KDIGO Clinical Practice Guideline for Acute Kidney Injury
Low-osmolar vs. iso-osmolar contrast media

Low-osmolar vs. iso-osmolar contrast media

The present hotly debated question is whether iso-osmolar contrast media are safer than low-osmolar contrast media in high-risk patients. This question has been the subject of a number of randomized trials as well as systematic reviews and meta-analyses (Suppl Tables 19–21).

We separated studies meeting our inclusion criteria (see Chapter 1.2) into those administering i.a. or i.v. contrast media. We used the general definitions of CI-AKI provided in the studies (an increase in SCr by > 25% or 0.5 mg/dl [44.2 µmol/l]) occurring within 72 hours after contrastmedium administration, in the absence of an alternative etiology for the decrease in kidney function.

Figure 14 | Risk for contrast-induced nephropathy. (a) Iodixanol vs. iohexol and risk for contrast-induced nephropathy; (b) iodixanol vs. nonionic low-osmolar contrast media other than iohexol and risk for contrast-induced nephropathy. Reprinted from Heinrich MC, Haberle L, Muller V et al. Nephrotoxicity of iso-osmolar iodixanol compared with nonionic low osmolar contrast media: meta-analysis of randomized controlled trials. Radiology 2009; 250: 68–86 with permission, copyright 2009, from Radiological Society of North America⁴⁵⁷; accessed http://radiology.rsna.org/content/250/1/68.long

In total, 14 RCTs fulfilling the search criteria were found. Ten RCTs were found with i.a. and four RCTs with i.v. injection, respectively (Suppl Tables 19–21). There is only moderate quality of evidence and overall, no benefit—or, at least, no consistent benefit—was found of nonionic isoosmolar (iodixanol) contrast media compared to lowosmolar ionic or nonionic contrast media. In eight studies comparing contrast media given i.a.^{401,450–456} some showed superiority of iso-osmolar contrast media (iodixanol), compared to iohexol⁴⁵⁰ and iopromide.⁴⁵⁵ There was no difference when iodixanol was compared to iopamidol,^401,452 iopromide,^451,453 and ioversal.⁴⁵⁶

The most recent prospective, multicenter, randomized, double-blind study compared the renal effects of iodixanol to the nonionic, low-osmolar agent iopamidol, in 526 subjects with CKD and diabetes mellitus undergoing diagnostic and/or therapeutic coronary angiography.⁴⁵⁴ The overall CI-AKI incidence was 10.5% (11.2% % in the iodixanol arm and 9.8% in the iopamidol arm, NS). The volume of contrast medium, volume of saline administered, frequency of coronary interventional procedures, and severity of baseline kidney disease and of diabetes mellitus were similar between treatments.

Finally, a recent meta-analysis⁴⁵⁷ (Figure 14) analyzed studies comparing iodixanol with low-osmolar contrast media. The pooled RR was 0.68 (95% CI 0.46–1.01; P = 0.06). In studies that included patients with normal renal function after i.a. contrast-media administration, the RR was 0.82 (95% CI 0.45–1.51; P = 0.53). In the studies that included only patients with decreased kidney function after i.a. contrast-media administration, the RR was 0.59 (95% CI 0.33–1.07; P = 0.08). However, in all three studies in which iohexol was the low-osmolar contrast medium used, the risk of CI-AKI was significantly lower with iodixanol (RR 0.38; 95% CI 0.21–0.68; P < 0.01). In contrast, the risk of CI-AKI did not significantly differ in the two studies in which iodixanol was compared to other low-osmolar contrast agents (RR 0.95; 95% CI 0.50–1.78; P = 0.86). Iodixanol is thus not associated with a significantly reduced risk of CIAKI compared to the low-osmolar contrast media pooled together. However, in patients with decreased kidney function, iodixanol is associated with a reduced risk of CIAKI compared to iohexol.

The clinical heterogeneity between all these studies, as far as basal kidney function and prevalence of diabetes mellitus are concerned, hampers the ability to compare the results across studies, but can widen the applicability of consistent findings across different risk groups provided the mechanisms of contrast-induced nephrotoxicity are the same. One should note, also, that in all these studies different definitions of CI-AKI have been used and that the timing of SCr measurements after contrast-media injection was not uniform. It has been shown that different time-points for the measurement of CI-AKI can give different results.⁴⁵⁸ One may expect that those studies with a standardized and simultaneous measurement of renal function between the two arms are probably the most conclusive. Finally, different types and amounts of volume expansion and different pharmacological preventive strategies have been used throughout the studies, making conclusive comparisons virtually impossible.