Renal hemodynamics and water excretion in Addison's disease

Abstract

Patients with Addison's disease have impaired ability to excrete free water. The mechanism of this defect is still not clear. These experiments were designed to help clarify the role of altered renal hemodynamics in the genesis of the defect. Six patients with Addison's disease were studied. Enough salt and water was administered to maintain adequate hydration throughout the study but no hormonal replacement was instituted. After a water load, the urine output (V), free water clearance (C H 2O ), sodium excretion (U NaV), total solute clearance (C Osm), inulin clearance (C ln), and para-aminohippurate clearance (C PAH) were measured by standard clearance techniques. In the control studies V and C H 2O were abnormally low. The studies were repeated after administration of DOCA, 2.5 mg daily, for a week. This medication decreased U NaV and improved the plasma electrolyte profile but did not cause a significant change in V, C H 2O , GFR, or RPF. The same studies were repeated once more after administration of prednisone, 5 mg daily in divided doses, for a week. This drug induced a marked water diuresis while GFR and RPF remained unchanged. It is concluded that hypovolemia and altered renal hemodynamics are not the only mechanisms of the impaired water excretion in Addison's disease. A severe defect remains after normalization of hypovolemia and this is corrected by prednisone but not by DOCA, through mechanisms which do not involve changes in GFR or RPF.