Urinary aquaporin-2 excretion in dogs: a marker for collecting duct responsiveness to vasopressin

Abstract

In humans, the urinary aquaporin-2 (U-AQP2) excretion closely parallels changes in vasopressin (VP) action and has been proposed as a marker for collecting duct responsiveness to VP. This report describes the development of a radioimmunoassay for the measurement of U-AQP2 excretion in dogs. In addition, the localization of AQP2 in the canine kidney was investigated by immunohistochemistry. Basal U-AQP2 excretion was highly variable among healthy dogs. Two hours after oral water loading, the mean U-AQP2/creatinine ratio decreased significantly from (231±30)×10 −9 to (60±15)×10 −9 ( P=0.01), while the median plasma VP concentration decreased from 4.2 pmol/l (range 2.2–4.8 pmol/l) to 1.2 pmol/l (range 1.0–1.9 pmol/l). Subsequent intravenous administration of desmopressin led to a significantly increased mean U-AQP2/creatinine ratio of (258±56)×10 −9 ( P=0.01). Two hours of intravenous hypertonic saline infusion (20% NaCl, 0.03 ml/kg body weight/min) significantly increased the mean U-AQP2/creatinine ratio from (86±6)×10 −9 to (145±23)×10 −9 ( P=0.045), while the median plasma VP concentration increased significantly from 2.2 pmol/l (range 1.1–6.3 pmol/l) to 17.1 pmol/l (range 8.4–67 pmol/l) ( P<0.001). Immunohistochemistry revealed extensive labeling for AQP2 in the kidney collecting duct cells, predominantly localized in the apical and subapical region. As in humans, U-AQP2 excretion in dogs closely reflects changes in VP exposure. Urinary AQP2 excretion may become a diagnostic tool in dogs for the differentiation of polyuric conditions such as (partial) central or nephrogenic diabetes insipidus, primary polydipsia, and inappropriate VP release.