The Story of Aldosterone Escape.

Abstract: Aldosterone escape refers to the spontaneous and compensatory diuresis that occurs in primary aldosteronism to correct and rebalance fluid homeostasis during conditions of sodium retention. Though widely observed in humans and animals, the precise mechanisms underpinning aldosterone escape remain unclear. The escape phenomenon is clinically relevant as primary aldosteronism affects nearly one in ten hypertensive adults and doubles the risk of stroke and atrial fibrillation. Studying the phenomenon provides additional insights into the intricate physiology of renal sodium handling that may inform future development of novel therapeutics. This perspective is a modern account of the complex interplay of renal hemodynamics, hormonal signaling, paracrine modulation, and tubular adaptations underlying aldosterone escape. By reexamining classical and emerging mechanisms, including the WNK system as a potassium-sensitive distal homeostasis mechanism, we suggest a general framework for this remarkable phenomenon.