COADMINISTRATION OF THIAZIDES INCREASES THE EFFICACY OF LOOP DIURETICS EVEN IN PATIENTS WITH ADVANCED RENAL-FAILURE

Coadministration of thiazides increases the efficacy of loop diuretics even in patients with advanced renal failure. It is commonly assumed that thiazide diuretics are ineffective in patients with advanced rena l failure (GFR < 30 ml/min/1.73 m(2)). Thiazides act on the nephron se g ment distal to the ascending thick loop of Henle, that is, the site of action of loop diuretics. Blockade of sodium reabsorption in the th iazide-sensitive segment should therefore obliterate the compensatory increase in sodium reabsorption seen after administration of loop diur etics and thus potentiate the natriuretic efficacy of loop diuretics e ven in advanced renal failure. In a single-blind, randomized, placebo controlled crossover study we compared the natriuretic and chloruretic effect of the loop diuretic, torasemide, given alone or in combinatio n with the thiazide diuretic, butizid, in 10 patients with advanced re nal failure (mean C, 13.1 +/- 5.9 ml/min/1.73 m(2)). For two weeks pat ients adhered to a diet containing a standardized amount of Na+ and K. On the 6th and 13th study days, two sham infusions were given to pat ients in order to assess basal 24-hour urinary electrolyte excretion. On the 7th and 14th days they were randomly allocated to receive eithe r 50 mg i.v. torasemide in combination with a sham infusion or torasem ide in combination with 20 mg i.v. butizid. Administration of torasemi de alone significantly (P < 0.01) increased mean cumulative 24-hour ex cretion of sodium (from 154 +/- 30 to 232 +/- 59 mmol/24 hr) and chlor ide (from 128 +/- 21 to 233 +/- 84 mmol/24 hr) as compared with baseli ne. Administration of torasemide in combination with butizid caused an even more marked increase of mean cumulative sodium (from 156 +/- 33 to 290 +/- 76 mmol/24 hr) and chloride excretion (from 128 +/- 29 to 3 09 +/- 99 mmol/24 hr). The mean cumulative sodium and chloride excreti on was significantly greater with coadministration of butizid as compa red with torasemide alone (P < 0.01). Despite the high sodium load wit h the diet three patients had an antinatriuretic rebound after the act ion of torasemide had dissipated. The rebound was abrogated by coadmin istration of butizid. In conclusion, thiazide diuretics markedly poten tiate the natriuretic and chloruretic action of loop diuretics even in patients with advanced renal failure: (i) by amplifying sodium and ch loride excretion and, at least in some patients, (ii) by interfering w ith the antinatriuretic rebound. Coadministration of thiazide diuretic s with loop diuretics is therefore rational even in advanced renal fai lure.