Which factors affect the ability of different classes of contrast media (CM) to cause contrast-induced nephropathy (CIN)?

Updated: Dec 18, 2018
  • Author: Anita Basu, MD, FACP; Chief Editor: Vecihi Batuman, MD, FASN  more...
  • Print
Answer

The ability of different classes of CM to cause CIN is influenced by their osmolality, ionicity (the ability of the contrast media to dissociate in water), and molecular structure. Each of these characteristics, in turn, influences their behavior in body fluid and their potential to cause adverse effects. [12] See Table 1, below.

Table 1. Physiochemical Properties of Contrast Media [13] (Open Table in a new window)

Class of Contrast Agent

Type of Contrast Agent

Iodine Dose

(mg/mL)

Iodine/Particle Ratio

Viscosity

(cPs at 37°C)

Osmolality

(mOsm/kg H2 O)

Molecular Weight (Da)

High-osmolar monomers

(ionic)

Diatrizoate (Renografin)

Ioxithalamate (Telebrix)

370

350

1.5

1.5

2.3

2.5

1870

2130

636

643

Low-osmolar dimers

(ionic)

Ioxaglate (Hexabrix)

320

3

7.5

600

1270

Low-osmolar monomers

(nonionic)

Iohexol (Omnipaque)

Iopamidol (Isovue)

Iomeprol (Iomeron)

Ioversol (Optiray)

Iopromide (Ultravist)

Iopentol (Imagopaque)

350

370

400

350

370

350

3

3

3

3

3

3

10.4

9.4

12.6

9

10

12

780

790

620

790

770

810

821

777

778

807

791

835

Iso-osmolar dimers

(nonionic)

Iodixanol (Visipaque)

Iotrolan (Isovist)

320

320

6

6

11.8

8.5

290

290

1550

1620

Agents are classified as high, low, or iso-osmolar depending on their osmolality in relation to blood. Low-osmolarity contrast media (LOCM) is actually a misnomer, since these agents have osmolalities of 600-900 mOsm/kg and so are 2-3 times more hyperosmolar than blood. High-osmolarity contrast media (HOCM) are 5-7 times more hyperosmolar than blood, with osmolalities greater than 1500 mOsm/kg.

Molecular structure of CM refers to the number of benzene rings. Most CM that were developed in the 1990s are dimers with 2 benzene rings. Dimeric CM, while nonionic and with low osmolarity, have high viscosity, which may influence renal tubular blood flow.

The ratio of iodine to dissolved particles describes an important relationship between opacification and osmotoxicity of the contrast agent. The higher ratios are more desirable. High-osmolar agents have a ratio of 1.5, low-osmolar agents have a ratio of 3, and iso-osmolar agents have the highest ratio, 6.

While the safety of LOCM over HOCM in terms of CIN seems intuitive, clinical evidence of it came from a meta-analysis by Barrett and Carlisle that showed the benefit of using LOCM over HOCM, mostly in high-risk patients. [14] The Iohexol Cooperative Study was a large, prospective, randomized, double-blinded, multicenter trial that compared the risk of developing CIN in patients receiving the low-osmolarity agent iohexol versus the high-osmolarity agent diatrizoate. While the HOCM group was 3.3 times more likely to develop CIN compared with the LOCM group, this was seen only in patients with preexisting CKD (baseline SCr of 1.5 mg/dL or higher). In addition to CKD, other independent risk factors were diabetes mellitus, male sex, and higher contrast volume.

Even within the LOCM category, the risk is not the same for all agents. High-risk patients have a higher likelihood of developing CIN if they receive iohexol than if they receive another agent (ie, iopamidol) in the same class.

A comparison of two iso-osmolar LOCM (iohexol and iodixanol) in the Nephrotoxicity in High-Risk Patients Study of Iso-Osmolar and Low-Osmolar Non-Ionic Contrast Media (NEPHRIC study), arguably the most definitive study in this category to date, found that the odds of developing CIN in high-risk patients were almost 9 times greater for the study's iohexol group than for the iodixanol group. The incidence of CIN was 3% in the iodixanol group versus 26% in the iohexol group. [15] However, these results were not duplicated in some subsequent studies.

When iodixanol was used, the Rapid Protocol for the Prevention of Contrast-Induced Renal Dysfunction (RAPPID) trial found a 21% incidence of CIN, [16] and the Contrast Media and Nephrotoxicity Following Coronary Revascularization by Angioplasty (CONTRAST) trial found a 33% incidence of CIN. [17] Finally, the Renal Toxicity Evaluation and Comparison Between Visipaque (Iodixanol) and Hexabrix (Ioxaglate) in Patients With Renal Insufficiency Undergoing Coronary Angiography (RECOVER) trial compared the iso-osmolar contrast medium iodixanol to the low-osmolarity agent ioxaglate and found a significantly lower incidence of CIN with iodixanol than with ioxaglate (7.9% vs 17%, respectively). [18]

Thus, although the data are by no means uniform, they seem to suggest that the iso-osmolar contrast agent iodixanol may be associated with smaller increases in SCr and lower rates of CIN when compared with other LOCM, especially in patients with CKD and in those with CKD and diabetes mellitus. [19]


Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!