KDIGO Clinical Practice Guideline for Acute Kidney Injury
Recommendations and Rationale

• 4.1: Define and stage AKI after administration of intravascular contrast media as per Recommendations 2.1.1–2.1.2. (Not Graded)
• • 4.1.1:In individuals who develop changes in kidney function after administration of intravascular contrast media, evaluate for CI-AKI as well as for other possible causes of AKI. (Not Graded)

Rationale

Pending the validation of future biomarkers which would allow a more straightforward comparison and integration of CI-AKI in the overall framework of AKI, we suggest that the same criteria, using the changes in SCr concentrations and urine output be used as for the other forms of AKI. TheWork Group is not aware of any pathophysiological or epidemiological reason why the definition and staging of CI-AKI should be different from the RIFLE/AKIN criteria. It should, however, be stressed that for the development of this guideline, the term contrast-induced nephropathy is widely used in the literature and usually defined as a rise in SCr of ≥ 0.5 mg/dl ( ≥ 44 µmol/l) or a 25% increase from baseline value, assessed at 48 hours after a radiological procedure. This definition also consistently predicted major adverse cardiovascular events after percutaneous coronary intervention.³⁸⁵ The Society of Urogenital Radiology used the same definition, but the creatinine changes were said to occur within 3 days after intravascular administration of contrast media without an alternative etiology.³⁸⁶ It should be recognized that, in a minority of cases, the peak increase of SCr may occur up until 5 days after contrast exposure. However, a recent prospective study³⁸⁷ showed that the percentage change of SCr 12 h after contrast vs. the basal value was the best predictor of CI-AKI (P < 0.001). A 5% increase of its value yielded 75% sensitivity and 72% specificity, with an area under the curve (AUC) of 0.80 and an OR of 7.37 (95% CI 3.34–16.23) for early detection. Furthermore, this 12-hour basal value strongly correlated with the development of renal impairment at 30 days (P = 0.002; sensitivity 87%, specificity 70%; AUC 0.85; OR 13.29; 95% CI 2.91–60.64).

It has been shown that substantial variation in SCr may occur from day to day in hospitalized patients who do not receive contrast-media injections.³⁸⁸ Depending on the threshold criterion for CI-AKI chosen, this variation can lead to rates of 6–35% of inpatients, not exposed to contrast media, who would be labeled as having CI-AKI had they received contrast media. The exact cause of this ‘‘hospitalinduced nephropathy’’³⁸⁹ is not known, but other studies have shown that AKI (various etiologies) is common in hospitalized patients.

The magnitude of the impact of the ‘‘background fluctuation of kidney function’’ in patients receiving iodinated contrast has not been prospectively studied, but a recent retrospective study compared the incidence of AKI among patients undergoing enhanced computed tomography (CT) with i.v. low-osmolar (iohexol) or iso-osmolar (iodixanol) contrast media to the AKI incidence among patients undergoing CT without contrast-media administration.³⁹⁰ The incidence of AKI (defined as an increase of SCr of 0.5mg/dl [44 µmol/l] or a ≥ 25% decrease in eGFR within 3 days after CT) was similar in all three groups (two receiving contrast agents and one not) up to a baseline SCr level of 1.8mg/dl (159 µmol/l). A high incidence of ‘‘AKI’’ among control subjects undergoing noncontrast CT was thus identified. Given the results of this retrospective study, it is clear that AKI after i.v. administration of iodine contrast media cannot be automatically attributed to the contrast agent, but may, in fact, reflect AKI from other causes, such as worsening underlying disease or drug toxicity. Therefore, the Work Group strongly recommends that individuals showing increases of SCr compatible with the definition of AKI after administration of intravascular contrast media be also evaluated for other possible causes of AKI.

In a study using cystatin C as an early marker for AKI, a cut-off cystatin C increase concentration of ≥ 10% at 24 hours after contrast-media exposure was detected in 87 patients (21.2%), and was the best cut-off value for the early identification of patients at risk for CI-AKI with a negative predictive value of 100% and a positive predictive value of 39%. As in other cases of AKI, it appears that, in patients with CKD, cystatin C may be a useful marker for the early diagnosis of CI-AKI.