Still under investigation

Abbreviations: NGAL, Neutrophil gelatinase-associated lipocalin

**Table 1.** The currently available definition of contrast-induced nephropathy

**Within 24 hours after procedure**

Contrast-Induced Nephropathy in Coronary Angiography and Intervention

Serum creatinine 0.5 mg/dL↑ 0.5 mg/dL↑

Serum creatinine 25%↑from baseline 25%↑from baseline

Other rapidly-responsive serum markers aiming at earlier detection of renal function change also are under investigation. Cystatin C is a cationic low molecular weight cys‐ teine protease, produced at a constant rate by all nucleated cells.[23] It is not metabo‐ lized in the serum, and is freely filtered by glomeruli, thus serving as a good marker for assessing glomerular filtration rate (GFR).[24] A japanese study utilizing cystatin C and sCr in evaluating post-computed tomographic coronary angiography AKI concluded that serum cystatin C at day one after examination significantly correlates with change of sCr, indicating AKI. [25] Cystatin C is particularly useful in patients with diabetic histo‐ ry. On the other hand, Ribichini et al, in another study comparing sCr and cystatin C for detecting AKI after PCI within 12 hours, found that serum cystatin C performed signifi‐ cantly worse than sCr, with an area under curve (AUC) value of 0.48 only. [26] Neutro‐ phil gelatinase-associated lipocalin (NGAL) is a small stress protein released from injured tubular cells after various stimuli. [27] A multitude of studies have documented its role in earlier detection of AKI, with excellent sensitivity and fair specificity.[28-30] Hirsch and coworkers first demonstrated in pediatric population that, with a cut-off val‐ ue of 100 ng/mL and timeframe of 2 hours, urinary NGAL predicts contrast-induced AKI well, with 73% sensitivity and 100% specificity. [31] Another study from Austria reached similar findings, with additional benefit of improving renal outcome, possibly due to ear‐ lier detection. [32] Besides, there are other potential candidate biomarkers implicated as possessing a role in contrast-induced AKI, including kidney-injury molecules -1 (KIM-1), urinary L type fatty acid-binding protein (L-FABP), but few human studies are available currently.[33] Finally, the exact diagnostic modality of choice for contrast-induced nephr‐ opathy remains uncertain. A recent study by Erselcan and colleagues discovered that sCr-based diagnosis can in fact differ substantially from radionuclide-based GFR estima‐ tion method. [34] Consequently, the reported incidence of contrast-induced nephropathy in the literature might contain certain degree of deviation. Nonetheless, a close monitor‐

**Within 48 hours after procedure**

http://dx.doi.org/10.5772/54081

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## **2. Epidemiology of contrast induced acute kidney injury (AKI)**

The reported incidence of contrast-induced AKI varies widely among the existing literature, ranging from 2% to 25% after contrast medium injection [2, 13-15]. The estimations differ ac‐ cording to the cohort being studied, the definition used to identify patients with contrastinduced AKI, the distinction of the baseline risk factors of the population studied, and the intervention administered for prevention. [2] Maioli and coworkers, in a randomized con‐ trolled trial (RCT) to evaluate the effectiveness of various preventive strategies, identified a 2~2.5 fold difference in the incidence of contrast-induced AKI (control group, 12%; interven‐ tion group, 27.3%). [16] Weisbord and colleagues, in another study, demonstrated the im‐ portance of the AKI definition to the estimated incidence (ranging from 0.3% if stringently defined by serum creatinine [sCr] change of 1.0 mg/dL, to 13.7% if loosely defined by sCr change of 0.25 mg/dL). [3] Consequently, a consistent definition of contrast-induced AKI is vital for both clinical and research interest in this field.

#### **2.1. Definition of contrast-induced acute kidney injury (AKI)**

The definition of contrast-induced AKI can be divided into 2 main components, the predefined time frame and the change of renal function markers (Table 1). Typically contrastinduced AKI is defined by the current literature as an increase in sCr within the first 24 or 48 hours after contrast injection. [2, 14] There are arguments, however, that a period of 24 hours best captures the group of patients who develop contrast-induced AKI and car‐ ry the most favorable outcome; others claim that the elevation of sCr for clinical dignosis of contrast-induced AKI takes at least 48 hours. [17] The European Society of Urogenital Radiology (ESUR) has produced guidelines on contrast-induced AKI in 1999, and updat‐ ed the content in 2011. [18, 19] Contrast-induced AKI (then termed contrast-induced nephropathy [CIN]) is defined as "a condition in which an impairment in renal function (an increase in sCr by more than 25% or 0.5 mg/dL) occurs within 3 days following intra‐ vascular administration of a contrast medium, in the absence of an alternative etiology". [18] Recently, the threshold of sCr change for diagnosis of AKI has been challenged, since minor sCr change has been shown to correlate with outcome measures. [20] In 2007, Acute Kidney Injury Network (AKIN) group has proposed a further fine-tuned classifica‐ tion scheme for staging AKI. [21] Milder AKI was staged as an elevation of sCre of 0.3 mg/dL within 48 hours. This concept further enhances the diagnostic probability of con‐ trast-induced nephropathy, but there concerns that this criteria might be over-sensitive and leads to false positive diagnosis. [22] The researchers are now gradully adopting this scheme in categorzing contrast-induced AKI.

