A double-blind randomized crossover trial of two loop diuretics in chronic kidney disease.
BACKGROUND
Torsemide has predictable absorption compared to furosemide. Thereby, torsemide results in more constant exposure to active drug. Our hypothesis was that this pharmacokinetic difference between these commonly used loop diuretics may translate into disparate antihypertensive responses in patients with chronic kidney disease (CKD).


METHODS
We conducted a randomized, double-blind, two-period, crossover trial to compare the pharmacodynamics of torsemide and furosemide, in 14 subjects with stage 2 or 3 CKD. We first performed an inpatient study, where after the subjects were brought into sodium balance on a 200 mEq per day diet, a single bioequivalent dose of oral loop diuretic was administered with an intervening washout period. Measurements of urinary electrolytes were made. Subjects then participated in an outpatient study, wherein they received daily therapy for 3 weeks with the loop diuretics in random order. Twenty four-hour ambulatory blood pressure monitoring was performed before and after each drug to assess the antihypertensive response.


RESULTS
In the inpatient phase, furosemide increased urinary sodium excretion from average (+/-SD) 199 +/- 49 mEq/day to 357 +/- 96 mEq/day and torsemide increased urinary sodium excretion from 213 +/- 79 mEq/day to 398 +/- 142 mEq/day. These differences between the diuretics were not significant, confirming bioequivalence. In the outpatient phase, furosemide reduced 24-hour ambulatory blood pressure from 147 +/- 17/78 +/- 11 mm Hg to 138 +/- 21/74 +/- 12 mm Hg (P = 0.021) and torsemide reduced it from 143 +/- 18/75 +/- 10 mm Hg to 133 +/- 19/71 +/- 10 mm Hg (P = 0.007). Although each diuretic was effective in reducing ambulatory blood pressure, the differences between diuretics were not statistically significant.


CONCLUSIONS
Bioequivalent doses of torsemide and furosemide given in a randomized, double-blind design fail to demonstrate superiority of torsemide with respect to natriuresis or 24-hour ambulatory blood pressure control in subjects with stages 2 and 3 CKD.
Vasavada
Nina
N
Division of Nephrology, Department of Medicine, Indiana University School of Medicine, and Richard L. Roudebush VA Medical Center, Indianapolis, Indiana 46202, USA.
Saha
Chandan
C
Agarwal
Rajiv
R
D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004232:Diuretics / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005665:Furosemide / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects; D012964:Sodium / Q000652:urine; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects; D000077786:Torsemide
D000959:Antihypertensive Agents; D004232:Diuretics; D013449:Sulfonamides; D005665:Furosemide; D012964:Sodium; D000077786:Torsemide