Numerous studies have attempted to isolate risk factors for CIN. There is consensus that the most important risk factor for CIN is pre-existing renal insufficiency. Multiple others have been proposed, including diabetes mellitus, dehydration, cardiovascular disease, diuretic use, advanced age, multiple myeloma, hypertension, hyperuricemia, and multiple iodinated contrast medium doses in a short time interval (<24 hours) [18-23], but these have not been rigorously confirmed as independent risk factors. Two studies have shown that CIN may occur after two closely spaced doses, but neither was designed to show that the risk was higher than after one or no dose of IV contrast medium .
Risk Thresholds
There is no universally agreed upon threshold of serum creatinine elevation (or degree of renal dysfunction) beyond which intravascular iodinated contrast medium should not be administered. In a 2006 survey of radiologists by Elicker et al [24], the cutoff value for serum creatinine beyond which intravascular iodinated contrast medium would not be administered varied widely among radiology practices. For patients with no risk factors other than elevated serum creatinine, thirty-five percent of respondents used 1.5 mg/dL, 27% used 1.7 mg/dL, and 31% used 2.0 mg/dL (mean, 1.78 mg/dL). Threshold values were slightly lower in patients with diabetes mellitus (mean: 1.68 mg/dL).
We believe that there is insufficient good data at this time to prescribe a specific recommended threshold. However, we also believe that the risk of CIN from intravenous iodinated contrast media is sufficiently low that a threshold of 2.0 mg/dL in the setting of stable chronic renal insufficiency is probably safe for most patients. As previously stated, no serum creatinine threshold is adequate to stratify patients with acute kidney injury because serum creatinine in this setting is unreliable.
In patients with acute kidney injury, the administration of iodinated contrast medium should only be undertaken with appropriate caution and only if the benefit to the patient clearly outweighs the risk. There has been no published series demonstrating that IV iodinated contrast medium administration to patients with acute kidney injury leads to worse or prolonged renal dysfunction than would occur in a control group. However, patients with acute kidney injury are particularly susceptible to nephrotoxin exposure and therefore it is probably prudent to avoid intravascular iodinated contrast medium in these patients (when possible), regardless of the generally low nephrotoxic risk.
Anuric patients with end-stage renal disease are no longer at risk for CIN and may receive intravascular iodinated contrast material without risk of additional renal injury (see Renal Dialysis Patients and the Use of Iodinated Contrast Medium, below).
The clinical benefit of using eGFR or calculated creatinine clearance in assessing preprocedural CIN risk in patients with stable renal function is uncertain because much of our published knowledge comes
from studies that used only serum creatinine measurements. The threshold values at which different clinical actions should be taken (e.g., active IV hydration, avoidance of contrast medium administration) are neither proven nor generally agreed upon for either serum creatinine measurement or calculated creatinine clearance. In addition, the accuracy of these formulae has only been validated in the patient population for whom they were developed. The MDRD formula is known to underestimate eGFR in patients with normal and near normal renal function [25]. Herts et al [26] showed that when patients’ eGFR was calculated by the MDRD formula, a significantly higher percentage of patients had an eGFR of <60 ml/min than had a serum creatinine of >1.4 mg/dL. These patients might have been denied contrast medium administration had eGFR been used to determine suitability for injection (15.3% vs. 6.2%).
Thomsen et al [27] reviewed the relative risk of CIN from two randomized trials using eGFR calculated from serum creatinine by the MDRD formula in patients who received IV contrast for computed tomography (CT) examinations. The risk of CIN was found to be 0.6% in patients with eGFR greater than 40 ml/min/1.73 m2 and 4.6% in patients with an eGFR of 30 to 40 ml/min/1.7 3 m2. The CIN rate was 7.8% in patients with an eGFR ˂30 ml/min/1.73 m2. In a study of 421 patients with an eGFR ˂60 ml/min/1.73 m2 who did not have end-stage kidney disease, Weisbord and colleagues [28] found that the rate of CIN following contrast-enhanced CT was 2.5% (8 of 316) in those patients who had an eGFR > 45 ml/min/1.73 m2 and 9.8% (5 of 51) in patients with an eGFR between 30 and 45 ml/min/1.73 m2. In a study by Kim and colleagues [29], which included 520 patients undergoing contrast-enhanced CT, none of the 253 patients who had an eGFR between 45 and 59 ml/min/1.73 m2 developed CIN, while six (2.9%) of 209 patients with an eGFR between 30 and 44 ml/min/1.73 m2 and seven (12.1%) of 58 patients with an eGFR lower than 30 ml/min/1.73 m2 developed CIN. All of these studies lacked a group of patients not exposed to contrast medium. Therefore, it is difficult to determine if these cases of “CIN” were due to contrast medium administration, another etiology, or background fluctuations in serum creatinine.
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