Δευτέρα 7 Μαΐου 2018

Increased Urinary Extracellular Vesicle Sodium Transporters in Cushing's Syndrome with Hypertension.

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Increased Urinary Extracellular Vesicle Sodium Transporters in Cushing's Syndrome with Hypertension.

J Clin Endocrinol Metab. 2018 May 02;:

Authors: Salih M, Bovée DM, van der Lubbe N, Danser AHJ, Zietse R, Feelders RA, Hoorn EJ

Abstract
Context: Increased renal sodium reabsorption contributes to hypertension in Cushing's syndrome (CS). Renal sodium transporters can be analyzed non-invasively in urinary extracellular vesicles (uEVs).
Objective: To analyze renal sodium transporters in uEVs of patients with CS and hypertension.
Design: Observational study.
Setting: University hospital.
Participants: uEVs were isolated by ultracentrifugation and analyzed by immunoblotting in 10 CS patients and 7 age-matched healthy subjects. In 7 CS patients uEVs were analyzed before and after treatment.
Main Outcome Measure: uEV protein abundance.
Results: The 10 CS patients were divided in those with suppressed and non-suppressed renin-angiotensin-aldosterone system (RAAS, n = 5/group). CS patients with suppressed RAAS had similar blood pressure but significantly lower serum potassium than CS patients with non-suppressed RAAS. Compared to healthy subjects, only those with suppressed RAAS had higher phosphorylated Na+-K+-Cl- cotransporter type 2 (pNKCC2) and higher total and phosphorylated Na+-Cl- cotransporter (NCC) in uEVs. Serum potassium but not urinary free cortisol correlated with pNKCC2, pNCC, and NCC in uEVs. Treatment of CS reversed the increases in pNKCC2, NCC, and pNCC.
Conclusions: CS increases renal sodium transporter abundance in uEVs especially in patients with hypertension and suppressed RAAS. As potassium has recently been identified as an important driver of NCC activity, low serum potassium may also contribute to increased renal sodium reabsorption and hypertension in CS. These results may also be relevant for hypertension induced by exogenous glucocorticoids.

PMID: 29726949 [PubMed - as supplied by publisher]



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