title: Determinants of outcome in ANCA-associated glomerulonephritis: a prospective clinico-histopathological analysis of 96 patients.
abstract: 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 micromol/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 x GFR0 (mL/min) + 0.34 x fibrinoid necrosis (%) + 0.33 x 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.
authors.affiliation: Department of Pathology and Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands. H.A.Hauer@LUMC.nl
authors.forename: Herbert A
authors.initials: HA
authors.lastname: Hauer
authors.forename: Ingeborg M
authors.initials: IM
authors.lastname: Bajema
authors.forename: Hans C
authors.initials: HC
authors.lastname: Van Houwelingen
authors.forename: Franco
authors.initials: F
authors.lastname: Ferrario
authors.forename: Laure-Hélène
authors.initials: LH
authors.lastname: Noël
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Waldherr
authors.forename: David R W
authors.initials: DR
authors.lastname: Jayne
authors.forename: Niels
authors.initials: N
authors.lastname: Rasmussen
authors.forename: Jan A
authors.initials: JA
authors.lastname: Bruijn
authors.forename: E Christiaan
authors.initials: EC
authors.lastname: Hagen
mesh_terms: D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D001379:Azathioprine / Q000008:administration & dosage; D001706:Biopsy; D003520:Cyclophosphamide / Q000008:administration & dosage; D005919:Glomerular Filtration Rate; D005921:Glomerulonephritis / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D014890:Granulomatosis with Polyangiitis / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012008:Recurrence; D018401:Sample Size; D016896:Treatment Outcome
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D001379:Azathioprine