Extrarenal potassium adaptation: review of a concept

Animals chronically fed a high-potassium diet may survive an acute potassium load which is lethal to animals fed a control diet. This 'potassium tolerance' is clearly related to an enhanced ability of the kidneys to excrete potassium. However, in their now classic studies, Alexander and Levinsky suggested that a nonrenal mechanism also contributes to this phenomenon. They showed that despite nephrectomy just prior to acute potassium loading, animals accustomed to a high-potassium diet had a smaller increment in plasma potassium than did controls. As a result of this work, it is now widely believed that chronic exposure to large amounts of potassium somehow directly enhances cellular potassium uptake, a process referred to as extrarenal potassium adaptation. However, it is important to note that in these studies, the animals were fasted prior to nephrectomy. We have shown that when potassium is withdrawn from potassium-adapted animals, high rates of potassium excretion persist and eventually result in the development of paradoxical potassium depletion. We believe that it is this potassium depletion which accounts for the enhancement of cellular potassium uptake sometimes seen in potassium-adapted animals. Indeed, extrarenal potassium adaptation can only be demonstrated after a prolonged period of dietary potassium withdrawal has provided the opportunity for potassium depletion to occur. Furthermore, there is actually little evidence that chronic potassium feeding directly enhances the cellular uptake of an acute potassium load. We conclude that extrarenal potassium adaption is a time-honored concept which, for practical purposes, does not exist.