Deficient renal cyclic adenosine 3'-5' monophosphate production in nephrogenic diabetes insipidus.

Abstract

Vasopressin (ADH) (10 mU/min) was infused for 2–4 hr in 6 water loaded normal subjects, 5 patients with primary diabetes insipidus, and 2 with nephrogenic diabetes insipidus. Cyclic AMP in hourly urine samples prior to and during ADH administration was measured by high pressure anion exchange chromatography. In normals, urinary cyclic AMP was 2.7 ± 0.5 μm/g Cr (1 sd) during H2O loads increasing to 4.8 ± 1.0 with ADH, and in diabetes insipidus, urinary cyclic AMP was 2.5 ± 0.3 on no therapy increasing to 3.9 ± 1.0 μm/g Cr with ADH as urine osmolality rose from less than 100 to more than 330 mOsm/kg. Urinary cyclic AMP was significantly (p < 0.001) greater, 1.7 ± 0.4 times control, with ADH. However, in 2 patients with nephrogenic diabetes insipidus, urinary cyclic AMP was 2.0 ± 0.1 and 2.7 ± 0.2 μm/g Cr prior to and remained less than or equal to control values during ADH infusion. Tolbutamide (1 g iv) increased urine osmolality from 101 to 579 mOsm/kg in a glucose loaded diabetes insipidus patient while urinary cyclic AMP rose to 1.6 times baseline; while in nephrogenic diabetes insipidus tolbutamide produced no increase in urine osmolality or urinary cyclic AMP. Parathyroid hormone (200 U iv) increased urinary cyclic AMP 71–121-fold in 6 normals, while urinary cyclic AMP increased only 10- and 30-fold in the 2 nephrogenic diabetes insipidus patients. Glucagon (1 mg iv) increased urinary cyclic AMP 7–25-fold in 6 normals, and 6 times in nephrogenic diabetes insipidus. These findings show that in nephrogenic diabetes insipidus, urinary cyclic AMP fails to rise with ADH or tolbutamide in contrast to normal and diabetes insipidus patients. Nephrogenic diabetes insipidus patients appear to have a defect in ADH and parathyroid hormone stimulated urinary cyclic AMP excretion.