MRP1 mRNA and protein expression were analyzed by real-time RT-PCR and immunoblot analysis, respectively
and higher risk of death. Several strategies, including using iso-osmolar contrast, limiting the amount of administered contrast media and volume expansion have become well established methods for the prevention of CIN. The pathophysiological mechanisms of CIN is not well known. However, multiple studies have suggested that renal vasoconstriction, oxidative stress, inflammation and direct tubular cell damage by contrast media may play crucial important roles in the renal injury process. Statins, drugs primarily associated with lowdensity lipoprotein Butein chemical information cholesterol-lowering effects, have been shown to possess pleiotropic effects that include enhancement of endothelial nitric oxide production, anti-inflammatory and antioxidative actions. Therefore, statins are considered as promising candidate agents for the prevention of CIN. A few studies focused on statin therapy as specific prophylactic measures of CIN have been published with conflicting results. In this meta-analysis of randomized controlled trials, we aimed to assess the effectiveness of short-term high-dose statin treatment for the prevention of CIN and clinical outcomes and reevaluate of the potential benefits of statin therapy. The literature search was performed on PubMed, OVID, EMBASE, Web of science and the Cochrane Central Register of Controlled Trials. We derived three comprehensive search themes that were then combined using the Boolean operator “AND”. For the theme “contrast media”, we used combinations of MeSH, entry terms and text words: contrast, radiocontrast, contrast 17125260” medium, contrast media, contrast dye, radiographic contrast, radiocontrast media, radiocontrast medium and contrast agent. For the theme “renal insuficiency”, we used: renal insufficiency, renal failure, diabetic nephropathies, nephritis, nephropathy, nephrotoxic, and, contrastinduced nephropathy and contrast-associated nephropathy. For the theme “statin”, statin, atorvastatin, rosuvastatin, cerivastatin, simvastatin, pravastatin, lovastatin, Hydroxymethylglutaryl-CoA reductase inhibitors and HMG-CoA reductase inhibitors were used. Appendix S1 shows the detailed search method. We did not restrict by language or type of article. To identify other relevant studies, we manually scanned reference lists from identified trials and review articles, and we also searched conference proceedings. We requested original data by directly contacting authors. dose of 80 mg or ” 40 mg) versus low-dose statin treatment or placebo. Studies that incorporated NAC were included only if both arms were administered NAC; studies reported the incidence of contrast-induced nephropathy in both arms. We did not restrict eligibility according to kidney function. The primary outcome measure was the development of contrast-induced nephropathy, defined as an increase in baseline serum creatinine level of 25% or an absolute increase of 44 mmol/L within 2 to 5 days after the exposure to contrast medium. Secondary outcome measures were need for dislysis, in-hospital mortality and length of hospital stay. Data extraction and quality assessment Data were collected independently by 2 reviewers. Extracted data included patient characteristics; inclusion criteria; type and dose of contrast media; protocol for the treatment of statins; periprocedural hydration protocol and specific definition of CIN. Quality assessment was judged on concealment of treatment allocation; similarity of both groups at baseline regarding prognostic factors; eligibil