DIURETIC EFFECTIVENESS OF HYDROCHLOROTHIAZIDE AND FUROSEMIDE ALONE AND IN COMBINATION IN CHRONIC-RENAL-FAILURE

In the absence of formal clinical trials, the efficacy of thiazide diu retics in patients with renal impairment remains in doubt. Our study w as therefore designed to evaluate the separate and combined effects of single and multiple doses of hydrochlorothiazide (HCTZ) and furosemid e (FU) on the glomerular filtration rate (GFR) and electrolyte excreti on in 19 patients with chronic renal insufficiency and in six normal c ontrol subjects by a randomized single-blind protocol. After establish ment of a steady state of urinary electrolyte excretion, a single oral dose of HCTZ (25 mg) induced increases in the urinary excretion of Na +, K+, Cl-, Ca2+, and Mg2+ over the subsequent 12 h, which was signifi cantly inversely related to the GFR for each electrolyte. The ratios o f HCTZ-induced excretion of the different electrolytes were constant a nd independent of the GFR. After HCTZ, there was a double peak of Naexcretion related to the abrupt reduction in GFR and Na+ excretion whe n the latter exceeded 40 mmol/h in normal subjects and 15 mmol/h in pa tients with advanced renal failure. The dose-response curves for HCTZ and FU were both relatively flat: doubling the dose of each produced s tatistically insignificant increases in sodium excretion. In contrast, when the lower doses of each were coadministered, there was a substan tial and statistically significant increase in Na+ excretion. The clin ical implication of these findings is that a combination of low doses of diuretics acting at different functional sites of electrolyte reabs orption in the nephron is superior in saluretic potency to increasing the dose of either diuretic alone.