IgA nephropathy presenting as macroscopic hematuria in 2 pediatric patients after receiving the Pfizer COVID-19 vaccine
Authors: Christian Hanna, Loren P. Herrera Hernandez, Lihong Bu, Sarah Kizilbash, Lydia Najera, Michelle N. Rheault, Jan Czyzyk, Anne M. Kouri
Journal: Kidney International (2021)

With 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.1Rahim S.E.G. Lin J.T. Wang J.C. 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 (83) 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 (80) Google Scholar, 3Perrin P. Bassand X. Benotmane I. Bouvier N. Gross hematuria following SARS-CoV-2 vaccination in patients with IgA nephropathy.Kidney Int. 2021; 100: 466-468Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar, 4Tan H.Z. Tan R.Y. Choo J.C.J. et al.Is COVID-19 vaccination unmasking glomerulonephritis?.Kidney Int. 2021; 100: 469-471Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar 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. Neither patient had COVID-19 infection before vaccination nor any history of reactions to any vaccinations. See Table 1 for clinical information.Table 1Clinical characteristics of 2 pediatric patients with IgAN flare following COVID-19 vaccinationPatient no.Age, yrRaceSexVariablesBefore COVID-19 vaccinationFollowing COVID-19 vaccination113WhiteMaleClinical symptomsMicroscopic hematuria and subnephrotic proteinuria noted on routine urine screening for diabetes, leading to IgAN diagnosisNew-onset gross hematuria × 2 d, vomiting × 1 dSerum creatinine, mg/dl0.54Day 2: 1.31Day 6: 0.66Serum albumin, g/dl3.4Day 2: 3.8Day 6: 3.0Urine protein-to-creatinine ratio, mg/mg1.6Day 2: 1.07Day 6: 0.86Oxford MEST-C scoreM0 E0 S0 T0 C0—TreatmentLisinopril, 10 mg/dayStopped lisinopril on day 5217WhiteMaleClinical symptomsFoamy urine for several monthsNew-onset macroscopic hematuria × 4 d and stage I hypertensionSerum creatinine, mg/dl—Day 6: 1.78Day 9: 1.47Day 22: 1.20 (following corticosteroid treatment)Serum albumin, g/dl—Day 9: 3.8Urine protein-to-creatinine ratio, mg/mg—Day 9: 1.75Oxford MEST-C score—Day 9: M1 E1 S1 T1 C1Treatment—Day 9: 1 g i.v. methylprednisolone daily ×3, followed by oral prednisoneCOVID-19, coronavirus disease 2019; IgAN, IgA nephropathy; MEST-C, M = mesangial hypercellularity, E = endocapillary proliferation, S = segmental glomerulosclerosis, T = tubular atrophy/interstitial fibrosis, C = crescents. Open table in a new tab COVID-19, coronavirus disease 2019; IgAN, IgA nephropathy; MEST-C, M = mesangial hypercellularity, E = endocapillary proliferation, S = segmental glomerulosclerosis, T = tubular atrophy/interstitial fibrosis, C = crescents. The first patient is a 13-year-old boy with a history of type 1 diabetes mellitus and known IgAN (Supplementary Figure S1). His initial IgAN diagnosis was made 6 months before this event during an evaluation for subnephrotic proteinuria and microscopic hematuria with normal renal function, and he was receiving treatment with lisinopril. Within 24 hours following the second dose of the COVID-19 vaccine, he developed new-onset gross hematuria and acute kidney injury. His gross hematuria self-resolved, and his kidney function recovered without intervention within 1 week. The second patient is a previously healthy 17-year-old boy who presented with new-onset gross hematuria, proteinuria, and acute kidney injury <24 hours following the second dose of the vaccine. He had no family history of autoimmune disease, and he was not taking any medications. His gross hematuria self-resolved, but his kidney insufficiency persisted. Kidney biopsy performed 9 days later was consistent with IgAN with cellular glomerular crescents and moderate to severe tubulointerstitial scarring (Supplementary Figure S2), suggesting an acute exacerbation of preexisting IgAN. He received i.v. methylprednisolone pulses, and his follow-up serum creatinine level showed improvement. The mechanism by which COVID-19 vaccination may be associated with IgAN flares is unclear. We concur with previous authors' statements that patients, including children, with IgAN should be monitored closely following COVID-19 vaccine, and COVID-19 vaccination may unmask previously undiagnosed glomerulonephritis in pediatric patients.1Rahim S.E.G. Lin J.T. Wang J.C. 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 (83) 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 (80) Google Scholar, 3Perrin P. Bassand X. Benotmane I. Bouvier N. Gross hematuria following SARS-CoV-2 vaccination in patients with IgA nephropathy.Kidney Int. 2021; 100: 466-468Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar, 4Tan H.Z. Tan R.Y. Choo J.C.J. et al.Is COVID-19 vaccination unmasking glomerulonephritis?.Kidney Int. 2021; 100: 469-471Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar All authors contributed in drafting, reviewing, and revising this letter. Download .pdf (.29 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 Gross hematuria following SARS-CoV-2 vaccination in patients with IgA nephropathyKidney InternationalVol. 100Issue 2PreviewAfter the publication of the 2 letters by Negrea and Rovin1 and Rahim et al.,2 we herein describe 3 additional patients with IgA nephropathy (IgAN) who developed gross hematuria after receiving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA-based vaccines. The clinical data of our cases are summarized in Table 1. In line with the 3 previously reported cases, patient 1 had normal kidney function. However, patients 2 and 3 were treated with kidney transplantation (KT) and hemodialysis, respectively. Full-Text PDF Is COVID-19 vaccination unmasking glomerulonephritis?Kidney InternationalVol. 100Issue 2PreviewWe 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).1,2 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. 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