Calcium isotopes as a biomarker for vascular calcification in chronic kidney disease

Abstract Chronic kidney disease (CKD) is a global health problem affecting ~10% of the global population. The largest contributor to morbidity and mortality in patients with CKD is cardiovascular disease, also the leading cause of death in those with kidney failure. One of the strongest predictors of cardiovascular risk is vascular calcification, however due to the lack of appropriate diagnostic tools it is not routinely screened. In this study, we investigate whether naturally occurring calcium (Ca) isotopes in serum or urine could be used as a non-invasive marker of vascular calcification in CKD. We recruited 28 controls, 9 participants with mild-moderate CKD, 22 undertaking dialysis and 19 who received a kidney transplant. While we found no significant association of urine Ca isotope composition between the different groups, Ca isotope compositions in serum were significantly different between groups (p<0.01). Receiver Operating Characteristic curve analysis shows that serum Ca isotopes are a very good diagnostic test for detecting medial calcification (AUC = 0.818, sensitivity 81.8% and specificity 77.3%, p<0.01) and perform better than existing biomarkers. As a minimally invasive diagnostic tool, serum Ca isotopes have the potential to be used as an early screening test for vascular calcification.