Department of Nephrology, The Royal Melbourne Hospital, Grattan Street, Parkville, VIC, 3052, Australia.
Department of Medicine (RMH), University of Melbourne, Parkville, Australia.
Sci Rep. 2022 May 5;12(1):7358. doi: 10.1038/s41598-022-11065-3.
Plasma approaches metastability with respect to its calcium and phosphate content, with only minor perturbations in ionic activity needed to sustain crystal growth once nucleated. Physiologically, calcium and phosphate are intermittently absorbed from the diet each day, yet plasma concentrations of these ions deviate minimally post-prandially. This implies the existence of a blood-borne mineral buffer system to sequester calcium phosphates and minimise the risk of deposition in the soft tissues. Calciprotein particles (CPP), endogenous mineral-protein colloids containing the plasma protein fetuin-A, may fulfill this function but definitive evidence linking dietary mineral loading with their formation is lacking. Here we demonstrate that CPP are formed as a normal physiological response to feeding in healthy adults and that this occurs despite minimal change in conventional serum mineral markers. Further, in individuals with Chronic Kidney Disease (CKD), in whom mineral handling is impaired, we show that both fasting and post-prandial levels of CPP precursors are markedly augmented and strongly inversely correlated with kidney function. This study highlights the important, but often neglected, contribution of colloidal biochemistry to mineral homeostasis and provides novel insight into the dysregulation of mineral metabolism in CKD.
血浆在钙和磷含量方面接近亚稳态,一旦成核,只需对离子活性进行微小的扰动即可维持晶体生长。在生理上,钙和磷每天都会从饮食中间歇性地被吸收,但这些离子的血浆浓度在进食后变化极小。这意味着存在一种血液来源的矿物质缓冲系统,以隔离钙磷并最大程度地降低在软组织中沉积的风险。钙结合蛋白颗粒(CPP)是含有血浆蛋白胎球蛋白-A 的内源性矿物质-蛋白质胶体,可能具有这种功能,但缺乏将膳食矿物质负荷与 CPP 形成联系起来的明确证据。在这里,我们证明 CPP 是健康成年人进食时正常的生理反应,尽管传统的血清矿物质标志物变化很小。此外,在矿物质处理受损的慢性肾脏病(CKD)患者中,我们发现 CPP 前体的空腹和餐后水平均显著增加,并且与肾功能呈强烈负相关。这项研究强调了胶体生物化学对矿物质动态平衡的重要但经常被忽视的贡献,并为 CKD 中矿物质代谢失调提供了新的见解。