Brandenburg Vincent M, Jahnen-Dechent Willi, Ketteler Markus
Department of Nephrology and Clinical Immunology, University Hospital, Rheinisch-Westfälische Technische Hochschule Aachen University, Aachen, Germany.
Kidney Int Suppl. 2009 Dec(114):S26-33. doi: 10.1038/ki.2009.404.
Hyperphosphatemia is a central characteristic feature of chronic kidney disease-mineral and bone disorder (CKD-MBD). Phosphorus excess is an independent cardiovascular risk factor for morbidity and mortality in patients with advanced CKD. Over the past 40 years, hyperphosphatemia has been a central therapeutic issue in advanced CKD. Mainstays of hyperphosphatemia treatment are reduction of dietary phosphorus, use of phosphate binders, and optimized phosphorus removal via dialysis. Currently, several phosphate binders are approved for use (aluminum, calcium, lanthanum, sevelamer); all share a common functionality in that they bind phosphorus and reduce the amount absorbed in the gastrointestinal lumen. Over the last decade, nephrologists have debated the relative tolerability and efficacy of these agents, especially the potential for vascular calcification and cardiovascular risk reduction. Recent research has focused on the question of whether a metal-free, calcium-free, and non-absorbed binder, such as sevelamer, offers advantages over other binder types. Most notable may be the potential benefit of reducing calcium load. In addition, sevelamer has several additional pleiotropic effects that may extend its basic indication, some of which may help attenuate vascular calcification. These include effects on bone turnover and the link between abnormal vascular processes and bone metabolism (the so-called 'bone-vascular axis'), as well as lipid metabolism, and systemic inflammatory mediators such as fetuin-A. We review the evidence for these pleiotropic effects, and suggest these may help in some way to improve the substantial disease burden in the CKD-MBD population.
高磷血症是慢性肾脏病 - 矿物质和骨异常（CKD - MBD）的核心特征。磷过量是晚期CKD患者发病和死亡的独立心血管危险因素。在过去40年中，高磷血症一直是晚期CKD的核心治疗问题。高磷血症治疗的主要方法是减少饮食中的磷摄入、使用磷结合剂以及通过透析优化磷清除。目前，几种磷结合剂已获批准使用（铝、钙、镧、司维拉姆）；它们都具有共同的功能，即结合磷并减少胃肠道内吸收的磷量。在过去十年中，肾病学家一直在争论这些药物的相对耐受性和疗效，尤其是血管钙化的可能性和心血管风险降低的问题。最近的研究集中在无金属、无钙且不被吸收的结合剂（如司维拉姆）是否比其他类型的结合剂具有优势这一问题上。最显著的可能是减少钙负荷的潜在益处。此外，司维拉姆还有几种额外的多效性作用，可能会扩展其基本适应症，其中一些可能有助于减轻血管钙化。这些作用包括对骨转换的影响以及异常血管过程与骨代谢之间的联系（所谓的“骨 - 血管轴”），以及脂质代谢和全身性炎症介质（如胎球蛋白 - A）。我们回顾了这些多效性作用的证据，并表明这些作用可能在某种程度上有助于改善CKD - MBD人群的重大疾病负担。
