Furosemide as a possible treatment of X‐linked nephrogenic diabetes insipidus (NDI)

In NDI due to mutations of the V2 vasopressin receptor, indomethacin (Indo) + thiazide (TZ) induce a modest reduction in diuresis (V). Here, we tested whether furosemide (FURO), which inhibits urinary dilution in the thick ascending limb of Henle's loop, could also reduce V and increase urine osmolality (Uosm, mosm/kg H2O) in NDI patients. Seven children with NDI (6–17 y) were included in a double‐blind study involving 2 weeks on placebo (P) and 2 weeks on FURO (0.5 mg/kg 3 times/d) in random order with 1 week washout between the two periods. Their usual Indo + TZ treatment was not interrupted. Data during FURO and P were compared by paired Student's t test. Results. Uosm was higher during FURO than during P: 155±48 vs 128±34, p=0.03, and V was significantly lower: 4.85 vs 7.12 l/d, p=0.015. Kalemia decreased by 0.3 mmol/l (NS). In Brattleboro rats with central DI (6 rats per group), FURO (50 mg/kg/d) and TZ (10 mg/kg/d) decreased V (ml/d) with additive effects: control=202±14, FU=139±19, TZ=80±6, FU+TZ=57±6. Conclusion. FURO could be a possible treatment for NDI. The benefit/risk of FURO and the withdrawal from NSAID need to be evaluated in a larger group of subjects.