Nevertheless, it is important to carefully examine the evidence on the effectiveness of interventions for preventing CIN while taking into consideration how the effectiveness may depend on factors such as the route of administration or the type of contrast media being used. Numerous strategies to prevent CIN have been used, including: oral fluids; volume expansion with sodium chloride, sodium bicarbonate, or a combination of both; administration of N-acetylcysteine, statins, angiotensin converting enzyme inhibitors, or angiotensin II receptor blockers; withdrawal of nonsteroidal anti-inflammatory drugs; and hemofiltration or hemodialysis. Withdrawal of metformin does not prevent CIN; it is discontinued before use of contrast because acute kidney injury may lead to metformin-associated lactic acidosis. Recent meta-analyses on the prevention of CIN have yielded contradictory results. A meta-analysis by Sun et al., 2013 concluded that the evidence on use of IV N-acetylcysteine to prevent CIN was too inconsistent to determine the efficacy.11 Another meta-analysis, performed by Loomba et al., 2014,12 concluded that N-acetylcysteine may help to prevent CIN in patients undergoing coronary angiography, but does not have any impact on clinical outcomes such as need for dialysis or mortality. A meta-analysis by Xie et al., 201413 concluded that statins given before angiography are effective in preventing CIN, but the optimum dose and duration for statin use are unknown. A recent review of randomized controlled trials (RCTs) of sodium bicarbonate administration for prevention of CIN revealed the conflicting nature of the evidence, with some studies showing benefit and others showing no benefit.14 Despite the number of previous reviews, uncertainty persists about several issues, including: 1. The efficacy of oral fluids versus IV fluids in preventing CIN;15,16 2. The optimal timing (pre- versus post-contrast media administration or both), duration, and type of IV fluids used to prevent CIN17; 3. The efficacy of low versus high-dose N-acetylcysteine; 4. The efficacy of a combination of interventions, such as N-acetylcysteine plus sodium bicarbonate; 5. The efficacy of statins, taking into consideration dose and duration of the medication; 6. The efficacy of vasoactive drugs; 7. The efficacy of hemodialysis and hemofiltration relative to the invasive nature and cost of these interventions; 8. Whether any intervention is needed for IV contrast media procedures when there is uncertainty about whether IV contrast media is associated with CIN; and 9. Effect of the volume of contrast media administered, and the possibility of preventing CIN by keeping the volume of contrast media below a threshold. 3 Guidelines around contrast media administration have been published by a number of organizations. The 2007 American College of Radiology practice guideline focused on the correct administration of contrast media and the patients who are most likely to benefit from using LOCM instead of HOCM, rather than the evidence for or against different preventive measures. Guidelines on the prevention of CIN were published in 2007 by the Canadian Association of Radiologists,19 and they were published following what they described as an “indepth literature search with critical review”; however, no further details were included about the methods. Guidelines were also issued in 2006 by the CIN Consensus Working Panel, an international multidisciplinary group; these guidelines were based on an evidence review through 2005.20 One section of the 2012 Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Acute Kidney Injury specifically addressed contrast-induced acute kidney injury. The method of synthesis varied among these guidelines and many were based on literature review and consensus opinions of clinical experts.21 In light of the increasing use of contrast media in radiologic and cardiologic procedures, the high prevalence of populations vulnerable to CIN (e.g., people having chronic kidney disease, diabetes mellitus, or hypertension as well as the elderly), and discrepant results from prior analyses, we sought to perform a comprehensive systematic review of this topic for the benefit of clinicians who wish to prevent CIN in patients undergoing imaging studies. Scope of the Review We reviewed studies that assess the effectiveness of one or more measures for preventing CIN in patients receiving either IOCM or LOCM, the two types of contrast media still in regular use in the United States (Figure 1 and Table 1). We included studies that reported on specific short-term or long-term outcomes (Table 2). When studies allowed, separate results for CIN prevention were reported for intra-arterial compared to IV contrast. Key Question In patients undergoing imaging studies requiring intravenous (IV) or intraarterial contrast media, what is the comparative effectiveness of interventions to prevent contrast-induced nephropathy for the outcomes of incidence of contrast-induced nephropathy, chronic kidney disease, end stage renal disease, mortality, and other adverse events? a. How does the comparative effectiveness of prevention measures vary by patient characteristics (known risk factors such as age, comorbidity, glomerular filtration rate, or creatinine level)? b. How does the comparative effectiveness of