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Urinary extracellular vesicles as markers to assess kidney sodium transport

Salih, Mahdi; Fenton, Robert A.; Zietse, Robert; Hoorn, Ewout J.

Current Opinion in Nephrology and Hypertension: March 2016 - Volume 25 - Issue 2 - p 67–72
doi: 10.1097/MNH.0000000000000192
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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.

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aDepartment of Internal Medicine, Nephrology, Erasmus Medical Center, Rotterdam, the Netherlands

bDepartment of Biomedicine, University of Aarhus, Aarhus, Denmark

Correspondence to Ewout J. Hoorn, MD, PhD, Department of Internal Medicine, Nephrology, Erasmus Medical Center, PO Box 2040, Room H-438, 3000 CA Rotterdam, the Netherlands. Tel: +31 10 7032860; fax: +31 10 7033008; e-mail:

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