Nephropathy following contrast media (CM) exposure is reduced by administration before, during, and after the contrast procedure of either isotonic sodium chloride solution (Saline) or isotonic sodium bicarbonate solution (IsoBicarb). The reasons for this reduction are not well established for either sodium salt; probable mechanisms are discussed in this paper. For Saline, the mechanism for the decrease in CIN is likely related primarily to the increased tubular flow rates produced by volume expansion and therefore a decreased concentration of the filtered CM during transit through the kidney tubules. Furthermore, increased tubular flow rates produce a slight increase in tubular pH resulting from a fixed acid excretion in an increased tubular volume. The mechanism for the decreased CIN associated with sodium bicarbonate includes the same mechanisms listed for Saline in addition to a renal pH effect. Increased filtered bicarbonate anion raises both tubular pH and tubular bicarbonate anion levels toward blood physiologic levels, thus providing increased buffer for reactive oxygen species (ROS) formed in the tubules as a result of exposure to CM in renal tubular fluid.