POS0117 RENAL AND OVERALL OUTCOMES OF DOUBLE-POSITIVE (ANCA AND ANTI-GBM ANTIBODIES) PATIENTS COMPARED TO ANCA-ASSOCIATED VASCULITIS PATIENTS WITH SEVERE RENAL INVOLVEMENT: A MULTICENTER RETROSPECTIVE STUDY WITH SYSTEMATIC RENAL PATHOLOGY ANALYSIS
Authors: M. Clerte, R. Philip, C. Levi, E. Cornec-Legall, V. Audard, A. Huart, X. Puéchal, M. Touzot, N. Rabot, E. Thervet, A. Aouba, A. Karras
Journal: Annals of the Rheumatic Diseases (2021)

Background: Among small vessel vasculitis, double-positive patients (DPP), combining serum and/or histologic findings for glomerular basement membrane (GBM) disease, and anti-neutrophil cytoplasmic antibodies (ANCA), is a rare, newly and poorly described condition. Objectives: We aimed to compare characteristics between DPP and ANCA-associated vasculitis patients (AAVP) with severe-renal-involvement. Methods: Retrospective multicenter study comparing 33 DPP and 45 severe-renal-involvement (serum creatinine &gt;300 μmol/L) AAVP, all with biopsy-proven nephropathy. Results: Except for 2 patients (6%) who had pure renal presentation during their entire follow-up period, others exhibited at least one extrarenal manifestation: pulmonary involvement (64%), weight loss (39%), gastrointestinal involvement (33%), ENT manifestations (21%), musculoskeletal symptoms (21%), fever (18%), neurological (12%), cutaneous (6%) and/or cardiac (6%) signs. All DPP (including up to 18% exhibiting negative serum anti-GBM antibodies) presented severe acute kidney failure with histologic GBM involvement. Compared to our AAVP, they had higher serum creatinine (719 versus 501 μmol/L; p=0.006) and a higher of patients requiring initial renal replacement therapy (82% vs 36%; p&lt;0.001). Berden classification significantly differed (p=0.003), with more crescentic glomerulonephritis and fewer sclerotic lesions in DPP. One-year renal survival was significantly lower in DPP than in AAVP (27% versus 64%; p&lt;0.0002). With comparable proportions of ANCA subtypes (2/3 with anti-MPO autoantibodies), numbers of extrarenal manifestations, remission-inducing immunosuppressants and median follow-ups (three years) between groups, relapse rates were similar: 9.1% of DPP and 10% of AAVP. Please, see the table 1 for more detailed data. Conclusion: Although DPP have features of both kinds of eponymous vasculitis, the anti-GBM component is the dominant phenotype, with more severe renal presentation and prognosis compared to AAVP with severe renal failure. Simultaneous testing of both antibodies and a systematically performed renal biopsy should be recommended in all rapidly progressive glomerulonephritis patients to recognize this difficult-to-treat, rare disease. Table 1. Comparison of clinical characteristics and outcomes between the cohorts of DPP and AAVP DPP n = 33 AAVP n = 45 p Age (year) 71,5 [14 - 89] 63 [45 - 93] 0.14 Male 16 (48) 19 (42) 0.65 Birmingham Vasculitis Activity Score 18,1 ± 4,8 20,4 ± 5,4 0.07 Organ involvement (except kidney) 1,7 ± 0,8 1,9 ± 1,1 0.31 Serum creatinine (µmol/L) 719 [238 - 2412] 501 [310 - 1683] 0.006 ANCA (MPO/PR3) 22/11 34/11 0.45 Berden classification n = 31 n = 44 0.003 s (sclerotic) / c (crescentic) 6 (19) / 22 (71) 12 (27) / 16 (37) f (focal) / m (mixed) 0 / 3 (10) 11 (25) / 5 (11) Brix renal risk score n = 27 n = 44 0.000014 Low / Medium / High 0 (0) / 4 (15) / 23 (85) 1 (2) / 29 (66) / 14 (32) Initial immunosuppressive therapy IV Cyclophosphamide 25 (76) 40 (82) 0.14 Rituximab 1 (3) 3 (7) 0.64 Plasma exchanges 25 (76) 19 (42) 0.005 Maintenance treatment 17 (48) 40 (89) 0.046 Initial RRT requirement 27 (82) 16 (36) 0.00007 Renal recovery (% initial RRT requirement) 4 (12) 6 (38) 0.9 1 year renal survival 9 (27) 29 (64) 0.0002 Values are displayed as absolute number (%) or as median [range]. DPP: double positive patients; AAVP: ANCA associated vasculitis patients; MPO: myeloperoxidase; PR3: proteinase 3; RRT: renal replacement therapy; IV: intravenous. Disclosure of Interests: None declared