Naturally occurring stable calcium isotope ratios are a novel biomarker of bone calcium balance in chronic kidney disease

Rukshana Shroff¹, Alexander D Lalayiannis², Mary Fewtrell³, Claus Peter Schmitt⁴, Aysun Bayazit⁵, Varvara Askiti⁶, Augustina Jankauskiene⁷, Justine Bacchetta⁸, Selmy Silva⁹, Nadine Goodman⁹, Louise McAlister¹⁰, Lorenzo Biassoni¹¹, Nicola Crabtree¹², Anja Rahn¹³, Dagmar-Christiane Fischer¹³, Alexander Heuser¹⁴, Ana Kolevica¹⁴, Anton Eisenhauer¹⁴

Affiliations

¹ Renal Unit, University College London Great Ormond Street Hospital and Institute of Child Health, London, UK. Electronic address: Rukshana.Shroff@gosh.nhs.uk.
² Renal Unit, University College London Great Ormond Street Hospital and Institute of Child Health, London, UK; Renal Unit, Birmingham Women's and Children's National Health Service Foundation Trust, Birmingham, UK.
³ Radiology Department, University College London Great Ormond Street Hospital and Institute of Child Health, London, UK; Childhood Nutrition Research Centre, Population, Policy & Practice Research & Teaching Department, University College London Great Ormond Street Hospital and Institute of Child Health, London, UK.
⁴ Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany.
⁵ Department of Pediatric Nephrology, Cukurova University, Adana, Turkey.
⁶ Department of Pediatric Nephrology, "P. & A. Kyriakou" Children's Hospital, Athens, Greece.
⁷ Vilnius University, Institute of Clinical Medicine, Pediatric Center, Vilnius, Lithuania.
⁸ Department of Pediatric Nephrology, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France.
⁹ Renal Unit, University College London Great Ormond Street Hospital and Institute of Child Health, London, UK.
¹⁰ Dietetics Department, University College London Great Ormond Street Hospital and Institute of Child Health, London, UK.
¹¹ Radiology Department, University College London Great Ormond Street Hospital and Institute of Child Health, London, UK.
¹² Radiology Department, Birmingham Women's and Children's National Health Service Foundation Trust, Birmingham, UK.
¹³ Department of Pediatrics, Rostock University Medical Centre, Rostock, Germany.
¹⁴ Department of Marine Environmental Geochemistry, GEOMAR Helmholtz Centre for Ocean Research Kiel, Kiel, Germany.

PMID: 35644284
DOI: 10.1016/j.kint.2022.04.024

Free article

Naturally occurring stable calcium isotope ratios are a novel biomarker of bone calcium balance in chronic kidney disease

Rukshana Shroff et al. Kidney Int. 2022 Sep.

Free article

. 2022 Sep;102(3):613-623.

doi: 10.1016/j.kint.2022.04.024. Epub 2022 May 27.

Authors

Affiliations

¹ Renal Unit, University College London Great Ormond Street Hospital and Institute of Child Health, London, UK. Electronic address: Rukshana.Shroff@gosh.nhs.uk.
² Renal Unit, University College London Great Ormond Street Hospital and Institute of Child Health, London, UK; Renal Unit, Birmingham Women's and Children's National Health Service Foundation Trust, Birmingham, UK.
³ Radiology Department, University College London Great Ormond Street Hospital and Institute of Child Health, London, UK; Childhood Nutrition Research Centre, Population, Policy & Practice Research & Teaching Department, University College London Great Ormond Street Hospital and Institute of Child Health, London, UK.
⁴ Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany.
⁵ Department of Pediatric Nephrology, Cukurova University, Adana, Turkey.
⁶ Department of Pediatric Nephrology, "P. & A. Kyriakou" Children's Hospital, Athens, Greece.
⁷ Vilnius University, Institute of Clinical Medicine, Pediatric Center, Vilnius, Lithuania.
⁸ Department of Pediatric Nephrology, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France.
⁹ Renal Unit, University College London Great Ormond Street Hospital and Institute of Child Health, London, UK.
¹⁰ Dietetics Department, University College London Great Ormond Street Hospital and Institute of Child Health, London, UK.
¹¹ Radiology Department, University College London Great Ormond Street Hospital and Institute of Child Health, London, UK.
¹² Radiology Department, Birmingham Women's and Children's National Health Service Foundation Trust, Birmingham, UK.
¹³ Department of Pediatrics, Rostock University Medical Centre, Rostock, Germany.
¹⁴ Department of Marine Environmental Geochemistry, GEOMAR Helmholtz Centre for Ocean Research Kiel, Kiel, Germany.

PMID: 35644284
DOI: 10.1016/j.kint.2022.04.024

Abstract

Dysregulated calcium homeostasis is common in chronic kidney disease and causally associated with disorders of bone mineralization. However, radiological measures and biomarkers do not allow accurate evaluation of bone calcium balance. Non-radioactive calcium isotopes, ⁴²Ca and ⁴⁴Ca, are present in our diet and sequestered into body compartments following principles of kinetic isotope fractionation. Isotopically light ⁴²Ca is preferentially incorporated into bone, while heavier ⁴⁴Ca is excreted. The ratio (^44/42Ca_serum) increases when bone formation exceeds resorption and vice versa, reflecting bone calcium balance. We measured these calcium isotopes by inductively coupled plasma mass-spectrometry in blood, urine and feces of 42 children with chronic kidney disease and 92 receiving dialysis therapy. We compared the isotope ratios with bone biomarkers and determined total bone mineral content by dual-energy x-ray absorptiometry and peripheral quantitative CT expressed as age-adjusted z-scores. The ^44/42Ca_serum ratio positively correlated with serum calcium, 25-hydroxyvitamin D and alkaline phosphatases and inversely with serum parathyroid hormone and other bone resorption markers. The ^44/42Ca_serum ratio positively correlated with age-adjusted z-scores of tibial trabecular bone mineral density and total bone mineral content measured by peripheral quantitative CT, and hip bone mineral density measured by dual-energy X-ray absorptiometry. Significant and independent predictors of total bone mineral content, measured by, were the ^44/42Ca_serum ratio and parathyroid hormone. The ^44/42Ca_serum ratio, repeated after four weeks, highly correlated with baseline values. When adjusted for calcium-containing medications and kidney impairment, the ^44/42Ca_serum ratio in patients receiving dialysis was 157% lower than that of age-matched children and 29% lower than levels in elderly women with osteoporosis, implying significantly lower bone mineral content. Thus, calcium isotope ratios may provide a novel, sensitive and non-invasive method of assessing bone calcium balance in chronic kidney disease.

Keywords: bone mineral density; calcium; chronic kidney disease; dialysis; dual-energy X-ray absorptiometry; isotopes.

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Natural stable calcium isotope ratios: a new gold standard for bone balance?
Hill Gallant KM, Zheng XY. Hill Gallant KM, et al. Kidney Int. 2022 Sep;102(3):473-476. doi: 10.1016/j.kint.2022.06.017. Kidney Int. 2022. PMID: 35988935

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Naturally occurring stable calcium isotope ratios are a novel biomarker of bone calcium balance in chronic kidney disease

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Naturally occurring stable calcium isotope ratios are a novel biomarker of bone calcium balance in chronic kidney disease

Authors

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Abstract

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Medical