Water and sodium metabolisms in kidney-skin crosstalk

Maintenance of body water and sodium homeostasis is essential to terrestrial life, with the kidney classically viewed as the principal regulator. However, this kidney-centric model does not fully account for the various physiological and pathophysiological states, including the paradoxical association between water loss and hypertension. This review proposes a shift in perspective toward "water conservation" as a core concept, highlighting the integrated and reciprocal crosstalk between the kidney and the skin. Evidence from animal models of skin barrier defects and renal injury demonstrates that primary water loss from one organ elicits a compensatory water-conserving response. A key mechanism in this adaptation is vasoconstriction, which reduces water loss across these barriers, and in turn, elevates systemic blood pressure. We further discuss evidence showing that the skin is not merely a passive barrier but also an active hemodynamic organ, with local molecular pathways—such as the hypoxia-inducible factor and renin–angiotensin systems—capable of directly influencing systemic blood pressure. Finally, we address the limitations of the current paradigms by examining tissue-specific sodium storage and the uncoupling of water and sodium balance, underscoring the need for integrated tissue-level analysis. This review provides a conceptual framework that reevaluates the roles of the kidney and skin in regulating body fluids and offers new insights into the physiology of body water and blood pressure regulation.