The messenger RNA-based vaccine for the coronavirus disease 2019 (COVID-19) may induce glomerulonephritis, including immunoglobulin A nephropathy (IgAN). New-onset IgAN triggered by vaccination against COVID-19 has been reported rarely, especially in children. Herein, we report a pediatric case of newly diagnosed IgAN after administration of the Pfizer vaccine for COVID-19. A 12-year-old girl was referred to our hospital for evaluation of gross hematuria after inoculation with the second dose of Pfizer’s COVID-19 vaccine; she had no adverse effects after the first dose. At the time of admission, she showed heavy proteinuria and persistent hematuria. Kidney biopsy revealed an IgAN, and she was treated with an oral steroid and an angiotensin-converting enzyme inhibitor. Four months after discharge, the proteinuria and hematuria resolved completely.
Immunoglobulin A (IgA) nephropathy (IgAN) is the most common type of glomerulonephritis in children globally, especially in Asian and European countries [
A 12-year-old girl was referred to our emergency department with gross hematuria and heavy proteinuria (random urine protein-to-creatinine ratio [PCR] of 4.94 g/g, normal <0.2 g/g) after the second dose of the messenger RNA (mRNA)-based COVID-19 vaccine (Pfizer). She had no hematuria after the first dose but developed dark-brown-to-red hematuria several hours after administration of the second dose of the vaccine 2 days prior to admission. The gross hematuria disappeared the next day; the patient had no fever or urinary symptoms except for hematuria, abdominal pain, and symptoms of upper respiratory infection over the previous 4 weeks. She denied performing strenuous exercise or experiencing recent trauma. Her initial vital signs were as follows: blood pressure of 137/80 mmHg (systolic >95th percentile +12 mmHg, diastolic >95th percentile), pulse rate of 90 beats/min, respiratory rate of 16 breaths/min, body temperature of 37.2°C, and oxygen saturation of 99% for room air. Her body weight was 55.2 kg (86th percentile) and her height was 150.1 cm (29th percentile), with a body mass index of 24.5 kg/m2 (95th percentile). Physical examination revealed no specific findings, and pretibial pitting edema was not obvious. Initial urinalysis showed severe microscopic hematuria (>60 red blood cells/high power field [RBCs/HPF]) and heavy proteinuria (urine PCR 2.9 g/g). Her 24-hour urine protein level was 2,455 mg/day (71.8 mg/m2/hr). The dysmorphic RBC content in the urine was 43% of the total RBC. The urine myoglobin level was mildly elevated at 91.7 ng/mL (reference: 0–25 ng/mL). The initial blood test results were as follows: blood urea nitrogen=15.5 mg/dL, creatinine=0.8 mg/dL, aspartate aminotransferase=20 U/L, alanine aminotransferase=9 U/L, protein=7.2 g/dL, albumin=4.4 g/dL, total cholesterol=246 mg/dL, myoglobin <21 ng/mL (reference: 25–72 ng/mL), C-reactive protein=0.49 mg/dL, procalcitonin=0.14 ng/mL (reference: <0.15 ng/mL), IgA=357 mg/dL (reference: 42–295 mg/dL), C3=149 mg/dL (normal: 75–175 mg/dL), and C4=17.6 mg/dL (normal: 14–40 mg/dL). On the 3rd day of hospitalization, her serum protein and albumin levels decreased (6.2 and 3.5 g/dL, respectively), and the cholesterol level remained persistently high (218 mg/dL). The creatine phosphokinase (CPK) level was 257 U/L (reference: 26–192 U/L), and urine myoglobin was normalized (<21 ng/mL). We started steroid (deflazacort) therapy at a dose of 1 mg/kg/day and an angiotensin-converting enzyme (ACE) inhibitor (enalapril) at 0.1 mg/kg/day owing to suspicion of acute glomerulonephritis. We then conducted a kidney biopsy to confirm the diagnosis on the 6th day of admission. Microscopic findings from the kidney biopsy revealed IgAN as shown in
This is a case report of pediatric IgAN presenting with gross hematuria and heavy proteinuria related to administration of the second dose of the mRNA-based COVID-19 vaccine. To the best of our knowledge, this is the first pediatric case report in Korea. Similar to other respiratory viruses, infection with the SARS-CoV-2 pathogen, which has become a global pandemic, can cause nephropathy in children [
The pathogenesis of IgAN has a multihit hypothesis. The production of galactose-deficient IgA1 in the hinge region contributes to revelation of N-acetylgalactosamine glycan, which is highly antigenic [
In case reports of renal complications after COVID-19 vaccination, most patients presented with fever and gross hematuria within 1 or 2 days after administration of the Pfizer mRNA COVID-19 vaccine and accompanied by proteinuria [
There have been reports of pediatric IgAN after COVID-19 vaccination. Horino et al. [
We report a rare case of newly diagnosed IgAN associated with mRNA-based COVID-19 vaccine in a 12-year-old girl who presented with gross hematuria and heavy proteinuria. While the short-term clinical outcome seems favorable, we need to establish long-term follow-up of our patient. Further studies with a larger scale of cases are required to unearth the precise mechanisms of IgAN following mRNA-based COVID-19 vaccination. Pediatricians should also take into account the possibility of renal complications after COVID-19 vaccination and during COVID-19 infection.
This report was approved by the Institutional Review Board of Korea University Ansan Hospital (IRB No. 2022AS0217). Informed consent was waived.
Hyung Eun Yim is an editor-in-chief and Kee Hwan Yoo is an editorial board member of the journal. However, they were not involved in the peer reviewer selection, evaluation, or decision processes of this article. The authors have no other potential conflicts of interest relevant to this article to disclose.
None.
We would like to express our gratitude to Professor Bo-Kyung Je (Department of Radiology, Korea University Ansan Hospital, Korea University College of Medicine) for performing the kidney biopsy.
Conceptualization: HEY, KHY
Data curation: DYK, HEY, MHS, KHY
Investigation: DYK
Methodology: DYK, HEY, MHS
Project administration: HEY
Visualization: DYK
Writing-original draft: DYK
Writing-review & editing: DYK, HEY, MHS, KHY
All authors have read and approved the final manuscript.
Microscopic findings from the kidney biopsy. (A) Mesangial cell proliferation (black arrows). (B) Interstitial fibrosis (black arrow). (C) Immunoglobulin A deposits. (D) Electron dense deposits (white arrows) in the mesangial area (A and B: hematoxylin and eosin stain, ×40 and ×20; C: immunofluorescence staining, ×20; D: electron microscopy, ×6,000).
Clinical course of our patient. The quantity of urine RBCs is scored according to five stages (0: 1–4 RBCs/HPF; 1: 5–9 RBCs/HPF; 2: 10–29 RBCs/HPF; 3: 30–60 RBCs/HPF; 4: >60 RBCs/HPF). RBCs, red blood cells; HPF, high power field; Cr, creatinine; PCR, protein-to-creatinine ratio; mRNA, messenger RNA; COVID-19, coronavirus disease of 2019.