Wollongong Isotope Geochronology Laboratory, School of Earth, Atmospheric and Life Sciences, University of Wollongong, Wollongong, New South Wales, Australia.
School of Medicine, University of Wollongong, Wollongong, New South Wales, Australia.
Metallomics. 2023 Mar 6;15(3). doi: 10.1093/mtomcs/mfad009.
Calcium balance is abnormal in adults with chronic kidney disease (CKD) and is associated with the development of vascular calcification. It is currently not routine to screen for vascular calcification in CKD patients. In this cross-sectional study, we investigate whether the ratio of naturally occurring calcium (Ca) isotopes, 44Ca and 42Ca, in serum could be used as a noninvasive marker of vascular calcification in CKD. We recruited 78 participants from a tertiary hospital renal center: 28 controls, 9 subjects with mild-moderate CKD, 22 undertaking dialysis and 19 who received a kidney transplant. For each participant, systolic blood pressure, ankle brachial index, pulse wave velocity, and estimated glomerular filtration rate were measured, along with serum markers. Calcium concentrations and isotope ratios were measured in urine and serum. While we found no significant association between urine Ca isotope composition (noted δ44/42Ca) between the different groups, δ44/42Ca values in serum were significantly different between healthy controls, subjects with mild-moderate CKD and those undertaking dialysis (P < 0.01). Receiver operative characteristic curve analysis shows that the diagnostic utility of serum δ44/42Ca for detecting medial artery calcification is very good (AUC = 0.818, sensitivity 81.8% and specificity 77.3%, P < 0.01), and performs better than existing biomarkers. Although our results will need to be verified in prospective studies across different institutions, serum δ44/42Ca has the potential to be used as an early screening test for vascular calcification.
钙平衡在慢性肾脏病(CKD)患者中异常,与血管钙化的发生有关。目前,对 CKD 患者进行血管钙化筛查并非常规。在这项横断面研究中,我们研究了血清中天然存在的钙(Ca)同位素 44Ca 和 42Ca 的比值是否可以作为 CKD 患者血管钙化的无创标志物。我们从一家三级医院肾内科招募了 78 名参与者:28 名对照者、9 名轻度至中度 CKD 患者、22 名透析患者和 19 名接受肾移植的患者。对每位参与者测量了收缩压、踝肱指数、脉搏波速度和估算肾小球滤过率,以及血清标志物。测量了尿液和血清中的钙浓度和同位素比值。虽然我们没有发现不同组之间尿液 Ca 同位素组成(即 δ44/42Ca)之间存在显著关联,但健康对照组、轻度至中度 CKD 患者和透析患者之间血清 δ44/42Ca 值存在显著差异(P < 0.01)。受试者工作特征曲线分析表明,血清 δ44/42Ca 对检测中层动脉钙化的诊断效用非常好(AUC = 0.818,灵敏度 81.8%,特异性 77.3%,P < 0.01),并且优于现有生物标志物。尽管我们的结果需要在不同机构的前瞻性研究中得到验证,但血清 δ44/42Ca 有可能被用作血管钙化的早期筛查试验。