on 12-Jan-2022 (Wed)

AKI that is related to iodinated contrast material has historically been called contrast-induced nephropathy (CIN) or contrast-induced AKI (CI-AKI). However, nephrology and radiology communities have also adopted the term "contrast-associated AKI (CA-AKI)," because it is not possible to exclude other causes of AKI in many clinical and most research settings

"Contrast-associated AKI (CA-AKI)" or, synonymously, "post-contrast AKI" are broad terms that refer to AKI occurring shortly after administration of iodinated contrast and that may or may not be directly caused by the contrast material. The term CA-AKI applies to situations in which a detailed clinical evaluation for other potential AKI etiologies has not been performed or in which other causes of AKI cannot be reasonably excluded. CA-AKI should also be used to refer to increases in creatinine (or decreases in estimated glomerular filtration rate [eGFR]) after contrast exposure in research studies

"Contrast-induced AKI (CI-AKI)," previously called "contrast-induced nephropathy (CIN)," is a specific term that refers to the subset of post-contrast AKI that is judged to be causally linked to contrast material administration. In an individual patient, the presence of a causal link between contrast exposure and AKI can only be judged after a thorough clinical evaluation for other potential causes of AKI. If after such an evaluation, no other causes (other than contrast exposure) are identified, then it is appropriate in these instances to use the term CI-AKI. Although some experts contend that, even after a thorough clinical evaluation fails to reveal an alternative etiology, it is not possible to establish causality. However, this is also the case for other causes of AKI, such as sepsis-induced acute tubular necrosis (ATN), or ATN caused by an alternative nephrotoxic agent

Intravascular iodinated contrast media have been considered nephrotoxic based in large part upon animal experiments and uncontrolled human studies [12,13].

Since coincident AKI is so common, true CI-AKI is difficult to diagnose accurately in the context of a clinical research study and generally requires a study design with a control arm not exposed to contrast material [12-23,26].

If other potential etiologies have not been excluded or if other potential etiologies are identified, then AKI occurring shortly after contrast exposure should be referred to as "CA-AKI" or "post-contrast AKI."

The best data related to the nephrotoxicity of contrast media come from animal models. Studies show evidence of acute tubular necrosis (ATN), but the mechanism by which ATN occurs is not well understood [27-29]. The two major theories are that ATN is caused by renal vasoconstriction resulting in medullary hypoxia, possibly mediated by effects of viscosity and by alterations in nitric oxide, endothelin, and/or adenosine, and that ATN is a direct result of the cytotoxic effects of the contrast agents on tubular cells [27-35]. Tubular cell injury may be exacerbated by renal vasoconstriction [27,28,33,36], and these two theories are not mutually exclusive

. If ATN contributes to CI-AKI, it is not clear why recovery occurs relatively quickly (ie, within a few days) compared with a longer duration (ie, one to three weeks), as with ATN due to other causes. One likely possibility is that the degree of tubular necrosis is much less severe than seen in other settings. It is also possible that the decline in glomerular filtration rate (GFR) is due to functional changes in tubule epithelial cells rather than necrosis. This phenomenon may be at least in part due to redistribution of membrane transport proteins from the basolateral to the luminal membrane [37].

In addition, it is possible that prerenal factors or intratubular obstruction contribute to the pathogenesis. This possibility is suggested by the observation that the fractional sodium excretion (FENa) may be <1 percent in patients with CI-AKI, which is characteristic of prerenal physiology [38]. (See "Fractional excretion of sodium, urea, and other molecules in acute kidney injury", section on 'Fractional excretion of sodium in acute kidney injury' and 'Clinical features' below.)

The major clinical manifestations of contrast-induced acute kidney injury (CI-AKI) include:

● Early, mild increase in serum creatinine – An increase in serum creatinine that is generally observed within 24 to 48 hours after the iodinated contrast exposure and that is usually mild. The serum creatinine typically starts to decline toward baseline within three to seven days of the exposure to contrast [8,39].

● Nonoliguria – Because the AKI is typically mild, most patients are nonoliguric [4,39]. Oliguria (if it occurs) develops immediately after the procedure. Oliguria and more significant elevations in creatinine can be seen with severe AKI or when CI-AKI develops in patients with moderate to severe chronic kidney disease (CKD) at baseline.

● Urinary sediment consistent with acute tubular necrosis – The urinary sediment may show classic findings of acute tubular necrosis (ATN), including muddy brown granular and epithelial cell casts and free renal tubular epithelial cells (picture 1 and picture 2). However, the absence of these urinary findings does not exclude the possibility of CA-AKI.

Other manifestations of reduced glomerular filtration rate (GFR) may be present, including hyperkalemia, acidosis, and hyperphosphatemia.

Although an ultrasound is often obtained among hospitalized patients with AKI, we generally do not obtain an ultrasound initially among patients whose presentation is characteristic of CI-AKI. However, we do obtain an ultrasound to exclude other causes of AKI among patients with risk factors for upper urinary tract obstruction who do not follow a classic clinical course of CI-AKI or if the diagnosis of CA-AKI is questionable (eg, oliguria, severe AKI).