In addition to Na+, urea forms an important part of the medullary osmotic gradient. Urea enters the filtrate by facilitated diffusion in the ascending thin limb of the loop of Henle. As the filtrate moves on, water is usually reabsorbed in the cortical collecting duct, leaving urea behind. When filtrate reaches the collecting duct in the deep medullary region, urea, now highly concentrated, is transported by facilitated diffussion out of the tubule into the interstitial fluid of the medulla, forming a pool of urea contributes substantially to the high osmolality in the medulla.
Anti diuretic hormone (ADH), which stimulates excretion of highly concentrated urine, enhances urea transport in the medullary collecting duct. When ADH is present, urea recycling is enhanced, the medullary osmotic gradient is enhanced, and more concentrated urine can be formed.