Gross Hematuria Following Vaccination for SARS-CoV2 in Two Patients with IgA Nephropathy

Abstract

To the Editor: Several of the SARS-CoV2 vaccines use a nucleoside-modified, purified mRNA lipid nanoparticle-encapsulated platform. Compared to traditional inactivated viral and adjuvanted protein vaccines, this RNA platform elicits far higher neutralizing antibody titers, stronger antigen-specific CD4+ and CD8+ T cells responses, and stronger germinal center B and TFH cell activation in experimental animals 1 . The activated CD4+ and CD8+ T cells produce several proinflammatory cytokines, including interferon-γ and tumor necrosis factor-α. This led us to wonder if these vaccines may activate or exacerbate immune-mediated glomerular diseases. Two individuals with biopsy-proven IgA nephropathy (IgAN) developed gross hematuria shortly following the second dose of the Moderna vaccine. The patients are described in the Table . At baseline, both had proteinuria below 1 gram/day and well-preserved kidney function. Several hours after the second dose of vaccine was given, both developed systemic symptoms ranging from body aches, headache, and fatigue to fever and chills. Between 8 and 24 hours after systemic symptoms appeared, the patients noticed gross hematuria that resolved after 3 days. Serum creatinine did not increase, but proteinuria increased in one patient (Table). Although we did not expect an exacerbation of IgAN after a non-mucosal immune challenge, IgAN patients have previously been reported to have a stronger IgA1 (albeit monomeric) response to intramuscular influenza vaccine than healthy subjects 2 . These episodes of apparent IgAN exacerbation should prompt the nephrology community to closely follow their patients with glomerular disease post SAR2-CoV2 vaccination to determine the frequency and consequences of vaccine-induced disease activation. Table 1 Patient Demographics and Clinical Characteristics Patient Age Sex Race Year IgAN diagnosed Treatment Gross hematuria events during disease course Persistent microscopichematuria ProteinuriaIn 2020 Proteinuria between SARS-Cov2 vaccine doses Proteinuria 3 weeks after last SARS-CoV2 vaccine dose 1 38 F 1 W 2005 RAASi At presentation;During one episode of gastroenteritis;Occasionally after yearly influenzavaccine Yes 0.63 g/d 0.82 g/d 1.40 g/d 2 38 F W 2019 Cyc+Pred (6 months) then RAASi At presentation only Yes 0.43 g/d 0.59 g/d 0.40 g/d 1Abbreviations: F, female; W, white; RAASi, renin-angiotensin-aldosterone system inhibitor; Cyc, cyclophosphamide; Pred, prednisone; g/d, grams/day