Is COVID-19 vaccination unmasking glomerulonephritis?

We read with great interest the reports of macroscopic hematuria occurring hours following coronavirus disease 2019 (COVID-19) vaccination in patients with known IgA nephropathy (IgAN).1Rahim S.E.G. Lin J.T. Wang J.C. et al.A case of gross hematuria and IgA nephropathy flare-up following SARS-CoV-2 vaccination.Kidney Int. 2021; 100: 238Abstract Full Text Full Text PDF PubMed Scopus (73) Google Scholar,2Negrea L. Rovin B.H. Gross hematuria following vaccination for severe acute respiratory syndrome coronavirus 2 in 2 patients with IgA nephropathy.Kidney Int. 2021; 99: 1487Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar We report 2 previously healthy individuals who presented with macroscopic hematuria shortly after COVID-19 vaccination and were diagnosed with IgAN and crescentic glomerulonephritis, respectively. A 41-year-old woman presented with headache, generalized myalgia, and new-onset macroscopic hematuria 1 day after the second dose of tozinameran (Pfizer-BioNtech COVID-19 vaccine). Her medical history was unremarkable except for gestational diabetes. She had no prior history of macroscopic or synpharyngitic hematuria, and urine analysis during pregnancy did not show any proteinuria. She was found to have subnephrotic range proteinuria, hypertension, and elevated serum creatinine on admission (Table 1). Renal biopsy performed showed IgAN with fibrocellular and fibrous crescents (Supplementary Figure S1). The chronic features on histopathology suggest preexisting undiagnosed IgAN that may have been unmasked after the vaccination.Table 1Patient demographics and clinical characteristicsPatient 1Patient 2Reference rangeClinical presentation Age, yr/race/sex41/Chinese/female60/Malay/female Medical historyGestational diabetes mellitusHyperlipidemia Date of vaccinationFirst doseMarch 3, 2021January 29, 2021Second doseMarch 26, 2021February 19, 2021 Date of hematuriaMarch 27, 2021February 20, 2021 Date of presentation to nephrologyMarch 28, 2021March 31, 2021 Blood pressure at presentation, mm Hg153/99188/95Significant laboratory resultsaOther autoantibodies, such as anti–streptomycin O titer (ASOT), anti–double-stranded DNA (anti-dsDNA), anti–neutrophil cytoplasmic antibody (ANCA) by IF, anti-myeloperoxidase, and anti–proteinase 3 antibodies, were not detected. Serum creatinine, μmol/L153541 Urine dysmorphic red blood cells/μl>200>200 Urine protein-to-creatinine ratio, g/g2.037.58 Serum IgSerum IgG, g/L12.909.955.49–17.11Serum IgA, g/L6.401.620.47–3.59Serum IgM, g/L1.100.350.15–2.59 Complement C3, g/L0.831.110.90–1.80 Complement C4, g/L0.200.240.10–0.40 Anti-nuclear antibody1:320; HomogeneousNegative Anti-GBM antibody (ELISA)<1.510.0<7 U/ml = negative; 7–10 U/ml = indeterminate; >10 U/ml = positive Anti-GBM antibody (IF)Not donePositiveHistopathology report Glomeruli36 Glomeruli; 5 globally sclerosed. Focal proliferative glomerulonephritis with focal segment glomerulosclerosis; 6% cellular and 8% fibrocellular crescents22 Glomeruli; 6 segmentally sclerosed. Diffuse crescentic glomerulonephritis with segmental sclerosis; 59% cellular, 14% fibrocellular, and 5% fibrous crescents Tubules and interstitiumMild tubulointerstitial inflammation. Mild tubular atrophy and interstitial fibrosisAcute tubular injuryMild tubular atrophy VesselsMild hyalinosis. No vasculitis or thrombotic microangiopathyMild intimal fibrosis IFDominant glomerular IgA stainingTrace to 1+ linear IgG staining of glomerular basement membrane Electron microscopyElectron-dense deposits mostly in mesangial and paramesangial locationsNo electron-dense depositsTreatmentPulse methylprednisolone, followed by oral prednisolone; i.v. cyclophosphamidePulse methylprednisolone, followed by oral prednisolone; oral cyclophosphamide; plasma exchangeELISA, enzyme-linked immunosorbent assay; GBM, glomerular basement membrane; IF, immunofluorescence.a Other autoantibodies, such as anti–streptomycin O titer (ASOT), anti–double-stranded DNA (anti-dsDNA), anti–neutrophil cytoplasmic antibody (ANCA) by IF, anti-myeloperoxidase, and anti–proteinase 3 antibodies, were not detected. Open table in a new tab ELISA, enzyme-linked immunosorbent assay; GBM, glomerular basement membrane; IF, immunofluorescence. A 60-year-old woman developed macroscopic hematuria 1 day after receiving the second dose of tozinameran. She was treated empirically for urinary tract infection, but presented 6 weeks later with persistent macroscopic hematuria, nephrotic-range proteinuria, hypertension, and acute kidney injury (Table 1). She had been well before her vaccination and did not have any respiratory, gastrointestinal, or constitutional symptoms, such as fever, chills, or myalgia, before and after vaccination. Kidney biopsy revealed crescentic glomerulonephritis with features consistent with anti–glomerular basement membrane nephritis (Supplementary Figure S2). Chest radiography showed no pulmonary involvement. Both patients did not have COVID-19 infection before vaccination, and the community transmission and infection rates were low during the time of vaccination. Seroconversion after vaccination was not evaluated in both patients. Although there is insufficient evidence to postulate causality as it may be coincidental that COVID-19 vaccination closely preceded macroscopic hematuria, these cases emphasize the need for pharmacovigilance. Vigilance should be exercised in patients presenting with new-onset