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Abstract: TH-OR16

Calcium Isotopes: A Novel Biomarker of Bone Mineralization in CKD

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Shroff, Rukshana, University College London Great Ormond Street Institute of Child Health, London, United Kingdom
  • Fewtrell, Mary, University College London Great Ormond Street Institute of Child Health, London, United Kingdom
  • Kolevica, Ana, Geomar Helmholtz Centre for Ocean Research, Kiel, Germany
  • Lalayiannis, Alexander D., University College London Great Ormond Street Institute of Child Health, London, United Kingdom
  • Schmitt, Claus peter, Center for Pediatrics and Adolescent Medicine, Heidelberg, Heidelberg, Germany
  • Fischer, Dagmar-Christiane, Rostock University Medical Center, Rostock, Germany
  • Eisenhauer, Anton, Geomar Helmholtz Centre for Ocean Research, Kiel, Germany
Background

Serum Ca, bone biomarkers and radiological imaging do not allow accurate evaluation of bone mineral balance (BMB), a key determinant of bone mineral density (BMD) and fracture risk. Naturally occuring stable (non-radioactive) Ca isotopes, 42Ca and 44Ca, are absorbed from our diet and sequestered into different body compartments following kinetic principles of isotope fractionation. Isotopically light 42Ca is preferentially incorporated into bone, and heavier 44Ca excreted in urine and feces. Their ratio (δ44/42Ca) in serum and urine gives a direct measure of BMB; δ44/42Ca is higher during bone formation than bone resorption.

Methods

Ca isotopes were measured by plasma-ionization mass-spectrometry in blood, urine, feces and dialysate. The relationship between bone Ca gain and loss was calculated using a compartment model, and expressed as δ44/42Ca.
128 children in CKD4-5 and on dialysis (CKD4-5D) and 117 healthy participants (age <30) underwent Ca isotope measurement, bone biomarkers, DXA and tibial peripheral quantitative CT (pQCT), an accurate measure of cortical BMD.

Results

In healthy children the δ44/42CaBlood and δ44/42CaUrine were higher than in adults (p<0.0001), reflecting avid Ca uptake during bone formation. Since urinary Ca excretion is impaired in CKD, δ44/42CaBlood was higher and δ44/42CaUrine lower in CKD4-5D compared to controls (p<0.0001 for both).

In CKD2-5D 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 positively correlated with biomarkers of bone formation (ALK, p=0.05) and inversely with resorption markers (PTH, p=0.013; TRAP5b, p<0.001 and CTX, p=0.006). δ44/42CaBlood correlated positively with tibial cortical BMD-Z-score (p=0.006, R2=0.39), and DXA hip BMD-Z-score (p=0.02). 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 mineralization. Defining an accurate biomarker of BMB forms the basis of future studies investigating Ca dynamics in disease states and the impact of treatments that affect bone homeostasis.

Funding

  • Government Support - Non-U.S.