Pathophysiology and causes of hyperkalemia: unraveling causes beyond kidney dysfunction

This review article series on water and electrolyte disorders is based on the "Electrolyte Winter Seminar" that is held annually for young nephrologists in Japan. This seminar includes lively discussions based on cases, which have been partly included in this series as self-assessment questions. In this fourth article of the series, we have focused on the pathophysiology of potassium and the diagnosis of hyperkalemia. Hyperkalemia is associated with increased overall mortality, cardiovascular mortality, hospitalization, and progression to end-stage renal disease. Although most patients with hyperkalemia exhibit impaired kidney function, some exhibit normal kidney function. Therefore, accurately diagnosing the underlying cause of hyperkalemia is crucial for its appropriate management. In this review, we have first discussed the pathophysiology of potassium regulation. We have then highlighted the causes of hyperkalemia other than chronic kidney disease, including pseudohyperkalemia, which is often overlooked in clinical practice, and hypoaldosteronism, which can cause hyperkalemia even in patients with normal or mildly impaired kidney function. Finally, we have shared practical "Tips and Pearls" on hyperkalemia for clinicians that are applicable in daily practice.