To the editor:
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.1, 2, 3, 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. Neither patient had COVID-19 infection before vaccination nor any history of reactions to any vaccinations. See Table 1 for clinical information.
Table 1.
Clinical characteristics of 2 pediatric patients with IgAN flare following COVID-19 vaccination
| Patient no. | Age, yr | Race | Sex | Variables | Before COVID-19 vaccination | Following COVID-19 vaccination |
|---|---|---|---|---|---|---|
| 1 | 13 | White | Male | Clinical symptoms | Microscopic hematuria and subnephrotic proteinuria noted on routine urine screening for diabetes, leading to IgAN diagnosis | New-onset gross hematuria × 2 d, vomiting × 1 d |
| Serum creatinine, mg/dl | 0.54 | Day 2: 1.31 Day 6: 0.66 |
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| Serum albumin, g/dl | 3.4 | Day 2: 3.8 Day 6: 3.0 |
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| Urine protein-to-creatinine ratio, mg/mg | 1.6 | Day 2: 1.07 Day 6: 0.86 |
||||
| Oxford MEST-C score | M0 E0 S0 T0 C0 | — | ||||
| Treatment | Lisinopril, 10 mg/day | Stopped lisinopril on day 5 | ||||
| 2 | 17 | White | Male | Clinical symptoms | Foamy urine for several months | New-onset macroscopic hematuria × 4 d and stage I hypertension |
| Serum creatinine, mg/dl | — | Day 6: 1.78 Day 9: 1.47 Day 22: 1.20 (following corticosteroid treatment) |
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| Serum albumin, g/dl | — | Day 9: 3.8 | ||||
| Urine protein-to-creatinine ratio, mg/mg | — | Day 9: 1.75 | ||||
| Oxford MEST-C score | — | Day 9: M1 E1 S1 T1 C1 | ||||
| Treatment | — | Day 9: 1 g i.v. methylprednisolone daily ×3, followed by oral prednisone |
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.1, 2, 3, 4
Author Contributions
All authors contributed in drafting, reviewing, and revising this letter.
Footnotes
Figure S1. IgAN with minor histomorphologic alterations on light microscopy. (A) Representative glomerulus showing mild mesangial matrix expansion without mesangial hypercellularity on periodic acid–Schiff stain, original magnification ×40. (B) Immunofluorescence microscopy with 3+ granular mesangial reactivity for IgA, original magnification ×10. Bar = 20 μm (A) and 50 μm (B).
Figure S2. IgAN with cellular glomerular crescents. (A) Moderate interstitial fibrosis is evident on the trichrome stain. (B) The glomerulus on the left shows a segmental cellular crescent, and the glomerulus on the right shows segmental mesangial hypercellularity with mild mesangial matrix expansion on periodic acid–Schiff stain. (C) Immunofluorescence staining shows 2+ granular mesangial staining for IgA. (D) Electron microscopy shows electron-dense deposits in mesangium. Bar = 600 μm (A), 60 μm (B,C), and 1 μm (D).
Supplementary Material
References
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