Nephrotoxicity related to X-ray contrast media

Abstract

This survey discusses pharmacokinetic aspects and the renal glomerular and tubular side-effects of modern low osmolar X-ray contrast media (LOCM). The clearance of X-ray contrast media (CM) approximates to the glomerular filtration rate (GFR) and the CM are concentrated during their passage through the renal tubular system up to 100 times the plasma concentration during peak diuresis in patients with normal GFR. The urinary CM concentration is relatively lower in patients with renal failure.

Methods for evaluation of GFR and renal tubular function are discussed. Serum creatinine is a rather insensitive parameter for estimation of GFR, especially in patients with a small reduction of GFR, and plasma or renal clearance methods are recommended. However, serum creatinine reflects major drug-induced fluctuations in GFR, and is a suitable parameter for determination of GFR in most instances. Serum creatinine often peaks more than 72 hours after administration of CM in’ patients with reduced GFR, and should be monitored for at least 5 days in such patients.

LOCM seem to be less toxic when administered intravenously than when given intra-arterially. However, from randomized trials one can conclude that LOCM reduce the incidence of acute renal failure, as defined as an increase in serum creatinine, especially in high-risk patients.

A dose-dependent increase in the urinary excretion of renal tubular lysosomal and brush border enzymes is regularly observed after administration of CM. Dimeric LOCM seem to affect the excretion of lysosomal enzymes less than monomeric LOCM. Enzymuria is also observed after intravenous administration of equimolar doses of mannitol, but urinary enzyme excretion is significantly greater and more long-lived after CM. Thus, the enzymuria cannot be explained only by osmotic effects of the CM.

The clinical importance of this enzymuria is discussed.