Journal of Nephrology Advances

Journal of Nephrology Advances

Current Issue Volume No: 1 Issue No: 4

Case-report Article Open Access
  • Available online freely Peer Reviewed

  • Primary Membranous Nephropathy Flare After COVID-19 Vaccination

    1 Department of Medicine, Division of Nephrology and Hypertension, Jared Grantham Kidney Institute, University of Kansas Medical Center, USA 

    2 Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh Medical Center, USA 

    3 Department of Pathology, University of Pittsburgh Medical Center, USA 

    Abstract

    Primary membranous nephropathy (MN) is due to autoantibodies to phospholipase A2 receptor (PLA2R Ab). It is unclear whether COVID-19 vaccines can trigger flares of glomerular diseases such as primary MN. There have been increasing reports of glomerular diseases presenting or flaring after receipt of COVID-19 vaccines. We present a patient with primary MN who developed nephrotic syndrome after receiving her second mRNA-1273 COVID-19 vaccine with positive PLA2R Ab. Renal biopsy confirmed primary MN. She was treated for her primary MN flare with rituximab in a manner similar to non-vaccine-associated MN, which led to significant reduction in both PLA2R Ab level and proteinuria. This case adds to the growing literature on MN flares after receipt of mRNA COVID-19 vaccines. Close follow-up of patients with primary MN and other glomerular diseases after COVID-19 vaccination is warranted. Further research is needed to determine the pathophysiology behind vaccine-induced MN flares and whether there is a potential association between exposure to SARS-CoV-2 antigens and loss of tolerance to the PLA2R antigen.
    Author Contributions
    Received Jul 31, 2024     Accepted Aug 28, 2024     Published Sep 05, 2024

    Copyright© 2024 V. Liang Kelly, et al.
    License
    Creative Commons License   This work is licensed under a Creative Commons Attribution 4.0 International License. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

    Competing interests

    The authors declare that they have no competing interests.

    Funding Interests:

    Citation:

    V. Liang Kelly, B. Ahmad Syeda, C. Kurtz Elizabeth, Pittappilly Matthew, I. Minervini Marta et al. (2024) Primary Membranous Nephropathy Flare After COVID-19 Vaccination Journal of Nephrology Advances. - 1(4):12-18
    DOI 10.14302/issn.2574-4488.jna-24-5219

    Introduction

    Introduction

    Primary membranous nephropathy (MN) is most commonly due to phospholipase A2 receptor antibodies (PLA2R Ab). It is unclear whether the COVID-19 vaccine can trigger flares of glomerular diseases such as primary MN. Recently, there have been increasing reports of MN either presenting de novo or flaring after receipt of a COVID-19 vaccine. We present a patient with MN and metastatic breast cancer who developed nephrotic syndrome after receiving her second mRNA-1273 COVID-19 vaccine with positive PLA2R Ab suggesting primary MN flare. The objectives of this case report include: 1) To raise awareness of the risk for relapse of primary MN after mRNA COVID-19 vaccination; and 2) To review the literature on the association between COVID-19 vaccines and glomerular disorders.

    Discussion

    Discussion

    There is insufficient data on the risk of flares after COVID-19 vaccines in glomerular diseases. Autoimmunity may be triggered by vaccines, including flares of autoimmune glomerulonephritis (GN). MN has been reported following administration of the influenza vaccine. 12 Increasingly, both de novo and relapse of pre-existing GN s have been reported after COVID-19 messenger RNA (mRNA) vaccines (Moderna mRNA-1273 and Pfizer-BioNTech BNT162b2). These cases are quite rare, and a causal link between COVID-19 vaccines and GN s is not firmly established. Although temporal association does not prove causality, these cases suggest immune-mediated GN flares may be induced by COVID-19 vaccines.

