Repeat Kidney Biopsies in ANCA-associated Vasculitis: Clinical and Histologic Progression

ANCA-associated vasculitis (AAV) is a multi-systemic autoimmune disease that affects small and medium blood vessels. AAV includes 3 distinct clinical phenotypes, granulomatosis with polyangiitis (GPA), microscopic (MPA), eosinophilic (EGPA). Circulating autoantibodies to neutrophil myeloperoxidase and/or proteinase are present in majority of patients while 10% can be ANCA-negative. Despite recent advancements induction maintenance therapies, relapse remains common. A challenging aspect management the assessment activity, particularly cases renal involvement. The presence hematuria proteinuria at diagnosis reflect kidney Studies have shown despite achieving remission, seen up 40% persist 45% [1,2]. While biopsy initial presentation often performed establish predict prognosis, only few studies looked utility repeat biopsies follow-up [3Benichou N, Charles P, Terrier B, et al. Proteinuria after remission associated outcome [published online ahead print, 2023 Mar 20]. Kidney Int. 2023;S0085-2538(23)00168-0. doi:10.1016/j.kint.2023.02.02Google Scholar, 4Rhee R.L. Davis J.C. Ding L. al.The Utility Urinalysis Determining Risk Renal Relapse ANCA-Associated Vasculitis.Clin J Am Soc Nephrol. 2018; 13: 251-257https://doi.org/10.2215/CJN.04160417Crossref PubMed Scopus (40) Google 5Hauer H.A. Bajema I.M. Hagen E.C. al.Long-term injury vasculitis: an analysis 31 biopsies.Nephrol Dial Transplant. 2002; 17: 587-596https://doi.org/10.1093/ndt/17.4.587Crossref (50) 6Neumann I. Kain R. Regele H. Soleiman A. Kandutsch S. Meisl F.T. Histological predictors early late vasculitis.Nephrol 2005; 20: 96-104https://doi.org/10.1093/ndt/gfh563Crossref (87) 7Aasarød K. Bostad Hammerstrøm J. Jørstad Iversen B.M. histopathology course 94 Wegener's granulomatosis.Nephrol 2001; 16: 953-960https://doi.org/10.1093/ndt/16.5.953Crossref (91) Scholar]. It has been demonstrated clinician’s impression activity incorrect 25% cases, supporting guide [6Neumann Given paucity data on indications, clinical, histologic progression ANCA glomerulonephritis (ANCA-GN), we sought study those parameters (KB1) for-cause (KB2) ANCA-GN. Supplementary References Methods included Material. Twenty-nine were included. median age was 73 years (IQR 61-81). mean (SD) time from KB1 KB2 42 (±3.6) months (IQR) 34 (12-59) months. 11 years. There 55% females, being Caucasian (83%). Fifty-nine percent MPO-ANCA positive 31% PR3-ANCA positive. At KB2, status persistently (28%), newly (31%), unknown (21%), negative (17%). most common indication for elevation serum creatinine (n=16), followed by (n=14), new or persistent (n=10) equally. details indications presented Table S1. Of 29 patients, eleven (38%) had active pauci-immune crescentic GN remaining alternate pathology KB2. Median (mg/dl) 2 (1.6-4.5) 1.9 (1.2-3.8) (p=0.322). eGFR (mL/min/1.73m2) 32 (13-46.5) 33 (15-60) (p=0.142) [Table 1]. Among 16 creatinine, 8 14 proteinuria, 4 10 hematuria, evidence onset 7 KB2.Table 1Patient characteristics, demographics, findings, treatment (n=29)Baseline characteristicsAge (years)73 (61-81)Age (years) KB1Age KB259 (54-66)65 (55.5-72)GenderFemaleMale16 (55%)13 (45%)RaceCaucasianAfrican AmericanOthers24 (83%)4 (14%)1 (3%)Clinical diagnosisGPAMPA10 (34%)19 (66%)Organ involvementKidneyLungSinusSkinJointEar, Nose ThroatNerve29 (100%)8 (28%)6 (21%)5 (17%)3 (10%)2 (7%)1 (3%)Indications KB2Elevation creatinineProteinuriaPersistent hematuriaNew hematuriaPositive ANCA16 (55%)14 (48%)10 (34%)10 (34%)1 (3%)Active KB211 (38%)ANCA type KB1PR3-ANCAMPO-ANCANegative-ANCA9 (31%)17 (58%)3 (10%)ANCA KB2Newly positivePersistently positiveUnknownNegative9 (31%)8 (17%)Serum (mg/dL) KB1Serum KB22 (1.6-4.45)1.9 (1.2-3.8)Histopathological class (n=29)FocalCrescenticMixedSclerotic8 (28%)5 (17%)13 (45%)3 (10%)Renal Score (n=29)LowMediumHigh8 (28%)17 (59%)4 (14%)Histopathological ANCA-GN (n=11)FocalCrescenticMixedSclerotic3 (27%)1 (9%)7 (64%)0Histopathological (27%)05 (27%)Renal (n=11)LowMediumHigh5 (45%)5 (45%)1 (3%)Renal (n=11)LowMediumHigh3 (27%)5 (27%)Induction KB1GlucocorticoidsCyclophosphamideRituximabMycophenolate Mofetil29 (100%)18 (62%)10 (3%)Data as number (%) (interquartile range).KB1; biopsy; GPA, polyangiitis; MPA, ANCA-GN, ANCA-glomerulonephritis Open table tab Data range). KB1; After performed, thirteen (45%) change their immunosuppression plan: requiring inactive who transitioned therapy. Progression end-stage (ESKD) occurred 12 (41%) which 5 In (n=11), developed ESKD. We analyzed histopathologic (37%) this cohort (82%), (36%), (54%), (27%). mixed (n=7) (n=5). Sclerotic absent KB1, whereas focal 1 sclerotic remained (RRS) low (n=5 equally). risk group, two progressed one severe [Figure a-b]. percentage global sclerosis increased 20% 43%, cellular crescents decreased 14% 0% (p=0.01 p=0.02, respectively). fibrous unchanged (p=0.81), trend fibrinoid necrosis segmental noted Severe interstitial fibrosis tubular atrophy (IFTA), This aimed evaluate histological underwent biopsy. shows 38% GN, elevated reason Active 70% hematuria. ESKD high Chapman reviewed 59 interval assess response therapy found 42% led immunosuppressive plan 75% Our similar (38%), but lower rate (45%). may due differences physician practices, extra-renal manifestations, Similar our study, received cyclophosphamide rituximab. However, it worth noting none plasma exchange, compared 47% cohort. value conflicting. One concluded not predicted future relapses. Interestingly, did correlate [2]. On other hand, correlation between end relapses, failure, death [1]. GN. Additionally, major biopsy, consistent current understanding marker damage rather than although its prognostic seems differ depending suggests instead pre-emptive escalation immunosuppression, should considered immunosuppression. finding chronicity higher percentages IFTA also previous protocolized [7Aasarød terms switching, 63% class-switched, (36%) class. switched, 36% 27% improved. These numbers addition, either less favorable outcome. could reflection sampling error characteristics response. (RRS), initially published Brix [S4]. RRS 45%, improved 10%, worsened again suggesting degree contrast where 30% showed improvement RRS. patient demographics practice patterns. Although limited sample size, support confirmation relying conventional markers improve prognostication decisions. Larger needed confirm findings study. 8Chapman G.B. Farrah T.E. F.A. al.Utility vasculitis.Rheumatology (Oxford). 2022; 61: 1966-1974https://doi.org/10.1093/rheumatology/keab695Crossref (5) 9Hruskova Z. Honsova E. Berden A.E. al.Repeat protocol 2014; 29: 1728-1732https://doi.org/10.1093/ndt/gfu042Crossref (25) Scholar. Duvuru Geetha supported Johns Hopkins Center Innovative Medicine. Download .pdf (.1 MB) Help pdf files