Wu-Wong Jinshyun Ruth, Mizobuchi Masahide
University of Illinois, Department of Pharmacy Practice , 2201 W. Campbell Park Dr., Suite 13, Chicago, IL 60612 , USA +1 847 863 9818 ; +1 847 680 6072 ;
Expert Opin Investig Drugs. 2014 Nov;23(11):1465-75. doi: 10.1517/13543784.2014.933808. Epub 2014 Jun 26.
Mineral and bone disorder (MBD) begins early in the course of chronic kidney disease (CKD). Phosphate imbalance in CKD-MBD can lead to various pathologies of clinical importance such as further deterioration of kidney function, cardiovascular complications, renal osteodystrophy and increased mortality.
The authors conducted a systematic review of the biomedical literature to evaluate currently available drugs and new phosphate binder therapeutics in development.
There is a need to continue searching for novel phosphate binders that better match an 'ideal' product profile. This profile should have: i) a product that is highly efficient in binding phosphate; ii) low patient compliance issues; iii) minimal interaction with other drugs; and iv) reduced side effects and safety concerns. Targeting alternative mechanisms, such as developing inhibitors for intestinal type II sodium-dependent phosphate co-transporter, may also improve the limitations of phosphate binder therapeutics. Current medical practice focuses on using serum phosphorus levels as the only marker for detecting, monitoring and treating phosphate imbalance in CKD. However, the consequences of phosphate imbalance are evident in non-dialysis patients before serum phosphate levels rise above the normal range. There is a need to search for other markers to guide detection and treatment of clinically significant alterations in phosphate metabolism of non-dialysis CKD.
矿物质和骨代谢紊乱（MBD）在慢性肾脏病（CKD）病程早期就已出现。CKD-MBD中的磷失衡可导致各种具有临床重要性的病理状况，如肾功能进一步恶化、心血管并发症、肾性骨营养不良及死亡率增加。
作者对生物医学文献进行了系统综述，以评估目前可用的药物及正在研发的新型磷结合剂疗法。
有必要继续寻找更符合“理想”产品特征的新型磷结合剂。该特征应具备：i）一种高效结合磷的产品；ii）低患者依从性问题；iii）与其他药物的相互作用最小；iv）副作用和安全问题减少。针对替代机制，如开发肠道II型钠依赖性磷共转运体抑制剂，也可能改善磷结合剂疗法的局限性。当前医学实践将血清磷水平作为检测、监测和治疗CKD中磷失衡的唯一指标。然而，在非透析患者中，血清磷水平升高至正常范围之前，磷失衡的后果就已很明显。有必要寻找其他标志物来指导非透析CKD患者磷代谢临床显著改变的检测和治疗。
