Regulation by macromolecules of calcium oxalate crystal aggregation in stone formers
Regulation by macromolecules of calcium oxalate crystal aggregation in stone formers
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DOI：
10.1007/s00240-004-0455-1
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发表时间：
2005-06-01
影响因子：
--
通讯作者：
Kleinman, JG
中科院分区：
文献类型：
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作者：
Wesson, JA;Ganne, V;Kleinman, JG
根据肾结石的结构，它们很可能是预先形成的晶体的聚集，主要是草酸钙一水（COM）。在这项研究中，我们通过测量预成型COM晶体聚集体的粒径分布（PSD）的变化，研究了从正常人和结石形成者的尿液中分离出的大分子混合物在简单离子溶液中抑制预成型COM种子晶体聚集的能力。我们还研究了在该实验中一些合成均聚物、天然存在的尿液大分子及其二元混合物的影响。正常人和大多数结石患者尿液中的大分子混合物降低了种子晶体的聚集程度，而22%的结石患者尿液中的大分子要么没有分解，要么实际上促进了进一步的聚集。在一个家庭中形成石头的人共享这个属性，但非形成石头的兄弟姐妹没有。聚阴离子，无论是合成的还是自然产生的，诱导的分解程度与正常尿液大分子相似，而聚阳离子对PSD没有影响。然而，将聚阴离子（聚天冬氨酸或骨桥蛋白）与聚阳离子聚精氨酸混合后，它们的行为从分解转变为促进聚集。正常尿液大分子的分解行为提供了对聚集的防御，但少数形成结石的个体缺乏这种防御，这可能有助于结石的形成。
Based on the structure of kidney stones, it is likely that they form as aggregations of preformed crystals, mostly calcium oxalate monohydrate (COM). In this study, we examined the ability of a macromolecular mixture isolated from the urine of normal individuals and stone formers to inhibit aggregation of preformed COM seed crystals in a simple ionic solution using measurements of changes in the particle size distribution (PSD) of preformed COM crystal aggregates. We also examined the effect in this assay of a number of synthetic homopolymers, naturally occurring urine macromolecules, and binary mixtures thereof. The macromolecular mixtures from urine of normals and most stone formers reduced the degree of aggregation of the seed crystals, whereas 22% of stone former urine macromolecules either did not disaggregate or actually promoted further aggregation. Stone formers within one family shared this property, but a non-stone forming sibling did not. Polyanions, either synthetic or naturally occurring, induced disaggregation to an extent similar to that exhibited by normal urine macromolecules, while polycations had no effect on the PSD. However, mixing a polyanion, either poly-aspartate or osteopontin, with the polycation poly-arginine, changed their behavior from disaggregation to aggregation promotion. The disaggregating behavior of normal urinary macromolecules provides a defense against aggregation, but a minority of stone forming individuals lacks this defense, which may contribute to stone formation.