Nephrogenic diabetes insipidus (DI) results from partial or complete resistance of the kidney to the effects of antidiuretic hormone. As a result, patients with this disorder are not likely to have a good response to hormone administration (as dDAVP) or to drugs that increase either the renal response to ADH or ADH secretion.
Nephrogenic DI can be hereditary or acquired. In adults, a concentrating defect severe enough to produce polyuria due to nephrogenic DI is most often due to chronic lithium use or hypercalcemia, and less frequently to other conditions that impair tubular function, such as Sjögren's syndrome . Release of ureteral obstruction is often associated with a diuresis, but this is short-lived and does not require specific therapy other than maintenance fluids. (See "Clinical manifestations and causes of nephrogenic diabetes insipidus" and "Urine output in urinary tract obstruction and postobstructive diuresis".)
Hereditary nephrogenic DI, which is largely an X-linked disease, may also be seen by internists since early recognition and treatment in infancy has led to survival to adulthood . In addition, affected women may be carriers with few or no symptoms until pregnancy or other stress.
In infants with hereditary nephrogenic DI, treatment is aimed at minimizing the polyuria and avoiding hypernatremia and volume depletion. In adults, therapy is usually aimed at correcting the underlying disorder or discontinuing an offending drug. In hypercalcemic patients, for example, normalization of the plasma calcium concentration usually leads to amelioration of polyuria. In contrast, lithium-induced nephrogenic DI may be irreversible if the patient already has severe tubular injury and a marked concentrating defect . (See "Renal toxicity of lithium".)
The approach to the treatment of polyuria in patients with nephrogenic DI will be reviewed here. The causes of nephrogenic DI, the diagnostic approach to polyuria, and the treatment of central diabetes insipidus are discussed separately. (See "Clinical manifestations and causes of nephrogenic diabetes insipidus" and "Diagnosis of polyuria and diabetes insipidus" and "Treatment of central diabetes insipidus".)