Mechanism of nephrogenic diabetes insipidus?

• A. Decreased ADH production
• B. Increased ADH clearance
• C. Increased water reabsorption in collecting ducts
• D. Renal insensitivity to ADH

Answer: (D)

Nephrogenic diabetes insipidus arises when the kidney cannot respond to antidiuretic hormone, so water reabsorption in the collecting ducts fails despite normal or high ADH levels. Normally, ADH binds to V2 receptors on collecting duct cells, triggering a signaling cascade that promotes insertion of aquaporin-2 channels into the apical membrane, increasing water reabsorption and concentrating the urine. If the tubules are insensitive to ADH—due to receptor or aquaporin defects or downstream signaling problems—the collecting ducts don’t reabsorb water effectively. This leads to the production of large volumes of dilute urine and compensatory polydipsia. The other scenarios would involve low ADH production or excessive ADH clearance (central causes) or would imply increased water reabsorption, which isn’t the issue here.