Background: Post-Contrast acute kidney injury (PC-AKI) is a severe complication of coronary angiography (CAG) and percutaneous coronary intervention (PCI). At present, the mechanism and effect of statins on PC-AKI and its mechanism are still unclear. Methods: It was a multicenter retrospective obeservational study. We reviewed 4386 patients who underwent CAG or PCI, with serum creatinine recorded pre- or post-procedure within 72hrs after PCI, from December, 2006 to December, 2019 admitted to

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... Run Run Shaw Hospital and its medical consortium hospitals. Multivariate logical regression was used to explore whether preoperative use of statins was a protective factor for PC-AKI, and then path analysis model was used to explore the specific mechanism of statins. Results: In total, 4386 patients were enrolled in the study, the mean age was 67 yrs old, 17.9% with PC-AKI, 83.3% with pre-operative statin therapy. The incidence of PC-AKI was significantly lower in statin therapy group than non-statins therapy group. Multivariate regression indicated that pre-operative statin therapy was significantly negatively associated with percentage of elevated creatinine (β: -0.118, p<0.001) and PC-AKI (OR: 0.575, p<0.001). In pre-operative statin therapy group, no statistically significant deference was detected between atorvastatin and rosuvastatin group (OR: 1.052, p=0.558). Pathway model analysis indicated the direct protective effectiveness of pre-operative statin therapy on PC-AKI (p<0.001), but neither with its lipid-lowering effect (p=0.277) nor anti-inflammatory effect (p=0.596). Furthermore, It was found that "LDL-C→CRP" mediated the relationship between pre-operative statin therapy and PC-AKI (p=0.007); however, only explained less than 1% of the pre-operative statin therapy's protective effects on PC-AKI. Conclusion: Pre-operative statin therapy is an independent protective factor of PC-AKI, which is not affected by the type of statins and not achieved by lipid-lowering effect or anti-inflammatory effect. Keywords : post-contrast acute kidney injury, statins, path analysis, mediation analysis.