Integrating effects of aquaporins, vasopressin, distal delivery of filtrate and residual water permeability on the magnitude of water diuresis.

In physiologic terms, water diuresis has two components, the ability to excrete a large volume of water and the need to ‘desalinate’ this urine. The basic concept is that nephron segments that lack aquaporins do not reabsorb an appreciable volume of water even though there is an extremely large transtubular osmolar driving force ( table 1 ). After a large and rapid intake of water, the concentration of sodium (Na + ) in arterial plasma (P Na ) falls and the volume of cells in the brain increases [2] . The function of water diuresis is to minimize this fall in the P Na and thereby, prevent the development of a dangerous degree of brain cell swelling [3] . On the other hand, control mechanisms are needed to permit the retention of a small and safe volume of ingested water ( 1 liter in an adult), which can be used at a later time for heat dissipation by evaporation of water in sweat [4] . This explains why the arterial P Na can fall to 136 mmol/l without inhibiting the release of vasopressin sufficiently to initiate a water diuresis providing that water is not ingested quickly. If water is ingested rapidly, the arterial (but not necessarily the brachial venous) P Na falls sufficiently to provide the signal to inhibit the release of vasopressin [2] . To add a quantitative perspective to the renal control system for water homeostasis, consider a 70-kg adult huIn this issue of Nephron , Bockenhauer et al. [1] describe a family with 6 members who had mutations in the gene encoding the V 2 receptor for vasopressin that should cause congenital nephrogenic diabetes insipidus. They gathered clinical data on these patients including their response to the administration of desaminoD -arginine vasopressin (dDAVP). They performed in vitro studies of V 2 receptor cell surface expression, the affinity of vasopressin to bind to its V 2 receptor and produce cyclic AMP, as well as on the effects of the chaperone SR121463 on these parameters. Thus this is an impressive state-ofthe-art investigation, which employs a breadth of techniques. Our goal is to provide a critique of the clinical parameters that are used to determine whether a sufficient number of aquaporin-2 water channels (AQP2) are inserted in the luminal membranes of the late distal nephron in patients with nephrogenic diabetes insipidus in response to certain interventions. If this occurred, the rate of excretion of electrolyte-free water in the urine must decrease appreciably, but other causes for this fall in urine output must first be ruled out. As a background, we begin with a succinct synopsis of the physiology of this process and this is followed by an examination of the three clinical tools commonly employed in this assessment – urine flow rate, osmole excretion rate, and urine osmolality (U Osm ). Published online: January 27, 2010