Kidney Week

Abstract: SA-PO1015

Urinary Exosomes as a Novel Tool to Study the NaCl Cotransporter in Hypertension

Session Information

• Fluid and Electrolytes: Basic - II
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid and Electrolytes

• 901 Fluid and Electrolytes: Basic

Authors

• Bindels, René J., Radboud University Medical Center, Nijmegen, Netherlands

René J. Bindels,

• Tutakhel, Omar, Radboud University Medical Centre, Nijmegen, Gelderland, Netherlands

Omar Tutakhel,

• Hoenderop, Joost, Radboud university medical center, Nijmegen, Netherlands

Joost Hoenderop,

Background

The NaCl cotransporter (NCC) is located at the apical membrane of epithelial cells lining the distal convoluted tubule of the kidney, and plays an instrumental role in blood pressure regulation by fine-tuning renal sodium excretion. Renal salt transporters such as NCC are excreted in urinary exosomes (uEs) after internalization into multivesicular bodies. The aims of this study were to investigate the effect of thiazides on the abundance of NCC in uEs of patients with hypertension, and to assess whether NCC abundance in exosomes can predict the blood pressure response to thiazides.

Methods

The NCC abundance was compared in uEs both before and after treatment in patients with hypertension (n=41) who did or did not respond to thiazides. Responders to treatment were defined as patients with a significant anti-hypertensive response to thiazides (≥5 mmHg, n=24), while non-responders had a minimal or no response (<5 mmHg in blood pressure, n=17). To analyze whether normalization by urinary creatinine resulted in a similar number of uEs loaded on a gel, the abundance of the exosomal-marker CD9 was measured.

Results

Despite the inhibitory action of thiazide on NCC, immunoblot analysis of exosomes showed increased abundance of NCC (>2.5-fold, P<0.05). The increase in NCC abundance in uEs after thiazide treatment correlated with the blood pressure response and change in plasma potassium levels (R²=0.22, P<0.05; R²=0.19, P<0.05, respectively). The abundance of NCC in uEs before treatment was significantly higher in responders compared to non-responders (>6-fold,P<0.05). Moreover, after thiazide treatment, the increase in abundance of NCC in uEs and decrease in plasma potassium levels was stronger in responders compared to non-responders (P<0.05). No significant differences in CD9 abundance were observed between the two experimental groups, suggesting comparable urinary exosomal numbers.

Conclusion

Our studies highlight that NCC is upregulated by thiazides and this increase correlates with the blood pressure response to thiazides and the change in plasma potassium levels. Additionally, we show that higher abundance of NCC prior to treatment with thiazides predicts the blood pressure response to thiazides. This implies that assessment of NCC in uEs could represent novel method to guide anti-hypertensive therapy in hypertensive patients.