天然稳定的钙同位素比值是慢性肾脏病骨钙平衡的新型生物标志物。
Naturally occurring stable calcium isotope ratios are a novel biomarker of bone calcium balance in chronic kidney disease.
机构信息
Renal Unit, University College London Great Ormond Street Hospital and Institute of Child Health, London, UK.
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.
出版信息
Kidney Int. 2022 Sep;102(3):613-623. doi: 10.1016/j.kint.2022.04.024. Epub 2022 May 27.
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, Ca and Ca, are present in our diet and sequestered into body compartments following principles of kinetic isotope fractionation. Isotopically light Ca is preferentially incorporated into bone, while heavier Ca is excreted. The ratio (Ca) 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 Ca ratio positively correlated with serum calcium, 25-hydroxyvitamin D and alkaline phosphatases and inversely with serum parathyroid hormone and other bone resorption markers. The Ca 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 Ca ratio and parathyroid hormone. The Ca ratio, repeated after four weeks, highly correlated with baseline values. When adjusted for calcium-containing medications and kidney impairment, the Ca 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.
钙稳态失调在慢性肾脏病中很常见，与骨矿物质化紊乱有因果关系。然而，影像学测量和生物标志物无法准确评估骨钙平衡。非放射性钙同位素 44Ca 和 46Ca 存在于我们的饮食中，并按照动力学同位素分馏的原理被隔离到身体的各个部位。较轻的 44Ca 优先被纳入骨骼，而较重的 46Ca 则被排泄。当骨形成超过骨吸收时，（44Ca/46Ca）比值增加，反之亦然，反映了骨钙平衡。我们通过电感耦合等离子体质谱法测量了 42 名慢性肾脏病儿童和 92 名接受透析治疗的儿童的血液、尿液和粪便中的这些钙同位素。我们将这些同位素比值与骨生物标志物进行了比较，并通过双能 X 线吸收法和外周定量 CT 测定了总骨矿物质含量，并用年龄校正 z 评分表示。（44Ca/46Ca）比值与血清钙、25-羟维生素 D 和碱性磷酸酶呈正相关，与血清甲状旁腺激素和其他骨吸收标志物呈负相关。（44Ca/46Ca）比值与外周定量 CT 测定的胫骨小梁骨矿物质密度和总骨矿物质含量的年龄校正 z 评分以及双能 X 线吸收法测定的髋部骨矿物质密度呈正相关。总骨矿物质含量的显著和独立预测因子为（44Ca/46Ca）比值和甲状旁腺激素。（44Ca/46Ca）比值在四周后重复测量时与基线值高度相关。在校正含钙药物和肾功能不全后，接受透析的患者的（44Ca/46Ca）比值比年龄匹配的儿童低 157%，比老年骨质疏松妇女低 29%，这意味着骨矿物质含量明显较低。因此，钙同位素比值可能为评估慢性肾脏病中的骨钙平衡提供一种新颖、敏感和非侵入性的方法。
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