Incidence and Risk Factors of Venous Thromboembolic Events in Patients with ANCA-Glomerulonephritis: A Cohort Study from the Maine-Anjou Registry.

Nicolas Henry,Jean-Philippe Coindre,Anne Sophie Garnier,Benoit Brilland,Agnès Duveau,Maud Cousin,Jean-François Subra,Assia Djema,Giorgina Barbara Piccoli,Samuel Wacrenier,Jean-François Augusto,Renaud Gansey,Virginie Besson

doi:10.3390/jcm9103177

Abstract

(1) Introduction: The incidence of venous thromboembolisms (VTE) has not been extensively analyzed in patients with antineutrophil cytoplasmic antibody (ANCA)-glomerulonephritis (ANCA-GN). Thus, the aim of the present study was to assess the frequency and the risk factors of VTE in patients with ANCA-GN. (2) Methods: Patients from the Maine-Anjou ANCA-associated vasculitis (AAV) registry with a biopsy showing pauci-immune glomerulonephritis were included. VTE events, site, and interval from AAV diagnosis were analyzed. (3) Results: 133 patients fulfilled the inclusion criteria of the study and were analyzed. VTE episodes were diagnosed in 23/133 (17.3%) patients at a median delay of 3 months from ANCA-GN diagnosis. Patients with VTE had lower serum albumin (p = 0.040), were less frequently on statin therapy (p = 0.009) and had less frequently proteinase-3 (PR3)-ANCAs (p = 0.078). Univariate analysis identified higher age (p = 0.022), lower serum albumin (p = 0.030), lack of statin therapy (p = 0.009), and rituximab treatment (p = 0.018) as significant risk factors of VTE. In multivariate analysis, only lack of statin therapy (HR 4.873; p = 0.042) was significantly associated with VTE. (4) Conclusion: Patients with ANCA-GN are at high risk of VTE, especially within the first months following AAV diagnosis. Our results suggest that statin therapy is associated with a lower risk of VTE in ANCA-GN patients.

Highlights

Venous thromboembolism (VTE) is a classical complication of chronic inflammatory diseases [1], reported to be increased in many auto-immune and rheumatic diseases, including antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) [2,3,4,5,6,7,8,9]
The first studies addressed in AAV were a case series of pediatric patients that developed deep vein thrombosis (DVT) shortly after disease diagnosis [10] and a post-hoc analysis of the Wegener’s Granulomatosis Etanercept Trial (WGET) [2,11]
In this prospective trial, which was limited to patients with granulomatosis with polyangiitis (GPA), about 10% of patients developed VTE after a median time of 2.1 months from disease onset [11]

Summary

Introduction

Venous thromboembolism (VTE) is a classical complication of chronic inflammatory diseases [1], reported to be increased in many auto-immune and rheumatic diseases, including ANCA-associated vasculitis (AAV) [2,3,4,5,6,7,8,9]. A similar incidence was observed in a recent analysis performed in 417 patients that were included in randomized controlled trials conducted by the European Vasculitis Society [5] In this analysis, patients with severe renal disease had a higher rate of VTE. Kronbichler et al analyzed VTE frequency and risk factors in patients included in the RAVE study which aimed at evaluating rituximab as a remission induction regimen [9,12] In these patients without severe kidney involvement, pulmonary hemorrhage, and positive PR3-ANCA, heart involvement and microscopic hematuria were found to be independently associated with VTE development. Isaacs et al found PR3-ANCA, hypoalbuminemia, and BMI to be independent risk factors of VTE in a retrospective analysis in 162 AAV patients [13]

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