Spatial and Temporal Clustering of Anti-Glomerular Basement Membrane Disease

Abstract

Background and objectives 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)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014) in Ireland, investigate clustering of cases in time and space, and assess the effect of spatial variability in incidence on outcome.Design, setting, participants, & measurements 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.Results 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.Conclusions 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.

Clustering of Anti-GBM Disease: Clues to an Environmental Trigger?

“…This allowed them to define, for the first time, a national incidence rate for this rare condition. This rate is higher than previous estimates in other European populations, as discussed by Canney et al (10), most likely reflecting the methodologic inadequacies of previous studies, which were prone to ascertainment bias and unable to accurately define at-risk populations. It might also reflect the moderate over-representation of the DR2 haplotype and DRB1 risk alleles in the Irish population (11) or perhaps a genuine increase in the frequency of anti-GBM disease in recent years compared with historical cohorts.…”

“…Previous reports of clustering or outbreaks of anti-GBM disease (8) and seasonal variations in disease incidence (9) support a role for environmental factors, such as infection, in triggering disease onset, although they are limited to anecdotal observation. The report by Canney et al (10) in this issue of the Clinical Journal of the American Society of Nephrology is the first to assess geographic or temporal clustering using formal statistical methods in a national cohort of patients.…”

Diagnostic and management challenges in Goodpasture’s (anti-glomerular basement membrane) disease

“…Additionally, seasonal variation has been reported in small patient cohorts (10,11) suggesting potential infectious triggers. Spatial and temporal clustering of disease incidence at a national level has been recently described (2). Over an 11 year period, incidence of anti-GBM disease was 1.6 (range 0.4 to 2.8) per million population per year in Ireland.…”

“…Spatial clustering in a rural county was identified, in which none of the 7 presenting patients had lung disease, but the majority (71%) had detectable anti-GBM antibodies with dual positivity for anti-neutrophil cytoplasm antibodies (ANCA) (2). Understanding the HLA allelic variation in this region and the exposure to a common environmental influence would be vital to further dissect out disease aetiology, while the disproportionate occurrence of dual antibody positivity could represent a difference in disease pathogenesis.…”

“…Although uncommon, with an incidence of 0.5-1.6 cases/million/year (2), approximately 20% of cases of rapidly progressive glomerulonephritis (RPGN) are caused by anti-GBM disease, with isolated renal involvement occurring in 40% of patients (1). Peak incidence is in the third and sixth decades and there is a male preponderance, reflecting increased alveolar haemorrhage in younger men.…”