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Pflugers Arch. 2018 Feb;470(2):427-438. doi: 10.1007/s00424-017-2049-0. Epub 2017 Aug 12.

Acute regulated expression of pendrin in human urinary exosomes.

Author information

1
Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 15, 3010, Bern, Switzerland.
2
Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland.
3
Swiss National Center of Competence in Research (NCCR) Transcure, University of Bern, Bern, Switzerland.
4
Division of Nephrology, University Hospital Zurich, Zurich, Switzerland.
5
National Center for Competence in Research (NCCR) Kidney.CH, Institute of Physiology, University of Zurich, Zurich, Switzerland.
6
Centre de Recherche des Cordeliers and Centre National de la Recherche Scientifique (ERL7226), INSERM (UMRS872), Université Pierre et Marie Curie-Université Paris-Descartes, 75270, Paris, France.
7
Children's Hospital Lucerne, Lucerne, Switzerland.
8
Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 15, 3010, Bern, Switzerland. Daniel.Fuster@insel.ch.
9
Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland. Daniel.Fuster@insel.ch.
10
Swiss National Center of Competence in Research (NCCR) Transcure, University of Bern, Bern, Switzerland. Daniel.Fuster@insel.ch.

Abstract

It is well known that pendrin, an apical Cl-/HCO3-exchanger in type B intercalated cells, is modulated by chronic acid-base disturbances and electrolyte intake. To study this adaptation further at the acute level, we analyzed urinary exosomes from individuals subjected to oral acute acid, alkali, and NaCl loading. Acute oral NH4Cl loading (n = 8) elicited systemic acidemia with a drop in urinary pH and an increase in urinary NH4 excretion. Nadir urinary pH was achieved 5 h after NH4Cl loading. Exosomal pendrin abundance was dramatically decreased at 3 h after acid loading. In contrast, after acute equimolar oral NaHCO3 loading (n = 8), urinary and venous blood pH rose rapidly with a significant attenuation of urinary NH4 excretion. Alkali loading caused rapid upregulation of exosomal pendrin abundance at 1 h and normalized within 3 h of treatment. Equimolar NaCl loading (n = 6) did not alter urinary or venous blood pH or urinary NH4 excretion. However, pendrin abundance in urinary exosomes was significantly reduced at 2 h of NaCl ingestion with lowest levels observed at 4 h after treatment. In patients with inherited distal renal tubular acidosis (dRTA), pendrin abundance in urinary exosomes was greatly reduced and did not change upon oral NH4Cl loading. In summary, pendrin can be detected and quantified in human urinary exosomes by immunoblotting. Acid, alkali, and NaCl loadings cause acute changes in pendrin abundance in urinary exosomes within a few hours. Our data suggest that exosomal pendrin is a promising urinary biomarker for acute acid-base and volume status changes in humans.

KEYWORDS:

Acid-base homeostasis; Distal renal tubular acidosis; Pendrin; SLC26A4; Urinary exosomes

PMID:
28803436
DOI:
10.1007/s00424-017-2049-0
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