Mahdi Salih1, Robert A Fenton, Robert Zietse, Ewout J Hoorn. 1. aDepartment of Internal Medicine, Nephrology, Erasmus Medical Center, Rotterdam, the Netherlands bDepartment of Biomedicine, University of Aarhus, Aarhus, Denmark.
Abstract
PURPOSE OF REVIEW: This article summarizes studies that have analyzed sodium transporters in urinary extracellular vesicles (uEVs) in relation to hypertension. RECENT FINDINGS: The majority of kidney sodium transporters are detectable in uEVs. Patients with loss or gain of function mutations in sodium transporter genes have concomitant changes in the abundances of their corresponding proteins in uEVs. The effects of aldosterone on kidney sodium transport, including activation of the sodium chloride cotransporter (NCC) and epithelial sodium channel (ENaC), are transferred to uEVs as increases in phosphorylated NCC and the γ-subunit of ENaC. Specific forms of hypertension, including aldosteronism and pseudohypoaldosteronism, are characterized by higher abundances of total or phosphorylated NCC in uEVs. The proteolytic processing of ENaC by urinary proteases is detectable in uEVs as cleaved γ-ENaC, as demonstrated in hypertensive patients with diabetic nephropathy. Analysis of uEVs from patients with essential or salt-sensitive hypertension identified potential candidates for uEV markers of hypertension, including retinoic acid-induced gene 2 protein and hsa-miR-4516. SUMMARY: Analysis of sodium transporters in uEVs is a promising approach to study renal epithelial transport processes noninvasively in human hypertension. VIDEO ABSTRACT: http://links.lww.com/CONH/A16.
PURPOSE OF REVIEW: This article summarizes studies that have analyzed sodium transporters in urinary extracellular vesicles (uEVs) in relation to hypertension. RECENT FINDINGS: The majority of kidney sodium transporters are detectable in uEVs. Patients with loss or gain of function mutations in sodium transporter genes have concomitant changes in the abundances of their corresponding proteins in uEVs. The effects of aldosterone on kidney sodium transport, including activation of the sodium chloride cotransporter (NCC) and epithelial sodium channel (ENaC), are transferred to uEVs as increases in phosphorylated NCC and the γ-subunit of ENaC. Specific forms of hypertension, including aldosteronism and pseudohypoaldosteronism, are characterized by higher abundances of total or phosphorylated NCC in uEVs. The proteolytic processing of ENaC by urinary proteases is detectable in uEVs as cleaved γ-ENaC, as demonstrated in hypertensivepatients with diabetic nephropathy. Analysis of uEVs from patients with essential or salt-sensitive hypertension identified potential candidates for uEV markers of hypertension, including retinoic acid-induced gene 2 protein and hsa-miR-4516. SUMMARY: Analysis of sodium transporters in uEVs is a promising approach to study renal epithelial transport processes noninvasively in humanhypertension. VIDEO ABSTRACT: http://links.lww.com/CONH/A16.
Authors: Mahdi Salih; Ivan Gautschi; Miguel X van Bemmelen; Michael Di Benedetto; Alice S Brooks; Dorien Lugtenberg; Laurent Schild; Ewout J Hoorn Journal: J Am Soc Nephrol Date: 2017-07-14 Impact factor: 10.121
Authors: Chih-Chiang Hu; Marina Katerelos; Suet-Wan Choy; Amy Crossthwaite; Susan P Walker; Gabrielle Pell; Mardiana Lee; Natasha Cook; Peter F Mount; Kathy Paizis; David A Power Journal: PLoS One Date: 2018-09-24 Impact factor: 3.240