Kidney Week

Abstract: TH-OR16

Calcium Isotopes: A Novel Biomarker of Bone Mineralization in CKD

Session Information

• Novel Approaches to Mineral and Bone Metabolism
  October 22, 2020 | Location: Simulive
  Abstract Time: 05:00 PM - 07:00 PM

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

Rukshana Shroff, MD, PhD



Rukshana Shroff is a Consultant in Paediatric Nephrology at Great Ormond Street Hospital for Children, London, and Associate Professor at University College London, UK. Her main research focuses on cardiovascular disease in childhood chronic kidney disease, where she is involved in clinical research studies, clinical trials and laboratory work. Dr Shroff is the Principal Investigator on multicentre research projects comparing long-term outcomes of conventional haemodialysis and hemodiafiltration in children, vitamin D and bone and cardiovascular outcomes. She holds a prestigious senior fellowship from the National Institute for Health Research (NIHR) to develop novel methods of estimating calcium balance. Dr Shroff is co-editor for the 8th edition of Pediatric Nephrology, the definitive textbook in our field. She was elected to serve as a member of the KDIGO Kidney Disease: Improving Global Outcomes (KDIGO) Executive Committee and the KDIGO CKD-MBD Guideline Working Group, as well as serving on two guideline committees for the National Institute for Health and Care Excellence (NICE) and the council of the European Society for Paediatric Nephrology. Currently an Associate Editor for Pediatric Nephrology and serving on the editorial board of the Clinical Journal of the American Society of Nephrology and Peritoneal Dialysis International, Dr Shroff has published more than 200 original articles, reviews and editorials in peer-reviewed journals. She has contributed to the scientific committee of several international meetings.

• Fewtrell, Mary, University College London Great Ormond Street Institute of Child Health, London, United Kingdom

Mary Fewtrell,

• Kolevica, Ana, Geomar Helmholtz Centre for Ocean Research, Kiel, Germany

Ana Kolevica,

• Lalayiannis, Alexander D., University College London Great Ormond Street Institute of Child Health, London, United Kingdom

Alexander D. Lalayiannis,

• Schmitt, Claus peter, Center for Pediatrics and Adolescent Medicine, Heidelberg, Heidelberg, Germany

Claus peter Schmitt,

• Fischer, Dagmar-Christiane, Rostock University Medical Center, Rostock, Germany

Dagmar-Christiane Fischer,

• Eisenhauer, Anton, Geomar Helmholtz Centre for Ocean Research, Kiel, Germany

Anton Eisenhauer,

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 (δ^44/42Ca) in serum and urine gives a direct measure of BMB; δ^44/42Ca 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 δ^44/42Ca_.
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 δ^44/42Ca_Blood and δ^44/42Ca_Urine were higher than in adults (p<0.0001), reflecting avid Ca uptake during bone formation. Since urinary Ca excretion is impaired in CKD, δ^44/42Ca_Blood was higher and δ^44/42Ca_Urine lower in CKD4-5D compared to controls (p<0.0001 for both).

In CKD2-5D δ^44/42Ca_Blood positively correlated with cholecalciferol (p=0.01) and alfacalcidol (p=0.002) doses, implying increased bone Ca uptake when Ca bioavailability is increased. δ^44/42Ca_Blood 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). δ^44/42Ca_Blood 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 δ^44/42Ca_Blood (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.