Department of Nephrology and Hypertension, University Hospital and University of Bern, Inselspital, 3010 Bern, Switzerland.
J Am Soc Nephrol. 2012 Oct;23(10):1744-52. doi: 10.1681/ASN.2012030240. Epub 2012 Sep 6.
Vascular and soft tissue calcification contributes to cardiovascular morbidity and mortality in both the general population and CKD. Because calcium and phosphate serum concentrations are near supersaturation, the balance of inhibitors and promoters critically influences the development of calcification. An assay that measures the overall propensity for calcification to occur in serum may have clinical use. Here, we describe a nanoparticle-based assay that detects, in the presence of artificially elevated calcium and phosphate concentrations, the spontaneous transformation of spherical colloidal primary calciprotein particles (CPPs) to elongate crystalline secondary CPPs. We used characteristics of this transition to describe the intrinsic capacity of serum to inhibit the precipitation of calcium and phosphate. Using this assay, we found that both the sera of mice deficient in fetuin-A, a serum protein that inhibits calcification, and the sera of patients on hemodialysis have reduced intrinsic properties to inhibit calcification. In summary, we developed a nanoparticle-based test that measures the overall propensity for calcification in serum. The clinical use of the test requires evaluation in a prospective study.
血管和软组织钙化可导致普通人群和 CKD 患者的心血管发病率和死亡率升高。由于血清中的钙和磷酸盐浓度接近过饱和状态，因此抑制剂和促进剂的平衡对钙化的发展至关重要。一种能够测量血清中发生钙化总体倾向的检测方法可能具有临床应用价值。在这里，我们描述了一种基于纳米颗粒的检测方法，该方法在人为升高的钙和磷酸盐浓度存在的情况下，检测到球形胶体初级钙结合蛋白颗粒 (CPP) 自发转化为拉长的结晶状二级 CPP。我们利用这一转变的特点来描述血清抑制钙和磷酸盐沉淀的固有能力。使用该检测方法，我们发现缺乏抑制钙化的血清蛋白胎球蛋白-A 的小鼠血清和接受血液透析的患者的血清均具有降低的抑制钙化的固有特性。总之，我们开发了一种基于纳米颗粒的检测方法，该方法可测量血清中钙化的总体倾向。该检测方法的临床应用需要在前瞻性研究中进行评估。
