Nephrotic edema is considered refractory if it does not respond to maximum or near-maximum
doses of loop diuretics. This condition can be treated with loop diuretics and thiazides.
However, animal studies show that the simultaneous downregulation of pendrin with
acetazolamide and inhibition of the sodium-chloride cotransporter with hydrochlorothiazide
generates significant diuresis, and furosemide administration following a pendrin
inhibitor potentiates furosemide’s diuretic effect. Therefore, we performed this study
to compare the efficacy of acetazolamide and hydrochlorothiazide followed by furosemide
versus furosemide and hydrochlorothiazide followed by furosemide for treatment of
refractory nephrotic edema.
Randomized, double-blind, 2-arm, parallel trial.
Setting & Participants
20 patients with refractory nephrotic edema despite treatment with 80 mg of furosemide daily and creatinine clearance > 60 mL/min.
Patients were randomly assigned to 2 groups: group 1 (n = 10) received 250 mg of acetazolamide and 50 mg of hydrochlorothiazide daily and group 2 (n = 10) received 40 mg of furosemide and 50 mg of hydrochlorothiazide daily for 1 week in phase 1. In phase 2, both groups received
40 mg of furosemide daily for 2 weeks.
The primary outcome was absolute change in weight before and at the end of each phase.
Weight and 24-hour urine volume at baseline and the end of each phase.
The mean weight decrease was of significantly larger magnitude in group 1 compared
with group 2 at the end of phase 1 (−1.4 ± 0.52 [SD] vs −0.65 ± 0.41 kg; P = 0.001) and phase 2 (−1.6 ± 0.84 vs −0.5 ± 0.47 kg; P = 0.005). The increase in 24-hour urine volume was also significantly higher in group
1 at the end of phase 2.
Small sample size, short follow-up duration, and lack of serum bicarbonate and chloride
Acetazolamide and hydrochlorothiazide followed by furosemide is more effective than
furosemide and hydrochlorothiazide followed by furosemide for the treatment of refractory