Dhillon-Jhattu Sangeet, Sprague Stuart M
NorthShore University HealthSystem and University of Chicago-Pritzker School of Medicine, Chicago, IL, USA.
Semin Dial. 2018 Jul;31(4):377-381. doi: 10.1111/sdi.12702. Epub 2018 Apr 19.
Hyperphosphatemia is a common complication of CKD. Prior to development of overt hyperphosphatemia, there are several adaptive mechanisms that occur to maintain normal phosphorus equilibrium in patients with CKD. These include an early and progressive rise in fibroblast growth factor 23 (FGF 23), followed by an increase in parathyroid hormone (PTH) with a decrease in 1,25-dihydroxyvitamin D (1,25 Vit D). Over the last 20 years, a large number of studies have shown that hyperphosphatemia is a strong predictor of adverse clinical outcomes including increased incidence of vascular calcification, cardiovascular disease, and all-cause mortality in both individuals with CKD as well as those with normal kidney function. In addition, elevations of both FGF 23 and PTH are independently associated with increased morbidity and mortality. Therefore, phosphorus lowering therapies are a vital part of the treatment strategy for patients with CKD and include dietary phosphorus restriction, treatment with phosphate binders and removal with dialysis. However, there has been a lack of high quality evidence demonstrating beneficial effects of phosphate lowering therapy on clinical outcomes. Furthermore, we do not have definitive data as to whether effective phosphate control with phosphate binders will prevent elevations in FGF 23, and whether lowering FGF 23 levels will lead to improved patient outcomes. As a result of the presently available data (or lack thereof) clinical guidelines recommend treatment only after hyperphosphatemia develops and in dialysis patients; KDOQI recommends a treatment target of less than 5.5 mg/dL, whereas KDIGO recommends treating "towards normal." We are left with a clinical dilemma, being whether these recommendations are adequate, or should we be more aggressive in phosphate management. In this article, our goal is to discuss some of the studies concerning the adverse consequences of phosphate excess and as well as elevated FGF 23 levels, and present our opinion on what we believe the goal of treatment should be.
高磷血症是慢性肾脏病常见的并发症。在明显的高磷血症出现之前，慢性肾脏病患者会出现多种适应性机制来维持正常的磷平衡。这些机制包括成纤维细胞生长因子23（FGF 23）早期逐渐升高，随后甲状旁腺激素（PTH）增加，而1,25 - 二羟维生素D（1,25 Vit D）减少。在过去20年中，大量研究表明，高磷血症是不良临床结局的有力预测指标，包括慢性肾脏病患者以及肾功能正常者血管钙化、心血管疾病发病率增加和全因死亡率上升。此外，FGF 23和PTH升高均与发病率和死亡率增加独立相关。因此，降磷治疗是慢性肾脏病患者治疗策略的重要组成部分，包括饮食限磷、使用磷结合剂治疗以及透析清除。然而，缺乏高质量证据证明降磷治疗对临床结局有有益影响。此外，我们尚无确切数据表明使用磷结合剂有效控制磷是否能预防FGF 23升高，以及降低FGF 23水平是否会改善患者结局。根据目前可得的数据（或缺乏数据的情况），临床指南建议仅在高磷血症出现后对透析患者进行治疗；美国肾脏病基金会肾脏病预后质量倡议（KDOQI）建议治疗目标低于5.5mg/dL，而改善全球肾脏病预后组织（KDIGO）建议“趋向正常”治疗。我们面临一个临床困境，即这些建议是否足够，或者我们在磷管理方面是否应该更积极。在本文中，我们的目标是讨论一些关于磷过量和FGF 23水平升高的不良后果的研究，并就我们认为的治疗目标提出我们的观点。
