BIOCHEMICAL AND MORPHOLOGICAL EFFECTS OF CONTRAST-MEDIA ON THE KIDNEY

The intravenous use of roentgen contrast media (CM) is associated with a low incidence of renal impairment. This paper considers the intrava scular handling and retention of CM in relation to effects on renal fu nction-specifically the ability of the kidney to reabsorb and cataboli se low molecular weight proteins. Renal morphology following experimen tal administration of a high dose of an isotonic dimeric CM (iodixanol at 3 g I/kg) in rats showed numerous, large, protein-containing vacuo les or droplets in the cells of the proximal convoluted tubule. These were fully formed within 3.5 hours. The process of vacuole-formation i nvolving the uptake of CM appears to be analogous to dextran uptake th at occurs via fluid phase endocytosis. These vacuoles or CM droplets a re abundant for 7 days but then slowly decline over several weeks. The quantitative recovery of C-14 iodixanol (3 g I/kg) from the kidney be tween 3.5 hours to 7 days after administration was about 1% of the dos e, with some 0.2% of the original dose still present at 28 days. Subce llular analysis to determine the site of the radiolabel showed that th e C-14 was associated with lysosomal mark er enzymes. The CM-induced v acuoles/droplets are most probably giant lysosomes, which contain the intracellularly retained CM. Co-administration of tracer doses of I-12 5-labelled cytochrome C with iodixanol showed some impairment of low m olecular weight protein reabsorption, but remarkably this process was not affected when the vacuoles were fully formed. The conspicuous morp hology of the vacuoles, the CM retention and the transient proteinuria and enzymuria cannot presently be associated with any functionally si gnificant impairment of tubular or cellular processes.