title: Spatial and Temporal Clustering of Anti-Glomerular Basement Membrane Disease.
abstract: An environmental trigger has been proposed as an inciting factor in the development of anti-GBM disease. This multicenter, observational study sought to define the national incidence of anti-GBM disease during an 11-year period (2003-2014) in Ireland, investigate clustering of cases in time and space, and assess the effect of spatial variability in incidence on outcome.
  
  
  
  We ascertained cases by screening immunology laboratories for instances of positivity for anti-GBM antibody and the national renal histopathology registry for biopsy-proven cases. The population at risk was defined from national census data. We used a variable-window scan statistic to detect temporal clustering. A Bayesian spatial model was used to calculate standardized incidence ratios (SIRs) for each of the 26 counties.
  
  
  
  Seventy-nine cases were included. National incidence was 1.64 (95% confidence interval [95% CI], 0.82 to 3.35) per million population per year. A temporal cluster (n=10) was identified during a 3-month period; six cases were resident in four rural counties in the southeast. Spatial analysis revealed wide regional variation in SIRs and a cluster (n=7) in the northwest (SIR, 1.71; 95% CI, 1.02 to 3.06). There were 29 deaths and 57 cases of ESRD during a mean follow-up of 2.9 years. Greater distance from diagnosis site to treating center, stratified by median distance traveled, did not significantly affect patient (hazard ratio, 1.80; 95% CI, 0.87 to 3.77) or renal (hazard ratio, 0.76; 95% CI, 0.40 to 1.13) survival.
  
  
  
  To our knowledge, this is the first study to report national incidence rates of anti-GBM disease and formally investigate patterns of incidence. Clustering of cases in time and space supports the hypothesis of an environmental trigger for disease onset. The substantial variability in regional incidence highlights the need for comprehensive country-wide studies to improve our understanding of the etiology of anti-GBM disease.
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material .
authors.forename: Mark
authors.initials: M
authors.lastname: Canney
authors.forename: Paul V
authors.initials: PV
authors.lastname: O'Hara
authors.forename: Caitriona M
authors.initials: CM
authors.lastname: McEvoy
authors.forename: Samar
authors.initials: S
authors.lastname: Medani
authors.forename: Dervla M
authors.initials: DM
authors.lastname: Connaughton
authors.forename: Ahad A
authors.initials: AA
authors.lastname: Abdalla
authors.forename: Ross
authors.initials: R
authors.lastname: Doyle
authors.forename: Austin G
authors.initials: AG
authors.lastname: Stack
authors.forename: Conall M
authors.initials: CM
authors.lastname: O'Seaghdha
authors.forename: Michael R
authors.initials: MR
authors.lastname: Clarkson
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Griffin
authors.forename: John
authors.initials: J
authors.lastname: Holian
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Dorman
authors.forename: Aileen
authors.initials: A
authors.lastname: Niland
authors.forename: Mary
authors.initials: M
authors.lastname: Keogan
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Wallace
authors.forename: Niall P
authors.initials: NP
authors.lastname: Conlon
authors.forename: Cathal
authors.initials: C
authors.lastname: Walsh
authors.forename: Alan
authors.initials: A
authors.lastname: Kelly
authors.forename: Mark A
authors.initials: MA
authors.lastname: Little
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019867:Anti-Glomerular Basement Membrane Disease / Q000453:epidemiology* / Q000209:etiology / Q000401:mortality; D016000:Cluster Analysis; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D006801:Humans; D015994:Incidence; D007494:Ireland / Q000453:epidemiology; D007676:Kidney Failure, Chronic / Q000453:epidemiology* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D062211:Spatio-Temporal Analysis; D015996:Survival Rate
keywords: ANCA; anti-glomerular basement membrane disease; autoantibodies; cluster analysis; epidemiology; follow-up studies; humans; incidence; kidney; kidney failure, chronic