Objective: Severe edema in children with nephrotic syndrome is often refractory to conventional diuretics. Tolvaptan has been used satisfactorily for managing edema in patients with heart failure and cirrhosis. The safety and efficacy of combination therapy with oral tolvaptan and intravenous (IV) furosemide was assessed in patients with furosemide refractory edema.
Methods: Patients, aged 5-18 y with nephrotic syndrome and severe edema, were screened for eligibility. After excluding hypovolemia, patients received IV furosemide (3-4 mg/kg/d) for 48 h. Those refractory to IV furosemide (weight loss < 3%) received tolvaptan (0.5-1 mg/kg once daily) and IV furosemide for the next 48 h. Parameters were compared between 48 h of furosemide alone and combination therapy.
Results: A total of 24 patients (18 boys) with mean age of 8.0 ± 3.0 y were enrolled. Urine volume significantly increased with combination therapy as compared to furosemide therapy (mean difference: 1.2 mL/kg/h; 95% CI: 0.8-1.65 mL/kg/h) (p < 0.001). Compared to therapy with furosemide alone, combination therapy resulted in significant reduction in body weight from 26.9 ± 10.3 kg to 24.8 ± 9.7 kg (p < 0.001). Estimated glomerular filtration rate did not change (p = 0.81) but serum sodium increased from 135.7 ± 3.3 mEq/L to 140.4 ± 4.8 mEq/L (p < 0.001) with combination therapy; 2 patients showed asymptomatic hypernatremia.
Conclusion: The combination of oral tolvaptan and IV furosemide is effective in augmenting diuresis and reducing weight in patients with furosemide refractory edema but requires monitoring of electrolytes and volume status.
Keywords: Aquaretic; Edema; Furosemide resistance; Hypernatremia; Minimal change disease.
© 2021. Dr. K C Chaudhuri Foundation.