Glomerular crescents with IgA-deposits, ANCA, infection - unraveling the diagnostic conundrum.

IntroductionGlomerulonephritis (GN) with crescents and IgA deposits on kidney biopsy poses a frequent diagnostic and therapeutic dilemma because of multiple possibilities. MethodsNative 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. ResultsA 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). ConclusionDiagnostic 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.