Minimum urine flow rate during water deprivation: Importance of the permeability of urea in the inner medulla

We evaluated whether altering the rate of excretion of sodium (Na) and chloride (Cl) when antidiuretic hormone (ADH) acts would cause urea to behave as an 'effective' or 'ineffective' urinary solute. Urine composition was compared to that in the excised papillary tip in rats treated with DDAVP while on a normal or a low electrolyte diet; half the rats were given a urea load. Studies were also carried out in humans who were water restricted for 12 to 16 hours and given DDAVP. One group had a high rate of NaCl excretion induced by a thiazide diuretic, while the other group consumed a low salt diet to decrease the rate of excretion of electrolytes. Urea (3 mmol/kg) was ingested after the control urine samples were collected. On the high salt protocols, the urine flow rate was directly proportional to the rate of excretion of electrolytes ('non-urea' osmoles) and there was no change in the 'non-urea' osmolality despite large changes in Na and Cl excretion rates. After urea was administered, there was no change in urine flow rate, 'non-urea' osmolality, or 'non-urea' osmole excretion rate, whereas the urinary urea concentration, urine osmolality and the rate of excretion of urea were higher. The papilla of the salt-loaded rats had a similar urea concentration to that in the urine. In contrast, in the low electrolyte excretion protocols, the sum of the concentrations of 'non-urea' osmoles in the urine was much lower than that in the excised papilla, and the converse applied to urea. Similar changes were observed in the composition of the urine in human subjects with high and low rates of excretion of electrolytes. We conclude that urea appears to be an 'ineffective' urine osmole when there is a high rate of salt excretion, whereas urea is an 'effective' osmole when there is a low rate of excretion of electrolytes.