Structure-function relationships of iodinated contrast media and risk of nephrotoxicity.

Characteristics of CM have greatly changed over time. First-generation ionic CM have many-fold (5-7) greater osmolalities than plasma. Subsequently non ionic CM generations were looked for to reduce osmolality, and encompass nonionic monomers and nonionic dimers reaching osmolality as low as that of plasma (iso-osmolar CM) but paying however dear, as viscosity is considerably increased. Intrarenal microcirculation has its "Achilles" heel in the outer medulla, where the smallness of capillary lumen and the slackness of the capillary mesh render regular blood flow at high risk, mainly because it is the same area in which the only renal work needing oxygen is made and? Iodinated CM may exert their nephrotoxic effects in three different ways: by interfering with vascular hemodynamics, by interfering with intratubular fluid volume and composition, and by producing direct cytotoxic effects to glomerular and tubular cells due to iodine by-itself. Furthermore, effects of oxygen free radical can damage glomerular cells by increasing the permeability and tubular cells impairing specific function and leading to apoptosis. Although clinical nephrotoxicity has considerably improved over time, there is no evidence for an a priori superiority of a specific CM. In general, low-osmolar (2-3 times blood) and iso-osmolar (the same as blood) CM are recommended, keeping in mind that within last generation CM dimeric iso-somolar compounds reach viscosity values higher than monomeric low-osmolar compounds and hyperviscosity is a neglected mechanisms of nephrotoxicity. We suggest that CM should be classified not only by osmolality, but also by viscosity.