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Article ; Online: Machine Learning Illuminates the Extraglomerular Microvasculature.

Kung, Vanderlene L / Nelson, Jonathan W

Kidney360

2023 Volume 4, Issue 5, Page(s) 578–579

MeSH term(s)	Kidney Glomerulus ; Glomerular Mesangium ; Microvessels ; Machine Learning
Language	English
Publishing date	2023-06-29
Publishing country	United States
Document type	Editorial ; Comment
ISSN	2641-7650
ISSN (online)	2641-7650
DOI	10.34067/KID.0000000000000111
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Article ; Online: NELL1 membranous nephropathy: clinical associations provide mechanistic clues.

Andeen, Nicole K / Kung, Vanderlene L / Avasare, Rupali S

Frontiers in nephrology

2024 Volume 4, Page(s) 1323432

Abstract: Neural epidermal growth factor-like 1 (NELL1) membranous nephropathy (MN) is notable for its segmental deposit distribution, IgG1 dominant deposits, and comparatively high rate of spontaneous remission. It has been associated with a variety of exposures ... ...

Abstract	Neural epidermal growth factor-like 1 (NELL1) membranous nephropathy (MN) is notable for its segmental deposit distribution, IgG1 dominant deposits, and comparatively high rate of spontaneous remission. It has been associated with a variety of exposures and secondary conditions, specifically use of thiol-containing medications - including lipoic acid, bucillamine, and tiopronin - as well as traditional indigenous medications (TIM) particularly those with high mercury content, and non-steroid anti-inflammatory drugs (NSAIDs). Malignancies, graft
Language	English
Publishing date	2024-03-26
Publishing country	Switzerland
Document type	Journal Article ; Review
ISSN	2813-0626
ISSN (online)	2813-0626
DOI	10.3389/fneph.2024.1323432
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Article ; Online: Kidney Histopathology of Patients with Hepatitis C Infection and Diabetes Mellitus before and after Availability of Direct-Acting Antiviral Therapy.

Kung, Vanderlene L / Giannini, Gabriel / Nast, Cynthia C

Glomerular diseases

2024 Volume 4, Issue 1, Page(s) 74–83

Abstract: Introduction: Type 2 diabetes mellitus (DM) and diabetic kidney disease are increasing. Hepatitis C infection (HCV) occurs in 1% of the world population and can induce several kidney diseases. DM prevalence is increased in individuals with HCV; however, ...

Abstract	Introduction: Type 2 diabetes mellitus (DM) and diabetic kidney disease are increasing. Hepatitis C infection (HCV) occurs in 1% of the world population and can induce several kidney diseases. DM prevalence is increased in individuals with HCV; however, kidney diseases in those with both DM and HCV have not been assessed. Direct-acting antiviral agents (DAAs) became available for HCV treatment in 2014; it is unknown if DAAs altered the spectrum of kidney disease in patients with DM and HCV. Methods: Case review identifying patients with kidney biopsy and clinical history of DM and HCV between 2009-2013 (pre-DAA) and 2016-2020 (post-DAA), excluding kidney transplant, hepatitis B, HIV, and inadequate biopsy, identified 245 biopsies. Biopsies were evaluated for diabetic glomerulosclerosis (DGS) class, global and focal segmental glomerulosclerosis (FSGS), other glomerular diseases, interstitial fibrosis/tubular atrophy (IFTA), interstitial nephritis, acute tubular injury and degree of arterial and arteriolar sclerosis. Kidney disease differences in pre-DAA versus post-DAA eras and in mild versus severe DGS were assessed by χ Results: The most common non-DGS lesions were non-collapsing FSGS (41%), HCV-related IgM dominant immune complex glomerulonephritis (IgM-ICGN, 18%), IgA nephropathy (9%), and membranoproliferative glomerulonephritis (MPGN, 7%). Collapsing FSGS was more common pre-DAA versus post-DAA (8% vs. 1%, Conclusion: Post-DAA there were reduced biopsies and MPGN, with more severe DGS class, non-collapsing FSGS, IFTA, and chronic vascular changes. This suggests a modulating effect of DAAs on HCV-related kidney pathology with DM and chronic changes driving indications for kidney biopsy.
Language	English
Publishing date	2024-03-15
Publishing country	Switzerland
Document type	Journal Article
ISSN	2673-3633
ISSN (online)	2673-3633
DOI	10.1159/000537977
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Article ; Online: ANCA-associated kidney disease preceded by orbital pseudotumor.

