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      The Diagnostic Conundrum of Glomerular Crescents With IgA Deposits

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          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.

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          Most cited references45

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          Oxford Classification of IgA nephropathy 2016: an update from the IgA Nephropathy Classification Working Group.

          Hernán Trimarchi, Jonathan Barratt, Daniel C. Cattran … (2017)
          Since the Oxford Classification of IgA nephropathy (IgAN) was published in 2009, MEST scores have been increasingly used in clinical practice. Further retrospective cohort studies have confirmed that in biopsy specimens with a minimum of 8 glomeruli, mesangial hypercellularity (M), segmental sclerosis (S), and interstitial fibrosis/tubular atrophy (T) lesions predict clinical outcome. In a larger, more broadly based cohort than in the original Oxford study, crescents (C) are predictive of outcome, and we now recommend that C be added to the MEST score, and biopsy reporting should provide a MEST-C score. Inconsistencies in the reporting of M and endocapillary cellularity (E) lesions have been reported, so a web-based educational tool to assist pathologists has been developed. A large study showed E lesions are predictive of outcome in children and adults, but only in those without immunosuppression. A review of S lesions suggests there may be clinical utility in the subclassification of segmental sclerosis, identifying those cases with evidence of podocyte damage. It has now been shown that combining the MEST score with clinical data at biopsy provides the same predictive power as monitoring clinical data for 2 years; this requires further evaluation to assess earlier effective treatment intervention. The IgAN Classification Working Group has established a well-characterized dataset from a large cohort of adults and children with IgAN that will provide a substrate for further studies to refine risk prediction and clinical utility, including the MEST-C score and other factors.
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            Histopathologic classification of ANCA-associated glomerulonephritis.

            Annelies Berden, Franco Ferrario, E Hagen … (2010)
            Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is the most common cause of rapidly progressive glomerulonephritis worldwide, and the renal biopsy is the gold standard for establishing the diagnosis. Although the prognostic value of the renal biopsy in ANCA-associated glomerulonephritis is widely recognized, there is no consensus regarding its pathologic classification. We present here such a pathologic classification developed by an international working group of renal pathologists. Our classification proposes four general categories of lesions: Focal, crescentic, mixed, and sclerotic. To determine whether these lesions have predictive value for renal outcome, we performed a validation study on 100 biopsies from patients with clinically and histologically confirmed ANCA-associated glomerulonephritis. Two independent pathologists, blinded to patient data, scored all biopsies according to a standardized protocol. Results show that the proposed classification system is of prognostic value for 1- and 5-year renal outcomes. We believe this pathologic classification will aid in the prognostication of patients at the time of diagnosis and facilitate uniform reporting between centers. This classification at some point might also provide means to guide therapy.
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              Rapidly progressive crescentic glomerulonephritis.

              Charles Jennette (2003)
              Article 0 comments Cited 121 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Anjali A. Satoskar
                Journal
                Journal ID (nlm-ta): Kidney Int Rep
                Journal ID (iso-abbrev): Kidney Int Rep
                Title: Kidney International Reports
                Publisher: Elsevier
                ISSN (Electronic): 2468-0249
                Publication date PMC-release: 31 December 2022
                Publication date Collection: March 2023
                Publication date (Electronic): 31 December 2022
                Volume: 8
                Issue: 3
                Pages: 507-518
                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
                Author notes
                [∗ ] Correspondence: Anjali A. Satoskar, Division of Renal and Transplant Pathology, Department of Pathology, The Ohio State University Wexner Medical Center, M015 Starling Loving Hall, 320 West 10th Avenue, Columbus, Ohio 43210, USA. anjali.satoskar@ 123456osumc.edu
                Article
                Publisher Item ID: S2468-0249(22)01920-9
                DOI: 10.1016/j.ekir.2022.12.024
                PMC ID: 10014387
                PubMed ID: 36938067
                SO-VID: f9b7b210-fd01-4bdc-88de-abb80afdf114
                Copyright © © 2022 Published by Elsevier Inc. on behalf of the International Society of Nephrology.
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 9 November 2022
                Date revision received : 21 December 2022
                Date accepted : 22 December 2022
                Categories
                Subject: Clinical Research

                Keywords: anca vasculitis,crescentic necrotizing glomerulonephritis,immunoglobulin a nephropathy,staphylococcus infection–associated glomerulonephritis
                Data availability:
                Keywords: anca vasculitis, crescentic necrotizing glomerulonephritis, immunoglobulin a nephropathy, staphylococcus infection–associated glomerulonephritis

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