ABSTRACT
Although the kidneys only comprise 1%–2% of total body weight, they can play an important, if not critical, role in overall drug metabolism in the body. There are several factors that are responsible for the ability of the kidneys to play such a disproportionately important role. First, despite their weight, the kidneys receive approximately 25% of the cardiac output, thereby delivering a large proportion of blood-borne chemicals to the renal circulation. A second major factor is that by multiple mechanisms that are a central, underlying part of the basic physiology of the kidneys, drugs and chemicals may become concentrated within renal epithelial cells to levels that are often markedly higher than those to which the tissue is exposed. These concentrating mechanisms include glomerular filtration, the counter-current circulatory system that operates in the distal nephron and has the physiological function of concentrating the tubular fluid several-fold over that in the plasma, and the existence of a large array of transporters for organic anions and cations on the basolateral and luminal membranes of renal epithelial cells. 340A third reason for the importance of the kidneys in drug metabolism is that once inside the renal cell, many of the same enzymes that have been classically studied in liver are also present, enabling metabolism to occur. A review of many of these enzymes, as well as some that are unique to the kidneys or that have unique characteristics compared to those in other organs because of renal morphology or physiology, are the primary areas of focus for this chapter.
