The effects of hydrochlorothiazide on the renin-aldosterone system

Abstract

This study prospectively evaluates the determinants and time course of diuretic-induced secondary hyperaldosteronism. Initial metabolic balance studies (days 5–7) and subsequent out-patient studies (days 8–28) were undertaken in 6 healthy subjects receiving hydrochlorothiazide 50 mg/day. Upon initiation of therapy, a discordance was observed between the natriuresis (maximal on day 1), the plasma renin activity (PRA) (maximal on day 3), and aldosterone secretion (maximal on day 7). The PRA increment correlated best with the urinary sodium deficit and the aldosterone increment correlated best with both PRA and urinary sodium deficit together. The secondary hyperaldosteronism persisted throughout the study, as determined by the aldosterone secretion rate, but the tetrahydroaldosterone excretion and the plasma aldosterone became normal within 3 wk of diuretic therapy. Hypokalemia also persisted throughout the study and was probably related to the secondary hyperaldosteronism since the urinary potassium deficit correlated with the aldosterone secretion but not the sodium excretion. In conclusion, (1) the urinary sodium deficit is the major determinant of diuretic-induced secondary hyperaldosteronism, (2) secondary hyperaldosteronism is the most important factor maintaining diuretic-induced hypokalemia, and (3) secondary hyperaldosteronism may be overlooked if only tetrahydroaldosterone excretion or plasma aldosterone levels are measured during diuretic therapy.