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Abstract: TH-OR27

Intracellular Water Shift and Disturbed Osmoregulatory Responses to High Sodium in Patients with Hereditary Multiple Exostosis

Session Information

Category: Fluid, Electrolyte, and Acid-Base Disorders

  • 902 Fluid, Electrolyte, and Acid-Base Disorders: Clinical

Authors

  • Oppelaar, Jetta J., Amsterdam UMC Locatie AMC, Amsterdam, North Holland, Netherlands
  • Rorije, Nienke M.G., Amsterdam UMC Locatie AMC, Amsterdam, North Holland, Netherlands
  • Olde Engberink, Rik Hg, Amsterdam UMC Locatie AMC, Amsterdam, North Holland, Netherlands
  • Chahid, Youssef, Amsterdam UMC Locatie AMC, Amsterdam, North Holland, Netherlands
  • van Vlies, Naomi, Amsterdam UMC Locatie AMC, Amsterdam, North Holland, Netherlands
  • Verberne, Hein J., Amsterdam UMC Locatie AMC, Amsterdam, North Holland, Netherlands
  • Van den born, Bert-jan, Amsterdam UMC Locatie AMC, Amsterdam, North Holland, Netherlands
  • Vogt, Liffert, Amsterdam UMC Locatie AMC, Amsterdam, North Holland, Netherlands
Background

Tissue Na+ accumulation plays an important role in Na+ homeostasis. During high Na+ diet, negatively charged glycosaminoglycans (GAGs) facilitate extracellular Na+ accumulation in various tissues. Patients with Hereditary Multiple Exostosis (HME) have a heterozygous loss of function mutation in a gene involved in heparan sulfate (HS) synthesis. HME patients may therefore respond differently to high Na+ conditions with regard to Na+ and water homeostasis.

Methods

We performed a randomized cross-over study in 7 male HME patients and 12 healthy controls, matched for age, body mass index, blood pressure and eGFR. All subjects followed randomized both an 8-day low Na+ diet (LSD, <50mmol/d) and high Na+ diet (HSD, >200mmol/d). After each diet, blood and urine samples were collected. Also, body fluid compartments measurements were performed by using the distribution curve of iohexol and 125I-albumin.

Results

After LSD, body fluid volume distribution over total body water (TBW) was equal (Fig 1A). HSD resulted in a different distribution between groups (Fig 1B), while absolute TBW increase was not different (1.4 L vs 1.5 L, p=0.91). HME patients showed 3.9% ICFV expansion without concurrent changes in plasma effective osmolality (p=0.18). Whereas, in healthy controls, 23.0% IFV expansion was accompanied by increased plasma effective osmolality (p<0.01). HSD-induced changes in HS excretion were associated with ICFV change in healthy controls (Fig 1C).

Conclusion

HME patients, characterized by defective HS, show distinct body fluid composition and altered osmoregulation after HSD when compared to controls. The incapacity to expand IFV may reflect reduced extracellular Na+ accumulation with reduced commensurate water. As a consequence, water shifts to the ICFV after hypertonic stress, indicating disturbed maintenance of a stable milieu intérieur. Our results underscore that intact HS synthesis is crucial for Na+ homeostasis and fluid balance.