Predictors of renal and patient outcomes in anti-GBM disease: clinicopathologic analysis of a two-centre cohort

Alchi, Bassam; Griffiths, Meryl; Sivalingam, Murugan; Jayne, David; Farrington, Ken

doi:10.1093/ndt/gfu399

Cited by 91 publications

(100 citation statements)

References 25 publications

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“…This was in a native kidney and was not associated with a positive ANCA result. Anti-GBM disease is classically a monophasic illness; although relapses can occur (20), they are often in the context of coexistent ANCA positivity (21,22). As seen in previous studies, we found that double-positive cases tended to be older (10,21,23).…”

Section: Discussionsupporting

confidence: 82%

“…Anti-GBM disease is classically a monophasic illness; although relapses can occur (20), they are often in the context of coexistent ANCA positivity (21,22). As seen in previous studies, we found that double-positive cases tended to be older (10,21,23). A diagnosis of "true" anti-GBM disease can be particularly challenging in this group because older patients may be less likely to undergo renal biopsy.…”

Section: Discussionsupporting

confidence: 75%

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Spatial and Temporal Clustering of Anti-Glomerular Basement Membrane Disease

Canney¹,

O’Hara²,

McEvoy³

et al. 2016

CJASN

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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.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 75%

Spatial and Temporal Clustering of Anti-Glomerular Basement Membrane Disease

Canney¹,

O’Hara²,

McEvoy³

et al. 2016

CJASN

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“…Other reports have described similarly low levels of renal recovery in patients presenting with dialysis-dependent kidney failure, with the highest rate of approximately 20% recovery in one series (66). Predictors of poor renal outcome include severity of renal dysfunction at presentation, the proportion of glomeruli affected by crescents, and oligoanuria at presentation (17,18,74). In the Hammersmith series, no patient who required hemodialysis and had 100% crescents on kidney biopsy recovered renal function, and so withholding treatment (and its incumbent toxicity) is often considered in these cases.…”

Section: Outcome and Prognosismentioning

confidence: 82%

Anti-Glomerular Basement Membrane Disease

McAdoo¹,

Pusey²

2017

CJASN

302

303

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Anti-glomerular basement membrane (anti-GBM) disease is a rare small vessel vasculitis that affects the capillary beds of the kidneys and lungs. It is an archetypic autoimmune disease, caused by the development of directly pathogenic autoantibodies targeting a well characterized autoantigen expressed in the basement membranes of these organs, although the inciting events that induce the autoimmune response are not fully understood. The recent confirmation of spatial and temporal clustering of cases suggests that environmental factors, including infection, may trigger disease in genetically susceptible individuals. The majority of patients develop widespread glomerular crescent formation, presenting with features of rapidly progressive GN, and 40%-60% will have concurrent alveolar hemorrhage. Treatment aims to rapidly remove pathogenic autoantibody, typically with the use of plasma exchange, along with steroids and cytotoxic therapy to prevent ongoing autoantibody production and tissue inflammation. Retrospective cohort studies suggest that when this combination of treatment is started early, the majority of patients will have good renal outcome, although presentation with oligoanuria, a high proportion of glomerular crescents, or kidney failure requiring dialysis augur badly for renal prognosis. Relapse and recurrent disease after kidney transplantation are both uncommon, although de novo anti-GBM disease after transplantation for Alport syndrome is a recognized phenomenon. Copresentation with other kidney diseases such as ANCAassociated vasculitis and membranous nephropathy seems to occur at a higher frequency than would be expected by chance alone, and in addition atypical presentations of anti-GBM disease are increasingly reported. These observations highlight the need for future work to further delineate the immunopathogenic mechanisms of anti-GBM disease, and how to better refine and improve treatments, particularly for patients presenting with adverse prognostic factors.

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“…Whether these findings hold true for European patients is less clear. In a recent study of 43 patients with GS referred to two departments in England over a 20-years period, 1-year patient survival was associated with the presence of multiple co-morbidities, ANCA positivity, being aged 60 years, and urinary output (oligoanuria) at presentation [8]. Oligoanuria at presentation and the percentage of crescents predicted the dependence on dialysis at 3 months.…”

Section: Introductionmentioning

confidence: 98%