urinary abnormalities and hypertension following COVID-19 vaccination. Besides urinary tract infection and urological causes, glomerulonephritis should be considered in patients with unresolving macroscopic hematuria. Meanwhile, these isolated reports should not lead to vaccine hesitation during this pandemic as the benefits of vaccination strongly outweigh potential risks. We would like to acknowledge our medical laboratory scientist, Yan Fei NG, for her technical assistance. Written informed consent was obtained from the patients with permission to publish the case report and accompanying images. All authors contributed significantly in drafting and revising the letter. Download .pdf (.81 MB) Help with pdf files Supplementary File (PDF) A case of gross hematuria and IgA nephropathy flare-up following SARS-CoV-2 vaccinationKidney InternationalVol. 100Issue 1PreviewWe read with great interest the report of Negrea and Rovin of 2 cases of IgA nephropathy with gross hematuria following the Moderna vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).1 We also cared for a 52-year-old Asian female with prior biopsy-proven IgA nephropathy who developed gross hematuria within 24 hours of receiving a second dose of the Pfizer vaccine. Table 1 summarizes clinical data. Her workup was notable for proteinuria of 4.2 g/g of creatinine with serum creatinine at baseline. Full-Text PDF Gross hematuria following vaccination for severe acute respiratory syndrome coronavirus 2 in 2 patients with IgA nephropathyKidney InternationalVol. 99Issue 6PreviewSeveral of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines use a nucleoside-modified, purified mRNA lipid nanoparticle-encapsulated platform. Compared with traditional inactivated viral and adjuvanted protein vaccines, this RNA platform elicits far higher neutralizing antibody titers, stronger antigen-specific cluster of differentiation (CD) 4+ and CD8+ T-cell 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. Full-Text PDF Relapse of class V lupus nephritis after vaccination with COVID-19 mRNA vaccineKidney InternationalVol. 100Issue 4PreviewSeveral of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines use an mRNA lipid nanoparticle-encapsulated platform. In experimental models, the induced antibody titers are higher, and T- and B-cell responses are enhanced, compared to the level with traditional vaccines. Possibly, due to this higher efficacy, more and more kidney-specific side effects of mRNA vaccines related to immune-mediated glomerular disease are being reported.1–3 Because of similar type I interferon and proinflammatory cytokine pathways in systemic lupus erythematodes and coronavirus disease 2019 (COVID-19), either potentiated or dysregulated immune responses to SARS-CoV-2 vaccines can be suspected to trigger disease activity in previously stable lupus. Full-Text PDF IgA nephropathy presenting as macroscopic hematuria in 2 pediatric patients after receiving the Pfizer COVID-19 vaccineKidney InternationalVol. 100Issue 3PreviewWith great interest, we read the recent reports of IgA nephropathy (IgAN) flare-up presenting as macroscopic hematuria, following the second dose of coronavirus disease 2019 (COVID-19) vaccination in adult patients.1–4 The US Food and Drug Administration granted an emergency use authorization for the Pfizer–BioNtech COVID-19 vaccination in December 2020 for individuals aged ≥16 years; the emergency use authorization was recently expanded to include children aged 12 to 15 years on May 10, 2021. Herein, we report 2 pediatric patients with IgAN presenting with macroscopic hematuria <24 hours after Pfizer COVID-19 vaccination. Full-Text PDF Histologic correlates of gross hematuria following Moderna COVID-19 vaccine in patients with IgA nephropathyKidney InternationalVol. 100Issue 2PreviewWe read with interest the recent reports of gross hematuria occurring in 4 patients with IgA nephropathy shortly following the second dose of mRNA vaccine for coronavirus disease 2019 (COVID-19).1–3 These include 2 cases following the Moderna vaccine1 and 2 following the Pfizer BioNTech vaccine.2,3 As only 1 of these patients had a postvaccination biopsy performed,3 we report the biopsy findings in 2 additional patients who underwent their first kidney biopsy due to the development of gross hematuria shortly following the second dose of the Moderna vaccine for COVID-19. Full-Text PDF Anti-GBM nephritis with mesangial IgA deposits after SARS-CoV-2 mRNA vaccinationKidney InternationalVol. 100Issue 2PreviewWe read with interest recent reports of minimal change disease and glomerulonephritis following receipt of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine, including 1 case of anti–glomerular basement membrane (anti-GBM) antibody disease.1 Full-Text PDF COVID-19 vaccination followed by activation of glomerular diseases: does association equal causation?Kidney InternationalVol. 100Issue 5PreviewTo date, >4 billion doses of the various severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been administered worldwide in response to the coronavirus disease 2019 (COVID-19) pandemic. Even as widespread vaccination campaigns have contributed to declining case rates, adverse events are appearing beyond those originally reported in the clinical trials of vaccine efficacy and safety. Of particular relevance to the kidney is the increasing number of reports of de novo or reactivation of glomerular diseases (Table 11–25). Full-Text PDF