Nephrogenic diabetes insipidus

Diabetes insipidus is a rare disease that causes frequent urination. The large volume of urine is diluted, mostly water.

Nephrogenic diabetes insipidus results from inability of the kidneys to concentrate urine. This due to failure of the kidneys to respond to antidiuretic hormone (ADH; and also named arginine vasopressin or AVP), resulting in increased excretion of dilute urine.

The kidneys’ ability to respond to ADH can be impaired by drugs—like lithium, for example—and by chronic disorders including polycystic kidney disease, sickle cell disease, kidney failure, partial blockage of the ureters, and inherited genetic disorders.

Polyuria, with hyposthenuria, and polydipsia are the fundamental clinical manifestations of the disease.

Nephrogenic diabetes insipidus may be caused by a defect in the vasopressin-induced permeability of the distal tubules and collecting ducts to water, an insufficient buildup of the corticopapillary interstitial osmotic gradient, or to a combination of these two factors.
Nephrogenic diabetes insipidus

AVP (arginine vasopressin)

AVP or arginine vasopressin, sometimes also called anti-diuretic hormone or ADH, or argipressin or vasopressin is a hormone synthesized as a peptide pro-hormone in magnocellular neurons in the hypothalamus, and is converted to AVP.

AVP is a small nine-amino-acid peptide secreted by the neuro-hypophysis in response to minor increases in plasma osmolality or to comparatively larger reductions in blood volume. There is growing evidence that supports a role of AVP in regulation of blood glucose concentration.

AVP is short-lived in plasma, with a mean half-life of 24 minutes, and this hormone plays a major role in water conservation by increasing the permeability of the collecting duct to water and stimulating urea movements in the kidney which promote more intense water reabsorption in the renal medulla.

Researchers discovered that diabetic rats, in contrast to control rats, have increased hypothalamic vasopressin synthesis due to upregulated chloride transporters and an excitatory response evoked by the neurotransmitter GABA. These findings thus reveal a potential mechanistic explanation for elevated vasopressin concentration in diabetes.

Plasma vasopressin levels are elevated in uncontrolled diabetes mellitus. Furthermore, experimental studies demonstrated increased AVP synthesis, which was thought to be a compensatory response to the elevated AVP secretion.
AVP (arginine vasopressin)