Autosomal dominant polycystic kidney disease (
ADPKD) is associated with a urine-concentrating defect attributed to renal cystic changes. As PKD genes are expressed in the brain, altered central release of
arginine vasopressin could also play a role. In order to help determine this we measured central and nephrogenic components of osmoregulation in 10 adults and 10 children with
ADPKD, all with normal renal function, and compared them to 20 age- and gender-matched controls. Overnight water deprivation caused a lower rise in urine osmolality in the patients with
ADPKD than controls, reflecting an impaired release of
vasopressin and a peripheral defect in the patients. The reactivity of plasma
vasopressin to water deprivation, as found in controls, was blunted in the patients with the latter showing lower urine osmolality for the same range of plasma
vasopressin. The maximal urine osmolality correlated negatively with total kidney volume. Defective osmoregulation was confirmed in the children with
ADPKD but was unrelated to number of renal
cysts or kidney size. Thus, patients with
ADPKD have an early defect in osmoregulation, with a blunted release of
arginine vasopressin. This reflects expression of
polycystins in hypothalamic nuclei that synthesize
vasopressin, and this should be considered when evaluating treatments targeting the
vasopressin pathway in
ADPKD.