Kidney Week

Abstract: TH-OR38

Calcium Isotope Ratios in Serum: A Novel Biomarker of Bone and Vessel Calcium Balance in Patients on Dialysis

Session Information

• Research Advances in Bone and Mineral Metabolism
  November 02, 2023 | Location: Room 111, Pennsylvania Convention Center
  Abstract Time: 05:33 PM - 05:42 PM

Category: Bone and Mineral Metabolism

• 502 Bone and Mineral Metabolism: Clinical

Authors

• Shroff, Rukshana, UCL Great Ormond Street Hospital and Institute of Child Health, London, United Kingdom

Rukshana Shroff, MD, PhD

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

Anton Eisenhauer,

• Heuser, Alexander, Geomar Helmholtz Centre for Ocean Research, Kiel, Kiel, Germany

Alexander Heuser,

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

Ana Kolevica,

• Mueller, Michael, University Medical Center Schleswig-Holstein (UKSH), Kiel, Germany

Michael Mueller,

• D'Haese, Patrick, Universiteit Antwerpen, Antwerpen, Belgium

Patrick D'Haese,

• Evenepoel, Pieter, KU Leuven, Department of Immunology and Microbiology, Laboratory of Nephrology, Leuven, Belgium

Pieter Evenepoel,

Background

Dysregulated mineral homeostasis in CKD can cause bone demineralization and vascular calcification. We have shown that non-radioactive calcium (Ca) isotopes, ⁴²Ca and ⁴⁴Ca, that are naturally present in our diet can be measured in serum, and their ratio (δ^44/42Ca_serum) quantitatively determines changes in bone Ca balance (BCaB). Isotopically light ⁴²Ca is preferentially incorporated into bone, so δ^44/42Ca_serum increases when bone formation exceeds resorption and vice versa.
We studied bone and arterial biopsies to determine the sensitivity of δ^44/42Ca_serum in estimating BCaB and vascular calcification.

Methods

⁴⁴Ca and ⁴²Ca were measured by inductively coupled plasma mass-spectrometry in the serum, bone and arterial biopsies of 19 chronic dialysis patients. Data were compared with adults with osteoporosis.

Results

δ^44/42Ca_serum and δ^44/42Ca_bone were significantly lower in dialysis patients (median age 59.8 years, time on dialysis 3.3 years) compared to adults with osteoporosis, implying lower BCaB in dialysis patients.(Fig 1). δ^44/42Ca_serum showed a strong positive correlation with δ^44/42Ca_bone and δ^44/42Ca_vessel.
δ^44/42Ca serum and bone correlated positively with the BAP/TRAP5-b ratio and osteoblastic markers P1NP and inversely with osteoclastic markers PTH and RANKL. Although δ^44/42Ca_serum indicated low BCaB in 89%, only 31% manifested DXA confirmed osteoporosis (T-scores <-2.5). On histology δ^44/42Ca_bone inversely correlated with osteoid area and positively with absolute mineralized area and trabecular thickness. Significant and independent predictors of δ^44/42Ca_serum were δ^44/42Ca_bone (p=0.01, 95%CI -1.35 to -0.26), BAP/TRAP5-b ratio (p=0.04, 95%CI 0.04 to 0.26) and osteoid area (p=0.03, 95%CI -1.11 to – 0.09), together predicting 79% of the variability in δ^44/42Ca_serum.

Conclusion

δ^44/42Ca_serum is a significant and independent maker of BCaB, correlating with bone histology, and may provide a more sensitive and non-invasive measure of BCaB than bone biomarkers or DXA.

Funding

• Government Support – Non-U.S.