Oleson, Ileisa / Fecker, Adeline / Richardson, Kelsey / Bauer, Abbie / Andeen, Nicole K / Kung, Vanderlene L

Pediatric nephrology (Berlin, Germany)

2023 Volume 39, Issue 3, Page(s) 741–744

Abstract: Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and IgG4-related disease (IgG4-RD) are distinct immune disorders with overlapping clinical and laboratory features. While ANCA positivity excludes IgG4-RD in the 2019 ... ...

Abstract	Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and IgG4-related disease (IgG4-RD) are distinct immune disorders with overlapping clinical and laboratory features. While ANCA positivity excludes IgG4-RD in the 2019 ACR/EULAR classification, this criterion is not uniformly applied, and AAV can form inflammatory masses in various organs and show increase in IgG4 + plasma cells, similar to IgG4-RD. Case diagnosis/treatment: A 5-year-old female with history of orbital mass diagnosed as IgG4-RD presents with acute kidney injury. She has a myeloperoxidase ANCA, and kidney biopsy shows pauci-immune crescentic glomerulonephritis and acute tubulointerstitial nephritis with increased IgG4 + plasma cells and tubular basement membrane (TBM) deposits. Conclusion: In isolation, TBM deposits and increased IgG4 + plasma cells are suggestive of IgG4-RD. In the context of a positive ANCA and pauci-immune crescentic glomerulonephritis, however, increased IgG4 + plasma cells due to AAV are favored. In cases with features of IgG4-RD, ANCA positivity suggests an alternate diagnosis of AAV to be more likely.
MeSH term(s)	Female ; Humans ; Child, Preschool ; Antibodies, Antineutrophil Cytoplasmic ; Orbital Pseudotumor/pathology ; Immunoglobulin G4-Related Disease/diagnosis ; Kidney/pathology ; Nephritis, Interstitial/complications ; Nephritis, Interstitial/diagnosis ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis ; Immunoglobulin G ; Glomerulonephritis/complications ; Glomerulonephritis/diagnosis
Chemical Substances	Antibodies, Antineutrophil Cytoplasmic ; Immunoglobulin G
Language	English
Publishing date	2023-10-19
Publishing country	Germany
Document type	Case Reports ; Journal Article
ZDB-ID	631932-4
ISSN	1432-198X ; 0931-041X
ISSN (online)	1432-198X
ISSN	0931-041X
DOI	10.1007/s00467-023-06172-w
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Article ; Online: Letter regarding:

Park, Ken / Miyake, Scott / Tai, Cynthia / Tseng, Mindy / Andeen, Nicole K / Kung, Vanderlene L

Kidney international reports

2021 Volume 6, Issue 8, Page(s) 2246–2247

Language	English
Publishing date	2021-06-19
Publishing country	United States
Document type	Journal Article
ISSN	2468-0249
ISSN (online)	2468-0249
DOI	10.1016/j.ekir.2021.06.007
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Article ; Online: Chronic active T cell-mediated rejection is variably responsive to immunosuppressive therapy.

Kung, Vanderlene L / Sandhu, Rana / Haas, Mark / Huang, Edmund

Kidney international

2021 Volume 100, Issue 2, Page(s) 391–400

Abstract: Chronic active T cell-mediated rejection (CA TCMR) is a newly described variant of kidney allograft rejection associated with long-term graft loss. Whether this form of rejection is related to under immunosuppression is debated and the benefit of ... ...

Abstract	Chronic active T cell-mediated rejection (CA TCMR) is a newly described variant of kidney allograft rejection associated with long-term graft loss. Whether this form of rejection is related to under immunosuppression is debated and the benefit of immunosuppressive therapy in CA TCMR is unknown. Here we investigate the amenability of CA TCMR to treatment and examine the impact of clinical, histologic, and molecular parameters on outcomes. In a retrospective single institution review, we identified 48 cases of isolated CA TCMR, of which 44 were treated with pulse steroids or anti-thymocyte globulin, or both. Defining treatment response as an at least 50% estimated glomerular filtration rate recovery, a response was achieved in 20% of cases at four weeks post initiation of immunosuppressive therapy. Treatment responsiveness did not reflect the presence of concomitant acute T cell-mediated rejection, and was not significantly different between cases with mild, moderate, and severe parenchymal scarring. Although not statistically significant, there was a trend toward greater treatment responsiveness in cases with moderate as opposed to severe tubulitis. By targeted transcriptional profiling, increased allograft mast cells and alterations in lipid metabolism were identified as possible features of treatment resistant CA TCMR. Thus, our study shows that although its prognosis is generally poor, CA TCMR is not a homogenous entity and in a subset of cases, improvement in kidney function can be achieved with immunosuppressive therapy.
MeSH term(s)	Graft Rejection/drug therapy ; Graft Rejection/prevention & control ; Graft Survival ; Immunosuppression ; Kidney Transplantation/adverse effects ; Retrospective Studies ; T-Lymphocytes
Language	English
Publishing date	2021-04-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1016/j.kint.2021.03.027
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Article ; Online: Fibrillary Glomerulonephritis, DNAJB9, and the Unfolded Protein Response.

