Kidney injury associated with direct oral anticoagulants: a comparative study of direct thrombin inhibitors and factor Xa inhibitors based on literature and database analysis

While direct oral anticoagulants (DOACs) are widely used, limited real-world studies have explored kidney injury linked to DOACs, particularly differences between direct thrombin inhibitors (DTIs) and factor Xa inhibitors (FXaIs). We conducted a comprehensive analysis of kidney injury cases from the FDA Adverse Event Reporting System (FAERS, 2008–2024) and systematically reviewed published case reports, comparing DTIs (dabigatran) with FXaIs (rivaroxaban, apixaban, edoxaban). Among 8,116 reports of suspected DOAC-associated kidney injury, 1,784 were linked to DTIs and 6,332 to FXaIs. Significant reporting rates were observed for DTIs [reporting odds ratio (ROR) = 2.081, 95% CI: 1.979–2.189; proportional reporting ratio (PRR) = 2.044, CI: 1.947–2.147)] and FXaIs (ROR = 1.483, 95% CI: 1.444–1.523; PRR = 1.472, CI: 1.434–1.510). Notably, substantial intra-class variation existed among FXaIs, with edoxaban showing the highest risk signal (ROR = 4.453, 95% CI: 4.021–4.932; PRR = 4.212, 95% CI: 3.831–4.632). Multivariable logistic regression analysis confirmed that significantly lower kidney injury reporting disproportionality signals with FXaIs versus DTIs after adjustment (ROR = 0.687, 95% CI: 0.650–0.727, P < 0.001). Analysis of 32 detailed cases revealed distinct clinical patterns: DTI-associated injury featured higher proteinuria rates (P = 0.029), while FXaI-associated injury occurred more frequently in settings of polypharmacy (P = 0.006) and was associated with poorer renal recovery (P = 0.023). This study demonstrates distinct kidney injury risks among DOAC classes and individual agents, with DTIs and edoxaban showing particularly strong signals. These findings emphasize the need for individualized DOAC selection and enhanced renal monitoring in clinical practice.