Impacts of UT‐A2 inhibition on urine composition: a mathematical model (1137.8)

The urea transporter UT‐A2 is expressed in the inner‐stripe segments of the thin descending limb of Henle in superficial nephrons (SDL), and in the initial inner medullary (IM) segments of the descending limb in juxtamedullary nephrons. It was previously assumed that some of the urea ascending from the IM in the ascending vasa recta was “recycled” in the SDL, which run in close proximity to the vascular bundles in rats and mice. However our model simulations suggest that when urea is actively secreted into the pars recta, a hypothetical scenario has yet to be demonstrated experimentally, there is net urea reabsorption along the SDL. We use a dynamic model of the urine concentrating mechanism to investigate the hypothesis that the role of the SDL UT‐A2 lies in the transient buildup of urea and osmolality gradient of the IM, rather than in the maintenance of the steady‐state gradients. This motivation for this hypothesis is that the transit time for urea reabsorbed in the SDL to return to the IM via the descending vasa recta is significantly shorter than for urea to traverse the thick ascending limb and subsequently be reabsorbed in the terminal collecting duct. Also, during the generation of the IM urea gradient, active urea secretion into the pars recta of the long loops may yield a transepithelial gradient favorable for urea delivery by the long thin descending limbs into the interstitium, thereby adding to the urea delivered to the IM interstitium through the terminal collecting duct. This research was supported in part by NIH grant DK‐89066. Grant Funding Source : NIH DK089066