Unlocking potassium secretion: the roles of aldosterone, ROMK, and WNK kinases in kidney potassium handling

The normal human kidney possesses a prodigious capacity to excrete dietary potassium (K+). This evolutionary adaptation is rooted in the high-K+ diets of prehistoric hominids, which are estimated to have reached 15,000 mg/day. Despite the progressive reduction in dietary K+ since the advent of agriculture, the modern distal nephron remains an exquisite K+ sensor. This review elucidates the molecular mechanisms governing kidney K+ handling, tracing the pathway from early enteric sensing to the structural reorganization of WNK (with-no-lysine [K+] kinase), and detailing how the interplay between aldosterone and angiotensin II ultimately resolves the aldosterone paradox in the distal nephron.