The Diagnostic Conundrum of Glomerular Crescents With IgA Deposits

Mineaki Kitamura; Salem Almaani; Bindu Challa; Mohankumar Doraiswamy; Isabelle Ayoub; Laura Biederman; Samir V Parikh; Ana Molovic-Kokovic; Jason Benedict; Nilesh Mhaskar; Zeid J Khitan; Sergey V Brodsky; Tibor Nadasdy; Anjali A Satoskar

doi:10.1016/j.ekir.2022.12.024

The Diagnostic Conundrum of Glomerular Crescents With IgA Deposits

Kidney Int Rep. 2022 Dec 31;8(3):507-518. doi: 10.1016/j.ekir.2022.12.024. eCollection 2023 Mar.

Authors

Affiliations

¹ Division of Renal and Transplant Pathology, Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
² Department of Nephrology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
³ Division of Nephrology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
⁴ Department of Medicine, Mercy Hospital, Fort Smith, Arkansas, USA.
⁵ Rochester General Hospital, Rochester, New York, USA.
⁶ Center for Biostatistics, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
⁷ Kettering Health, Kettering, Ohio, USA.
⁸ Marshall University School of Medicine, Huntington, West Virginia, USA.

Abstract

Introduction: Glomerulonephritis (GN) with crescents and IgA deposits in kidney biopsy poses a frequent diagnostic and therapeutic dilemma because of multiple possibilities.

Methods: Native kidney biopsies showing glomerular IgA deposition and crescents (excluding lupus nephritis) were identified from our biopsy archives between 2010 and 2021. Detailed clinicopathologic features were assessed. One-year clinical follow-up on a subset of cases was obtained.

Results: A total of 285 cases were identified, and these clustered into IgA nephropathy (IgAN, n = 108), Staphylococcus or other infection-associated GN/infection-related GN (SAGN/IRGN, n = 43), and antineutrophil cytoplasmic antibody-associated GN (ANCA-GN, n = 26) based on a constellation of clinicopathologic features, but 101 cases (group X) could not be definitively differentiated. The reasons have been elucidated, most important being atypical combination of clinicopathologic features and lack of definitive evidence of active infection. Follow-up (on 72/101 cases) revealed that clinicians' working diagnosis was IgAN in 43%, SAGN/IRGN in 22%, ANCA-GN in 28%, and others in 7% of the cases, but treatment approach varied from supportive or antibiotics to immunosuppression in each subgroup. Comparing these cases as "received immunosuppression" versus "non-immunosuppression," only 2 features differed, namely C3-dominant staining, and possibility of recent infection (both higher in the no-immunosuppression group) (P < 0.05). Renal loss was higher in the non-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.

Keywords: ANCA vasculitis; Staphylococcus infection–associated glomerulonephritis; crescentic necrotizing glomerulonephritis; immunoglobulin A nephropathy.