In central diabetes insipidus, after desmopressin (dDAVP) administration, urinary osmolality rises to >800 mOsm/kg. In nephrogenic DI, it rises by less than 50%. This distinction occurs because dDAVP:
- A Is a V1/V2 mixed agonist; central DI has partial hypothalamic response to vasopressin, while nephrogenic DI has intact central axis but blocked V1 renal receptors
- B Is a V2-selective agonist; in central DI, intact renal V2 receptors and AQP2 machinery respond; in nephrogenic DI, post-receptor defect prevents AQP2 mobilization ✓
- C Bypasses ADH axis completely and directly inserts AQP2 channels into the collecting duct membrane
- D Acts on thirst center in hypothalamus to restrict water intake, concentrating urine independently of renal tubular mechanisms
Explanation
Desmopressin (dDAVP) is a synthetic V2-receptor selective analogue with no V1 (vasoconstrictor) activity and prolonged duration. In central DI, the defect is insufficient ADH secretion from the posterior pituitary, but the renal collecting duct expresses functional V2 receptors and a normal AQP2 trafficking system. Exogenous dDAVP therefore binds V2R, activates Gs/cAMP/PKA, phosphorylates AQP2, and inserts water channels into the apical membrane — producing concentrated urine. In nephrogenic DI, the V2 receptor or AQP2 gene is mutated, so even supraphysiological V2 agonist doses cannot restore AQP2 function, and the urine remains hypotonic.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
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