Arteritis Status and Renal Involvement in ANCA-Associated Vasculitis
Authors: Joop P. Aendekerk, Sjoerd A.M.E.G. Timmermans, Matthias H. Busch, Pieter van Paassen
Journal: Journal of the American Society of Nephrology (2022)

Boudhabhay et al. demonstrated that patients with ANCA-associated vasculitis (AAV) and arteritis of small arteries on renal biopsy (AAV_A+) present with more systemic involvement and inflammation as compared with patients with AAV and renal involvement but no arteritis.1 Furthermore, arteritis was associated with poor outcomes, i.e., ESKD) and mortality, and may improve the ANCA renal risk score. We tested this premise in an independent cohort of 318 patients with AAV, ANCA serum reactivity, and renal involvement who presented between January 1990 and July 2021. None of the patients had coexisting antiglomerular basement membrane disease. Twenty-five (8%) out of 318 patients had AAV_A+, seven of whom had arteritis in isolation (i.e., no glomerulonephritis on renal biopsy). AAV_A+ was associated with older age and more severe renal disease as compared with those without arteritis (Table 1), corroborating the findings of Boudhabhay et al.1 Median follow-up was 1.2 (interquartile range, 0.4–6.1) years. Patients with AAV_A+ were treated with high-dose steroids, either with (cyclophosphamide, n=20; rituximab, n=4) or without (n=1) immunosuppressive drugs. The ANCA renal risk score, developed to predict ESRD,2 classified five, 13, and seven patients as low, moderate, and high risk. ESRD did develop in one (n=13, 8%) moderate- and four (n=7, 57%) high-risk patients, similar to studies not including arteritis status2,3 and the RENVAS cohort.1 None of the patients with arteritis in isolation (risk score: mild, n=2; moderate, n=4; high, n=1) progressed to ESKD. We therefore assume that glomerular and tubulointerstitial lesions are more important to predict ESKD.2,3 Thirteen (52%) out of 25 patients with AAV_A+ died after 0.4 (interquartile range, 0.2–3.2) years. Ninety-eight (33%) out of 293 patients without arteritis died, corresponding to previous EUVAS cohorts4; median time to event was 3.1 (interquartile range, 0.3–8.7) years. AAV_A+ was associated with poor 5-year survival (hazard ratio, 0.30; 95% confidence interval, 0.12 to 0.77) as compared with those without arteritis. Table 1. - Baseline characteristics of patients with AAV and renal involvement Variables AAV_A+ No arteritis P Value Patients, N 25 293 Male/female ratio 13/12 202/91 0.08 Age, y (SD) 68 (±13) 62 (±13) 0.03 Clinical diagnosis, % 0.2 GPA 18 (72) 157 (54) MPA 7 (28) 129 (44) EGPA 0 7 (2) ANCA specificity, % 0.5 MPO 10 (40) 149 (51) PR3 15 (60) 140 (48) Double positivity 0 4 (1) Serum creatinine, µmol/L (IQR) 341 (235–560) 220 (130–376) 0.006 Berden classification, % a 0.7 Focal 6 (24) 124 (42) Crescentic 7 (28) 90 (31) Mixed 3 (12) 64 (22) Sclerotic 2 (8) 15 (5) No glomerulonephritis a 7 (28) 0 ANCA renal risk score, % 0.008 Low 5 (20) 138 (47) Moderate 13 (52) 123 (42) High 7 (28) 32 (11) Differences in continuous variables were checked using the independent samples t test or Mann–Whitney U test as appropriate. Differences in categorical variables were checked using the chi-square or Fisher's exact test as appropriate. GPA, granulomatosis with polyangiitis; MPA, microscopic polyangiitis; EGPA, eosinophilic granulomatosis with polyangiitis; MPO, myeloperoxidase; PR3, proteinase 3; IQR, interquartile range.aPatients with arteritis in isolation have not been classified according to Berden classification. Taken together, AAV_A+ accounts for approximately 10% of patients with AAV and kidney involvement. We confirm that AAV_A+ defines a specific phenotype that is associated with older age, severe renal disease, and poor survival. The value of arteritis status on renal biopsy to predict the risk of ESRD, however, warrants further evaluation. Disclosures All authors have nothing to disclose. Funding None.