Both the thin ascending limb of the loop of Henle and the inner medullary collecting duct are relatively permeable to urea, whereas the thin descending and thick ascending limbs of the loop of Henle, the distal tubule, and early parts of the collecting system are relatively impermeable to urea. The reabsorption of water along the nephron thus leads to a rise in the tubular urea concentration. During hypovolemia, when levels of vasopressin are high and water is maximally reabsorbed, the inner medullary interstitial fluid urea concentration concomitantly rises, owing to the increased concentration gradient for the passive transport of urea out of the collecting duct system. This effect is enhanced because urea transporter UT-A1 in the inner medullary collecting duct is directly sensitive to vasopressin and upregulates its expression. Thus, the increased steady-state level of urea in the plasma of acutely dehydrated patients is a reflection of the increased urea concentration in the medullary interstitium, owing to a vasopressin-mediated elevation in urea reabsorption in the collecting ducts.
