Cardiovascular Literature—Beyond Nephrology (2008)

Findings. A total of 482 patients could be evaluated. The two groups were comparable with respect to all relevant parameters, particularly eGFR (49.3 11.6 versus 50.2 13.0 ml/min per 1.73 m 2 ). The primary end point of an increase in serum creatinine 0.5 mg/dl was not significantly different between the two groups (6.7% iodixanol versus 4.4% iopamidol). The secondary end points of a 25% increase of serum creatinine occurred in 12.4% on iodixanol versus 9.8% on iopamidol (NS) and a decrease of eGFR in 10.0% on iodixanol versus in 5.9% on iopamidol. The secondary end points of postdose increase in serum creatinine and decrease of eGFR, respectively, were even in favor of iopamidol (serum creatinine 0.07 0.22 mg/dl on iopamidol versus 0.12 0.23 mg/dl on iodixanol; P 0.03) particularly in the subgroup of patients with diabetes (0.07 0.26 mg/dl versus 0.16 0.27; P 0.01). None of the patients required hemodialysis. Commentary. The sufficiently powered CARE study documents that the rate of radiocontrast nephropathy is no better with the isosmolar dimeric nonionic radiocontrast agent iodixanol compared with the nonionic monomer iopamidol after intra-arterial administration to patients with moderate to severe CKD. In the smaller previous RECOVER study (7), the rate of radiocontrast nephropathy was also not significantly different when the nonionic dimer iodixanol was compared with the low-osmolality ionic dimer ioxaglate. In contrast, the Nephrotoxicity in High-Risk Patients Study of Iso-Osmolar and Low-Osmolar Non-Ionic Contrast Media (NEPHRIC) (5) had found a significant difference in the mean peak postdose increase of serum creatinine: It was lower with iodixanol (0.13 0.22 mg/dl) compared with iohexol (0.55 0.98 mg/dl). These results are also in contrast to a recent meta-analysis (8) of randomized, controlled trials that found a significantly smaller increase in serum creatinine 3 d postdose on iodixanol compared with a pooled group of other low-osmolality agents; one can criticize, however, that in these mostly smaller studies, the serum creatinine measurements were not standardized, the timing of the postdose measurements varied, and the two groups were not sufficiently balanced. It is therefore of note that in the one study (9) with a head-on comparison between iodixanol and iopamidol, a similar trend in favor of iopamidol was found, as observed in the above CARE study. How can one reconcile the somewhat diverse findings? Systematic reviews and the analysis of renal adverse events in the Food and Drug Administration postmarketing safety database (10,11) are in agreement with the data of the CARE study and would be compatible with the interpretation that all depends on what is compared with what: When iodixanol is compared with these two low-osmolar compounds, iohexol is associated with a higher and iopamidol with a lower incidence of radiocontrast nephropathy. This is not without interest for the underlying pathophysiology. It has not been resolved whether it is ionicity, osmolality, or viscosity that is the main culprit: If the two equally low-osmolar agents differ with respect to renal risk, then it is unlikely that osmolality (which is comparable in the two groups) plays a major pathogenetic role. It is remarkable that in an investigational environment with standardized pretreatment, the rate of adverse renal events was