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 intravascular handling and retention of CM in relation to effects on renal function - specifically the ability of the kidney to reabsorb and catabolise low molecular weight proteins. Renal morphology following experimental administration of a high dose of an isotonic dimeric CM (iodixanol at 3 g I/kg) in rats showed numerous, large, protein-containing vacuoles or droplets in the cells of the proximal convoluted tubule. These were fully formed within 3.5 hours. The process of vacuole-formation involving the uptake of CM appears to be analogous to dextran uptake that occurs via fluid phase endocytosis. These vacuoles or CM droplets are abundant for 7 days but then slowly decline over several weeks. The quantitative recovery of (14)C iodixanol (3g I/kg) from the kidneys between 3.5 hours to 7 days after administration was about 1% of the dose, with some 0.2% of the original dose still present at 28 days. Subcellular analysis to determine the site of the radiolabel showed that the (14)C was associated with lysosomal marker enzymes. The CM-induced vacuoles/droplets are most probably giant lysosomes, which contain the intracellularly retained CM. Co-administration of tracer doses of (125)I-labelled cytochrome C with iodixanol showed some impairment of low molecular weight protein reabsorption, but remarkably this process was not effected when the vacuoles were fully formed. The conspicuous morphology of the vacuoles, the CM retention and the transient proteinuria and enzymuria cannot presently be associated with any functionally significant impairment of tubular or cellular processes.