Division of Nephrology, Klinikum Coburg GmbH, Coburg, Germany.
Curr Opin Nephrol Hypertens. 2013 Jul;22(4):413-20. doi: 10.1097/MNH.0b013e32836214d4.
Hyperphosphatemia is a paradigmatic finding in late-stage chronic kidney disease (CKD) and consistently associated with adverse outcomes. Preclinical and epidemiological studies strongly support a causative role of hyperphosphatemia for cardiovascular complications, especially with regard to vascular, valvular and soft-tissue calcifications, and for subsequent mortality. Therefore, phosphate management is thought to play a pivotal role in health and longevity of CKD patients. In this regard, phosphate binders are considered the prime option; however, dietary phosphate restriction and intensified dialysis are also valuable supportive tools.
Studies on available calcium-free phosphate binders demonstrate potential to interfere with phosphate regulatory factors, such as fibroblast growth factor-23 (FGF23). Magnesium-containing phosphate binding may possess a pleiotropic potential due to its calcification inhibitory properties. Novel phosphate lowering compounds, including colestilan, iron-containing binders and nicotinamide, are underway to extend the armamentarium of phosphate-lowering strategies. An open question remains when to therapeutically counteract phosphate retention by binders. A recent prospective randomized trial in patients with moderate CKD (stages 3b-4) and phosphate levels in the upper normal range demonstrated only moderate reductions in serum phosphate levels, no effects on FGF23, but increased vascular calcification progression with active treatment versus placebo. Another small trial in patients with similar renal function given diets containing approximately 1 g of calcium and 1.4 g of phosphate per day showed neutral calcium and phosphate balances, whereas addition of calcium carbonate as a phosphate binder only caused a positive calcium, but no negative phosphate balance.
Adequate phosphate management in end-stage CKD remains a mainstay of our therapeutic approaches in this population, and additional promising drugs are in development and may shortly be available. The timing and indication for phosphate-lowering strategies in predialysis CKD is currently unclear.
高磷血症是终末期慢性肾脏病（CKD）的典型表现，且始终与不良结局相关。临床前和流行病学研究强烈支持高磷血症在心血管并发症中的致病作用，特别是在血管、瓣膜和软组织钙化方面，以及随后的死亡率方面。因此，人们认为磷酸盐管理在 CKD 患者的健康和长寿中起着关键作用。在这方面，磷酸盐结合剂被认为是首选方案；然而，饮食磷酸盐限制和强化透析也是有价值的支持工具。
现有无钙磷酸盐结合剂的研究表明，它们具有干扰磷酸盐调节因子（如成纤维细胞生长因子 23（FGF23））的潜力。含镁的磷酸盐结合剂由于其抑制钙化的特性，可能具有多种潜在作用。新型降磷化合物，包括考来替兰、含铁结合剂和烟酰胺，正在研发中，以扩展降磷策略的手段。一个悬而未决的问题是何时通过结合剂来治疗性地对抗磷酸盐的保留。最近一项针对中重度 CKD（3b-4 期）和磷酸盐水平在上限正常范围内的患者的前瞻性随机试验表明，与安慰剂相比，仅能使血清磷酸盐水平适度降低，对 FGF23 没有影响，但活性治疗会增加血管钙化进展。另一项针对类似肾功能患者的小型试验，每天给予含有约 1g 钙和 1.4g 磷的饮食，结果显示钙和磷平衡中性，而添加碳酸钙作为磷酸盐结合剂仅导致钙呈阳性，但磷无负平衡。
在终末期 CKD 中，适当的磷酸盐管理仍然是我们在该人群中治疗方法的主要手段，并且还有更多有前途的药物正在开发中，可能很快就会上市。在透析前 CKD 中，降磷策略的时机和适应证目前尚不清楚。
