Contrast agents, nephrotoxicity

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 ultrasound contrast agents are manufactured from nontoxic natural or synthetic biodegradable materials (e.g., lipids or proteins), and a small amount of an inert low-solubility non-reactive gas (e.g., perfluorocarbon). These components have been shown to be harmless to the patient unlike the tens of milliliters of concentrated viscous solutions of the widely used X-ray contrast agents (which may sometimes result in nephrotoxicity). 

Briguori C, Manganelli R Scarpato R et al. Acetylcysteine and contrast agent-associated nephrotoxicity. J Am Coll Cardiol 2002 40 298-303. 

This case underlines the fact that there is still misunderstanding about the nephrotoxic potential of gadolinium-based contrast agents. They should not replace iodinated contrast agents in patients with renal insufficiency. The recommended doses of up to 0.3 mmol/kg will not give satisfactory radiographic diagnostic information in most cases. 

There are wide variations in the reported incidence of contrast nephrotoxicity because of differences in patient selection, the type of radiological procedure, and the definition of renal impairment. Contrast nephrotoxicity is relatively uncommon in people with normal renal function, in whom it is 0-10%. Pre-existing renal impairment increases the frequency, with a reported incidence of 12-27% in several prospective controlled studies. In some studies the incidence was as high as 50%, in spite of the use of low-osmolar contrast agents and adequate hydration. Dialysis may be required in some of these patients (SEDA-22, 502). 

There are several susceptibility factors for the development of contrast agent-induced renal damage, including pre-existing renal insufficiency, particularly if it is secondary to diabetes melhtus, dehydration, multiple repeat exposure to contrast media within a short period of time (72 hours), congestive heart failure, or concurrent administration of nephrotoxic drugs, such as non-steroidal antiinflammatory drugs (171). 

Hepatic cirrhosis is not a susceptibihty factor, according to the results of a study in 72 patients with hepatic cirrhosis and 72 controls, who received 100-150 ml of low-osmolar contrast media intravenously for abdominal or chest CT scans (174). Serum creatinine was measured before and 48-72 hours after the administration of the contrast agent. The incidence of contrast nephrotoxicity was comparable in the two groups (two patients in the cirrhosis group and one control). 

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... 

The use of prophylactic hemodialysis, in most cases starting more than 20 minutes after injection of a contrast agent, has been investigated in 113 patients with renal insufficiency (serum creatinine concentration over 200 pmol/l) (186). Hemodialysis did not reduce the incidence of contrast nephrotoxicity. This failure could have been related to the rapid onset of renal injury after the administration of the contrast agent. 

Studies on the mechanisms of radiocontrast nephrotoxicity have been performed in IPRK with conflicting results. While some studies provided modest support for the contrast -induced renal vasoconstriction theory, perhaps resulting from reduced nitric oxide or increased endothelin release, others demonstrated that different contrast agents had varying effects on the renal circulation. For example, pretreatment with BQ123 (a selective endothehn (ETA) receptor antago-... 

Schwab SJ, Fllatky MA, Pieper KS, Davidson CJ, Morris KG, Skelton TN, BashoreTM. Contrast nephrotoxicity a randomized controlled trial of a nonionic and an ionic radiographic contrast agent. N Engl J Med 1989 320 149-153. 

Briguori C, Manganelli E, Scarpato P, Elia PP, Golia B, Riviezzo G, Lepore 5, Librera M, Villari B, Colombo A, Ricciardelli B. Acetylcysteine and contrast agent-associated nephrotoxicity. J Am Coll Cardiol. 2002 40 298-303. 

R. Safirstein, L. Andrade, and J. M. Vieira Acetylcysteine and nephrotoxic effects of radiographic contrast agents—a new use for an old drug. The New England Journal of Medicine 343, 210 (2000). 

Davidson CJ, Hlatky M, Morris KG, Pieper K, Skelton TN, Schwab SJ, Bashore TM. Cardiovascular and renal toxicity of a nonionic radiographic contrast agent after cardiac catheterization. A prospective trial. Ann Intern Med 1989 110 119-124. D Elia JA, Gleason RE, Alday M, Malarick C, Godley K, Warram J, Kaldany A, Weinrauch LA. Nephrotoxicity from angiographic contrast material. A prospective study. Am J Med 1982 72 719-725. 

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