**Contrast Medium-Induced Nephropathy (CIN) Gram-Iodine/GFR Ratio to Predict CIN and Strategies to Reduce Contrast Medium Doses**

Ulf Nyman *Lund University Sweden* 

#### **1. Introduction**

194 Coronary Interventions

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> Radiographic iodine contrast media (I-CM) has been recognized as the third leading cause of hospital-acquired renal insufficiency or the most common cause among pharmaceutical agents (Nash et al., 2002) with an overall incidence of contrast medium-induced nephropathy (CIN) of 1-2% following percutaneous coronary angiography (PCA) and interventions (PCI) (Mehran & Nikolsky, 2006). The presence of multiple CIN risk factors or high-risk clinical scenarios may create a substantial risk of CIN (≈50%), acute renal failure (≈15%) requiring dialysis and an increased morbidity and mortality (Marenzi et al., 2004; McCullough et al., 2006a, 2006b). At the same time it has been argued that the risk of CIN is lower following IV administration of CM in connection with computed tomography (CT) than after IA injections during cardiac procedures (Davidson et al., 2006; Katzberg & Barrett, 2007; Katzberg & Newhouse, 2010), though there exist no comparative studies based on matched risk factors and CM doses.

> Reliable prediction of pre-procedural renal function, identification of CIN risk factors, institution of adequate prophylactic regimens and to modify examination technique to reduce CM-dose are crucial to reduce patient suffering and cost since curative treatment is not available. A wide spectrum of CIN risk factors including high age, diabetes mellitus, poor cardiac function, and hemodynamic instability has been thoroughly outlined in recent reviews (McCullough et al., 2006b; Mehran & Nikolsky, 2006).

> A number of prophylactic regimen studies has been performed and meta-analyzed (Kelly et al., 2008). So far no adjunctive medical pharmacological treatment has convincingly been proved to be efficacious in reducing the risk of CIN (Stacul et al., 2006) including acetylcysteine (Biondi-Zoccai et al., 2006) and hydration with sodium bicarbonate instead of saline (Zoungas et al., 2009). Haemodialysis is ineffective and hemofiltration is impractical in routine clinical practice (Stacul et al., 2006).

> Thus, treating modifiable risk factors (Mehran & Nikolsky, 2006), instituting adequate intravenous volume expansion with isotonic crystalloid (Stacul et al., 2006) and withdrawal of nephrotoxic drugs, mannitol and loop diuretics are three of the four corner stones to reduce the risk of CIN (Thomsen et al., 2008a). The fourth one is to minimize the dose of the

Contrast Medium-Induced Nephropathy (CIN)

mechanisms as an IV injection will do.

or even longer.

after IA administration.

**3. Evaluation of renal function** 

≤50 mL/min (Duncan et al., 2001).

prediction equation the following should be considered:

Gram-Iodine/GFR Ratio to Predict CIN and Strategies to Reduce Contrast Medium Doses 197

ventriculography (6-8 mL of an injected volume of 30-40 mL of 320 to 370 mg I/mL) of a total mean dose commonly ranging between 50 to 100 grams of iodine during a coronary procedures. Spill-over into the aorta also occurs during selective coronary artery injections and through side-holes of guiding catheters during PCI. However, the amount during each injection is so small that it will hardly affect plasma osmolality to cause any hypertonic renal effects and will therefore only affect the kidneys with the same pathophysiological

In the relatively few published reports of CIN following CM-enhanced CT the incidence may vary between 0 and 42% depending on definitions, degree of renal impairment and number and degree of risk factors (Katzberg & Newhouse, 2010; Nguyen et al., 2008; Polena et al., 2005; Tepel et al., 2000; Thomsen et al., 2008b). In a recent prospective study of unselected emergency patients 11% (n=70/633) increased their serum creatinine ≥44 μmol/L or ≥25% of whom 9% (n=6) developed CM-induced severe renal failure, which contributed to death in 4 of the 6 patients (Mitchell et al., 2010). Another CIN study showed that IV CM injections were actually associated with a higher mortality risk than IA administration (From et al., 2008). One explanation may be that the entire CM dose in CT is injected within one minute and thus may strike the kidneys at a considerable higher dose rate compared with a coronary arterial procedure that may last for 15-30-60 minutes

It should also be noted that in randomized studies comparing renal effects of various CM, high-risk patients (e.g. unstable renal function, heart failure, uncontrolled diabetes, recent CM examinations, etc.) are often excluded (Barrett et al., 2006; Kuhn et al., 2008; Nguyen et al., 2008; Thomsen et al., 2008b). This bias in patient selection compared with coronary studies, where high-risk patients can not be excluded from life-saving procedures, may in part explain the illusive opinion that an IV CM injection implies a lesser risk of CIN than an IA. Thus, it may seem premature to consider the risk of CIN less following IV injections than

It is well recognized that serum creatinine is a poor predictor of renal function (Perrone et al., 1992), especially in elderly patients with decreasing muscle mass, the major source of creatinine. In one study 50% of patients ≥70 years with a normal serum creatinine had a GFR

Measurement of GFR based on exogenous markers such as inulin and I-CM is regarded the best indices of the level of renal function in health and disease (Stevens et al., 2006), but is work-intensive, relatively expensive, time-consuming and therefore unsuitable in clinical practice prior to CM administration. Instead, GFR should be estimated (eGFR) taking into account not only serum creatinine but also anthropometric (weight and height) and/or demographic (gender and age) data as a measure of muscle mass by using dedicated GFR prediction equations (Stevens et al., 2006) such as the MDRD (Modification of Diet in Renal Disease) (Levey et al., 2007), CKD-EPI (Levey et al., 2009) and Lund-Malmö equations (Nyman et al., 2006). Consequently, newly developed CIN risk scores include eGFR using prediction equations (Bartholomew et al., 2004; Mehran et al., 2004). Before adapting a GFR

offending agent itself, i.e. the contrast medium (Davidson et al., 2006; Kane et al., 2008; Sterner et al., 2001). Though low- and iso-osmolal CM should be substituted for highosmolal CM (Barrett & Carlisle, 1993; Rudnick et al., 1995), the benefit of iso- over lowosmolal CM is only suggestive but not statistically significant according to a recent metaanalysis (From et al., 2010).

The present chapter will focus on:

