Rivaroxaban for Thromboembolism Prophylaxis in Patients with Nephrotic Syndrome: A Single-Arm, Prospective Study.

Introduction: 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.

Methods: 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_trough and C_max) of rivaroxaban. The influence of clinical and genetic factors on these concentrations was examined using multivariate logistic regression.

Results: The median C_max and C_trough 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_max (ρ = 0.55; p < 0.001) and was also significantly associated with TEs (0.81; 0.71-0.91 per 1.0 g/dL increase; p = 0.001) and bleeding risks (1.11; 1.03-1.19 per 1.0 g/dL increase; p = 0.008). Single nucleotide polymorphisms in the ABCB1 gene significantly influenced C_trough but were not associated with clinical outcomes.

Conclusion: 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.