Ketteler Markus, Westenfeld Ralf, Schlieper Georg, Brandenburg Vincent
Department of Nephrology and Clinical Immunology, University Hospital Aachen, Pauwelsstrasse 30, D-52057, Aachen, Germany.
Clin Exp Nephrol. 2005 Dec;9(4):265-270. doi: 10.1007/s10157-005-0385-4.
Soft-tissue and vascular calcification are highly prevalent in end-stage renal disease (ESRD). Vascular calcifications manifest as both medial and intimal calcification of arteries and are a hallmark of the accelerated atherosclerosis observed in uremia. The nature of vascular calcification is progressive, and is associated with arterial stiffness and increased cardiovascular mortality. Age, duration of dialysis, and diabetes mellitus are clear determinants of the severity of vascular calcification; however, more recently novel insights into the pathomechanisms of unwanted calcification processes have been gained. Disturbances of mineral metabolism such as hyperphosphatemia and hypercalcemia appear to contribute to progressive calcification, not only by passive precipitation but by actively inducing changes in vascular smooth muscle cell behavior toward an osteoblast-like phenotype. Specific calcium-regulatory proteins may act locally or systemically as calcification inhibitors. Dysregulations of calcification inhibitors, including fetuin-A, matrix Gla protein, osteoprotegerin, and pyrophosphates may also be pathophysiologically relevant factors in the context of uremic extraosseous calcification. In this context, low serum fetuin-A levels were recently found to be associated with increased mortality in cohorts of dialysis patients. This overview intends to summarize current knowledge of the scientific concepts involved in the pathogenesis of extraosseous calcification in ESRD.
软组织和血管钙化在终末期肾病（ESRD）中极为常见。血管钙化表现为动脉中层和内膜钙化，是尿毒症中加速动脉粥样硬化的一个标志。血管钙化的性质是渐进性的，与动脉僵硬和心血管死亡率增加相关。年龄、透析时间和糖尿病是血管钙化严重程度的明确决定因素；然而，最近对不必要钙化过程的发病机制有了新的认识。矿物质代谢紊乱，如高磷血症和高钙血症，似乎不仅通过被动沉淀，而且通过积极诱导血管平滑肌细胞向成骨细胞样表型转变，从而促进渐进性钙化。特定的钙调节蛋白可能在局部或全身作为钙化抑制剂起作用。钙化抑制剂的失调，包括胎球蛋白-A、基质Gla蛋白、骨保护素和焦磷酸盐，在尿毒症性骨外钙化的背景下也可能是病理生理学相关因素。在此背景下，最近发现透析患者队列中低血清胎球蛋白-A水平与死亡率增加有关。本综述旨在总结目前关于ESRD骨外钙化发病机制中涉及的科学概念的知识。
