Supplementary Material for: Upacicalcet Preserves Albumin Levels in Patients on Hemodialysis with Secondary Hyperparathyroidism: A Post-hoc Analysis of a Randomized Trial

Introduction: Parathyroid hormone (PTH) induces browning of adipose tissue, leading to increased resting energy expenditure and loss of adipose and muscle tissues in animal models of kidney failure. However, its clinical significance in humans remains unclear. This study aimed to investigate whether PTH-lowering therapy with upacicalcet, a novel injectable calcimimetic, affects serum albumin levels as a surrogate marker of protein–energy wasting in patients on hemodialysis with secondary hyperparathyroidism (SHPT).
Methods: This was a post-hoc analysis of a phase 3, double-blind, placebo-controlled study of upacicalcet for the treatment of SHPT in patients on hemodialysis. Participants were randomized in a 2:1 ratio to receive either upacicalcet or placebo after each hemodialysis session for 24 weeks. Longitudinal changes in serum albumin levels were compared between groups using mixed-effects models for repeated measures. The rate of change (slope) in serum albumin over time was also estimated using a linear mixed-effects model.
Results: A total of 99 patients in the upacicalcet group and 46 patients in the placebo group were included in the analysis. While serum albumin levels tended to decline in the placebo group, they remained relatively stable in the upacicalcet group, with a significant treatment-by-time interaction. In the linear mixed-effects model, the slope was less steep in the upacicalcet group than in the placebo group, although the between-group difference (0.09 g/dL per year; 95% CI, −0.04 to 0.23) did not reach statistical significance.
Conclusion: These findings raise the hypothesis that PTH suppression with upacicalcet mitigates the gradual decline in serum albumin levels over time. Further studies are warranted to investigate the long-term impact of PTH control on protein–energy wasting and related clinical outcomes.

引言：甲状旁腺激素（Parathyroid hormone, PTH）可诱导脂肪组织褐变，在肾衰竭动物模型中可使静息能量消耗增加，并导致脂肪组织与肌肉组织丢失。然而，其在人体中的临床意义仍不明确。本研究旨在探讨新型注射用拟钙剂西帕卡塞（upacicalcet）的降PTH治疗，是否会影响维持性血液透析继发性甲状旁腺功能亢进（secondary hyperparathyroidism, SHPT）患者的血清白蛋白水平——该指标是蛋白质能量消耗的替代标志物。
方法：本研究为一项针对西帕卡塞治疗维持性血液透析继发性甲状旁腺功能亢进患者的Ⅲ期双盲安慰剂对照研究的事后分析。受试者以2:1的比例随机分组，分别在每次血液透析结束后接受西帕卡塞或安慰剂治疗，疗程共24周。采用重复测量混合效应模型，对比两组患者血清白蛋白水平的纵向变化；同时采用线性混合效应模型，估算血清白蛋白水平随时间的变化速率（斜率）。
结果：本分析共纳入西帕卡塞组患者99例，安慰剂组患者46例。安慰剂组患者血清白蛋白水平呈下降趋势，而西帕卡塞组患者该指标相对稳定，两组间存在显著的治疗-时间交互效应。线性混合效应模型分析显示，西帕卡塞组血清白蛋白水平的下降斜率较安慰剂组更平缓，但组间差异（0.09 g/dL/年；95%置信区间：-0.04~0.23）未达到统计学显著性。
结论：本研究结果提出假说：西帕卡塞通过抑制甲状旁腺激素，可延缓血清白蛋白水平随时间的渐进性下降。未来仍需开展进一步研究，探讨甲状旁腺激素控制对蛋白质能量消耗及相关临床结局的长期影响。