维维美对慢性肾脏病合并代谢性酸中毒女性患者血清碳酸氢盐和身体功能的影响：一项随机对照试验的亚组分析。
Effects of veverimer on serum bicarbonate and physical function in women with chronic kidney disease and metabolic acidosis: a subgroup analysis from a randomised, controlled trial.
机构信息
MathurConsulting LLC, 25 Upenuf Road, Suite 100, Woodside, CA, 94062-2633, USA.
Texas A&M Health Sciences Center College of Medicine, Dallas, TX, USA.
出版信息
BMC Nephrol. 2022 Feb 25;23(1):82. doi: 10.1186/s12882-022-02690-1.
BACKGROUND
Globally, the prevalence of chronic kidney disease (CKD) is higher in women than in men; however, women have been historically under-represented in nephrology clinical trials. Metabolic acidosis increases risk of progressive loss of kidney function, causes bone demineralization and muscle protein catabolism, and may be more consequential in women given their lower bone and muscle mass. Veverimer, an investigational, non-absorbed polymer that binds and removes gastrointestinal hydrochloric acid, is being developed as treatment for metabolic acidosis.
METHODS
This was a Phase 3, multicenter, randomised, blinded, placebo-controlled trial in 196 patients with CKD (eGFR: 20-40 mL/min/1.73 m) and metabolic acidosis who were treated for up to 1 year with veverimer or placebo. We present the findings from a pre-specified subgroup analysis evaluating the effects of veverimer on metabolic acidosis and physical function among women (N = 77) enrolled in this trial.
RESULTS
At week 52, women treated with veverimer had a greater increase in mean (± standard error) serum bicarbonate than the placebo group (5.4 [0.5] vs. 2.2 [0.6] mmol/L; P < 0.0001). Physical Function reported by patients on the Kidney Disease and Quality of Life - Physical Function Domain, a measure that includes items related to walking, stair climbing, carrying groceries and other activities improved significantly in women randomized to veverimer vs placebo (+ 13.2 vs. -5.2, respectively, P < 0.0031). Objectively measured performance time on the repeated chair stand test also improved significantly in the veverimer group vs. placebo (P = 0.0002).
CONCLUSIONS
Veverimer was effective in treating metabolic acidosis in women with CKD, and significantly improved how they felt and functioned.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03390842 . Registered on January 4, 2018.
背景
全球范围内，女性慢性肾脏病（CKD）的患病率高于男性；然而，在肾脏病学临床试验中，女性的代表性历来不足。代谢性酸中毒会增加肾功能进行性丧失的风险，导致骨质脱矿和肌肉蛋白分解代谢，而且由于女性的骨量和肌肉量较低，其影响可能更为严重。Veverimer 是一种正在开发中的、不可吸收的聚合物，可与胃肠道盐酸结合并将其去除，被用作代谢性酸中毒的治疗药物。
方法
这是一项在 196 名 CKD 患者（eGFR：20-40 mL/min/1.73 m）中进行的 3 期、多中心、随机、双盲、安慰剂对照试验，这些患者接受了长达 1 年的 Veverimer 或安慰剂治疗。我们报告了这项试验中纳入的女性（N=77）亚组分析评估 Veverimer 对代谢性酸中毒和身体功能影响的结果。
结果
在第 52 周时，接受 Veverimer 治疗的女性血清碳酸氢盐平均（±标准误差）增加量大于安慰剂组（5.4 [0.5] vs. 2.2 [0.6] mmol/L；P<0.0001）。接受 Veverimer 治疗的女性患者在肾脏病和生活质量 - 身体功能域报告的身体功能明显改善，这是一项包含与行走、爬楼梯、提杂货和其他活动相关的项目的衡量标准，与安慰剂组相比增加了+13.2（分别为，P<0.0031）。Veverimer 组与安慰剂组相比，重复椅立测试的客观测量的动作时间也显著改善（P=0.0002）。
结论
Veverimer 可有效治疗 CKD 女性的代谢性酸中毒，并显著改善她们的感受和功能。
试验注册
ClinicalTrials.gov 标识符：NCT03390842。于 2018 年 1 月 4 日注册。
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