Andeen, Nicole K / Kung, Vanderlene L / Robertson, Josh / Gurley, Susan B / Avasare, Rupali S / Sitaraman, Sneha

Glomerular diseases

2022 Volume 2, Issue 4, Page(s) 164–175

Abstract: Background: Fibrillary glomerulonephritis (FGN) is found in approximately 1% of native kidney biopsies and was traditionally defined by glomerular deposition of fibrils larger than amyloid (12-24 nm diameter) composed of polyclonal IgG. Recent ... ...

Abstract	Background: Fibrillary glomerulonephritis (FGN) is found in approximately 1% of native kidney biopsies and was traditionally defined by glomerular deposition of fibrils larger than amyloid (12-24 nm diameter) composed of polyclonal IgG. Recent identification of DNAJB9 as a sensitive and specific marker of FGN has revolutionized FGN diagnosis and opened new avenues to studying FGN pathogenesis. In this review, we synthesize recent literature to provide an updated appraisal of the clinical and pathologic features of FGN, discuss diagnostic challenges and pitfalls, and propose molecular models of disease in light of DNAJB9. Summary: DNAJB9 tissue assays, paraffin immunofluorescence studies, and IgG subclass testing demonstrate that FGN is distinct from other glomerular diseases with organized deposits and highlight FGN morphologic variants. Additionally, these newer techniques show that FGN is only rarely monoclonal, and patients with monoclonal FGN usually do not have a monoclonal gammopathy. Key messages: DNAJB9 aids in distinguishing FGN from other glomerular diseases with organized deposits. Further investigations into the role of DNAJB9 in FGN pathogenesis are necessary to better understand disease initiation and progression and to ultimately develop targeted therapies.
Language	English
Publishing date	2022-06-16
Publishing country	Switzerland
Document type	Journal Article ; Review
ISSN	2673-3633
ISSN (online)	2673-3633
DOI	10.1159/000525542
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Article ; Online: Targeted Transcriptional Analysis of IgA Vasculitis, IgA Nephropathy, and IgA-Dominant Infection-Related Glomerulonephritis Reveals Both Distinct and Overlapping Immune Signatures.

Kung, Vanderlene L / Avasare, Rupali / Friedman, Marcia A / Koon, Stephanie Mengden / Neff, Tanaya L / Protzek, Sara / Corless, Christopher / Krajbich, Victoria / Setthavongsack, Naly / Ditmore, Rebecca / Woltjer, Randall / Andeen, Nicole K

Kidney360

2023 Volume 4, Issue 6, Page(s) e759–e768

MeSH term(s)	Humans ; Glomerulonephritis, IGA/genetics ; IgA Vasculitis ; Immunoglobulin A
Chemical Substances	Immunoglobulin A
Language	English
Publishing date	2023-04-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2641-7650
ISSN (online)	2641-7650
DOI	10.34067/KID.0000000000000123
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Article ; Online: Characteristics and Outcomes of NELL1 Membranous Nephropathy in Lipoic Acid Users and Nonusers.

Avasare, Rupali S / Clark, Samantha / Spain, Rebecca I / Wusirika, Raghav / Rope, Robert / Gurley, Susan / Stanaway, Madison / Sekulic, Miroslav / Santoriello, Dominick / Bomback, Andrew S / Canetta, Pietro / Iyer, Sitalakshmi J / Kung, Vanderlene / Charu, Vivek / Troxell, Megan L / Kudose, Satoru / Andeen, Nicole K

Kidney international reports

2024 Volume 9, Issue 5, Page(s) 1379–1386

Abstract: Introduction: Neural epidermal growth factor like 1 membranous nephropathy (NELL1 MN) is associated with various secondary etiologies. However, previous studies on the frequency of these associations and their impact on outcomes are limited. We report a ...

