Effect of urea on urine concentration in the rat.

Urea is the principal end-product of nitrogen metabolism in mammals and is excreted almost entirely through the kidney. Studies by Shannon (1, 2) in the dog and by Chasis and Smith (3, 4) in man have shown that the renal clearance of urea is less than the inulin or creatinine clearance at all rates of urine flow, and that the clearance of urea increases as the urine flow rises. These observations are consistent with the hypothesis that urea is filtered at the glomerulus and that a portion of this filtered load diffuses out of the nephron as the fluid passes from glomerulus to renal pelvis. During the past few years a considerable amount of evidence has accumulated that urea has a unique role in the renal concentrating mechanism. The maximal urinary concentration achieved during antidiuresis is reduced by a low protein diet (5-8). The addition of urea to such a low protein diet will return the maximal urine concentration to near normal levels. In medullary tissue slices removed from the kidneys of antidiuretic dogs, it has been shown that urea is one of the principal solutes (9-11). Levinsky, Davidson, Berliner and Eden (11, 12) have proposed a mechanism by which urea, accumulated in the inner medulla passively, is able to add to the urine osmolality. During the passage of tubular fluid along the collecting duct, the urea concentration rises progressively as water moves into the medullary interstitial space along the osmotic gradient created by the active transport of sodium in the medulla. The rising urea concentration in the collecting duct establishes a concentration gradient along which urea moves into the inner medulla. The urea which diffuses into the inner medulla serves to balance an equiosmolal amount of urea in the collecting duct, leaving most of the medullary sodium free to balance other osmotic constituents in the urine. It has recently been demonstrated that the permeability of the collecting duct to urea is increased by vaso-