Cell Biology – Immunology – Pathology
Kidney International (2002) 61, 80–89; doi:10.1046/j.1523-1755.2002.00089.x
Renal histology in ANCA-associated vasculitis: Differences between diagnostic and serologic subgroups
Herbert A Hauer, Ingeborg M Bajema, Hans C Van Houwelingen, Franco Ferrario, Laure-Hélène Noël, Rüdiger Waldherr, David R W Jayne, Niels Rasmussen, Jan A Bruijn and E Christiaan Hagen on behalf of the European Vasculitis Study Group (EUVAS)1
Departments of Pathology and Medical Statistics, Leiden University Medical Center, Leiden, Department of Pathology, Erasmus University Medical Center, Rotterdam, and Department of Internal Medicine, Eemland Hospital, Amersfoort, the Netherlands; Renal Immunopathology Center, Ospedale San Carlo Borromeo, Milan, Italy; INSERM U507, Hôpital Necker, Paris, France; Department of Pathology, University of Heidelberg, Heidelberg, Germany; Renal Unit, Addenbrooke's Hospital, Cambridge, England, United Kingdom; and Department of Otolaryngology, Rigshospitalet, Copenhagen, Denmark
Correspondence: H.A. Hauer, M.D., Department of Pathology, Leiden University Medical Center, P.O. Box 9600, Building 1, L1-Q, 2300 RC Leiden, The Netherlands. E-mail: H.A.Hauer@LUMC.nl
1A complete list of EUVAS participants is in the Acknowledgments.
Received 8 June 2001; Revised 31 July 2001; Accepted 1 August 2001.
Abstract
Renal histology in ANCA-associated vasculitis: Differences between diagnostic and serologic subgroups.
Background
Differences in renal histopathology between microscopic polyangiitis (MPA) and Wegener's granulomatosis (WG), and between anti-neutrophil cytoplasm autoantibody (ANCA) test results in patients with ANCA-associated vasculitis may provide insight into the differences in pathogenesis and raise the opportunity of classifying the vasculitides more accurately. The possible differences in histopathology are investigated in this study.
Methods
We report an analysis of 173 patients with renal disease in microscopic polyangiitis or Wegener's granulomatosis. A total of 173 renal biopsies, performed at diagnosis, were scored by two observers separately, using a previously standardized protocol. Consensus on each biopsy was achieved during a central review.
Results
Normal glomeruli were more common in WG than in MPA (P < 0.001). Glomerulosclerosis was more prominent in MPA than in WG (P = 0.003). Interstitial fibrosis (P < 0.001), tubular atrophy (P < 0.001), and tubular casts (P = 0.005) were more frequently present and more severe in MPA than in WG. Presence of glomerulosclerosis was more extensive in patients with myeloperoxidase (MPO)-ANCA than with proteinase 3 (PR3)-ANCA (P = 0.022). Interstitial fibrosis (P = 0.008), tubular necrosis (P = 0.030), tubular atrophy (P = 0.013), and intra-epithelial infiltrates (P = 0.006) were more frequently present and more severe in MPO-ANCA than in PR3-ANCA.
Conclusions
Glomerulonephritis in relation to MPA has more characteristics of chronic injury at the time of presentation than glomerulonephritis in relation to WG. This difference may be due to a delayed establishment of diagnosis in patients with MPA compared to patients with WG. Both active and chronic lesions are more abundantly present in MPO-ANCA–positive patients than in patients with PR3-ANCA–positivity, which suggests that the pathogenesis of renal disease in these ANCA subsets could be different. Our results also suggest that ANCA test results may be useful in classifying ANCA-associated vasculitides.
Keywords:
renal biopsy, glomerulonephritis, microscopic polyangiitis, Wegener's granulomatosis, renal limited vasculitis, ANCA-associated vasculitis
Abbreviations:
ANCA, anti-neutrophil cytoplasm autoantibodies; C-ANCA, ANCA with a cytoplasmic staining as determined by indirect immunofluorescence; CYCAZAREM, randomized trial of CYClophosphamide versus AZAthioprine during REMission of ANCA-positive systemic vasculitis; ELISA, enzyme-linked immunosorbent assay; EUVAS, EUropean VAsculitis Study group; GFR, glomerular filtration rate; IIF, indirect immunofluorescence; MEPEX, randomized trial of adjunctive therapy for severe glomerulonephritis in ANCA-associated systemic vasculitis–intravenous administration of MEthylprednisolone versus Plasma EXchange; MPA, microscopic polyangiitis; MPO, myeloperoxidase; MPO-ANCA, ANCA directed against myeloperoxidase as determined by ELISA; P-ANCA, ANCA with a perinuclear staining as determined by IIF; PR3, proteinase-3; RLV, renal limited vasculitis; SD, standard deviation; WG, Wegener's granulomatosis
