Are isotonic contrast agents safer than the low-osmolar variety for patients with impaired kidney function? Not according to the results of a recent multicenter trial, which compared the two classes of intravenous contrast agents in patients presenting with high creatinine levels prior to CT imaging. The risk of contrast-induced nephropathy (CIN) was similarly low in both agents, the researchers found.
"The idea that isotonic contrast media may have better renal tolerance in high-risk patients compared with low-osmolar contrast media has had considerable impact in the scientific community," lead author Dr. Brendan Barrett from the Health Science Center in St. John's, Newfoundland, Canada, and colleagues wrote in Investigative Radiology (November 2, 2006, Vol. 41:11, pp. 815-821).
"It has even influenced the recommendations of several guidelines despite the fact that it has only been shown in one single study," they added.
That study, published in 2003 in the New England Journal of Medicine, compared another nonionic monomer-based agent, iohexol (Omnipaque, GE Healthcare, Chalfont St. Giles, U.K.) with the nonionic dimer iodixanol (NEJM, February 6, 2003, Vol. 348:6, pp. 491-499).
The NEJM study authors Dr. Peter Aspelin et al found that two of the 64 (3%) patients in the iodixanol group had an increase in serum creatinine (SCr) of 0.5 mg/dL or more, compared to 17 of the 65 (26%) patients in the iohexol group (p = 0.002; odds ratio for such an increase in the iodixanol group, 0.09 [95% CI, 0.02 to 0.41]). Moreover, no patient receiving iodixanol had an increase of 1.0 mg/dL or more, but 10 patients in the iohexol group (15%) did, they reported.
Based on this trial, it was suggested that the contrast agent iodixanol, which is isotonic to human plasma, may be less nephrotoxic than other nonionic contrast agents in renally impaired patients after intra-arterial injection.
However, the NEJM results are at odds with those of other studies, Barrett and his team wrote. Most studies comparing the nephrotoxicity of the nonionic monomers have been in patients having intra-arterial injections either to the heart or peripheral arteries.
Although the relative nephrotoxicity of low-osmolal nonionic monomers has not been established in head-to-head comparisons of the different agents, "the reported rates of CIN were higher with iohexol than with iopamidol in three recent pooled analyses of clinical studies," they wrote. Still, all of these studies had major shortcomings, such as small sample size, unblinded reading, or retrospective design.
To sort it all out, the Impaired Patients Undergoing Computed Tomography (IMPACT) study was the "largest, prospectively randomized, double-blinded comparison of the dimer iodixanol with a nonionic monomer," the team wrote. The study was conducted at 12 centers in North America and three in China, including the Health Science Center in St. John's; the University of California, Davis Medical Center in Sacramento, CA; Massachusetts General Hospital in Boston; the Centre hospitalier de l'Université de Montreal in Canada; and Rui Jin Hospital and Ren Ji Hospital, both in Shanghai, China.
The study examined 166 patients 18 or older with stable moderate-to-severe chronic kidney disease (screening and baseline serum creatinine, ≥ 1.5 mg/dL and/or creatinine clearance [CrCl], ≤ 60 mL/min) who were undergoing contrast-enhanced MDCT of the liver or peripheral arteries.
Individuals were excluded if they had undergone another contrast-enhanced study the previous week, or had congestive heart failure or other conditions that were likely to render the data unreliable, such as hypothyroidism, diabetes, or unstable renal function.
The patients were randomized to receive either 40 gI of iopamidol-370 (370 mg/mL, Isovue, Bracco Diagnostics, Princeton, NJ) or iodixanol-320 (320 mgI/mL, Visipaque, GE Healthcare) administered intravenously at 4 mL/sec. Iodine doses were equal for the two agents.
To monitor the incidence of CIN, serum creatinine levels were taken at multiple points in the process: at baseline, screening, and 48-72 (±6, mean 57.4) hours after contrast administration, and the results for all 15 sites were tabulated at a central laboratory.
CIN was defined as an absolute increase in serum creatinine (≤ 44.2 µmol/L) and or a relative increase of 25% or more from baseline.
In all, 153 of 166 patients were deemed evaluable by the Renal Data Monitoring board and included in the results, including 77 patients who received iopamidol-370, and 76 who were given iodixanol-320. The patients were comparable with regard to age, gender distribution, presence of diabetes, other medications, hydration, and contrast dose.
"Mean predose SCr was 1.6 ± 0.4 mg/dL in both groups (p = 0.9)," the authors reported. "An absolute increase ≥ 0.5 mg/dL (44.2 µmol/L) in SCr was observed in none of the patients receiving iopamidol-370 and in 2.6% (2/76) of patients receiving iodixanol-320 (95% CI -6.2, 1.0, p = 0.2)."
A relative increase of 25% or more in serum creatinine was observed in 4% (3/77) of patients receiving iopamidol-370 and in 4% (3/76) of those receiving iodixanol-320 (95% confidence interval -6.2, 6.1, p = 1.0).
The findings failed to demonstrate any difference in CIN regardless of which contrast agent was administered, concluded Barrett and colleagues at the 15 centers. The results contradict those of a previous trial comparing iohexol to iodixanol, but consistent with the findings of other studies, they noted.
"The true cause of acute renal failure after contrast is difficult to determine clinically, particularly in populations having cardiac angiography, where hemodynamic instability, atheroembolism, and the effects of other drugs may all play a role," they explained. Studies comparing intravenously administered agents may be less prone to kidney failure by causes other than CIN; however, small, transient changes in renal function have been seen even after noncontrast CT exams, they wrote. In addition, contrast dose to the kidney necessarily varies from patient to patient due to cardiovascular status, stents, etc.
The present study was particularly rigorous in determining kidney function stability, the group stated. Its limitations included the exclusion of 13 subjects, the fact that hydration was not uniform by patient though it was by group. And the cohort was relatively small considering the unexpectedly low rate of CIN they encountered.
"A study of about 3,800 cases would be required to detect even a 50% reduction in the incidence of CIN with one contrast medium over the other," the group wrote.
By Eric Barnes
AuntMinnie.com staff writer
November 10, 2006
Related Reading
Timing is everything in contrast-enhanced CT, September 28, 2006
Part II: Palliative steps prevent contrast-induced nephropathy, September 20, 2006
Part I: Identifying patients at risk of contrast-induced nephropathy, September 13, 2005
Iso-osmolar contrast medium recommended in chronic kidney disease, August 22, 2006
N-acetylcysteine reduces incidence of contrast-induced nephropathy, June 29, 2006
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