Association Between Tolvaptan Exposure and Venous Thromboembolism Risk in ADPKD: A Real-World Propensity-Matched EHR...

Venous thromboembolism (VTE) has increasingly been reported in autosomal dominant polycystic kidney disease (ADPKD), although the mechanisms underlying this association remain incompletely understood. Whether tolvaptan exposure influences VTE risk in ADPKD has not been well studied.

We performed a retrospective cohort study using the TriNetX Global Collaborative Network, including adults with ADPKD (ICD-10-CM Q61.2) from 2000 to 2025. Patients with inherited thrombophilia or prothrombin G20210A mutation were excluded. Propensity score matching (1:1) was conducted across 24 covariates to balance demographics, comorbidities, medications, and laboratory data. Exposure was analysed as a fixed treatment variable defined at cohort entry. Primary outcomes were VTE incidence, all-cause mortality, and use of antithrombotic medications.

Among 39 180 adults with ADPKD, 1338 received tolvaptan therapy, whereas 37 362 were without tolvaptan. After 1:1 propensity score matching, 1333 matched pairs were analysed. Tolvaptan exposure was associated with lower risks of VTE (2.1% vs. 3.9%; RR 0.538, 95% CI 0.342-0.847; p = 0.006) and all-cause mortality (1.28% vs. 3.9%; RR 0.327, 95% CI 0.190-0.562; p < 0.001). Lower utilisation of warfarin, aspirin, DOAC, heparin, or enoxaparin was observed (14.8% vs. 21.4%; RR 0.689, 95% CI 0.572-0.830; p < 0.001). Subgroup analyses demonstrated generally consistent directional associations across several demographic categories, although some subgroup analyses were limited by low event counts.

In this large propensity-matched real-world cohort, tolvaptan exposure was associated with lower risks of VTE and mortality among patients with ADPKD. Given the retrospective observational design and the possibility of residual confounding, these findings should be interpreted as associative and hypothesis-generating rather than causal. Further prospective studies incorporating imaging-based measures of disease severity are warranted.