TY - JOUR
T1 - Perturbed body fluid distribution and osmoregulation in response to high salt intake in patients with hereditary multiple exostoses
AU - Oppelaar, Jetta J.
AU - Rorije, Nienke M. G.
AU - Olde Engberink, Rik H. G.
AU - Chahid, Youssef
AU - van Vlies, Naomi
AU - Verberne, Hein J.
AU - van den Born, Bert-Jan H.
AU - Vogt, Liffert
N1 - Funding Information: This work was supported by the Dutch Kidney Foundation (Junior Kolff grant number KJPB 11.22 and Senior Kollf grant number 18OKG12 to LV) and The Netherlands Organization for Health Research and Development (clinical fellowship grant number 90700310 to LV). Publisher Copyright: © 2021 The Authors
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Background: Hereditary Multiple Exostoses (HME) is a rare autosomal disorder characterized by the presence of multiple exostoses (osteochondromas) caused by a heterozygous loss of function mutation in EXT1 or EXT2; genes involved in heparan sulfate (HS) chain elongation. Considering that HS and other glycosaminoglycans play an important role in sodium and water homeostasis, we hypothesized that HME patients have perturbed whole body volume regulation and osmolality in response to high sodium conditions. Methods: We performed a randomized cross-over study in 7 male HME patients and 12 healthy controls, matched for age, BMI, blood pressure and renal function. All subjects followed both an 8-day low sodium diet (LSD, <50 mmol/d) and high sodium diet (HSD, >200 mmol/d) in randomized order. After each diet, blood and urine samples were collected. Body fluid compartment measurements were performed by using the distribution curve of iohexol and 125I-albumin. Results: In HME patients, HSD resulted in significant increase of intracellular fluid volume (ICFV) (1.2 L, p = 0.01). In this group, solute-mediated water clearance was significantly lower after HSD, and no changes in interstitial fluid volume (IFV), plasma sodium, and effective osmolality were observed. In healthy controls, HSD did not influence ICFV, but expanded IFV (1.8 L, p = 0.058) and increased plasma sodium and effective osmolality. Conclusion: HME patients show altered body fluid distribution and osmoregulation after HSD compared to controls. Our results might indicate reduced interstitial sodium accumulation capacity in HME, leading to ICFV increase. Therefore, this study provides additional support that HS is crucial for maintaining constancy of the internal environment.
AB - Background: Hereditary Multiple Exostoses (HME) is a rare autosomal disorder characterized by the presence of multiple exostoses (osteochondromas) caused by a heterozygous loss of function mutation in EXT1 or EXT2; genes involved in heparan sulfate (HS) chain elongation. Considering that HS and other glycosaminoglycans play an important role in sodium and water homeostasis, we hypothesized that HME patients have perturbed whole body volume regulation and osmolality in response to high sodium conditions. Methods: We performed a randomized cross-over study in 7 male HME patients and 12 healthy controls, matched for age, BMI, blood pressure and renal function. All subjects followed both an 8-day low sodium diet (LSD, <50 mmol/d) and high sodium diet (HSD, >200 mmol/d) in randomized order. After each diet, blood and urine samples were collected. Body fluid compartment measurements were performed by using the distribution curve of iohexol and 125I-albumin. Results: In HME patients, HSD resulted in significant increase of intracellular fluid volume (ICFV) (1.2 L, p = 0.01). In this group, solute-mediated water clearance was significantly lower after HSD, and no changes in interstitial fluid volume (IFV), plasma sodium, and effective osmolality were observed. In healthy controls, HSD did not influence ICFV, but expanded IFV (1.8 L, p = 0.058) and increased plasma sodium and effective osmolality. Conclusion: HME patients show altered body fluid distribution and osmoregulation after HSD compared to controls. Our results might indicate reduced interstitial sodium accumulation capacity in HME, leading to ICFV increase. Therefore, this study provides additional support that HS is crucial for maintaining constancy of the internal environment.
KW - Glycosaminoglycans
KW - Heparan sulfate
KW - Hereditary Multiple Exostoses
KW - Osmoregulation
KW - Sodium
KW - Water balance
UR - http://www.scopus.com/inward/record.url?scp=85118837857&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ymgmr.2021.100797
DO - https://doi.org/10.1016/j.ymgmr.2021.100797
M3 - Article
C2 - 34815940
SN - 2214-4269
VL - 29
JO - Molecular Genetics and Metabolism Reports
JF - Molecular Genetics and Metabolism Reports
M1 - 100797
ER -