32. Age and time-dependent increase in incident anti-glomerular basement membrane (anti-GBM) disease-a nation-wide cohort study

Background: Anti-GBM disease is a rare type of severe small vessel vasculitis that can lead to pulmonary haemorrhage and kidney failure. Epidemiologic studies of unselected patients have been challenged due to the low disease incidence and non-relapsing nature. Accordingly, we examined incidence and outcomes based on data from multiple Danish nationwide healthcare registries.

Method: All patients with incident anti-GBM disease defined by ICD10 code DM31.0A between 1998 and 2018, were ascertained by cross-referencing of data from the Danish nationwide administrative registries. Controls were matched 2:1 by Exposure Density Sampling on age and sex.  Risks of death was compared based on adjusted absolute risk ratios (ARR) and cumulative incidences assessed based on the Aalen-Johansen estimator.

Results: We identified 97 patients with incident anti-GBM disease from the Danish National Patient Registry corresponding to an overall incidence of 0.91 (SD 0.6) cases/million/year. Cumulative frequencies of AAV diagnoses exhibited significant seasonal variation, with the highest number of incident cases observed during spring and fall (P=0.014). Incidence increased with age with 0.76 (SD 0.4), 1.5 (SD 1.04) and 4.9 (SD 2.6) cases/million/year for patients < 45, 45-75 and >75 years, respectively. Mean age at time of diagnosis was 52.4 (SD 22.8) years with an equal distribution of men and women (51.6%). A total of 45 (58.4%), 60 (61.9%) and 61(62.9%) patients had commenced haemodialysis at day 30, 180 and 360 after first day of admission, respectively. 36 (37.1%) patients were registered as having had an ICU stay and plasma exchange was employed in 74.2% of the cases. There was a significant increase in incidence of anti-GBM disease over time [1998-2004: 0.50 (SD 0.2); 2005-2011: 0.80 (SD 0.4); 2012-2018: 1.4 (SD 0.5), P=0.02] (figure 1); these findings were sustained in sub-analyses of gender and age groups >45 years, with the highest increase in incidence amongst patients between 45-75 years. The trend in incident anti-GBM tests in the northern administrative region of Denmark during 1998-2012 was decreasing, and there was no correlation between the incident anti-GBM testing and ICD10 registered anti-GBM disease during the period (P=0.43). Five-year mortality was 34.4%, and among the primary contributing causes of death were cardiovascular disease (52.9%), vasculitis (23.5), cerebral disease (23.5%) and infection (17.7%). Risk of death from anti-GBM disease was higher than the background population [ARR 5.27 (CI 2.45-11.3, P< 0.001)] and comparable to patients with incident ANCA-associated vasculitis (AAV) dependent on dialysis at day 30 after first day of admission [ARR 0.82 (CI 0.48-1.41, P= 0.50)] (figure 1).

Conclusion: Incidence of anti-GBM disease increased over the test period, possibly related to temporal demographic changes, as incidence increased with older age. Mortality remained high and was comparable with an age- and sex-matched cohort of dialysis-dependent AAV patients.

Disclosures: None

Figure 1. Incidence and mortality in anti-GBM disease during 1998-2018