In the 12 studies[28, 31-33, 35, 37, 39, 41, 43-46] reporting the association of statin use and AKI requiring RRT, the incidence of AKI requiring RRT ranged from 0.049%[46] to 9%[28] (Table 1). The pooled incidence of AKI requiring RRT for all 12 studies was 0.94%. The pooled incidence of AKI requiring RRT among statin user and nonstatin user were 1.31% and 0.76%, respectively (Table 2). Two studies[34, 40] were not included in the calculation of the pooled incidence because the numbers of RRT events signaling pathway were not reported. For the same reason, we used the number of RRT events in the PSM cohort

instead of the source population in one study.[45] Among all the 24 studies, only three RCTs described adverse effects of statin therapy. One study[28] adopted a clinically significant elevation or serum creatinine kinase and alanine aminotransferase within the first five postoperative days as safety outcomes. The incidence of these adverse events was the same in the statin and the

placebo group in this study (10% vs. 10%). The other two RCTs[25, 27] merely reported no observed significant side-effects in the statin group, and the incidence was not specified. The 21 studies with use of statins and risk of postoperative AKI included a total of 106 586 cases and 869 889 controls (Table 1). When the results from all 21 studies[24-30, 32, 34-38, 40-47] were combined, the use of statins was associated with a significant Unoprostone protective effect for perioperative Palbociclib AKI (pooled OR 0.87, 95% CI 0.79–0.95, I2 = 58.8%) (Fig. 2A). If multiple effect sizes of different methodological quality were reported in the same study, only the one with the highest quality was included in this analysis of the 21 studies. In general, the propensity score matching (PSM) adjusted effect size was viewed as of the highest quality, the crude effect size of the lowest quality, and the multivariate adjusted effect size in between. In each study, the variables adjusted for in the multivariate

models and the variables used to calculate the propensity score, if available, were listed in the Appendix 1 (Table App2). To determine other sources of heterogeneity, we performed several sensitivity analyses (Table 3). First, we examined the impact of selection of studies of different methodological quality. We excluded RCTs from analysis, and the pooled summary effect estimate of the remaining 19 observational studies was still significant and was very similar (pooled OR, 0.87; 95% CI 0.79–0.96, I2 = 67.0%). We combined crude OR reported in 14 studies[29, 30, 32, 34, 35, 37, 38, 40-44, 46, 47] and an insignificant effect of statins on perioperative AKI was shown (pooled OR, 1.02; 95% CI 0.84–1.23, I2 = 90.6%). However, after pooling of the 13 studies[30, 34-38, 40-43, 45-47] with PSM or multivariate adjusted effect sizes, use of statins was associated with a significant protective effect (pooled OR, 0.