Wang Angela Yee-Moon, Pasch Andreas, Wong Chun-Kwok, Chu Ida Miu-Ting, Tang Tak-Ka, Chu Jessie, Cheuk-Ying Fong Charmaine, Yau Yat-Yin, Lo Wai-Kei
Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China.
Institute for Physiology and Pathophysiology, Johannes Kepler University Linz, Linz, Austria.
Kidney Med. 2021 Nov 2;4(2):100384. doi: 10.1016/j.xkme.2021.10.002. eCollection 2022 Feb.
RATIONALE & OBJECTIVE: There is a concern regarding increased risk of vascular calcification with the use of calcium-based phosphorus binders. This study aimed to compare the effects of sevelamer used as a second-line, low-dose therapy with calcium-based phosphorus binders with those of sevelamer used as a first-line, high-dose therapy on coronary artery and heart valve calcification, aortic pulse wave velocity (PWV), and calcification propensity over 2 years in patients with hyperphosphatemia receiving peritoneal dialysis (PD).
A 2-year-long prospective, multicenter, open-label, randomized pilot study.
SETTING & PARTICIPANTS: Prevalent patients with hyperphosphatemia receiving PD from 2 university-affiliated hospitals in Hong Kong.
The patients were randomized to receive sevelamer either as a first-line therapy at a high dose of 800 mg thrice daily (can titrate up to 1,200 mg thrice daily as required) or a second-line therapy at a low dose of 400 mg thrice daily with calcium carbonate to achieve a serum phosphorus target of ≤5.5 mg/dL.
The primary endpoints were changes in coronary artery calcium score and aortic PWV over 104 weeks. The secondary endpoints were changes in heart valve calcium scores, calcification propensity measure, and biochemical parameters of chronic kidney disease-mineral bone disease over 104 weeks.
Among 60 prevalent patients receiving PD, with a mean age of 53 ± 10 years and with 57% men, changes in the coronary artery calcium score (median [interquartile range], 225 [79-525] vs 223 [56-1,212], respectively; = 0.21), aortic PWV (mean ± standard error, 0.3 ± 0.1 vs 0.8 ± 0.2 m/s, respectively; = 0.31), heart valve calcium score, maturation or transformation time, serum calcium levels, and phosphorus levels over 104 weeks were similar for the second-line, low-dose and first-line, high-dose sevelamer groups. Alkaline phosphatase and intact parathyroid hormone levels increased and low-density lipoprotein cholesterol decreased in both the groups, with no significant between-group differences.
The sample size was small, and the dropout rates were relatively high.
Low-dose sevelamer used as a second-line therapy for hyperphosphatemia in combination with a calcium-based phosphorus binder had similar effects on vascular calcification, valvular calcification, and arterial stiffness compared with high-dose sevelamer used as a first-line therapy. This approach may be considered in resource-constrained countries to minimize calcium loading.
The study was supported by a competitive grant from SK Yee Medical Foundation. T50 assays and other biochemical assays were funded by a research grant from Sanofi Renal Corporation.
NCT00745589.
人们担心使用钙基磷结合剂会增加血管钙化风险。本研究旨在比较在接受腹膜透析（PD）的高磷血症患者中，二线低剂量使用司维拉姆与钙基磷结合剂联合治疗，和一线高剂量使用司维拉姆治疗对冠状动脉和心脏瓣膜钙化、主动脉脉搏波速度（PWV）以及2年内钙化倾向的影响。
一项为期2年的前瞻性、多中心、开放标签随机试验性研究。
来自香港两所大学附属医院的接受PD的高磷血症现患患者。
患者被随机分为接受司维拉姆治疗，一线治疗为每日三次高剂量800毫克（可根据需要滴定至每日三次1200毫克），或二线治疗为每日三次低剂量400毫克并联合碳酸钙，以实现血清磷目标≤5.5毫克/分升。
主要终点是104周内冠状动脉钙化评分和主动脉PWV的变化。次要终点是104周内心脏瓣膜钙化评分、钙化倾向测量以及慢性肾脏病 - 矿物质骨病的生化参数变化。
在60名接受PD的现患患者中，平均年龄53±10岁，男性占57%，二线低剂量和一线高剂量司维拉姆组在104周内冠状动脉钙化评分（中位数[四分位间距]，分别为225[79 - 525]和223[56 - 1212]；P = 0.21）、主动脉PWV（平均值±标准误，分别为0.3±0.1和0.8±0.2米/秒；P = 0.31）、心脏瓣膜钙化评分、成熟或转化时间、血清钙水平和磷水平相似。两组碱性磷酸酶和完整甲状旁腺激素水平升高，低密度脂蛋白胆固醇降低，组间无显著差异。
样本量小，脱落率相对较高。
对于高磷血症，二线低剂量使用司维拉姆联合钙基磷结合剂治疗与一线高剂量使用司维拉姆治疗相比，在血管钙化、瓣膜钙化和动脉僵硬度方面具有相似效果。在资源有限的国家可考虑这种方法以尽量减少钙负荷。
本研究由SK Yee医学基金会的竞争性赠款支持。T50检测和其他生化检测由赛诺菲肾脏公司的研究赠款资助。
NCT00745589。
