Contrast media nephrotoxicity

Enzymuria has been reported after the intravascular administration of high-osmolar or low-osmolar contrast media (180). The study suggested that the brush-border enzyme gamma-glutamyl transpeptidase is a better marker for tubular toxicity due to contrast media than alanine aminopeptidase. However, no relation has been established between a reduction in glomerular filtration rate, a rise in serum creatinine (the characteristic features of contrast nephrotoxicity), and the presence of enzymuria. It has been argued that the detection of urinary enzymes is of httle importance to the clinical assessment and management of contrast medium nephrotoxicity (161). 

Table 5 European Society of Urogenital Radiology (ESUR) simple guidelines to avoid Contrast Medium Nephrotoxicity (227)...

Contrast medium nephrotoxicity is a condition in which an impairment in renal function (an increase in serum creatinine by more than 25% or 44 pmol/l) occurs within 3 days after the intravascular administration of a contrast medium in the absence of an alternative cause... 

Discontinue nephrotoxic drugs—Nonsteroidal antiinflammatory drugs and diuretics should be withheld for at least 24 hours before and after exposure to contrast medium, if possible. Metformin should be withheld for 48 hours before the administration of CM and until it is certain that CIN has not occurred. 

Acute reduction in renal perfusion is considered important in the pathophysiology of contrast agent-induced nephrotoxicity. Color-coded duplex sonography has been used in assessing intrarenal vascular resistance in 10 patients (mean age 51 years) after intravenous injection of 100 ml of the low-osmolar contrast medium iopamidol (iodine 300 mg/ml) (182). The resistive index was measured at 1-minute intervals over 10 minutes after injection in each patient. There was a statistically significant rise in resistive index at 2, 3, 4, and 5 minutes after injection, mean values 0.74, 0.75, 0.72, and 0.75... 

In addition to using a small dose of low-osmolar non-ionic contrast medium and offering hydration, some authors have recommended the use of calcium channel blockers in patients at high risk of contrast nephrotoxicity. However, the effectiveness of this class of drugs in preventing contrast nephrotoxicity has not been consistently... 

A report from Italy has suggested that intravenous saline 0.4% before and after administration of the contrast medium, an infusion of dopamine 3 micrograms/kg/ minute for 24 hours after the contrast medium, intravenous furosemide 80 mg 30 minutes before the contrast medium, or intravenous mannitol (20%) 250 ml 1 horn-before and 1 hour after the contrast medium each prevented the reduction in renal function caused by the nonionic agents iobitridol, ioversol, or iodixanol (193). However, the protocol of the study was not described, and previous studies have shown that dopamine, furosemide, and mannitol do not offer good protection against contrast media-induced nephrotoxicity. On the other hand, volume expansion with intravenous saline has been found to offer some protection (190). 

Theophylline, a non-selective adenosine receptor antagonist, has also been recommended, since adenosine has been suggested to be an important mediator of contrast-induced nephrotoxicity. Patients undergoing coronary angiography with the high-osmolar contrast medium dia-trizoate (iodine 370 mg/ml) were randomized to receive either theophylline (200 mg bd orally 24 hours before and for 48 hours after coronary angiography, n = 35, mean age 54 years, mean dose of contrast medium 78 ml) or placebo (n = 35, mean age 52 years, mean dose of contrast medium 80 ml) (197). The glomerular filtration rate... 

The protective effects of intravenous hydration alone (0.45% isotonic saline, 1 ml/kg/hour for 12 hours before and 12 hours after contrast administration), fenoldopam (0.1 microgram/kg/minute for 4 hours before and 4 hours after the procedure), and acetylcysteine (600 mg bd 24 for hours before and 24 hours after the procedure) have been compared in preventing contrast nephrotoxicity after intravascular administration of low-osmolar non-ionic contrast medium (199). The incidence of nephrotoxicity was 15% in the hydration group, 16% in the fenoldopam group, and 18% in the acetylcysteine group. AU the groups were comparable and basehne creatinine clearance was about 60 ml/minute in aU the patients who received a similar dose of the contrast medium (1.5 ml/ kg). The authors concluded that fenoldopam and acetylcysteine do not offer extra protection against contrast nephrotoxicity over hydration alone. 

Gerlach AT, Pickworth KK. Contrast medium-induced nephrotoxicity pathophysiology and prevention. Pharmacotherapy 2000 20 540-548. 

More recently referred to as contrast-induced acute kidney injury (CIAKI), contrast medium-induced nephrotoxicity can occur after intravascular administration of iodinated contrast media. It is the third leading cause of acute kidney failure in hospitalized patients in the USA and Europe [11 ]. It leads to prolonged hospital stay and is associated with increased long-term morbidity and mortality. Traditionally it has been defined as an acute rise in serum creatinine by at least 44 pmoUl (0.5 mg/dl) or at least 25% above baseline within 48-72 hours of administration. The incidence is 5-50% [125], depending on the... 

Prevention Several agents have been tried in the past in order to prevent contrast-induced nephrotoxicity. These have all been directed at various proposed methods of causation [SEDA-32, 848]. The most effective to date has been intravenous hydration before and after administration of the iodinated contrast medium, either with 0.9% saline or sodium bicarbonate bicarbonate is superior to saline. 

Baumgarten DA, EUis JH. Contrast-induced nephropathy contrast material not required AJR Am J Roentgenol August 2008 191(2) 383-6. Katzberg RW, Newhouse JH. Intravenous contrast medium-induced nephrotoxicity is the medical risk really as great as we have come to believe Radiology July 2010 256(l) 21-8. 

Most contrast agents elicit nephrotoxicity because they are primarily excreted by the kidneys. However, when administered in small doses, they constitute a rich source of GFR markers. The two major classes of contrast agents that are finding clinical utility as GFR markers are iodinated aromatic compounds and metal complexes. lodinated aromatics such as iohexol and iothalamate (Fig. 13) are commonly used as contrast agents for computed tomography (GT). They also have pharmacokinetics similar to inulin and hence are useful indicators of renal status [215]. The iodinated molecules used for GFR measurements consist of a triiodo-benzene core and hydrophilic groups to enhance solubility in aqueous medium. 

The clinical and biological tolerance of iobitridol (Xenetix, a non-ionic medium, osmolality 915 mosmol/ kg at an iodine concentration of 350 mg/ml) has been assessed in a placebo-controlled study in 21 patients with chronic renal insufficiency (glomerular filtration rate less than 60 ml/minute) (170). Serum creatinine and creatinine clearance remained stable 24 and 48 hours after the procedure. No patient had a nephrotoxic reaction or acute oliguria. Only one patient given iobitridol had an increase in serum creatinine of more than 15% from baseline the serum creatinine normalized within 4 days of contrast administration. One patient given placebo had... 

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