Sodium accumulation in the skin of children.

Rationale: The role of high sodium intake in blood pressure (BP) and worse
cardiovascular health has been extensively investigated, but is to date still
incompletely understood. For a long time, it was thought that sodium
homeostasis in the body was based on a two-compartment model, which assumed
that an increase in dietary salt intake leads to a water shift from the
intracellular to the extracellular compartment, thirst and increased renal
water uptake. These effects, to maintain plasma osmolality, and thus increase
in extracellular volume was considered to be mainly responsible for BP
increases. However, consecutive long-term sodium balance studies have shown no
weight gain or increase in total body water during a high sodium intake. It was
found that sodium can accumulate non-osmotically in tissue interstitium and the
endothelial surface layer (ESL), thus forming a third sodium compartment in the
body. Highly sulfated glycosaminoglycans (GAGs) are thought to facilitate
tissue sodium accumulation, but also increased immune cell infiltration into
tissues. How these phenomena affect BP is unknown. Yet, modification in GAG
status by oral GAG supplementation has recently been shown to lower BP. Large
variations in skin sodium accumulation capacity have been found in various
pathological conditions associated with worse cardiovascular health, including
high BP. Whether this third compartment is relevant in early life and whether
alterations of tissue sodium accumulation at a young age may translate in BP
alterations and worse cardiovascular (CV) outcome later in life is unknown.

Objective: The aim of this study is to define: i. the environmental and
biological factors that drive skin sodium accumulation according to the novel
3-compartment concept in the skin of children; ii. whether these factors are
associated with risk factors for future cardiovascular disease; and iii. the
association between skin sodium accumulation and alterations in GAG metabolism
and local immune cell infiltration.

This study has a multicenter observational study design.

The findings of this study will contribute to our understanding of the ability
of the skin to accumulate sodium non-osmotically in healthy, children without
the need to perform a skin or tissue biopsy for the purpose of this study.
Furthermore, it will give more insight in the association between non-osmotic
sodium accumulation and already known risk factors for worse CV health.
Participation in this research will not lead to personal benefit for the
subjects. There will be no burden to the study subjects, except of children at
age of 5 or higher in whom BP will be measured. Furthermore, subjects* parents
will be requested to participate in two questionnaires and BP levels will be
measured in all parents.