Kidney Week

Abstract: TH-OR125

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

Session Information

• Pediatric Nephrology Research
  November 07, 2019 | Location: 152, Walter E. Washington Convention Center
  Abstract Time: 05:54 PM - 06:06 PM

Category: Pediatric Nephrology

• 1700 Pediatric Nephrology

Authors

• Shroff, Rukshana, Great Ormond Street Hospital, London, United Kingdom

Rukshana Shroff, MD, PhD



Rukshana Shroff, MD, FRCPCH, PhD, is a Consultant in Paediatric Nephrology at Great Ormond Street Hospital for Children in London UK, and Associate Professor at the University College London Institute of Child Health. Her research focuses on cardiovascular disease in childhood chronic kidney disease (CKD), including laboratory work, clinical research studies and clinical trials. She leads a European trial comparing long-term outcomes of conventional hemodialysis and hemodiafiltration in children. She currently holds a prestigious senior fellowship from the National Institute for Health Research (NIHR) to continue research into mineral dysregulation in CKD. She has published more than 180 original articles, reviews and book chapters in the fields of nephrology and dialysis. Dr Shroff in on the executive committee of KDIGO and has served on the recent KDIGO CKD-MBD guideline update and two guideline committees for the UK National Institute for Health and Care Excellence (NICE). She has served on the Council for the European Society for Pediatric Nephrology. She serves on the editorial board of the Clinical Journal of the American Society of Nephrology, Pediatric Nephrology and Peritoneal Dialysis International. Dr Shroff has served on the scientific committee of several international meetings including the ERA-EDTA, IPNA, ESPN and EuroPD congresses and given over 75 invited talks.

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

Ana Kolevica,

• Lalayiannis, Alexander D., Great Ormond St Hospital for Children NHS Foundation Trust, Birmingham, United Kingdom

Alexander D. Lalayiannis,

• Fischer, Dagmar-Christiane, University Hospital Rostock, Rostock, Germany

Dagmar-Christiane Fischer,

• Bayazit, Aysun, Cukurova University, Adana, Turkey

Aysun Bayazit,

• Askiti, Varvara, Children''s Hospital "P. & A. Kyriakou", Athens, Greece

Varvara Askiti,

• Mitsioni, Andromachi, Children''s Hospital "P&A Kyriakou", Athens, Greece

Andromachi Mitsioni,

• Jankauskiene, Augustina, Children hospital, affiliate of Vilnius university hospital Santaros clinic, Vilnius, Lithuania

Augustina Jankauskiene,

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

Anton Eisenhauer,

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 (δ^44/42Ca) 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 δ^44/42Ca_Blood and δ^44/42Ca_Urine were significantly different in children with CKD4-5D compared to healthy controls (p<0.001 for both). In healthy children the δ^44/42Ca_Blood and δ^44/42Ca_Urine were higher than values reported in adults (-0.27 vs -0.84 ‰ for δ^44/42Ca_Blood and 0.94 vs 0.35‰ for δ^44/42Ca_Urine), reflecting avid Ca uptake during bone formation.
There was a linear association between estimated GFR and δ^44/42Ca_Urine (p<0.0001) in CKD. 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 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). δ^44/42Ca_Blood 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 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 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.