Are sodium transporters in urinary exosomes reliable markers of tubular sodium reabsorption in hypertensive patients?
BACKGROUND
Altered renal sodium handling has a major pathogenic role in salt-sensitive hypertension. Renal sodium transporters are present in urinary exosomes. We hypothesized that sodium transporters would be excreted into the urine in different amounts in response to sodium intake in salt-sensitive versus salt-resistant patients.


METHODS
Urinary exosomes were isolated by ultracentrifugation, and their content of Na-K-2Cl cotransporter (NKCC2) and Na-Cl cotransporter (NCC) was analyzed by immunoblotting. Animal studies: NKCC2 and NCC excretion was measured in 2 rat models to test whether changes in sodium transporter excretion are indicative of regulated changes in the kidney tissue. Human studies: in hypertensive patients (n = 41), we investigated: (1) a possible correlation between sodium reabsorption and urinary exosomal excretion of sodium transporters, and (2) the profile of sodium transporter excretion related to blood pressure (BP) changes with salt intake. A 24-hour ambulatory BP monitoring and a 24-hour urine collection were performed after 1 week on a low- and 1 week on a high-salt diet.


RESULTS
Animal studies: urinary NKCC2 and NCC excretion rates correlated well with their abundance in the kidney. Human studies: 6 patients (15%) were classified as salt sensitive. The NKCC2 and NCC abundance did not decrease after the high-salt period, when the urinary sodium reabsorption decreased from 99.7 to 99.0%. In addition, the changes in BP with salt intake were not associated with a specific profile of exosomal excretion.


CONCLUSIONS
Our results do not support the idea that excretion levels of NKCC2 and NCC via urinary exosomes are markers of tubular sodium reabsorption in hypertensive patients.
Esteva-Font
Cristina
C
Molecular Biology Laboratory, Universitat Autònoma de Barcelona, Fundació Puigvert, Barcelona, Spain.
Wang
Xiaoyan
X
Ars
Elisabet
E
Guillén-Gómez
Elena
E
Sans
Laia
L
González Saavedra
Isabel
I
Torres
Ferran
F
Torra
Roser
R
Masilamani
Shyama
S
Ballarín
José Aurelio
JA
Fernández-Llama
Patricia
P
D000818:Animals; D001794:Blood Pressure; D055354:Exosomes; D005260:Female; D006801:Humans; D006973:Hypertension / Q000378:metabolism* / Q000652:urine; D007668:Kidney / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D051381:Rats; D012964:Sodium / Q000378:metabolism* / Q000652:urine; D049992:Sodium Chloride Symporters / Q000378:metabolism / Q000652:urine*; D012982:Sodium, Dietary / Q000008:administration & dosage; D064466:Solute Carrier Family 12, Member 1 / Q000378:metabolism / Q000652:urine*
C578714:SLC12A1 protein, human; C578716:Slc12a1 protein, rat; D049992:Sodium Chloride Symporters; D012982:Sodium, Dietary; D064466:Solute Carrier Family 12, Member 1; D012964:Sodium