Wei Meng, Wu Xue, Wang Liteng, Gu Zhichun, Tu Yuanmao, Zhang Lihua, Zhang Jiong, Xie Honglang, Zhou Qing, Chu Yanan, Cheng Zhen, Zhou Guohua, Song Qinxin
Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, School of Pharmacy, China Pharmaceutical University, Nanjing, China.
Department of Clinical Pharmacy, Jinling Hospital Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Kidney Dis (Basel). 2024 Aug 16;10(5):346-358. doi: 10.1159/000540107. eCollection 2024 Oct.
Thromboembolism is a recognized complication of nephrotic syndrome (NS). Evidence supporting the use of rivaroxaban to prevent NS-related thrombosis is limited and controversial. This study aimed to explore the impact of NS on rivaroxaban pharmacokinetics and to collect observational data on the efficacy and safety of rivaroxaban as primary thromboprophylaxis in patients with NS.
This prospective study analyzed 141 patients with NS who received rivaroxaban (10 mg/day) for thromboprophylaxis. High-performance liquid chromatography-tandem mass spectrometry was used to measure the trough and peak plasma concentrations (C and C) of rivaroxaban. The influence of clinical and genetic factors on these concentrations was examined using multivariate logistic regression.
The median C and C were 68.5 ng/mL (interquartile range [IQR], 31.7-105.5 ng/mL) and 4.4 ng/mL (IQR, 1.2-11.9 ng/mL), respectively. The incidence of thromboembolic events (TEs) was 12.8%, while that of bleeding events was 14.2%, although all were classified as minor. Albumin level was the most significant factor affecting C (ρ = 0.55; < 0.001) and was also significantly associated with TEs (0.81; 0.71-0.91 per 1.0 g/dL increase; = 0.001) and bleeding risks (1.11; 1.03-1.19 per 1.0 g/dL increase; = 0.008). Single nucleotide polymorphisms in the gene significantly influenced C but were not associated with clinical outcomes.
Hypoalbuminemia significantly affects the pharmacokinetics of rivaroxaban in NS patients. A dose-adjustment strategy based on rivaroxaban concentrations, accounting for variable albumin levels, may improve the safety and efficacy of thromboprophylaxis in this population.
血栓栓塞是肾病综合征（NS）公认的并发症。支持使用利伐沙班预防NS相关血栓形成的证据有限且存在争议。本研究旨在探讨NS对利伐沙班药代动力学的影响，并收集关于利伐沙班作为NS患者主要血栓预防措施的疗效和安全性的观察数据。
这项前瞻性研究分析了141例接受利伐沙班（10毫克/天）进行血栓预防的NS患者。采用高效液相色谱-串联质谱法测量利伐沙班的谷浓度和峰浓度（C谷和C峰）。使用多因素逻辑回归分析临床和遗传因素对这些浓度的影响。
C谷和C峰的中位数分别为68.5纳克/毫升（四分位间距[IQR]，31.7 - 105.5纳克/毫升）和4.4纳克/毫升（IQR，1.2 - 11.9纳克/毫升）。血栓栓塞事件（TEs）的发生率为12.8%，出血事件的发生率为14.2%，尽管所有事件均被分类为轻度。白蛋白水平是影响C谷的最显著因素（ρ = 0.55；P < 0.001），并且也与TEs显著相关（每增加1.0克/分升，比值比为0.81；95%置信区间为0.71 - 0.91；P = 0.001）以及出血风险（每增加1.0克/分升，比值比为1.11；95%置信区间为1.03 - 1.19；P = 0.008）。基因中的单核苷酸多态性显著影响C谷，但与临床结局无关。
低白蛋白血症显著影响NS患者中利伐沙班的药代动力学。基于利伐沙班浓度并考虑白蛋白水平变化的剂量调整策略可能会提高该人群血栓预防的安全性和有效性。
