Role Of Repeated Renal Biopsy In Anca Vasculitis

Abstract Background and Aims Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) is a systemic disease characterized by inflammation of small vessels and presence of ANCA. Pauci-immune necrotizing crescentic glomerulonephritis is a severe renal complication of AAV. Despite immunosuppressive therapy, relapses are frequent during the course of the disease, affecting up to 50% of the patients. Kidney biopsy is routinely used to diagnose AAV at initial presentation and to predict renal prognosis. Although the activity of renal AAV is not easily evaluated by plasma or urine biomarkers, kidney biopsy is rarely performed when relapse is suspected. We herein analyze the clinical, laboratory and renal pathology data from patients who underwent repeated kidney biopsies during the course of AAV. Method We retrospectively reviewed data from 37 patients who underwent at least 2 kidney biopsies in our centre, between 2002 and 2018. The first renal biopsy (B1) was constantly performed at diagnosis. A follow-up biopsy (B2) was performed for purpose, either for suspicion of refractory disease or confirmation of renal relapse. Modifications of renal pathology between B1 and B2 were studied, by comparing presence of active and chronic lesions. Active lesions were defined by the presence of cellular crescents and/or fibrinoid necrosis. Chronic lesions were quantified by the percentage of globally sclerotic glomeruli and the percentage of interstitial fibrosis / tubular atrophy (IF/TA). Results Median age at diagnosis was 57 years, M/F ratio was 21/16. ANCA specificity was anti-MPO in 65% of cases, anti-PR3 in 32%. The median delay between B1 and B2 was 3,3 [0,9-5,8] years. B2 was done for suspicion of refractory disease (n=8) or of renal relapse (n=29). Causes of B2 were : persistence or reappearance of haematuria in 78% of cases, increase of creatinine in 43%, increase of ANCA titer in 67%. Systemic AAV activity was more important at B1 vs B2 (median BVAS 18 vs 9), as well as renal dysfunction (median sCreat 200 vs 156 μmol/l). Active glomerulonephritis was constantly found at B1 but was present in only 35% of B2. Presence of cellular crescents decreased from 71,4 to 29,7% (p = 0,002), whereas fibrinoid necrosis decreased from 80,6 to 35,1% (p = 0.0003). Five factors were significantly associated with the presence of active lesions : presence of at least one extra-renal AAV manifestation (p = 0.0006), increase of ANCA titer (p = 0.0022), CRP>30mg/l (p = 0.001), absence of IF/TA (p=0,02) and high percentage of normal glomeruli (p=0,014) at B1. Interestingly, level of proteinuria and persistence of hematuria were not associated with histological activity at B2 (p =0,64 and 0,22 respectively). In contrast, chronic lesions such as glomerulosclerosis and IF/TA were more severe at B2 compared to B1 (p <0,0001 and 0,014 respectively). The worsening of fibrotic lesions was not associated with ANCA specificity (anti-MPO vs -PR3). Conclusion This is the largest cohort reporting on repeated renal biopsy in AAV. Despite several clinical and laboratory signs suggesting active renal AAV, B2 revealed no relapse in 2/3 of cases, allowing avoidance of a new immunosuppressive induction treatment. Our results suggest that rebiopsy is crucial when renal relapse is suspected, as proteinuria and hematuria do not predict active disease, suggesting that their persistence could be explained by glomerular scarring.