HealthDay News – Iodixanol is associated with lower risk for contrast-induced nephropathy (CIN) versus low-osmolar contrast media (LOCM). Among those receiving LOCM, the greatest risk reduction is seen for N-acetylcysteine and statins plus N-acetylcysteine, according to two reviews published online Feb. 2 in the Annals of Internal Medicine.

John Eng, MD, from the Johns Hopkins University School of Medicine in Baltimore, and colleagues conducted a systematic review to compare CIN risk with contrast media in patients receiving diagnostic or therapeutic imaging procedures.1 Data were included from trials that reported CIN-related outcomes in patients receiving LOCM or iso-osmolar contrast media for imaging. The researchers observed a slight reduction in CIN risk with the iso-osmolar contrast media agent iodixanol versus with a diverse group of LOCM in 25 randomized controlled trials; the reduction reached statistical significance in meta-analysis (pooled relative risk, 0.80; 95% confidence interval, 0.65 to 0.99; P = 0.045).

Rathan M. Subramaniam, MD, PhD, also from the Johns Hopkins University School of Medicine, and colleagues reviewed the literature to assess the comparative effectiveness of interventions to reduce CIN in adults receiving contrast media.2 The researchers found that, compared with intravenous (IV) saline, low-dose N-acetylcysteine correlated with reduced risk (risk ratio, 0.75). Clinically important and statistically significant benefits were seen for N-acetylcysteine versus IV saline in patients receiving LOCM (relative risk, 0.69) and for those receiving statins plus N-acetylcysteine versus N-acetylcysteine (relative risk, 0.52).

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“The greatest reduction in CIN was seen with N-acetylcysteine in patients receiving LOCM and with statins plus N-acetylcysteine,” Subramaniam and colleagues write.

Summary and Clinical Applicability

The iso-osmolal nonionic contrast agent iodixanol appears to reduce the risk of CIN in high-risk patients, such as diabetic patients with renal insufficiency.2

CIN is a generally reversible form of acute kidney injury (AKI) that occurs soon after the administration of radiocontrast media.  Patients at increased risk of CIN include those with a serum creatinine ≥1.5 mg/dL(132 micromol/L) or an estimated glomerular filtration rate (eGFR) <60 mL/1.73 m2, particularly in those with diabetes.3  

There is no specific treatment of AKI once it develops, so prevention of CIN is essential. If clinically possible, the use of ultrasonography, magnetic resonance imaging (MRI), or computed tomography (CT) scanning without radiocontrast agents is recommended, particularly in high-risk patients.4  Systematic reviews have found a reduction in CIN with certain prophylactic measures, such as administering N-acetylcysteine in the setting of LOCM and with statins.2 

Further Information

Statins may improve endothelial function by reducing arterial stiffness (via improved endothelin-mediated vasodilatation) and reducing inflammation and oxidative stress.5 Acetylcysteine is a thiol compound with antioxidant and vasodilatory properties that may minimize both vasoconstriction and oxygen-free radical generation after radiocontrast agent administration.5 Iodixanol is the only available iso-osmolal nonionic contrast agent (approximately 290 mosmol/kg) proposed to be associated with a lower risk of nephropathy than some low-osmolal agents.2


1. Eng J, Wilson RF, Subramaniam RM, et al. Comparative Effect of Contrast Media Type on the Incidence of Contrast-Induced Nephropathy: A Systematic Review and Meta-analysis. Ann Intern Med. [Epub ahead of print 2 February 2016] doi:10.7326/M15-1402

2. Subramaniam RM, Suarez-Cuervo C, Wilson RF,  et al. Effectiveness of Prevention Strategies for Contrast-Induced Nephropathy: A Systematic Review and Meta-analysis. Ann Intern Med. [Epub ahead of print 2 February 2016] doi:10.7326/M15-1456

3. Kitajima K, Maeda T, Watanabe S, et al. Recent issues in contrast-induced nephropathy. Int J Urol. 2011; 18:686-90. 

4. Asif A, Epstein M. Prevention of radiocontrast-induced nephropathy. Am J Kidney Dis 2004; 44:12.

5. Pannu N, Wiebe N, Tonelli M, Alberta Kidney Disease Network. Prophylaxis strategies for contrast-induced nephropathy. JAMA 2006; 295:2765.