title: The phosphorylated sodium chloride cotransporter in urinary exosomes is superior to prostasin as a marker for aldosteronism.
abstract: Urinary exosomes are vesicles derived from renal tubular epithelial cells. Exosomes often contain several disease-associated proteins and are thus useful targets for identifying biomarkers of disease. Here, we hypothesized that the phosphorylated (active) form of the sodium chloride cotransporter (pNCC) or prostasin could serve as biomarkers for aldosteronism. We tested this in 2 animal models of aldosteronism (aldosterone infusion or low-sodium diet) and in patients with primary aldosteronism. Urinary exosomes were isolated from 24-hour urine or spot urine using ultracentrifugation. In rats, a normal or a high dose of aldosterone for 2, 3, or 8 days increased pNCC 3-fold in urinary exosomes (P<0.05 for all). A low-sodium diet also increased pNCC in urinary exosomes approximately 1.5-fold after 4 and after 8 days of treatment. The effects of these maneuvers on prostasin in urinary exosomes were less clear, showing a significant 1.5-fold increase only after 2 and 3 days of high-aldosterone infusion. In urinary exosomes of patients with primary aldosteronism, pNCC was 2.6-fold higher (P<0.05) while prostasin was 1.5-fold higher (P=0.07) than in patients with essential hypertension. Urinary exosomal pNCC and, to a lesser extent, prostasin are promising markers for aldosteronism in experimental animals and patients. These markers may be used to assess the biological activity of aldosterone and, potentially, as clinical biomarkers for primary aldosteronism.
authors.affiliation: Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Nils
authors.initials: N
authors.lastname: van der Lubbe
authors.forename: Pieter M
authors.initials: PM
authors.lastname: Jansen
authors.forename: Mahdi
authors.initials: M
authors.lastname: Salih
authors.forename: Robert A
authors.initials: RA
authors.lastname: Fenton
authors.forename: Anton H
authors.initials: AH
authors.lastname: van den Meiracker
authors.forename: A H Jan
authors.initials: AH
authors.lastname: Danser
authors.forename: Robert
authors.initials: R
authors.lastname: Zietse
authors.forename: Ewout J
authors.initials: EJ
authors.lastname: Hoorn
mesh_terms: D000450:Aldosterone / Q000009:adverse effects / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers / Q000652:urine; D004039:Diet, Sodium-Restricted / Q000009:adverse effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D055354:Exosomes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006929:Hyperaldosteronism / Q000139:chemically induced / Q000175:diagnosis* / Q000652:urine*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010766:Phosphorylation; D011237:Predictive Value of Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D012697:Serine Endopeptidases / Q000187:drug effects / Q000652:urine*; D049992:Sodium Chloride Symporters / Q000187:drug effects / Q000652:urine*; D012982:Sodium, Dietary / Q000494:pharmacology; D000099271:Prostasin
chemical_list: D000450:Aldosterone; D015415:Biomarkers; D012697:Serine Endopeptidases; D049992:Sodium Chloride Symporters; D012982:Sodium, Dietary; D000099271:Prostasin