R.H.G. Olde Engberink
- Clinical impact of nonosmotic sodium storage
J.J. Homan van der Heide
E.T. van Bavel
B.J.H. van den Born
- Award date
- 29 September 2017
- Number of pages
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
High sodium intake is associated with hypertension and increased cardiovascular and renal risk. In this thesis we assessed whether these negative effects of sodium can be neutralised by glycosaminoglycans in the endothelial surface layer (i.e. nonosmotic sodium storage). Also, we investigate the clinical consequences of nonosmotic sodium storage.
This thesis demonstrates that glycosaminoglycans are crucial for normal sodium and water homeostasis and that nonosmotic sodium storage significantly impacts daily clinical practice. For example, after infusion of NaCl we were only able to retrieve 50% of the infused sodium. The existence of a third compartment in which sodium can be (temporarily) stored therefore complicates treatment of hypo- or hypernatremias. In additio, we show that a single 24-hour urine collection is not suitable for estimation of a daily salt intake and the associated cardiovascular risk, and should therefore not be used in daily clinical practice.
Nonosmotic sodium storage in the endothelial surface layer may also have positive effects. We demonstrate that restoration of the endothelial surface layer with sulodexide, a new oral drug consisting of glycosaminoglycans, lower blood pressure control and lower cardiovascular risk.
Finally, we showed that hypertension treatment can be improved by optimizing the current treatment. By changing from thiazide-type to thiazide-like diuretics we may be able to reduce cardiovascular events by 12-20%.
In conclusion, this thesis demonstrates the significance of nonosmotic sodium storage in clinical practice and provides new therapeutic options to optimize hypertension treatment and cardiovascular protection.
Thesis (complete) (Embargo up to and including 29 September 2019)
Chapter 3: Abnormal sodium and water homeostasis in mice with defective heparan sulfates (Embargo up to and including 29 September 2019)
Chapter 4: Quantification of non-osmotic sodium storage capacity following acute hypertonic saline infusion in healthy subjects (Embargo up to and including 29 April 2018)
Chapter 5: Use of a single baseline versus multi-year 24-hour urine collections for estimation of long-term sodium intake and associated cardiovascular and renal risk (Embargo up to and including 29 October 2018)
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