We found that after iodixanol administration for conventional coronary angiography or contrast enhanced CT, renal parenchymal enhancement can persist and be seen by non-contrast CT for 7 days or longer. While the presence and intensity of delayed renal parenchymal enhancement is loosely associated with an intra-arterial route of contrast material administration at simple univariate analysis, our multivariate model showed that the route of contrast material administration was not an independent predictor of delayed renal enhancement. Instead, a high dose of contrast material, short time delay to non-contrast CT imaging, high baseline serum creatinine, and older age were the primary predictors of finding persistent renal parenchymal enhancement. In other words, while persistent renal enhancement was seen more frequently and intensely in patients who had undergone coronary angiography, the enhancement was primarily due to use of a higher dose of contrast and a shorter time interval between the intra-arterial administration of contrast and the subsequent non-contrast CT.
Our findings also contribute data to the poorly studied question regarding whether an intra-arterial versus intravenous route of contrast material administration contributes to renal injury. Similar to what was found in prior studies (6
), we found that the vast majority of patients with persistent renal parenchymal enhancement, regardless of the route of contrast material administration, displayed either global renal parenchymal enhancement or diffuse cortical enhancement, and that these patterns of enhancement were not associated with CIN. However, we also observed another pattern of persistent renal enhancement, which we described as striated and which was only seen after coronary angiography. While the underlying mechanism for this striated pattern was not clear, we speculate that a possible explanation for the striated wedge-shaped or segmental hyper- or hypo attenuation appearance may be related to multiple segmental infarcts from micro-emboli during mechanical catheterization of the aorta or heart proximal to the renal arteries. Importantly, 2 of the 4 patients with the striated pattern of enhancement (50%) subsequently developed CIN. Further study of this type of persistent renal enhancement pattern in larger patient populations will be useful to assess whether it is truly associated with renal injury.
As noted above, our finding of a loose association between persistent renal enhancement at CT and the development of CIN builds on the findings of prior studies. In a cohort of 16 diabetic patients and additional normal volunteers who underwent intravenous or intra-arterial contrast material, Jakobsen and colleagues observed persistent renal cortical CT enhancement in chronic renal failure patients, but none had significant changes in their GFR after contrast administration (9
). In a study of 50 patients who received iohexol or diatrizoate and imaged by non-contrast CT one day later, Love and colleagues reported that their only patient who had persistent renal enhancement > 100 HU subsequently developed contrast-induced nephropathy (6
). Our results are also in agreement with those of Yamazaki et al who found that a slightly higher incidence of CIN was seen in patients with intense persistent renal enhancement on non-contrast CT scans obtained 1 day after conventional angiography (CIN developed in 2 of 49 patients) compared with those without intense enhancement (CIN developed in 6 of 221 patients) (7
). Our results build on prior works in two ways. First, we studied a relatively large number of patients with either intra-arterial or intravenous contrast material, all of whom received iodixanol. Secondly, we evaluated time points ranging from 1.4 to 175.7 hours after contrast administration, which reflects the practice pattern in our hospital rather than an arbitrary time point 1 day after contrast administration. Our data was therefore amenable to a multiple regression model which clearly shows the multi-factorial nature of finding delayed renal enhancement, which relates to a shorter time lag from the contrast administration to the unenhanced CT, higher dose of contrast material, and elevated baseline serum creatinine. Notably, these predictors of persistent renal enhancement are the same as those that predispose patients to contrast-induced nephropathy, and a more intense persistent renal enhancement is not a particularly strong prognosticator of worsened renal outcome.
Our study has several limitations. Firstly, all patients in our study received iodixanol, which is an isoosmolar nonionic dimeric contrast material that is associated with a higher incidence of prolonged nephrograms than other nonionic iodinated contrast materials (10
). While the pharmacokinetics of iodixanol are similar to those of other commercially available iodinated contrast material (16
), and the clinical and renal toxicity of iodixanol has been shown to be similar to or better than that of other non-ionic contrast materials (9
), our findings may reflect a relatively high rate of prolonged renal enhancement compared to what would have been observed with other non-ionic contrast materials. While no clinical sequela has been ascribed to the association between iodixanol administration and prolonged nephrograms, two recent studies in rats associated iodixanol administration with increased urine viscosity and upregulation of renal injury biomarkers (21
).. A second important limitation to recognize about our study is that it was neither intended nor powered to find a difference in the incidence of CIN between intra-arterial and intravenous contrast material administration (13
), but rather focused on the significance of the common finding delayed renal parenchymal enhancement. A larger prior comparison of 430 patients receiving intra-arterial versus 499 receiving intravenous contrast material showed a 3.44 times increased risk of contrast-induced nephropathy in patients receiving intra-arterial contrast materials (23
). Though a higher percentage of our patients who received intra-arterial versus intravenous contrast material developed CIN, this difference was not statistically significant. In addition, in our study, serum creatinine levels after angiography were often obtained within 24 hours post-procedure. Because serum creatinine can rise up to 48 hours after contrast administration and maintain for 2–5 days, it is likely that we have under-estimated the incidence of contrast-induced nephropathy in the intra-arterial contrast administration arm since no serum creatinine value was available beyond 24 hours and within 120 hours post-contrast in many patients. A third limitation of our study is that, much like prior reports, the intra-arterial and intravenous patient groups were not matched for the prevalence of coronary artery disease, weight, dose of contrast material administered, nor time delay to non-enhanced CT. Nevertheless, we evaluated for the effect of left ventricular ejection fraction and congestive heart failure within and between groups and did not find an association between these clinical predictors and the prevalence of either delayed renal enhancement or CIN. Fourthly, since our study was performed at a Veterans Affairs site, women are underrepresented in our patient sample. Nevertheless, our patient population reflects that of a clinically relevant hospital practice where follow-up CT scans are obtained for clinical indications, rather than artificial, reasons.
Persistent renal enhancement at follow-up non-contrast CT suggests a greater risk for contrast-induced nephropathy, but the increased frequency of striking renal enhancement in patients who received intra-arterial rather than intravenous contrast material also reflects the larger doses of contrast and shorter time to subsequent follow-up CT scanning for such patients. Other contributing factors to persistent renal enhancement include a higher baseline serum creatinine and increased age. Whether the route of iodixanol delivery contributes to contrast-induced nephropathy requires a more sufficiently powered study.