Combination therapy with furosemide and metolazone as compared to furosemide alone for treatment of edema in children with nephrotic syndrome: a randomized controlled trial

Nephrotic syndrome (NS) in children often presents with debilitating edema and optimal use of diuretics in presence of hypoalbuminemia is uncertain. Early initiation of a combination diuretic therapy can be efficacious in greater. The primary objective was to compare cumulative urine output over 48 h between children receiving furosemide plus metolazone and those receiving furosemide alone. Children aged 1-14 years with NS presenting with moderate to severe edema were enrolled and randomized into two groups, furosemide plus metolazone and furosemide-alone group. The urine volumes and weight were monitored twice daily for 48 h. Serum urea, creatinine, electrolytes, hematocrit, and hospital stay were recorded as secondary outcomes. Fifty children were randomized (25 per group) with comparable baseline characteristics and urine output. Mean urine output over 48 h was 3.13 (± 1.5) ml/kg/h in furosemide plus metolazone group and 2.96 (± 1.32) ml/kg/h in furosemide alone which did not significantly differ between the groups (p > 0.05). The change in urine output from baseline was significantly higher in combination group (2.15 ± 1.31 vs 1.44 ± 1.28 ml/kg/h; p = 0.03) in the unadjusted comparison, but it was not statistically significant after adjustment for baseline urine output by ANCOVA. Dyselectrolytemia, percentage of weight loss, and hospital stay were similar in both groups. Sixteen percent of children in the combination group had significant weight loss requiring discontinuation of therapy.