Safety and Efficacy of Oral Direct Factor Xa Inhibitors in Patients With Nephrotic Syndrome: Results From a National Retrospective Study

Introduction

The optimal management of thromboembolism (TE) in patients with nephrotic syndrome (NS) remains challenging. Until now, anticoagulation therapy for NS consisted of vitamin K antagonists (VKAs) or heparin. Data on direct oral anticoagulant (DOAC) use in NS are limited, and their safety and convenience have been well-demonstrated in other indications.

Methods

We conducted a multicenter retrospective study of adult patients with NS treated with therapeutic-dose anticoagulation between 2014 and 2022. We compared the incidences of bleeding and TE events between patients receiving DOAC and those receiving VKAs or heparin (standard-of-care [SOC]). Patients with end-stage kidney disease were excluded.

Results

The overall population consisted of 144 patients (median [interquartile range] age of 54 [38–67] years, 34.7% women) with a median albumin level at 1.5 (1.2–1.8) g/dl and a median urinary protein-to-creatinine ratio of 8.8 (5.5–12.3)g/g. Membranous nephropathy was the main NS etiology (45.8%). No significant differences were observed between the DOAC (n = 72) and the SOC (n = 72) groups. The anticoagulant strategy was primary prophylaxis in 79.2% of patients taking DOAC and 83.3% of patients with SOC (P = 0.67). DOAC use was not associated with an increased rate of TE (4.2% vs. 0%, P = 0.25) or bleeding events (6.9% vs. 13.9%, P = 0.28) compared with the SOC group. Univariate analysis identified female sex, age > 75 years, and anticoagulant exposure > 90 days as risk factors for bleeding.

Conclusion

This study suggests that DOAC are safer and more effective than conventional anticoagulant strategies for both primary and secondary prophylaxis in patients with NS.