    The following de novo glomerular diseases have been described following COVID-19 vaccination 3:

    IgA nephropathy (IgAN)45

    Anti-neutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV)6789

    Minimal change disease (MCD)310

    Primary membranous nephropathy (MN)1112

    Anti-glomerular basement membrane (anti-GBM) disease3

    The following relapsedglomerular diseases have been reported following COVID-19 vaccination3:

    IgAN

    MCD

    Primary MN13

    Complement-mediated thrombotic microangiopathy

    IgG4-related disease (IgG4RD)

    Lupus nephritis (LN) class V

    Scleroderma renal crisis

    Summaries of reported cases of kidney diseases linked to COVID-19 vaccination have been published. 1415 The number of reported cases likely is an underestimate of true cases. Flares of glomerular diseases have long been reported in association with other vaccines. Examples include MCD after influenza, pneumococcal, smallpox, hepatitis B, and Tdap vaccines; vasculitis after influenza vaccine; and IgAN after recombinant zoster vaccine (Shingrix).15 Therefore, it is not surprising to find GN s following COVID-19 vaccines.

    The pathogenesis of vaccine-associated glomerular diseases is unclear, particularly for the COVID-19 mRNA vaccines, which utilize either a lipid nanoparticle (Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273 vaccines) or an adenoviral vector (AstraZeneca) for mRNA delivery. The mRNA vaccines induce the recipient s cells to synthesize the COVID-19 spike protein via transcription of the injected mRNA. The immune response to vaccination involves both B and T cells. T cell responses, including T follicular helper (Tfh) cells, are stimulated by the lipid nanoparticle-mRNA vaccines. T-cell responses to foreign mRNA provoke swift production of cytokines, which could trigger podocytopathies and augment B-cell production of antibodies and glomerular diseases (e.g., MN).15

    Different immune mechanisms may play prominent roles in different glomerular diseases following vaccination. It appears that onset of IgAN following COVID-19 vaccination occurs within 1-2 days. In these cases, COVID-19 vaccines may stimulate gut-associated lymphoid tissue (Peyer patches) responsible for IgA1 production, as IgA1 hyperresponsiveness has been observed in IgAN after influenza vaccination.14 In contrast, onset of MCD, MN, AAV, anti-GBM disease, and IgG4RD following COVID-19 vaccination occurs around 7-14 days later.1415 The COVID-19 mRNA vaccines trigger Tfh responses that peak 7 days after immunization. The later presentation of MN, including our case which presented 2 weeks after the second COVID-19 vaccine, may be due to induction of vaccine-associated autoimmunity via antigen-specific and nonspecific mechanisms.14 The pathophysiologic mechanism behind MN and COVID-19 vaccination requires further study. Furthermore, other confounding factors could also potentially play a role in the risk of MN flare after vaccination. Examples of these confounders include alternative infections (e.g., other upper respiratory viruses or bacterial infections that happen to be present at the time of vaccination), genetic predisposition to autoimmune conditions, or underlying malignancy which may itself cause activation of the immune system.

    This case of primary MN flare is only the second reported case of relapse of MN after mRNA COVID-19 vaccination. Only three total cases of MN after COVID-19 vaccination have been reported (two de novo and one relapse). 111213 Our case adds to the literature supporting this association between MN and COVID-19 vaccination. Most cases of glomerular diseases after COVID-19 vaccination have been reported for MCD and IgAN, but there is a growing number of MN, AAV and other GN s. Interestingly, only one case of LN (class V) has been reported, despite cytokine profiles after vaccination being similar to those from lupus patients (IFN-α, IL-6 and TNF-α).14 Clinicians should become more aware of the association between vaccination and GN flares, even if patients were in remission for a prolonged time.

    Our patient was treated for her primary MN flare with rituximab in a manner similar to non-vaccine-associated MN. Like other reported cases, immunosuppression led to reduced proteinuria and decreased PLA2R Ab significantly. Therefore, close monitoring of patients with MN or other GN s after mRNA COVID-19 vaccination is warranted to allow early treatment to prevent progression to chronic kidney disease or end-stage renal disease.

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