Sodium in the skin: a summary of the physiology and a scoping review of disease associations

A large and growing body of research suggests that the skin plays an important role in regulating total body sodium, challenging traditional models of sodium homeostasis that focused exclusively on blood pressure and the kidney. In addition, skin sodium may help to prevent water loss and facilitate macrophage-driven antimicrobial host defence, but may also trigger immune dysregulation via upregulation of proinflammatory markers and downregulation of anti-inflammatory processes. We performed a systematic search of PubMed for published literature on skin sodium and disease outcomes and found that skin sodium concentration is increased in patients with cardiometabolic conditions including hypertension, diabetes and end-stage renal disease; autoimmune conditions including multiple sclerosis and systemic sclerosis; and dermatological conditions including atopic dermatitis, psoriasis and lipoedema. Several patient characteristics are associated with increased skin sodium concentration including older age and male sex. Animal evidence suggests that increased salt intake results in higher skin sodium levels; however, there are conflicting results from small trials in humans. Additionally, limited data suggest that pharmaceuticals such as diuretics and sodium-glucose co-transporter-2 inhibitors approved for diabetes, as well as haemodialysis may reduce skin sodium levels. In summary, emerging research supports an important role for skin sodium in physiological processes related to osmoregulation and immunity. With the advent of new noninvasive magnetic resonance imaging measurement techniques and continued research on skin sodium, it may emerge as a marker of immune-mediated disease activity or a potential therapeutic target.