Minimum urine flow rate during water deprivation: Importance of the nonurea versus total osmolality in the inner medula

Antidiuretic hormone leads to an increase in the permeability for water and urea in the inner medullary collecting duct. Hence, urea may not be an 'effective' osmole in the inner medulla during maximal renal water conservation. Accordingly, the purpose of this study was to evaluate whether differences in the rate of urea excretion would influence maximum renal water conservation in humans. In water-deprived rats, the concentration of urea and total osmolality were somewhat higher in the urine exiting the inner medullary collecting duct than in interstitial fluid obtained from the entire papillary tip. Nevertheless, the 'nonurea' (total osmolality minus urea in millimolar terms) osmolality was virtually identical in both locations. Chronically fasted human subjects that were water-deprived for 16 h had a lower rate of urea excretion (71 ± 7 versus 225 ± 14 μmol/min) and a somewhat lower urine osmolality (745 ± 53 versus 918 ± 20 mosmol/kg H₂O). Nevertheless, they had identical urine flow rates (0.5 ± 0.01 and 0.5 ± 0.02 ml/min, respectively), and their nonurea osmolality also was similar (587 ± 25 and 475 ± 14 mosmol/kg H₂O, respectively) to the water-deprived normal subjects. The composition of their urine differed in that the principal nonurea osmoles became NH₄⁺ and β-hydroxybutyrate rather than Na and Cl. During water deprivation in normal subjects, the ingestion of urea caused a twofold rise in urine flow rate, a fall in the nonurea osmolality, and a rise in the rate of excretion of nonurea osmoles. The nonurea osmolality of the urine, and presumably the medullary interstitial fluid as well, was inversely related to the urea excretion rate. In chronic fasting, the nature, but not the quantity, of nonurea osmoles changed. The similar minimum urine volume was predictable from an analysis based on nonurea osmole considerations.