Sodium balance is not just a renal affair

Purpose of review The equilibration theory of extracellular body fluids is tightly linked to sodium (Na+) metabolism. It is accepted that with changes in salt intake, renal sodium elimination will prevent any change in interstitial Na+ content and concentration. This review summarizes recent anomalous findings regarding salt and water homeostasis that are inconsistent with current assumptions. Recent findings Recent findings from chemical analysis studies of laboratory animals, as well as noninvasive quantitative Na+ MRI (Na-MRI) studies in patients, have shown that remarkable amounts of Na+ are stored in muscle and in skin without commensurate water retention. Furthermore, an ultra-long Na+ balance study in humans suggests the presence of endogenous clocks that generate weekly and monthly infradian rhythmicity of Na+ storage independent of salt intake. Animal experiments suggest that fluids in the skin interstitium are hypertonic compared with plasma, and that interstitial osmotic stress induces local extrarenal immune cell and lymph-capillary driven mechanisms for electrolyte clearance and maintenance of the internal environment. Recent quantitative evidence challenges current ideas on salt and water homeostasis, and suggests that Na+ homeostasis cannot be maintained without additional previously unappreciated extrarenal regulatory mechanisms.