Dietary potassium restriction attenuates urinary sodium wasting in the generalized form of pseudohypoaldosteronism type 1.

Owing to its rarity and severe nature, the treatment for generalized pseudohypoaldosteronism type 1 (PHA1), a genetic disorder in the epithelial sodium channel (ENaC), is exclusively experience-based. In particular, the usefulness of dietary potassium restriction in PHA1 remains unclear with the absence of theoretical background to elucidate its utility. First, we demonstrated the effect of potassium restriction in a 13-month-old patient with ENaC γ-subunit gene mutations via a retrospective chart review; reduction of daily dietary potassium intake from 40 to 20 mEq induced rapid restoration of volume depletion, as evidenced by weight gain, elevation of the serum sodium level from 133 to 141 mEq/L, decreased urinary sodium excretion, and normalized renin activity. The serum potassium level decreased from 5.6 to 4.5 mEq/L. Next, we attempted to elucidate the pathophysiological basis of the usefulness of potassium restriction, leveraged by the increased knowledge regarding the roles of with-no-lysine kinases (WNKs) in the distal nephron. When potassium is restricted, the WNK signal will turn "on" in the distal nephron via reduction in the intracellular chloride level. Consequently, the sodium reabsorption from the Na