Clinical Nephrology-Epidemiology-Clinical Trials
Kidney International (2002) 62, 1732–1742; doi:10.1046/j.1523-1755.2002.00605.x
Determinants of outcome in ANCA-associated glomerulonephritis: A prospective clinico-histopathological analysis of 96 patients
Herbert A Hauer, Ingeborg M Bajema, Hans C Van Houwelingen, Franco Ferrario, Laure-Hélène Noël, Rüdiger Waldherr, David RW Jayne, Niels Rasmussen, Jan A Bruijn and E Christiaan Hagen for 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; Department of Nephrology, Hôpital Necker, Paris, France; Department of Pathology, University of Heidelberg, Germany; Renal Unit, Addenbrooke's Hospital, Cambridge, England, United Kingdom; and Department of Otolaryngology, Rigshospitalet, Copenhagen, Denmark
Correspondence: Herbert 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
1Participants in EUVAS are listed in the ACKNOWLEDGEMENTS section.
Received 29 January 2002; Revised 15 April 2002; Accepted 30 May 2002.
Abstract
Determinants of outcome in ANCA-associated glomerulonephritis: A prospective clinico-histopathological analysis of 96 patients.
Background
The predictive value of clinical and renal histological features for renal outcome in patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis was investigated in a prospective analysis of 96 patients with ANCA-associated vasculitis, and moderate renal involvement (creatinine <500 
mol/L).
Methods
The extent of 39 histological features in 96 biopsies (performed at entry in a clinical trial) was scored by two independent observers, according to a standardized protocol. Age, gender, diagnosis, glomerular filtration rate at entry (GFR0), ANCA-specificity, proteinuria, and treatment of these 96 patients were also taken into account. Treatment was standardized and started after the biopsy was performed. End-points included renal function at 18 months (GFR18), GFR18 corrected for GFR0 (CORGFR18), and the occurrence of relapse or death.
Results
Parameters that most strongly correlated with GFR18 were GFR0 (r = 0.67), interstitial fibrosis (r = -0.45), glomerulosclerosis (r = -0.37), and tubular atrophy (r = -0.36). Parameters that most strongly correlated with CORGFR18 were segmental (r = 0.45) and cellular (r = 0.30) crescents, and fibrinoid necrosis (r = 0.46). None of the clinical and histological features predicted the occurrence of relapse or death. By applying a stepwise linear multiple regression analysis, we designed a formula for the estimation of renal function at 18 months: GFR18 (mL/min) = 17 + 0.71 
GFR0 (mL/min) + 0.34 fibrinoid necrosis (%) + 0.33 segmental crescents (%), (r2 = 0.60; standard deviation = 19 mL/min). Our results were independent of diagnosis, ANCA-specificity, and treatment limb.
Conclusions
These data suggest that in ANCA-associated glomerulonephritis, GFR0 and predominantly chronic renal lesions are potent predictors of GFR18. Active lesions are associated with renal function recovery and may be reversible. The formula for the estimation of GFR18 shows that a combination of GFR0 and renal histology is a better predictor for GFR18 than GFR0 only.
Keywords:
ANCA-associated vasculitis, Wegener's granulomatosis, microscopic polyangiitis, renal biopsy, pauci-immune crescentic necrotizing glomerulonephritis
Abbreviations:
ANCA, anti-neutrophil cytoplasm autoantibodies; BVAS, Birmingham Vasculitis Activity Score; C-ANCA, ANCA with cytoplasmic staining as determined by IIF; CYCAZAREM, randomized trial of CYClophosphamide versus AZAthioprine during REMission of ANCA-associated systemic vasculitis; ELISA, enzyme-linked immunosorbent assay; EUVAS, EUropean VAsculitis Study group; GFR, glomerular filtration rate; GFR0, GFR at entry (baseline GFR); GFR18, GFR at eighteen months; CORGFR18, corrected GFR at eighteen months; IIF, indirect immunofluorescence; MPA, microscopic polyangiitis; MPO-ANCA, ANCA directed against myeloperoxidase as determined by ELISA; P-ANCA, ANCA with a perinuclear staining as determined by IIF; PR3-ANCA, ANCA directed against proteinase-3 as determined by ELISA; r, correlation coefficient; r2, predictive value; RLV, renal limited vasculitis; SD, standard deviation; WG, Wegener's granulomatosis
