Renal excretory profiles of loop diuretics: consequences for therapeutic application

In healthy subjects, 24-h natriuresis, kaliuresis, calciuresis, and magnesiuresis increase in response to the first oral dose of a standard (diuretic) formulation of a loop diuretic, such as furosemide 40 mg. However, low-dose formulations of loop diuretics, such as torasemide 2.5 mg, do not elevate 24-h natriuresis after the first dose is administered to normal individuals who are in steady-state habitual sodium balance; these formulations of loop diuretics are consequently labeled as nondiuretic formulations (of diuretic substances). Nondiuretic formulations of loop diuretics do not increase the 24-h urinary outputs of sodium, potassium, calcium, or magnesium after the first dose or in the course of repeated once-daily administration to healthy subjects. The 24-h natriuretic response to the first dose of standard (diuretic) formulations of loop diuretics wanes during repeated once-daily administration to healthy individuals, whereas the kaliuretic response becomes slightly attenuated, and calciuresis and magnesiuresis bear little change. Once-daily treatment with any formulation of a loop diuretic may result in an increase in plasma urate concentration. Nondiuretic formulations of loop diuretics, which are efficacious as once-daily monopharmacotherapy for high blood pressure, should be tried before standard (diuretic) formulations of diuretics are used in the treatment of uncomplicated essential hypertension. When loop diuretics are employed in the treatment of congestive heart failure, the minimal dose compatible with the attainment of clinical objectives should be used.