Treatment of nephrogenic diabetes insipidus with prostaglandin synthesis inhibitors

The antidiuretic effect of two prostaglandin synthetase inhibitors, ibuproten (25 mg/kg/day) and indomethacin (2 mg/kg/day), was studied in patients aged 8 to 18 years with hereditary nephrogenic diabetes insipidus. Ibuprofen (studied in five patients) did not have demonstrable effects on urine volume, free water clearance, or osmolar clearance, but fractional excretion of sodium ecreased from a mean of 0.38% to 0.19% (P<0.05). In contrast, indomethacin (studied in three patients) was associated with a decrease in mean urine volume from 5.8 to 2.8 mL/min and a decrease in mean free water clearance from 3.1 to 1.1 mL/min (both P<0.05). Fractional excretion of sodium decreased from 0.77% to 0.27% (P<0.01) and was accompained by an increase in serum urea nitrogen level (P<0.01) and a decrease in urea nitrogen clearance (P<0.025). Thus, prostaglandin synthetase inhibitors are not uniformly effective in treatment of nephrogenic diabetes insipidus. The inhibitory effect of indomethacin on urine volume and free water clearance in our patients may have been mediated by an enhancement of antidiuretic hormone (ADH)-stimulated cyclic adenosine monophosphate generation, or by increased ADH-independent water reabsorption resulting from an increase in solute reabsorption and consequent medullary hypertonicity.