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English⧼Colon⧽ F2: Water balance disorders. (A) Diabetes insipidus describes the abnormal loss of hypoosmotic urine (polyuria) along with increased thirst (polydipsia). The antidiuretic peptide hormone arginine-vasopressin (AVP) is synthesized in the hypothalamus as a prohormone. Mature AVP is secreted from the neurohypophysis to stimulate the kidneys to retain water. Mutations in the AVP gene impede correct processing or reduce its affinity for the V2 receptor, which precludes AVP-mediated water reabsorption from primary urine and is termed central diabetes insipidus (CDI). In the rare case of gestational diabetes insipidus, placenta-released vasopressinase degrades AVP, counteracting antidiuretic signaling. Similarly, mutations in the gene encoding the V2 receptor (AVPR2) render renal principal cells AVP-resistant. Defects in AQP2 protein expression, channel function, intracellular sorting, or membrane translocation disrupt the responsiveness of principal cells to antidiuretic stimuli and maintains low water permeability of the kidney collecting duct. (B) Deregulated accumulation of AVP enhances antidiuretic stimulation of renal principal cells through the V2 receptor and triggers enhanced AQP2-conducted water reabsorption from the primary urine urine (SIADH, heart failure, liver cirrhosis). The same effect is caused by a mutation in the AVPR2 gene constitutively activating the receptor. Both defects abnormally elevate water retention.