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.
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 hypertensivepatients (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 hypertensivepatients.
Authors: J Andrew McKEE; Shailesh Kumar; Carolyn A Ecelbarger; Patricia Fernández-Llama; James Terris; Mark A Knepper Journal: J Am Soc Nephrol Date: 2000-11 Impact factor: 10.121
Authors: J Loffing; L Pietri; F Aregger; M Bloch-Faure; U Ziegler; P Meneton; B C Rossier; B Kaissling Journal: Am J Physiol Renal Physiol Date: 2000-08
Authors: Kimberly M Hoagland; Averia K Flasch; Annette J Dahly-Vernon; Elisabete Alcantara dos Santos; Mark A Knepper; Richard J Roman Journal: Hypertension Date: 2004-02-16 Impact factor: 10.190
Authors: Shyama Masilamani; Xiaoyan Wang; Gheun-Ho Kim; Heddwen Brooks; Jakob Nielsen; Soren Nielsen; Kenzo Nakamura; John B Stokes; Mark A Knepper Journal: Am J Physiol Renal Physiol Date: 2002-10
Authors: Rembert Pieper; Christine L Gatlin; Andrew M McGrath; Anthony J Makusky; Madhu Mondal; Michael Seonarain; Erin Field; Courtney R Schatz; Marla A Estock; Nasir Ahmed; Norman G Anderson; Sandra Steiner Journal: Proteomics Date: 2004-04 Impact factor: 3.984
Authors: María Yáñez-Mó; Pia R-M Siljander; Zoraida Andreu; Apolonija Bedina Zavec; Francesc E Borràs; Edit I Buzas; Krisztina Buzas; Enriqueta Casal; Francesco Cappello; Joana Carvalho; Eva Colás; Anabela Cordeiro-da Silva; Stefano Fais; Juan M Falcon-Perez; Irene M Ghobrial; Bernd Giebel; Mario Gimona; Michael Graner; Ihsan Gursel; Mayda Gursel; Niels H H Heegaard; An Hendrix; Peter Kierulf; Katsutoshi Kokubun; Maja Kosanovic; Veronika Kralj-Iglic; Eva-Maria Krämer-Albers; Saara Laitinen; Cecilia Lässer; Thomas Lener; Erzsébet Ligeti; Aija Linē; Georg Lipps; Alicia Llorente; Jan Lötvall; Mateja Manček-Keber; Antonio Marcilla; Maria Mittelbrunn; Irina Nazarenko; Esther N M Nolte-'t Hoen; Tuula A Nyman; Lorraine O'Driscoll; Mireia Olivan; Carla Oliveira; Éva Pállinger; Hernando A Del Portillo; Jaume Reventós; Marina Rigau; Eva Rohde; Marei Sammar; Francisco Sánchez-Madrid; N Santarém; Katharina Schallmoser; Marie Stampe Ostenfeld; Willem Stoorvogel; Roman Stukelj; Susanne G Van der Grein; M Helena Vasconcelos; Marca H M Wauben; Olivier De Wever Journal: J Extracell Vesicles Date: 2015-05-14
Authors: Ying Qi; Xiaojing Wang; Kristie L Rose; W Hayes MacDonald; Bing Zhang; Kevin L Schey; James M Luther Journal: J Am Soc Nephrol Date: 2015-06-25 Impact factor: 10.121
Authors: Charles J Blijdorp; Omar A Z Tutakhel; Thomas A Hartjes; Thierry P P van den Bosch; Martijn H van Heugten; Juan Pablo Rigalli; Rob Willemsen; Usha M Musterd-Bhaggoe; Eric R Barros; Roger Carles-Fontana; Cristian A Carvajal; Onno J Arntz; Fons A J van de Loo; Guido Jenster; Marian C Clahsen-van Groningen; Cathy A Cuevas; David Severs; Robert A Fenton; Martin E van Royen; Joost G J Hoenderop; René J M Bindels; Ewout J Hoorn Journal: J Am Soc Nephrol Date: 2021-03-29 Impact factor: 10.121