 47.8 ± 10.4 years; sham:45.4 ± 10.2 years) with a relatively good preoperative health status. From our clinical experience and some previous studies, patients with preexisting renal injury have worse outcomes compared with patients with normal kidney function in terms of mortality and the need for renal replacement therapy [14–16]. The 90-day follow-up study of Zarbock et al.  had the same clinical endpoint as our study, but the results of the two studies were contrary. A possible explanation was that 74 patients had CKD before surgery in the study of Zarbock et al. , whereas there was only one patient with CKD before surgery in our study . In addition, patients with comorbidities such as hypertension and diabetes mellitus make it difficult to recover from AKI . The proportion of patients with comorbidities (diabetes mellitus, hypertension, etc.) in our research was much less than that in the Zarbock et al. study. Patients with chronic diseases, such as diabetes mellitus and hypertension, may have diminished glomerular reserve . Diabetes mellitus itself is the main cause of CKD. Therefore, patients in proper preoperative status in our study recovered easily at 90 days after surgery.
Second, RIPC may have a diminished long-term protective effect in patients undergoing open total aortic arch replacement. We enrolled only patients who underwent open total aortic alone or combined with other types of surgery. Patients often have potentially unstable cardiovascular conditions before surgery. Open total aortic arch replacement is a complex type of cardiac surgery with a potentially unstable perioperative course and obvious hemodynamic fluctuations. Studies have suggested that patients suffer from prerenal AKI, which could be caused by decreased renal perfusion due to hypotension and cardiovascular instability . We speculated that the AKI following open total aortic arch replacement was mostly prerenal AKI, and doctors in the intensive care unit usually compensated for the insufficiency of the blood volume at our clinical center. Furthermore, CPB, hypothermia and cardioplegia itself are known to have renoprotective effects during the perioperative period, and RIPC may not have obvious renoprotection effects in the long term . In summary, in terms of patients receiving open total aortic arch replacement, RIPC in our study may not affect 90-day MAKE, possibly because timely treatment and other protective measures (CPB, etc.) are applied during the perioperative period.
Third, we included a relatively small sample of patients. The findings were exploratory. This study was considered very different from short-term studies on renal outcomes. Despite the lack of statistical significance for MAKE (P = 0.061), patients in the sham arm died more than twice as those in the RIPC group, and the key endpoint of MAKE was almost twice as common in the sham group as in the RIPC group. Interestingly, in patients who developed AKI after surgery, RIPC significantly reduced MAKE (P = 0.046). RIPC improved renal recovery of patients with AKI at 90 days after surgery to some extent. This study will shape our future research efforts to conduct a large randomized sham-controlled study concerning the long-term efficacy of RIPC.
The negative results of this study may have been relatively unaffected by the use of propofol. Propofol, which was reported to attenuate the protective effect of RIPC , was used in our study. Nearly 90% of the included patients were treated with propofol alone or combined with sevoflurane for anesthesia maintenance. However, in the subgroup analysis of propofol anesthesia recipients in terms of the key endpoint (MAKE) in our study , we found propofol may not affect the results(P < 0.774).
The strength of our study includes the relatively long period of follow-up assessing the effect of RIPC treatment on MAKE in a population at very high risk for kidney injury. Our study has some limitations. First, the study is a post-hoc analysis, and the sample size of patients was relatively small. Thus, the study faces a risk of type I and II errors. The findings were exploratory and should be interpreted with caution. Second, the diagnosis of AKI was principally based on an increase in serum creatinine, which may not accurately reflect real changes in the glomerular filtration rate. At present, however, serum creatinine remains the most widely used biomarker to evaluate kidney function . Third, our study did not include any mechanistic exploration of the effects of RIPC application in patients undergoing open total aortic arch replacement.