ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: TH-OR125

Stable Calcium Isotopes: A Novel Biomarker of Bone Mineral Density in Children with CKD

Session Information

Category: Pediatric Nephrology

  • 1700 Pediatric Nephrology

Authors

  • Shroff, Rukshana, Great Ormond Street Hospital, London, United Kingdom
  • Kolevica, Ana, Geomar Helmholtz Centre for Ocean Research, Kiel, Germany
  • Lalayiannis, Alexander D., Great Ormond St Hospital for Children NHS Foundation Trust, Birmingham, United Kingdom
  • Fischer, Dagmar-Christiane, University Hospital Rostock, Rostock, Germany
  • Bayazit, Aysun, Cukurova University, Adana, Turkey
  • Askiti, Varvara, Children''s Hospital "P. & A. Kyriakou", Athens, Greece
  • Mitsioni, Andromachi, Children''s Hospital "P&A Kyriakou", Athens, Greece
  • Jankauskiene, Augustina, Children hospital, affiliate of Vilnius university hospital Santaros clinic, Vilnius, Lithuania
  • Eisenhauer, Anton, Geomar Helmholtz Institute for Ocean Research, Kiel, Germany
Background

In CKD dysregulated calcium (Ca) homeostasis is common and causally associated with reduced bone mineral content and vascular calcification. Currently available radiological measures and biomarkers do not allow an accurate evaluation of bone mineralisation.

Methods

We measured stable Ca isotope fractions (δ44/42Ca) by plasma ionization mass spectrometry in blood and urine as biomarkers for bone mineralization. The relationship between bone Ca gain and loss is described mathematically using a compartment model based on Ca kinetics. 104 children in CKD4-5 and on dialysis (CKD4-5D) and 40 matched controls underwent Ca isotope measurement, bone biomarkers, dual energy x-ray absorptiometry (DXA) and tibial peripheral quantitative CT scan (pQCT). pQCT accurately defines cortical and trabecular bone mineral density (BMD), and tibial cortical BMD Z-score is shown to predict fracture risk.

Results

Both the δ44/42CaBlood and δ44/42CaUrine were significantly different in children with CKD4-5D compared to healthy controls (p<0.001 for both). In healthy children the δ44/42CaBlood and δ44/42CaUrine were higher than values reported in adults (-0.27 vs -0.84 ‰ for δ44/42CaBlood and 0.94 vs 0.35‰ for δ44/42CaUrine), reflecting avid Ca uptake during bone formation.
There was a linear association between estimated GFR and δ44/42CaUrine (p<0.0001) in CKD. δ44/42CaBlood positively correlated with cholecalciferol (p=0.01) and alfacalcidol (p=0.002) doses, implying increased bone Ca uptake when Ca bioavailability is increased. δ44/42CaBlood showed a linear association with established biomarkers of bone formation (alkaline phosphatase, p=0.05) and bone resorption (TRAP5b, p<0.001 and CTX, p=0.006). δ44/42CaBlood strongly correlated with tibial cortical BMD Z-score (p<0.0001, R2=0.39), and DXA hip Z-score (p=0.02). On multivariable linear regression analysis significant and independent predictors of tibial cortical BMD Z-score were δ44/42CaBlood (β=0.68, p=0.006) and PTH (β-0.39, p=0.04), together predicting 67% of the variability in BMD.

Conclusion

Ca isotope ratios provide a novel, non-invasive method of assessing bone mineral density in children with CKD and may be used to guide safe and effective treatment that prevents Ca deficiency or overload.

Funding

  • Government Support - Non-U.S.