Clinical impact of tissue sodium storage

Abstract

In recent times, the traditional nephrocentric, two-compartment model of body sodium has been challenged by long-term sodium balance studies and experimental work on the dermal interstitium and endothelial surface layer. In the new paradigm, sodium can be stored without commensurate water retention in the interstitium and endothelial surface layer, forming a dynamic third compartment for sodium. This has important implications for sodium homeostasis, osmoregulation and the hemodynamic response to salt intake. Sodium storage in the skin and endothelial surface layer may function as a buffer during periods of dietary depletion and excess, representing an extra-renal mechanism regulating body sodium and water. Interstitial sodium storage may also serve as a biomarker for sodium sensitivity and cardiovascular risk, as well as a target for hypertension treatment. Furthermore, sodium storage may explain the limitations of traditional techniques used to quantify sodium intake and determine infusion strategies for dysnatraemias. This review is aimed at outlining these new insights into sodium homeostasis, exploring their implications for clinical practice and potential areas for further research for paediatric and adult populations.

Keywords: Blood pressure; Endothelial surface layer; Glycocalyx; Glycosaminoglycan; Nonosmotic; Skin; Sodium.

Fig. 1

Sodium storage in a third compartment. The extracellular fluid compartment consists of an interstitial (blue) and intravascular (red) space that were considered to be osmotically equilibrated. However, significant higher sodium concentrations can be found in the skin and endothelial surface layer (ESL), comprising a third compartment that is not in osmotic equilibration with the other fluid compartments

Fig. 2

Consequences of estimating sodium intake with a single measurement. a Differences in estimated sodium intake when estimated at baseline or within 1 year after follow-up. b Differences in the associated risk for the composite of cardiovascular events and death when using baseline or 1-year follow-up estimates of sodium intake. Adapted from [52]