Acetazolamide and Hydrochlorothiazide Followed by Furosemide Versus Furosemide and Hydrochlorothiazide Followed by Furosemide for the Treatment of Adults With Nephrotic Edema: A Randomized Trial.

BACKGROUND

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.

STUDY DESIGN

Randomized, double-blind, 2-arm, parallel trial.

SETTING & PARTICIPANTS: 20 patients with refractory nephrotic edema despite treatment with 80mg of furosemide daily and creatinine clearance > 60mL/min.

INTERVENTION

Patients were randomly assigned to 2 groups: group 1 (n=10) received 250mg of acetazolamide and 50mg of hydrochlorothiazide daily and group 2 (n=10) received 40mg of furosemide and 50mg of hydrochlorothiazide daily for 1 week in phase 1. In phase 2, both groups received 40mg of furosemide daily for 2 weeks.

OUTCOMES

The primary outcome was absolute change in weight before and at the end of each phase.

MEASUREMENTS

Weight and 24-hour urine volume at baseline and the end of each phase.

RESULTS

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±0.41kg; P=0.001) and phase 2 (-1.6±0.84 vs -0.5±0.47kg; P=0.005). The increase in 24-hour urine volume was also significantly higher in group 1 at the end of phase 2.

LIMITATIONS

Small sample size, short follow-up duration, and lack of serum bicarbonate and chloride measurement.

CONCLUSIONS

Acetazolamide and hydrochlorothiazide followed by furosemide is more effective than furosemide and hydrochlorothiazide followed by furosemide for the treatment of refractory nephrotic edema.