From the Research
Liddle syndrome causes hypokalemia through excessive sodium reabsorption in the distal nephron of the kidney, resulting from gain-of-function mutations in the epithelial sodium channel (ENaC), as reported in the most recent study 1. This rare genetic disorder makes the ENaC channels constitutively active even without aldosterone stimulation. The overactive ENaC channels continuously reabsorb sodium from the tubular fluid into the bloodstream, creating an electrical gradient that drives potassium secretion into the urine.
Key Points
- This persistent potassium loss leads to hypokalemia.
- The increased sodium reabsorption causes volume expansion, hypertension, and metabolic alkalosis.
- The condition mimics hyperaldosteronism but with suppressed renin and aldosterone levels.
- Treatment involves potassium-sparing diuretics that directly block ENaC, such as amiloride or triamterene, rather than spironolactone which would be ineffective since the pathway is aldosterone-independent, as supported by 2 and 1.
Pathophysiology and Treatment
The pathophysiology of Liddle syndrome is characterized by the excessive activity of ENaC, leading to increased sodium reabsorption and potassium secretion.
- Dietary sodium restriction and potassium supplementation may also be necessary to manage the condition.
- Understanding this pathophysiology explains why Liddle syndrome patients present with the triad of hypertension, hypokalemia, and metabolic alkalosis despite low aldosterone levels, as described in 3, 4, and 5.