The tubule fluid entering the collecting duct is at about the same solute concentration as the blood plasma, but its solute composition is considerably different from that of the plasma. The major solute in the tubule fluid is now urea, since salts were reabsorbed earlier in the nephron. As the tubule fluid flows down the collecting duct, it loses water osmotically to the interstitial fluid, and that water returns to the circulatory system via the vasa recta (see Figure 51.10, note 4).

The concentration gradient established in the renal medulla by the countercurrent multiplier actions of the loops of Henle creates the osmotic potential that withdraws water from the collecting ducts. The collecting ducts begin in the renal cortex and run through the renal medulla before emptying into the ureter at the tips of the renal pyramids. During this journey, the solute concentration of the surrounding interstitial fluid increases, and more and more water can be absorbed from the urine in the collecting duct. By the time the urine reaches the ureter, it can become greatly concentrated, with urea as the major solute.

As water is withdrawn from the collecting duct, some urea also leaks out into the medullary interstitial fluid, adding to its osmotic potential. This urea diffuses back into the loop of Henle and is returned to the collecting duct. The recycling of urea in the renal medulla contributes significantly to the concentration gradient and therefore the ability of the kidney to concentrate the urine in the collecting duct. The ability of a mammal to concentrate its urine is determined by the maximum concentration gradient it can establish in its renal medulla.