Background: Cardiovascular disease (CVD) is a major cause of death in patients with chronic kidney disease (CKD) on dialysis. Mortality rates are still unacceptably high even though they have fallen in the past 2 decades. Hyperphosphatemia (elevated serum phosphate levels) is seen in almost all patients with advanced CKD and is by far the largest remaining modifiable contributor to CKD mortality. Summary: Phosphate retention drives multiple physiological mechanisms linked to increased risk of CVD. Fibroblast growth factor 23 and parathyroid hormone (PTH) levels, both of which have been suggested to have direct pathogenic CV effects, increase in response to phosphate retention. Phosphate, calcium, and PTH levels are linked in a progressively worsening cycle. Maladaptive upregulation of phosphate absorption is also likely to occur further exacerbating hyperphosphatemia. Even higher phosphate levels within the normal range may be a risk factor for vascular calcification and, thus, CV morbidity and mortality. A greater degree of phosphate control is important to reduce the risk of CV morbidity and mortality. Improved phosphate control and regular monitoring of phosphate levels are guideline-recommended, established clinical practices. There are several challenges with the current phosphate management approaches in patients with CKD on dialysis. Dietary restriction of phosphate and thrice-weekly dialysis alone are insufficient/unreliable to reduce phosphate to #x3c;5.5 mg/dL. Even with the addition of phosphate binders, the only pharmacological treatment currently indicated for hyperphosphatemia, the majority of patients are unable to achieve and maintain phosphate levels #x3c;5.5 mg/dL (or more normal levels) [PhosLo® gelcaps (calcium acetate): 667 mg (prescribing information), 2011, VELPHORO®: (Sucroferric oxyhydroxide) (prescribing information), 2013, FOSRENAL®: (Lanthanum carbonate) (prescribing information), 2016, AURYXIA®: (Ferric citrate) tablets (prescribing information), 2017, RENVELA®: (Sevelamer carbonate) (prescribing information), 2020, RealWorld dynamix. Dialysis US: Spherix Global Insights, 2019]. Phosphate binders do not target the primary pathway of phosphate absorption (paracellular), have limited binding capacity, and bind nonspecifically [PhosLo® gelcaps (calcium acetate): 667 mg (prescribing information). 2013, VELPHORO®: (Sucroferric oxyhydroxide) (prescribing information), 2013, FOSRENAL®: (Lanthanum carbonate) (prescribing information), 2016, AURYXIA®: (Ferric citrate) tablets (prescribing information), 2017, RENVELA®: (Sevelamer carbonate) (prescribing information) 2020]. Key Messages: Despite current phosphate management strategies, most patients on dialysis are unable to consistently achieve target phosphate levels, indicating a need for therapeutic innovations [RealWorld dynamix. Dialysis US: Spherix Global Insights, 2019]. Given a growing evidence base that the dominant mechanism of phosphate absorption is the intestinal paracellular pathway, new therapies are investigating ways to reduce phosphate levels by blocking absorption through the paracellular pathway.
Cardiorenal Med

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磷酸盐控制：透析心血管死亡率的下一个前沿

背景：心血管疾病（CVD）是慢性肾病（CKD）透析患者死亡的主要原因。尽管死亡率在过去 20 年中有所下降，但仍然高得令人无法接受。几乎所有晚期 CKD 患者都会出现高磷血症（血清磷酸盐水平升高），并且是迄今为止导致 CKD 死亡率的最大的剩余可改变因素。概括：磷酸盐滞留驱动多种生理机制，与 CVD 风险增加有关。成纤维细胞生长因子 23 和甲状旁腺激素 (PTH) 水平，两者都被认为具有直接的致病性 CV 效应，随着磷酸盐潴留而增加。磷酸盐、钙和 PTH 水平与逐渐恶化的循环有关。磷酸盐吸收的适应不良上调也可能发生进一步加剧高磷血症。即使在正常范围内更高的磷酸盐水平也可能是血管钙化的危险因素，因此是心血管发病率和死亡率的危险因素。更高程度的磷酸盐控制对于降低 CV 发病率和死亡率的风险很重要。改进磷酸盐控制和定期监测磷酸盐水平是指南推荐的、既定的临床实践。目前的 CKD 透析患者磷酸盐管理方法存在一些挑战。饮食限制磷酸盐和每周三次透析不足以/不可靠地将磷酸盐减少到 #x3c;5.5 mg/dL。即使添加磷酸盐结合剂（目前用于治疗高磷血症的唯一药物治疗方法），大多数患者仍无法达到和维持磷酸盐水平 #x3c；5.5 mg/dL（或更高的正常水平）[PhosLo® gelcaps（醋酸钙） ：667 毫克（处方信息），2011 年，VELPHORO®：（三氧化二氢铁）（处方信息），2013 年，FOSRENAL®：（碳酸镧）（处方信息），2016，AURYXIA®：（柠檬酸铁）片信息） ，2017 年，RENVELA®：（碳酸司维拉姆）（处方信息），2020 年，RealWorld dynamix。透析美国：Spherix 全球洞察，2019 年]。磷酸盐结合剂不针对磷酸盐吸收的主要途径（细胞旁），结合能力有限，并且非特异性结合 [PhosLo® gelcaps（醋酸钙）：667 mg（处方信息）。2013，VELPHORO®：（Sucroferric oxyhydroxide）（处方信息），2013，FOSRENAL®：（碳酸镧）（处方信息），2016，AURYXIA®：（柠檬酸铁）片剂（处方信息），2017：（SeNVELA）碳酸盐）（处方信息）2020]。关键信息：尽管目前采用了磷酸盐管理策略，但大多数透析患者无法始终如一地达到目标磷酸盐水平，这表明需要进行治疗创新 [RealWorld dynamix. 透析美国：Spherix 全球洞察，2019 年]。鉴于越来越多的证据表明磷酸盐吸收的主要机制是肠道旁细胞途径，新疗法正在研究通过阻断细胞旁途径吸收来降低磷酸盐水平的方法。
心肾医学