The role of urea in the urine concentrating mechanism.

Many years ago, Gamble, McKhann, Butler and Tuthill (1) described "an economy of water in renal function referable to urea." Recently, experiments in the rat (2-4) and man (5) have confirmed their suggestion that the urine volume required to excrete a given solute load is reduced when urea is a principal urinary solute. An hypothesis assigning a unique role to urea in the urine concentrating process has been presented in the preceding paper (6) and elsewhere (7). In this paper, it is demonstrated that urine concentrating ability is reduced in dogs on a low protein diet, and that this defect is reversed acutely when urea is given. A similar acute effect of urea is also shown to occur in man. The data support the hypothesis that the passive accumulation of urea in the medullary interstitial fluid accounts for its ability to enhance urine concentration.