Changes in V-ATPase subunits of human urinary exosomes reflect the renal response to acute acid/alkali loading and the defects in distal renal tubular acidosis.
- Pathare G Division of Nephrology and Hypertension, Bern University Hospital, University of Bern, Bern, Switzerland; Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland; National Centre of Competence in Research Transcure, University of Bern, Bern, Switzerland.
- Dhayat NA Division of Nephrology and Hypertension, Bern University Hospital, University of Bern, Bern, Switzerland.
- Mohebbi N Division of Nephrology, University Hospital Zurich, Zurich, Switzerland.
- Wagner CA Institute of Physiology, University of Zurich, Zurich, Switzerland; National Center for Competence in Research Kidney.CH, Zurich, Switzerland.
- Bobulescu IA Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA; Charles and Jane Pak Center of Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
- Moe OW Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA; Charles and Jane Pak Center of Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA; Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
- Fuster DG Division of Nephrology and Hypertension, Bern University Hospital, University of Bern, Bern, Switzerland; Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland; National Centre of Competence in Research Transcure, University of Bern, Bern, Switzerland. Electronic address: Daniel.Fuster@insel.ch.
- 2018-01-10
Published in:
- Kidney international. - 2018
distal tubule
renal tubular acidosis
urinary exosome
Acidosis, Renal Tubular
Adult
Ammonium Chloride
Animals
Bicarbonates
Exosomes
Humans
Hydrogen-Ion Concentration
Kidney Tubules
Male
Mice, Knockout
Middle Aged
Mutation
Saccharomyces cerevisiae
Vacuolar Proton-Translocating ATPases
Water-Electrolyte Balance
Young Adult
English
In the kidney, final urinary acidification is achieved by V-ATPases expressed in type A intercalated cells. The B1 subunit of the V-ATPase is required for maximal urinary acidification, while the role of the homologous B2 subunit is less clear. Here we examined the effect of acute acid/alkali loading in humans on B1 and B2 subunit abundance in urinary exosomes in normal individuals and of acid loading in patients with distal renal tubular acidosis (dRTA). Specificities of B1 and B2 subunit antibodies were verified by yeast heterologously expressing human B1 and B2 subunits, and murine wild-type and B1-deleted kidney lysates. Acute ammonium chloride loading elicited systemic acidemia, a drop in urinary pH, and increased urinary ammonium excretion. Nadir urinary pH was achieved at four to five hours, and exosomal B1 abundance was significantly increased at two through six hours after ammonium chloride loading. After acute equimolar sodium bicarbonate loading, blood and urinary pH rose rapidly, with a concomitant reduction of exosomal B1 abundance within two hours, which remained lower throughout the test. In contrast, no change in exosomal B2 abundance was found following acid or alkali loading. In patients with inherited or acquired distal RTA, the urinary B1 subunit was extremely low or undetectable and did not respond to acid loading in urine, whereas no change in B2 subunit was found. Thus, both B1 and B2 subunits of the V-ATPase are detectable in human urinary exosomes, and acid and alkali loading or distal RTA cause changes in the B1 but not B2 subunit abundance in urinary exosomes.
- Language
-
- English
- Open access status
- bronze
- Identifiers
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- DOI 10.1016/j.kint.2017.10.018
- PMID 29310826
- Persistent URL
- https://sonar.ch/global/documents/185083
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