A7813 Variations in abundance of urinary exosomal renal sodium transporters in response to mineralocorticoid administration and oral salt loading and in relation to baseline plasma aldosterone and potassium

Abstract

Objectives: To quantify changes in abundance of sodium transporters [Na-Cl cotransporter (NCC), its phosphorylated form (pNCC), Na-K-Cl cotransporter (NKCC2) and epithelial sodium channel g-subunit (g-ENaC)] and prostasin in urinary exosomes in response to mineralocorticoid administration and oral salt loading, and explore associations with plasma aldosterone (aldo) and K+, in patients undergoing fludrocortisone suppression testing (FST).Methods: Baseline (D0) and day 4 (D4) morning urine samples were collected from 13 patients, including 10 with hypertension and raised aldo/renin ratio undergoing FST to confirm or exclude primary aldosteronism (PA; confirmed in 9) and 3 cured of PA by unilateral adrenalectomy. Urinary exosomes were isolated by ultracentrifugation and analysed by immunoblotting.Results: Increases in abundance of NCC (1.48 fold, p = 0.03) and pNCC (1.52 fold, p = 0.04) and trends towards increases in prostasin (p = 0.07), NKCC2 (p = 0.09) and cleaved g-ENaC (p = 0.11) were observed among the 13 subjects after 4 days FST. Abundance of cleaved g-ENaC rose significantly (p = 0.02) in the 10 non-operated subjects. Among the 13 subjects, D0 aldo and K+ did not correlate significantly with abundance of the target proteins, although D0 pNCC showed a trend towards positive correlation with aldo (p = 0.09). In the 10 non-operated subjects, D0 pNCC showed a negative correlation with plasma K+ that almost reached significance (p = 0.06).Conclusion: FST is associated with significant increases in NCC and pNCC and trends towards increases in ENaC, prostasin and NKCC2. The negative correlation between baseline plasma K+ and abundance of pNCC observed in adrenal-intact subjects suggests a possible role for K+ in the regulation of tubular salt handling and blood pressure.