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Background  Treatment of patients with ANCA-associated vasculitis (AAV) and severe renal involvement is not established. We describe outcomes in response to rituximab (RTX) versus cyclophosphamide (CYC) and plasma exchange (PLEX).    Methods  A retrospective cohort study of MPO- or PR3-ANCA–positive patients with AAV (MPA and GPA) and severe kidney disease (eGFR &lt;30 ml/min per 1.73 m 2 ). Remission, relapse, ESKD and death after remission-induction with CYC or RTX, with or without the use of PLEX, were compared.    Results  Of 467 patients with active renal involvement, 251 had severe kidney disease. Patients received CYC ( n =161) or RTX ( n =64) for remission-induction, and 51 were also treated with PLEX. Predictors for ESKD and/or death at 18 months were eGFR &lt;15 ml/min per 1.73 m 2  at diagnosis (IRR 3.09 [95% CI 1.49 to 6.40],  P =0.002), renal recovery (IRR 0.27 [95% CI 0.12 to 0.64],  P =0.003) and renal remission at 6 months (IRR 0.40 [95% CI 0.18 to 0.90],  P =0.027). RTX was comparable to CYC in remission-induction (BVAS/WG=0) at 6 months (IRR 1.37 [95% CI 0.91 to 2.08],  P =0.132). Addition of PLEX showed no benefit on remission-induction at 6 months (IRR 0.73 [95% CI 0.44 to 1.22],  P =0.230), the rate of ESKD and/or death at 18 months (IRR 1.05 [95% CI 0.51 to 2.18],  P =0.891), progression to ESKD (IRR 1.06 [95% CI 0.50 to 2.25],  P =0.887), and survival at 24 months (IRR 0.54 [95% CI 0.16 to 1.85],  P =0.330).    Conclusions  The apparent benefits and risks of using CYC or RTX for the treatment of patients with AAV and severe kidney disease are balanced. The addition of PLEX to standard remission-induction therapy showed no benefit in our cohort. A randomized controlled trial is the only satisfactory means to evaluate efficacy of remission-induction treatments in AAV with severe renal involvement.

Efficacy of Rituximab and Plasma Exchange in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis with Severe Kidney Disease