Glomerular crescents, IgA-deposits, ANCA, infection – unravelling the diagnostic conundrum

Abstract

Introduction: Glomerulonephritis (GN) with crescents and IgA deposits on kidney biopsy poses a frequent diagnostic and therapeutic dilemma because of multiple possibilities. Methods: Native kidney biopsies showing IgA deposition and crescents (excluding lupus nephritis) were identified from our biopsy archives between January 2010 and December 2021. Detailed clinico-pathologic features were assessed. One-year clinical follow-up on a subset of cases was performed. Results: A total of 285 cases were identified and these clustered into IgA nephropathy (IgAN, n=108), Staphylococcus or other infection-associated-GN (SAGN/IRGN, n=46), and anti-neutrophil cytoplasmic antibody associated-GN (ANCA-GN, n=24) based on constellation of clinico-pathologic features, but 101 cases (Group X) could not be definitively differentiated. The reasons have been elucidated, most important being atypical combination of clinico-pathologic features and lack of definitive evidence of active infection. Follow-up (on 72/101 cases), revealed that clinicians' working diagnosis was IgAN in 42%, SAGN/IRGN in 24%, ANCA-GN in 24%, and others in 7% of the cases, but treatment approach varied from supportive/antibiotics to immunosuppression in each subgroup. Comparing these cases as - received immunosuppression versus no-immunosuppression, only two features - C3-dominant staining; and possibility of recent infection differed (higher in the no-immunosuppression group [p<0.05]). Renal loss was higher in the no-immunosuppression subgroup, but not statistically significant (p=0.11). Conclusion: Diagnostic overlap may remain unresolved in a substantial number of kidney biopsies with glomerular crescents and IgA deposits. A case-by-case approach, appropriate antibiotics if infection is ongoing, and consideration for cautious immunosuppressive treatment for progressive renal dysfunction may be needed for best chance of renal recovery.