Journal
KIDNEY INTERNATIONAL
Volume 82, Issue 10, Pages 1121-1129Publisher
ELSEVIER SCIENCE INC
DOI: 10.1038/ki.2012.225
Keywords
arginine vasopressin; cAMP; hypothalamus; polycystins; PKD1; PKD2; vasopressin receptor V2R
Categories
Funding
- Belgian agency FNRS
- Belgian agency FRSM [3.4.592.06F]
- Chaire Spadel 'Eau et Sante' (Fondation Louvain), a Concerted Research Action [10/15-029]
- Inter-university Attraction Pole [IUAPP6/05]
- Programme d'excellence Marshall DIANE (Region Wallone)
- National Centre of Competence in Research (NCCR) Kidney
- SSSTC [IP17-092009]
- STCSM [09ZR1410400]
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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. Kidney International (2012) 82, 1121-1129; doi:10.1038/ki.2012.225; published online 20 June 2012
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