Elevated levels of the sodium-chloride cotransporter (NCC) and phosphorylated NCC (pNCC) are possible indicators of primary aldosteronism (PA), however, these effects might also be caused by hypokalemia.
In PA patients, plasma potassium was measured. Patients were given enough oral potassium chloride (KCl) over the course of 24 hours if their potassium level was less than 4.0 mmol/L in order to get it as near to that level as feasible. To ascertain the effects on NCC, urine extracellular vesicles (uEVs) and clinical chemistries were evaluated.
Plasma potassium increased (from 3.4 to 4.0 mmol/L, P<0.001), aldosterone increased (from 305 to 558 pmol/L, P=0.01), and renin increased (from 1.2 to 2.5 mU/L, P<0.001) among 21 PA patients who received a median total dose of 6.0 [2.4, 16.8] g KCl, while uEV levels of NCC decreased (median fold change [FC] (post/basal) = 0.71 [0.09, 1.99], P=0.02), pT60-NCC (FC=0.84 [0.06, 1.66], P=0.05) and pT55/60-NCC (FC=0.67 [0.08, 2.42], P=0.02). However, there were increases in plasma aldosterone (from 178 to 418 pmol/L, P=0.006) and renin (from 2.0 to 3.0 mU/L, P=0.009), but there were no obvious changes in plasma potassium, NCC abundance, or phosphorylation status in the 10 PA patients who did not receive KCl. Plasma potassium had an inverse relationship with the uEV levels of NCC (R2=0.11, P=0.01), pT60-NCC (R2=0.11, P=0.01), and pT55/60-NCC (R2=0.11, P=0.01).
Despite a considerable increase in plasma aldosterone, acute oral KCl loading restored plasma potassium in PA patients and reduced NCC abundance and phosphorylation. This was in line with the theory that potassium supplementation in patients with PA canceled off the NCC-stimulating effects of aldosterone. The elevated plasma aldosterone in PA patients without supplemental KCl may be the result of the hormone’s reaction to a posture-related stressor.