The kidney is responsible for maintaining the body balance of electrolytes (e.g., sodium, potassium, and chloride), and non-electrolytes (e.g., glucose). Many studies have demonstrated the importance of renal handling of these compounds for maintaining normal human health and in the pathogenesis of a host of diseases including diabetes and hypertension. Renal maintenance of the body balance of a compound is achieved primarily by the net directional movement of the compound across the epithelial cells that form the renal tubules, moving the compound from the blood into the forming urine (secretion) or from the forming urine into the blood (reabsorption). This net compound movement is mediated by the asymmetric distribution of specific proteins (transporters, channels, and primary active pumps) between the distinct domains of the renal tubular cell plasma membrane that face the forming urine (apical membrane) and the interstitium and blood (basolateral membrane). The rate of secretion or reabsorption of a compound across the tubular epithelium is controlled, in part, by modulating the activities of the specific transporters at each membrane involved in moving this compound.

Laboratories in the Division of Nephrology are actively engaged in research to understand how a variety of compounds move across or into the tubular epithelial cells. One group is examining the mechanism by which the renal tubular cells transport urate. This group has identified, characterized, cloned, and reconstituted a functional urate channel. They are currently defining how it functions at the molecular level to move urate across the membrane and how its functional activity is regulated by the renal epithelial cell.

Another group is pursuing their finding that DNA is moved across cell membranes by a specific channel. They have characterized the channel properties and have identified multiple proteins that combine to form the functional channel. Their current research is continuing to identify all of the proteins that comprise this channel, to determine how its functional activity is regulated by the cell, and to understand the role of this channel in normal cell and renal physiology.

A third group is studying the mechanisms by which the kidney regulates the body balance of potassium. They are defining the transporters that move potassium across the apical and the basolateral membrane of the multiple portions of the tubule. Their studies also are defining how these transporters are expressed during development, a process that has critical implications for pediatric medicine, and how they are regulated in response to various body stresses.

A fourth group is studying the role of sodium transport in the pathogenesis of Autosomal Recessive Polycystic Kidney Disease. They have demonstrated that, in contrast to expectations, sodium reabsorptive capacity is increased in renal epithelial cells lining the forming renal cysts, as compared to renal epithelial cells lining the normal tubular regions. They are pursuing these studies to understand if and how this impacts cyst formation and disease progression.