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Table 1: Iodinated Contrast Media intervention (PCI), coronary artery bypass grafting (CABG), other
Structure and Properties
revascularization procedure, cardiac arrest, congestive heart failure (CHF),
pulmonary edema, or need for permanent pacing. Due to the potentially
Contrast Medium Ionicity Chemical Class Osmolality
serious consequences of CIN, multiple studies were conducted in the
Generic Trade Structure (mOsm/kg)*
1990s to investigate whether the incidence of CIN could be reduced by
Diatrizoate, Renografin, Ionic Monomer HOCM 1,500–1,860
the use of a LOCM. Overall, these studies found that compared with
high-osmolality CM (HOCM), the incidence of CIN is reduced in patients
receiving LOCM, and that this reduction is most striking in patients with
Ioxaglate Hexabrix Ionic Dimer LOCM ~600 pre-existing chronic kidney disease.
In a trial by Rudnick et al.
Iohexol Omnipaque Non-ionic Monomer LOCM 521–695
which 1,196 patients were randomized to receive the non-ionic LOCM
iohexol or the ionic agent diatrizoate meglumine, differences in the
incidence of CIN were demonstrated only in patients with chronic kidney
disease with or without diabetes. In patients with a baseline SCr
Iodixanol Visipaque Non-ionic Dimer IOCM 290–320
>1.4mg/dl, an increase in SCr of >1mg/dl was demonstrated in 7.2% of
HOCM = high-osmolality contrast medium; LOCM = low-osmolality contrast medium;
patients receiving the LOCM versus 15.8% of those receiving the
IOCM = iso-osmolality contrast medium.
*With a concentration of 300–320mg/ml. high-osmolality agent. This effect was more pronounced if the patients
had coexisting diabetes: 11.8% developed CIN with LOCM versus 27%
Figure 1: Incidence of Contrast-induced Nephropathy in
Patients with Chronic Kidney Disease Receiving the
The largest pool of data comparing the relative
Low-osmolality Contrast Media Iohexol and Iopamidol and
nephrotoxicity of high- versus low-osmolality agents in patients with
the Iso-osmolality Contrast Media Iodixanol in Various pre-existing chronic kidney disease is found in a meta-analysis by
In this analysis of 25 clinical trials, the pooled OR for a rise in SCr
of >0.5mg/dl following administration of LOCM was 0.61 (95% confidence
interval [CI] 0.48–0.77) times that of HOCM. For patients with pre-existing
p<0.001 renal failure, this OR was 0.5 (CI 0.36–0.68), while in patients without
30 prior renal failure it was 0.75 (CI 0.52–1.1).
As use of LOCM results in fewer immediate adverse effects and less
commonly results in CIN compared with HOCM, the former have become
the preferred agents for most arterial and venous imaging. More
22% 10% 11%
controversial has been the issue of whether there is a difference in the
Incidence of contr
incidence of CIN among the newer-generation contrast agents. Much of
Iohexol Iodixanol Iopamidol
the controversy was generated by the Nephrotoxicity in High-Risk Patients
Omnipaque Visipaque Isovue
844mOsm/kg 290mOsm/kg 796mOsm/kg
Study of Iso-Osmolar and Low-Osmolar Non-Ionic Contrast Media
(NEPHRIC) trial published in 2003 by Aspelin et al.
The NEPHRIC study
p = not significant
was a small trial that enroled 129 patients with chronic kidney disease
cardiology patients and its occurrence is a potent predictor of mortality. In and diabetes and randomized the patients to the iso-osmolar CM
a prospective trial of 439 patients with chronic kidney disease (SCr (IOCM) iodixanol or the LOCM iohexol. Baseline SCr in the study ranged
≥1.8mg/dl) undergoing coronary angiography and intervention, an from 1.5 to 3.5mg/dl and CIN was defined as an increase in SCr of at least
increase in SCr ≥25% was associated with an increase of both in-hospital 0.5mg/dl. CIN occurred in 3% of patients given iodixanol versus 26% of
mortality (17.0 versus 3.9%; p<0.01) and one-year mortality (43.3 versus those who received iohexol.
Although this initial study found a lower
In a larger retrospective analysis of 7,586 patients incidence of CIN in patients treated with iodixanol, several more
undergoing coronary intervention at the Mayo Clinic, CIN was a strong recent, larger trials with different comparator agents failed to show an
predictor of in-hospital death with an odds ratio (OR) of 10.8 (p<0.0001), advantage for iodixanol. In fact, in 2005 a meta-analysis of 17 primary
and was second only to pre-procedure shock (OR=12.1).
In patients for studies including a total of 1,365 patients was published
whom CIN requires treatment with dialysis, in-hospital mortality increases that among LOCM, iohexol significantly increased the risk for CIN, while
even further: in a study of 1,826 patients undergoing coronary there was no difference between other LOCM and the IOCM iodixanol
intervention, in-hospital mortality was 35.7% in patients who developed (see Figure 1).
CIN and required dialysis, 7.1% in patients who developed CIN but did not
require dialysis, and 1.1% in patients who did not develop CIN In the 2008 Visipaque Angiography/Interventions with Laboratory
(p=0.0000001). Moreover, in this large group of patients, survival at two Outcomes in Renal Insufficiency (VALOR) trial, 337 patients with stable
years in dialyzed patients was only 18.8%.
In the 12-month follow-up data chronic kidney disease undergoing coronary angiography were
from the Cardiac Angiography in Renally Impaired Patients (CARE) study,
randomized to receive the IOCM iodixanol or the LOCM ioversol.
the incidence of negative outcomes was increased in patients who VALOR investigators found no difference in the overall incidence of CIN
developed CIN compared with those who did not, including adverse in the iodixanol subjects compared with the ioversol subjects (21.8
events (i.e. death, stroke, myocardial infarction [MI], and end-stage renal versus 23.8%; p=0.78). However, in the subset of patients with diabetes,
disease [ESRD] requiring dialysis), as well as percutaneous coronary CIN was significantly lower in the iodixanol compared with the ioversol
98 US CARDIOLOGY