ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on Twitter

Kidney Week

Abstract: SA-PO1047

Cushing’s Syndrome Increases Renal Sodium Transporters in Urinary Extracellular Vesicles

Session Information

  • Na+, K+, Cl-
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Fluid, Electrolytes, and Acid-Base

  • 703 Na+, K+, Cl- Basic


  • Bovee, Dominique M., Erasmus Medical Center, Rotterdam, Netherlands
  • Salih, Mahdi, Erasmus Medical Center, Rotterdam, Netherlands
  • Danser, Alexander H., Erasmus Medical Center, Rotterdam, Netherlands
  • Zietse, Robert, Erasmus Medical Center, Rotterdam, Netherlands
  • Feelders, Richard, Erasmus Medical Center, Rotterdam, Netherlands
  • Hoorn, Ewout J., Erasmus Medical Center, Rotterdam, Netherlands

Increased renal sodium (Na+) reabsorption contributes to hypertension in Cushing’s syndrome (CS). Renal Na+ transporters can be analyzed non-invasively in urinary extracellular vesicles (uEVs). The aim of this study was to analyze renal Na+ transporters in uEVs of patients with newly diagnosed CS.


uEVs were isolated by ultracentrifugation and analyzed by immunoblotting in 10 CS patients and 7 age-matched healthy subjects. The majority had an ACTH-producing pituitary adenoma (n=8). In 3 CS patients uEVs were analyzed before and after treatment (unilateral adrenalectomy or ketoconazole). uEVs were isolated without interfering medication (renin-angiotensin system inhibitors or diuretics).


The 10 patients with CS were hypertensive (144 ± 14 / 92 ± 17 mmHg) and had a 2-fold higher abundance of the Na+/H+exchanger type 3 (NHE3) in uEVs compared to healthy controls (p<0.05). CS patients were subsequently divided in those with a suppressed and non-suppressed renin-angiotensin-aldosterone system (RAAS, n=5/group). CS patients with suppressed vs. non-suppressed RAAS had similar blood pressure but significantly lower serum K+ (3.9 ± 0.2 vs. 4.4 ± 0.3 mmol/l, p=0.04). Furthermore, only those with suppressed RAAS had 3- to 4-fold higher phosphorylated Na+-K+-Cl-cotransporter type 2 (pNKCC2) and higher total and phosphorylated Na+-Cl-cotransporter (NCC) in uEVs. Serum K+ but not urinary free cortisol correlated with pNKCC2, pNCC, and NCC in uEVs (r = -0.9, -0.8, and -0.7, respectively; p<0.05 for all). In the 3 CS patients with uEV-analysis before and after treatment, pNKCC2, pNCC, and NCC abundances normalized after treatment in parallel with serum K+. No changes were observed in other uEV proteins of interest, including prostasin (a regulator of the epithelial sodium channel), Rac1 (which reflects mineralocorticoid activity), and aquaporin-2.


CS increases renal Na+ transporter abundance in uEVs especially in patients with suppressed RAAS. In addition to a mineralocorticoid effect of excess glucocorticoids, low serum K+ may also contribute to increased renal Na+ reabsorption and hypertension in CS. Our findings recapitulate previously characterized effects of glucocorticoids on NHE3, NKCC2, and NCC in experimental animals and of mineralocorticoids in patients with primary aldosteronism.