The intravascular administration of contrast media (CM) can produce acute haemodynamic changes in the kidney characterized by an increase in renal vascular resistance and a decrease in the glomerular filtration rate (GFR). These changes may lead to clinically significant reduction in renal function in patients with pre-existing risk factors such as diabetic nephropathy, congestive heart failure and dehydration. The pathophysiology of the renal haemodynamic effects of CM involves activation of the tubuloglomerular feedback (TGF) mechanism and the modulation of the intrarenal production of vasoactive mediators such as prostaglandins, nitric oxide, endothelin and adenosine. The TGF response is osmolality-dependent and accounts for about 50% of the acute functional effects of high osmolar CM on the kidney. Reduction in the synthesis of the endogenous vasodilators nitric oxide and prostaglandins increases the nephrotoxicity of CM. Endothelin and adenosine play a crucial role in mediating the acute functional effects of CM. Antagonists of these mediators attenuate the reduction in renal function induced by contrast agents. Vacuolization of the cells of the proximal tubules and necrosis of those of the medullary ascending limbs of loops of Henle are the main structural effects of CM in the kidney. The reduction in renal function induced by CM could be minimized by the use of low osmolar CM and adequate hydration. The prophylactic administration of calcium channel blockers and adenosine antagonists such as theophylline may also offer some protective effect.

Adverse reactions to iodinated contrast media (ICM) are more likely to develop in patients with asthma, a history of allergy or contrast reaction and in those who are debilitated or medically unstable. These reactions can be divided into renal and general, and the latter are subdivided into acute and delayed. Acute general reactions can be minor, intermediate or severe. Fatal reactions are rare. The introduction of low-osmolality agents has caused an overall reduction in the number of non-fatal contrast reactions. Prompt recognition and treatment of acute adverse side effects to ICM is invaluable and may prevent a reaction from becoming severe. Familiarity with cardiopulmonary resuscitation is essential for successful management of life-threatening reactions. Contrast-media-induced renal impairment can be reduced with the use of low-osmolality contrast media and extracellular volume expansion. The use of ICM in diabetic patients receiving metformin should be carried out with care to avoid metformin-induced lactic acidosis. However, this problem is mainly observed in patients with diabetic nephropathy.

Combined acute inhibition of the synthesis of nitric oxide with L-nitroarginine methyl ester (L-NAME) and of prostacycline synthesis with indomethacin predisposes rats to severe renal injury from radiographic contrast media. The reliability of this pharmacological manipulation in the study of radiographic contrast medium induced nephropathy (RCMN) was investigated. Adult male Sprague-Dawley rats were injected with iv L-NAME (10 mg kg(-1)) and iv indomethacin (10 mg kg(-1)) 15 min apart and prior to injection of RCM or normal saline (control group). A dose-dependent reduction in renal function was observed after intravascular injection of the high osmolar RCM diatrizoate (Angiografin, 306 mgI ml(-1)). A significant (p<0.01) increase in serum creatinine (Cr) (from 54.66+/-8.39 micromol l(-1) to 171.96+/-24.49 micromol l(-1) and from 80.95+/-6.73 micromol l(-1) to 204.76+/-16.73 micromol (-1), n=5 per group) was observed 24 h after injection of 6 ml and 8 ml of diatrizoate, respectively. The increase in serum Cr after injection of 8 ml of diatrizoate recovered spontaneously to 80.87+/-8.70 micromol l(-1) 7 days after injection. No significant change in renal function was observed in the control group (n=5) receiving 8 ml kg(-1) of normal saline or after injection of 4 ml of diatrizoate (serum Cr 69.84+/-5.5 micromol l(-1) pre contrast injection and 66.67+/-13.47 micromol l(-1) 24 h post contrast injection, n=5). The increase in serum Cr observed with 6 ml of diatrizoate was significantly higher (p<0.01) than the rise induced by equivolume of the low osmolar non-ionic monomer iopromide (Ultravist, 300 mgI ml(-1)) (serum CR 68.47+/-8.39 micromol l(-1) pre contrast injection and 143.59+/-32.03 micromol l(-1) 24 h post contrast injection, n=5). The calcium channel blocker diltiazem (10 mg kg(-1) injected intraperitoneally 30 min prior to RCM injection) prevented the rise in serum Cr observed with 6 ml of diatrizoate (serum Cr pre contrast injection 70.31+/-7.28 micromol(-1) and 78.21+/-17.81 micromol(-1) 24 h post contrast injection in animals pre-treated with diltiazem, n=5). The protective effect against RCM-induced reduction in renal function was less with lower doses of diltiazem. In conclusion, the animal model used is reliable and reproduced previously established observations in the field of RCMN. The protective effect of a calcium channel blocker at the appropriate dose against RCMN has also been shown. The clinical effectiveness of this class of drugs in preventing RCMN requires further evaluation.

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