Endocrine and metabolic regulation of renal drug transporters

Abstract

Renal xenobiotic transporters are important determinants of urinary secretion and reabsorption of chemicals. In addition to glomerular filtration, these processes are key to the overall renal clearance of a diverse array of drugs and toxins. Alterations in kidney transporter levels and function can influence the efficacy and toxicity of chemicals. Studies in experimental animals have revealed distinct patterns of renal transporter expression in response to sex hormones, pregnancy, and growth hormone. Likewise, a number of disease states including diabetes, obesity, and cholestasis alter the expression of kidney transporters. The goal of this review is to provide an overview of the major xenobiotic transporters expressed in the kidneys and an understanding of metabolic conditions and hormonal factors that regulate their expression and function.

Figure 1. Transporters in kidneys

The tubule cell on the left illustrates the proposed and demonstrated localization of basolateral uptake and apical efflux transporters involved in tubular secretion or excretion. The tubule cell on the right illustrates the apical uptake and basolateral efflux transporters involved in tubular reabsorption. It has been proposed that Oatp1a4, 1a6, 2a1, 2b1, and 3a1 are localized to the luminal surface with Oatp4c1 on the basolateral membrane (136).