Efficacy of combining acetazolamide with loop diuretics versus double dose loop diuretics for decongestion in patients with chronic kidney disease: a randomized controlled trial

Abstract The combination of acetazolamide and loop diuretics in hospitalized heart failure patients has demonstrated positive results in improving diuresis and decongestion. However, the effectiveness of this combination in chronic kidney disease (CKD) patients with volume overload remains to be determined. CKD patients with fluid overload confirmed by bioimpedance spectroscopy were randomized to receive oral acetazolamide 250 mg/day plus furosemide or a doubled dose of furosemide. Volume status, body fluid compartments (assessed by body composition monitoring), and urinary sodium were evaluated at baseline and 2 weeks. The primary endpoint was the change in body weight at 2 weeks. Categorical weight reduction thresholds (≥ 2 kg or > 5%) were analyzed as exploratory outcomes. Fifty-two patients with a mean estimated glomerular filtration rate of 38 ml/min/1.73 m² were included. The combination group achieved a greater reduction in body weight compared with the double-dose group, with a mean between-group difference of − 1.37 kg (95% CI − 2.50 to − 0.24). Exploratory analyses showed a higher proportion of patients achieving ≥ 2 kg weight loss (40.7% vs. 12%; RR 3.39, 95% CI 1.06–10.7) and > 5% weight loss (25.9% vs. 0%; RR 2.25, 95% CI 1.62–3.12) in the combination group. No serious adverse events were observed. Adding acetazolamide to loop diuretics improves decongestion in CKD patients, as reflected by greater weight reduction, without significant safety concerns. Clinical trial registration: Registration code TCTR20240329006 approved on 29 March 2024.