Abstract
<jats:p>The aim of this study was to evaluate the efficacy, safety, and potential pleiotropic effects of apixaban compared to warfarin in patients with nephrotic syndrome (NS) secondary to primary glomerulonephritis (GN). A prospective cohort study was conducted involving 65 adult patients with biopsy-proven primary GN presenting with NS. To prevent thromboembolic events, patients were assigned to two treatment groups: Group I (n = 32) received warfarin, and Group II (n = 33) received apixaban. The follow-up duration was 6 months, during which clinical and laboratory evaluations were performed at baseline, after 1 month, and after 6 months of therapy. Serum and urinary concentrations of inflammatory (IL-6, TNF-α), fibrotic (TGF-β₁) biomarkers, and thrombin were measured using enzyme-linked immunosorbent assay (ELISA). The primary endpoints included the incidence of thromboembolic and hemorrhagic events; secondary endpoints comprised changes in laboratory markers reflecting inflammation, fibrosis, and coagulation activity. Throughout the 6-month observation period, no thromboembolic complications were detected in either group, confirming the high efficacy of both anticoagulant regimens in thrombosis prevention. However, the incidence of hemorrhagic complications was significantly lower in the apixaban group (9.1 % vs 37.5 % in the warfarin group, p = 0.01). All bleeding episodes were minor — including epistaxis, gingival bleeding, and subcutaneous hematomas — and did not require discontinuation of therapy or hospitalization. Both groups showed a gradual reduction in serum and urinary IL-6, TNF-α, TGF-β₁, and thrombin levels, reflecting a decline in systemic and local inflammatory and coagulative activity. This effect was more pronounced and statistically significant in the apixaban group (p₂ < 0.05). After 6 months, patients on apixaban had a greater decrease in IL-6 and TNF-α, suggesting inhibition of pro-inflammatory cytokine pathways. A marked reduction in TGF-β₁ — a key marker of fibrosis — was also observed, indicating a potential antifibrotic effect. The decrease in urinary thrombin levels, particularly in the apixaban group, may reflect suppression of local thrombo-inflammatory processes at the glomerular microvascular level, thereby contributing to renal protection and stabilization of kidney function. In summary, apixaban proved to be an effective and safe agent for preventing thromboembolic complications in patients with NS associated with primary GN. Compared with warfarin, apixaban demonstrated a lower rate of minor bleeding and a more pronounced reduction in inflammatory, fibrotic, and coagulation biomarkers, supporting its potential pleiotropic properties. These results suggest that, beyond anticoagulation, apixaban may exert nephroprotective effects by modulating renal inflammation and fibrosis and improving microvascular homeostasis. Further large-scale, multicenter, randomized studies with longer follow-up and molecular analyses are needed to confirm these findings and elucidate the mechanisms underlying the pleiotropic effects of apixaban.</jats:p>