4. After the 4-hour water deprivation test, Mr.

Kessler’s serum osmolarity was

305 mOsm/L (normal, 290 mOsm/L) and his urine osmolarity was 90 mOsm/L.
Administration of an ADH analogue (dDAVP) by nasal spray did not alter his
serum or urine osmolarity. The physician concluded that Mr. Kessler had
nephrogenic diabetes insipidus. Why? What might be the cause of this
condition?
After a water deprivation test, Mr. Kessler’s serum osmolarity was elevated
at 305 mOsm/L (normal,
290 mOsm/L). In the face of this elevated serum osmolarity, his urine
osmolarity was very dilute
(hyposmotic) at 90 mOsm/L. Something is wrong with this picture! Shouldn’t Mr.
Kessler be making
concentrated (hyperosmotic) urine when his serum osmolarity is elevated? This
abnormal
pattern suggests that Mr. Kessler had diabetes insipidus caused by ADH
deficiency (central diabetes
insipidus) or by ADH resistance of the collecting ducts (nephrogenic diabetes
insipidus).
Results of the test with dDAVP nasal spray (an ADH analogue) confirmed that
Mr. Kessler had
nephrogenic diabetes insipidus—even exogenous ADH couldn’t cause his
urine to become concentrated.
His nephrogenic diabetes insipidus (or ADH resistance) was caused by
hypercalcemia. In
this condition, Ca2deposition in the inner medulla of the kidney inhibits ADH-
dependent adenylyl
cyclase and prevents the ADH action to increase water permeability of the
collecting ducts.
Thus, even in the presence of exogenous ADH, the urine cannot be
concentrated.