Effects of Hydroflumethiazide in Congestive Heart Failure: Renal Electrolyte Excretion Related to Urinary Thiazide Excretion and Aldosterone

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Abstract
The effect of hydroflumethiazide (HFT) on renal excretion of Na+, Cl- and K+ was studied in congestive heart failure and related to urinary excretion of thiazide and aldosterone. HFT 75 or 150 mg was administered orally once daily for 4 days to 8 male patients with roentgenological evidence of enlarged heart and slight or no peripheral edema receiving digitalis and controlled diet. Urinary excretion of HFT did not change after repeated doses; urinary excretion of a metabolite increased significantly. Initially, HFT induced a significant increase in the urinary excretion of Na+ and K+. After repeated doses, the natriuretic effect declined gradually in 6 of the patients. There was consistently a small natriuretic effect and a large kaliuretic effect at high serum aldosterone concentrations and high urine aldosterone excretion rates; at low aldosterone levels, there was a wide range in magnitude of these effects. Relationships of the log urinary excretion rate of HFT to the increase in urinary excretion rate of Na+, Cl- and K showed positive and significant correlations. Evidently reduced natriuretic effect of HFT in congestive heart failure is not due to reduced delivery of thiazide to renal tubular cells but to compensatory adjustments of the kidney in part induced by aldosterone.