Abstract	Introduction: Neural epidermal growth factor like 1 membranous nephropathy (NELL1 MN) is associated with various secondary etiologies. However, previous studies on the frequency of these associations and their impact on outcomes are limited. We report a large multiinstitutional series of patients with NELL1 MN with a focus on secondary associations, pathology findings, and their impact on outcome. Methods: We retrospectively reviewed clinicopathologic features of NELL1 MN from 3 institutions and analyzed clinical and histologic associations with outcome. Results: Of 70 patients, 53% were male with a median age of 66 years; median proteinuria was 5.9 g/d. NELL1 MN was associated with lipoic acid (36%), heavy nonsteroidal antiinflammatory drug (NSAID) use (27%), autoimmune disease (23%), malignancy (10% recent, 23% any), mercury exposure (1%), and 11% had no known secondary association. At median follow-up of 11 months, 72% achieved complete or partial remission. Remission rate was 91% in patients with lipoic acid-associated NELL1 MN and ≥6 months of follow-up. On multivariable analyses, patients with primary NELL1 MN (adjusted odds ratio [OR]: 19.7, Conclusion: Our findings strengthen the association between lipoic acid and NELL1 MN. Furthermore, our findings suggest that discontinuation of lipoic acid without immunosuppression should be considered as the first-line treatment.
Language	English
Publishing date	2024-02-24
Publishing country	United States
Document type	Journal Article
ISSN	2468-0249
ISSN (online)	2468-0249
DOI	10.1016/j.ekir.2024.02.1401
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Article ; Online: AA amyloidosis With Ig-Dominant Staining and Diagnostically Unusual Features.

Andeen, Nicole K / DiFranza, Lanny / Kung, Vanderlene L / Henriksen, Kammi / Gupta, Renu / Dinesh, Kumar / Akilesh, Shreeram / Kudose, Satoru / Smith, Kelly D / Troxell, Megan L

Kidney international reports

2023 Volume 9, Issue 1, Page(s) 162–170

Abstract: Introduction: Although serum amyloid A (AA) amyloid may occasionally show nonspecific staining by immunofluorescence (IF), the correct diagnosis can usually be determined by integrating pathologic features and clinical scenario, and using AA amyloid ... ...

Abstract	Introduction: Although serum amyloid A (AA) amyloid may occasionally show nonspecific staining by immunofluorescence (IF), the correct diagnosis can usually be determined by integrating pathologic features and clinical scenario, and using AA amyloid immunohistochemistry (IHC) and/or mass spectrometry. A recent mass spectrometry-based study described false-positive Ig IF staining in a subset of AA amyloid cases. Methods: We sought to delineate clinicopathologic features of AA amyloid with Ig-dominant staining by using a retrospective review. Results: AA amyloid with Ig-dominant staining was identified in 10 patients from 5 institutions, representing 1.2% to 4% of AA amyloid kidney biopsies. Evidence of a monoclonal protein was documented in 0% to 2.7% of patients with AA amyloid screened for inclusion, but 30% of those with Ig-dominant staining. The patient population had equal sex distribution and presented at median age of 68.5 years with nephrotic proteinuria and kidney impairment. Etiologies of AA amyloid included injection drug use (30%), autoimmune disease (20%), and chronic infection (10%); 40% had no identified clinical association. On biopsy, heavy chain (co)dominant staining by IF (in 80%), discordant distribution in Ig staining (in 20%), tubulointerstitial nephritis (in 30%), and/or crescents (in 10%) were present. Two of 3 patients with paraproteinemia had concordant heavy and/or light chain dominant staining within the AA amyloid. Two cases were initially misdiagnosed as Ig-associated amyloidosis. Conclusion: We describe the morphologic spectrum of AA amyloidosis with Ig-dominant staining which may have clinical, laboratory, and pathologic overlap with amyloid light chain (AL), amyloid heavy chain, and heavy and light chain (AHL) amyloidosis.
Language	English
Publishing date	2023-10-17
Publishing country	United States
Document type	Journal Article
ISSN	2468-0249
ISSN (online)	2468-0249
DOI	10.1016/j.ekir.2023.10.005
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