#2842 Increased incidence of anti-glomerular basement membrane disease in Madrid in the past two decades
Authors: León-Machado Lina María , Sierra-Torres Gonzalo , Shabaka Amir , Corona Clara Maria Cases , Vega-Cabrera Cristina , Rivas-Becerra Begoña , Juarez Gema Maria Fernandez 
Published: May 2024

Abstract

Background and Aims
Recently, epidemiological changes have been identified in the incidence of anti-glomerular basement membrane (GBM) in different European regions, reporting an increased incidence in population-based studies in Ireland and Denmark, possibly due to demographic changes and exposure to environmental triggers, since the evidence of spatial and temporal clustering of cases suggests that environmental factors could be playing a role in this trend. The aim of our study was to evaluate the changes in incidence of anti-GBM disease in the past two decades in two different urban areas in Madrid (North and Southwest), identify possible environmental triggers, and analyse temporal and within-area differences in presentation and outcome of the disease.

Method
We performed a retrospective observational study using data between 2006 and 2022 from the hospital coding databases and laboratory databases of two hospitals in Madrid covering a population of 884000 residents. We collected data from patients who were diagnosed with anti-GBM disease with confirmed positive anti-GBM antibodies and renal and/or pulmonary manifestations. We excluded patients with positive anti-GBM antibodies without clinical manifestations suggestive of the disease. Incidence was described as per 100000 person-years at risk, and 95% confidence intervals were computed assuming a Poisson distribution. In order to detect changes in incidence, we divided the analysis into three time periods: 2006-2010, 2011-2016 and 2017-2022. We also compared the incidence before and after the onset of COVID-19 pandemic in Madrid (March 2020). Demographic data, clinical data at presentation, previous exposure to environmental factors (smoking, exposure to hydrocarbons, infections, vaccination), and treatments received and outcome was collected. Renal survival was defined as a state free from renal replacement therapy.

Results
During the 17-year study period, 26 cases of anti-GMN disease were identified (incidence rate 2.94 per 100000 persons); with a mean age of 52 ± 26 years at presentation, and 53.6% were females. 30.8% of patients were double-seropositive for ANCA and anti-GBM, 42.3% presented only renal involvement, 3.8% with only pulmonary involvement, and 53.8% with both renal and pulmonary involvement. At presentation, 19.2% of patients required mechanical ventilation and 65.4% required renal replacement therapy. After induction treatment, 13 patients (50%) remained on maintenance dialysis. After a median follow-up of 33 months, 46.2% patients died. Renal and patient survival after 1 year was 30.8% and 73.1% respectively.
The incidence rate gradually increased from time periods 2006-2010 to 2017-2022, from 1.81 cases per 100000 persons (CI95% 0.78-3.57) to 2.83 cases per 100000 persons (CI95% 1.58-4.66) (OR 1.56, CI95%0.66-3.69, p = 0.30). We observed that the incidence rate significantly increased from 1.13 cases per 100000 persons (95% CI 0.62-1.90) before March 2020 to 4.53 cases per 100000 persons (95% CI 2.34-7.90) after the onset of the COVID-19 pandemic (OR 4, P &lt; 0.001). Serum creatinine at presentation was significantly lower in cases diagnosed after COVID-19 (5.09 ± 4 vs 8.7 ± 3.9 mg/dl, p = 0.037). We found no differences within time periods in demographic data, previous exposure to environmental triggers, presence of double-seropositivity, or treatments received or patient survival after 1 year. However, we found that renal survival after 1 year has improved from 0% in 2006-2010 to 46.7% in 2017-2022 (p = 0.023) and 14.3% pre-COVID to 50% post-COVID (p = 0.049).

Conclusion
There is a gradual increase in the incidence rate of anti-GBM disease in our population, which has markedly increased after the COVID-19 pandemic, with a significantly lower serum creatinine at presentation with improved renal survival. We did not find any changes in the rate of exposure to known environmental triggers within time periods. These findings suggest that the rising incidence may be attributable to an increased awareness and diagnosis of anti-GBM disease, which leads to a better renal survival.