Elemental Content of Calcium Oxalate Stones from a Canine Model of Urinary Stone Disease

One of the most common types of urinary stones formed in humans and some other mammals is composed of calcium oxalate in ordered hydrated crystals. Many studies have reported a range of metals other than calcium in human stones, but few have looked at stones from animal models such as the dog. Therefore, we determined the elemental profile of canine calcium oxalate urinary stones and compared it to reported values from human stones. The content of 19 elements spanning 7-orders of magnitude was quantified in calcium oxalate stones from 53 dogs. The elemental profile of the canine stones was highly overlapping with human stones, indicating similar inorganic composition. Correlation and cluster analysis was then performed on the elemental profile from canine stones to evaluate associations between the elements and test for potential subgrouping based on elemental content. No correlations were observed with the most abundant metal calcium. However, magnesium and sulfur content correlated with the mineral hydration form, while phosphorous and zinc content correlated with the neuter status of the dog. Inter-elemental correlation analysis indicated strong associations between barium, phosphorous, and zinc content. Additionally, cluster analysis revealed subgroups within the stones that were also based primarily on barium, phosphorous, and zinc. These data support the use of the dog as a model to study the effects of trace metal homeostasis in urinary stone disease.在人类及部分其他哺乳动物体内形成的最常见尿路结石（urinary stones）类型之一，由呈有序排列的水合草酸钙（calcium oxalate）晶体构成。既往多项研究已在人类尿路结石中检出钙以外的多种金属元素，但针对犬类等动物模型结石的相关研究却较为稀缺。为此，本研究对53份犬类草酸钙尿路结石的元素谱（elemental profile）进行了定量分析，检测了覆盖7个数量级的19种元素含量，并将犬类结石的元素谱与已公开的人类结石元素谱数据进行对比。 分析结果显示，犬类结石的元素谱与人类结石高度重合，表明二者的无机组成极为相似。随后，研究团队基于犬类结石的元素谱开展相关性分析（correlation analysis）与聚类分析（cluster analysis），以评估元素间的关联，并检验基于元素含量划分潜在亚组的可行性。 研究未发现丰度最高的金属元素钙与其他元素存在相关性。不过，镁与硫的含量与结石的矿物水合形式存在显著关联，而磷与锌的含量则与犬只的绝育状态（neuter status）相关。元素间相关性分析进一步显示，钡、磷与锌的含量之间存在显著的强关联。此外，聚类分析揭示了结石内部存在亚组，且这些亚组的划分同样主要基于钡、磷与锌的含量。 本研究数据支持将犬类作为模型，用于探究尿路结石疾病中微量元素稳态（trace metal homeostasis）的相关影响机制。