Main points on physiological basis underlying development of AVP-D and AVP-R

ConditionsDescriptionReference(s)
AVP-DInvolves insufficient production or release of AVP from the hypothalamus or posterior pituitary gland, leading to reduced water reabsorption in the kidneys, resulting in dilute urine and dehydration.[53]
AVP-RThe kidneys are unable to respond to AVP, despite normal hormone levels. This is often due to defects in AVP receptors or downstream signaling pathways in the renal tubules.[38]
AVP pathway dysfunctionV2 receptor defects: in AVP-R, mutations in the V2 receptor (found in the collecting ducts of the kidney) prevent AVP from binding and triggering the molecular cascade required for water reabsorption. AVP-D: in AVP-D, insufficient AVP production or release results in a lack of hormonal signaling to the kidneys, preventing activation of downstream mechanisms needed for urine concentration.[54, 55]
AQP-2 channel deficiencyAVP normally promotes the insertion of AQP-2 water channels into the apical membrane of collecting duct cells, allowing water reabsorption. Defects in AQP-2 gene expression or trafficking in AVP-R impair this process, leading to an inability to concentrate urine.[56]
Disruption in countercurrent mechanismThe countercurrent multiplier and exchanger systems in the nephron create the osmotic gradient needed for water reabsorption. Disruptions in solute transporters (e.g., Na+/K+/2Cl– co-transporters) within the loop of Henle impair the creation of a hyperosmotic medullary environment, reducing the efficiency of water conservation in AVP-D and AVP-R.[57]

AQP-2: aquaporin-2; AVP: arginine vasopressin; AVP-D: AVP deficiency; AVP-R: AVP resistance; V2: vasopressin 2