Potassium homeostasis and dyskalemias: the respective roles of renal, extrarenal, and gut sensors in potassium handling.

Integrated mechanisms controlling the maintenance of potassium homeostasis are well established and are defined by the classic "feedback control" of potassium balance. Recently, increasing investigative attention has focused on novel physiological paradigms that increase the complexity and precision of homeostasis. This review briefly considers the classic and well-established feedback control of potassium and then considers subsequent investigations that inform on an intriguing and not widely recognized complementary paradigm: the "feed-forward control of potassium balance." Feed-forward control refers to a pathway in a homeostatic system that responds to a signal in the environment in a predetermined manner, without responding to how the system subsequently reacts (i.e., without responding to feedback). Studies in several animal species, and recently in humans, have confirmed the presence of a feed-forward control mechanism that is capable of mediating potassium excretion independent of changes in serum potassium concentration and aldosterone. Knowledge imparted by this update of potassium homeostasis hopefully will facilitate the clinical management of hyperkalemia in patients with chronic and recurrent hyperkalemia. Awareness of this updated integrative control mechanism for potassium homeostasis is more relevant today when the medical community is increasingly focused on leveraging and expanding established renin-angiotensin-aldosterone system inhibitor treatment regimens and on successfully coping with the challenges of managing hyperkalemia provoked by renin-angiotensin-aldosterone system inhibitors. These new insights are relevant to the future design of clinical trials delineating renal potassium handling.