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 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.
Hauer
Herbert A
HA
Department of Pathology and Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands. H.A.Hauer@LUMC.nl
Bajema
Ingeborg M
IM
Van Houwelingen
Hans C
HC
Ferrario
Franco
F
Noël
Laure-Hélène
LH
Waldherr
Rüdiger
R
Jayne
David R W
DR
Rasmussen
Niels
N
Bruijn
Jan A
JA
Hagen
E Christiaan
EC
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
D019268:Antibodies, Antineutrophil Cytoplasmic; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D001379:Azathioprine