What is a common cause of nephrogenic diabetes insipidus?

• A. Kidney insensitivity to ADH, commonly due to lithium or chronic hypercalcemia.
• B. ADH deficiency due to pituitary damage.
• C. Excess ADH production.
• D. Kidney failure due to dehydration.

Answer: (A)

Nephrogenic diabetes insipidus happens when the kidney doesn’t respond to ADH, so water reabsorption in the collecting ducts is impaired despite normal or high ADH levels. The most common causes are lithium therapy and chronic hypercalcemia. Lithium interferes with the action of ADH in the collecting ducts by reducing the insertion of aquaporin-2 water channels, so water reabsorption drops and large volumes of dilute urine result. Chronic hypercalcemia also dampens the kidney’s response to ADH and can damage the structures involved in concentrating urine. This combination leads to polyuria and polydipsia.

In contrast, ADH deficiency from pituitary damage causes central diabetes insipidus, where there isn’t enough ADH. Excess ADH leads to SIADH with water retention, not polyuria. Dehydration-related kidney injury isn’t a direct cause of nephrogenic DI.