Nephrogenic Diabetes Insipidus

Clinical Principles

Patients with diabetes insipidus produce large quantities of dilute urine.

Diabetes insipidus can result from failure of the posterior pituitary to make or secrete vasopressin (antidiuretic hormone) or end-organ (kidney) insensitivity.

Patients with congenital nephrogenic diabetes insipidus now live well into adulthood and need to be followed by internists to avoid bladder dysfunction, renal dysfunction, and complications related to inaccessibility to water.

Optimal therapy for nephrogenic diabetes insipidus involves drinking enough water to avoid dehydration, which can be difficult in patients at the extremes of age.

Additional therapy includes a very low-sodium diet, thiazide diuretics, and indomethacin.

Exogenous vasopressin is not useful because the kidney is insensitive to its actions.

Acquired nephrogenic diabetes insipidus can result from lithium therapy, protein malnutrition, hypercalcemia, or hypokalemia, or may occur after the release of urinary tract obstruction.

Normal aging can result in a partial form of nephrogenic diabetes insipidus.

Pathophysiologic Principles

Vasopressin (antidiuretic hormone) is secreted by the posterior pituitary.

Vasopressin acts on the collecting duct of the kidney to increase water reabsorption.

Transcellular water reabsorption is mediated by water channels (aquaporins).

Congenital nephrogenic diabetes insipidus can result from mutations in the type 2 vasopressin receptor or aquaporin-2.

A mild urine-concentrating defect results from mutations in the urea transporter-B.

Polyuria in hereditary hypokalemic salt-losing tubulopathies (the Bartter syndrome) can result from mutations in several transport proteins in the thick ascending limb.