Nephrogenic DI (NDI) is most common in its acquired forms, meaning that the defect was not present at birth. These acquired forms have numerous potential causes. The most obvious cause is a kidney or systemic disorder, including amyloidosis,^[1] polycystic kidney disease,^[2] electrolyte imbalance,^[3][4] or some other kidney defect.^[1]

The major causes of acquired NDI that produce clinical symptoms (e.g. polyuria) in the adult are lithium toxicity and hypercalcemia. Chronic lithium ingestion – appears to affect the tubules by entering the collecting tubule cells through sodium channels, accumulating and interfering with the normal response to ADH (ADH Resistance) in a mechanism that is not yet fully understood. Hypercalcemia causes natriuresis (increased sodium loss in the urine) and water diuresis, in part by its effect through the calcium-sensing receptor (CaSR).

Osmotic

Other causes of acquired NDI include: hypokalemia, post-obstructive polyuria, sickle cell disease/trait, amyloidosis, Sjogren syndrome, renal cystic disease, Bartter syndrome and various drugs (Amphotericin B, Orlistat, Ifosfomide, Ofloxacin, Cidofovir, Vaptanes).

In addition to kidney and systemic disorders, nephrogenic DI can present itself as a side-effect to some medications. The most common and well known of these drugs is lithium,^[5] although there are numerous other medications that cause this effect with lesser frequency.^[1]

This form of DI can also be hereditary: