Clinicopathologic Characteristics of Focal Crescentic Anti-GBM Disease

Background: Anti-Glomerular Basement Membrane (Anti-GBM) disease is a rare crescentic glomerulonephritis (CGN) that manifests as a rapidly progressive glomerulonephritis or pulmonary-renal syndrome. Histologically, it shows a diffuse CGN in 93% of patients with an average of 72-84% glomeruli with crescents. Occasional renal biopsies show a focal CGN (<50% of crescents ± fibrinoid necrosis). The clinicopathologic and prognostic significance of focal CGN has not been well-described. Methods: The study included a total of 74 cases of anti-GBM disease between 2001-2020, including 37 focal CGN and 37 cases of diffuse CGN. We compared demographics, clinical information, and biopsy findings. We used data from the United States Renal Data System (USRDS) to identify patients with end stage kidney disease (ESKD). T-tests and Chi-Square analysis were used to examine differences between groups. Results: Of 379 cases of anti-GBM disease, focal CGN was found in 9.8%. Lung involvement was present in 22% in focal group CGN and 27% of diffuse CGN. The focal group had a lower mean creatinine (4.2 vs. 9.6 mg/dL, p< .00001). On average the focal group had 30% glomeruli involved with crescents ± fibrinoid necrosis, compared to 89% in diffuse CGN. Fibrinoid necrosis was identified in 70% of focal CGN and 92% in diffuse CGN. A trend toward increased interstitial fibrosis and tubular atrophy was seen in diffuse CGN (25.2% vs. 16.7%, p=0.37). Follow up data from the USRDS showed a significantly lower frequency of ESKD progression in those with focal CGN (8.1% vs. 70.3% of diffuse CGN, p<.00001). There was a trend towards increased dual ANCA involvement in focal CGN (21.6% vs. 13.5%, p=0.54). Conclusion: Our study is the first known study to characterize focal anti-GBM disease. Prognosis of anti-GBM disease is significantly influenced by the percentage of crescents involved.Focal and diffuse crescentic glomerulonephritis with anti-GBM disease.