Chapter 6 Renal Conservation of Folates

Folates play vital roles in one-carbon metabolism that produces the early substrates necessary for nucleotide synthesis and salvage. Folates are essential vitamins in that humans cannot synthesize them and are totally dependent on the diet to obtain them. As water-soluble vitamins, they would be easily filtered by the kidney and lost to the tubular fluid but for a highly efficient renal conservation mechanism. This renal "folate trap" is made up of alpha-folate receptors and reduced folate carriers. The locations of these transporters are such that they direct folate transport from the apical/luminal sides of kidney cells to the basolateral/plasma sides. In addition, other transporters such as organic anion transporters and multidrug resistance proteins are also found in kidney cells and play a role in renal elimination of folate analogues such as antifolate cancer chemotherapy drugs. This chapter discusses how these transporter activities manifest themselves in folate and antifolate pharmacokinetics. It also discusses effects of alcohol on renal reabsorption of folates.