Autosomal dominant polycystic kidney disease is associated with central and nephrogenic defects in osmoregulation.
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.
Division of Nephrology, Cliniques Universitaires Saint-Luc, Université catholique de Louvain Medical School, Brussels, Belgium.
Thien Anh
TA
Ho
Nathalie
N
Godefroid
Damien
D
Gruzon
Jean-Philippe
JP
Haymann
Céline
C
Maréchal
Xueqi
X
Wang
Andreas
A
Serra
Yves
Y
Pirson
Olivier
O
Devuyst
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism / Q000503:physiopathology*; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009481:Neurophysins / Q000097:blood; D009994:Osmolar Concentration; D064587:Osmoregulation; D016891:Polycystic Kidney, Autosomal Dominant / Q000097:blood / Q000473:pathology / Q000503:physiopathology* / Q000652:urine; D011498:Protein Precursors / Q000097:blood; D050396:TRPP Cation Channels / Q000378:metabolism; D013997:Time Factors; D014667:Vasopressins / Q000097:blood; D014868:Water Deprivation; D055815:Young Adult
C438657:AVP protein, human; D009481:Neurophysins; D011498:Protein Precursors; D050396:TRPP Cation Channels; D014667:Vasopressins