Skip to main content

IgA nephropathy relapse following COVID-19 vaccination treated with corticosteroid therapy: case report

Abstract

Background

The flare of immune-mediated disease following coronavirus disease of 2019 (COVID-19) vaccination is a rare adverse event following immunization. De novo, as well as relapsing IgA nephropathy (IgAN) cases, have been reported following either mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) vaccination. To our knowledge, the majority of IgAN relapses did not result in severe acute kidney injury (AKI) and resolved spontaneously.

Case presentation

This is a case of a 54-year-old female with a previous diagnosis of IgAN who developed IgAN relapse following the second dose of Moderna vaccine. Gross hematuria developed 2 days after vaccination, which was accompanied by significant AKI. Kidney biopsy showed mild tubular atrophy and IgA staining in mesangium without crescent formation. Significant improvement in serum creatinine (Cr) was observed on day 10 after initiating prednisone. Cr came back to normal within 3 months after initiating corticosteroid.

Conclusion

COVID-19 vaccination is associated with a flare of IgAN that may cause significant AKI. Steroid therapy is associated with recovery. IgAN flare after COVID-19 vaccination should be closely monitored to elucidate any adverse effect associated with the novel vaccine.

Peer Review reports

Background

The flare of immune-mediated disease (IMD) following coronavirus disease of 2019 (COVID-19) vaccination is a rare adverse event following immunization. Previous studies reported flare-up of various IMDs, such as rheumatoid arthritis, systemic lupus erythematosus (SLE), Behcet’s disease, psoriasis, vasculitis, sarcoidosis, and multiple sclerosis [1,2,3,4]. De novo, as well as relapsing IgA nephropathy (IgAN) cases, have been reported following either mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) vaccination [5,6,7,8,9,10]. The majority of relapsed IgAN in previous reports did not result in severe acute kidney injury (AKI) and resolved without intervention (Table 1). However, Plasse et al. reported an IgAN relapse following the second dose of Pfizer vaccine, which caused significant AKI and subnephrotic range proteinuria. Kidney biopsy was not reported. AKI resolved 1 month after starting steroid therapy, and proteinuria returned to baseline level within 2 months [11]. Here we report an IgAN relapse with significant AKI after administration of Moderna vaccine, which resolved after initiating steroid therapy. Renal biopsy was performed to rule out other de-novo glomerulonephropathies.

Table 1 IgAN relapses following COVID-19 vaccination

Case presentation

A 54-year-old, Caucasian female with history of IgAN after strep throat infection that was diagnosed with renal biopsy in 2006. Other significant co-morbidity includes obesity (BMI 31.6), hypertension, and GERD. She had no prior documented infection with COVID-19. She was on enalapril 20 mg daily, hydrochlorothiazide 12.5 mg daily, and propranolol 120 mg daily. Her baseline creatinine level (Cr) was 1.2 (eGFR 46 mL/min/1.73m2). Urinalysis was positive for 2 + protein, 3 + blood, and red blood cell (RBC) 15 /high-power field (HPF). The total urine protein to Cr ratio was 1.03.

Two days after receiving the second Moderna vaccine, she developed gross hematuria that resolved spontaneously after 2 days. Vital sign upon examination: body temperature 36.5 °C, blood pressure 122/88 mmHg, heart rate 78 beats/minute. Physical exam was unremarkable without lower extremity edema. Follow-up Cr increased to 3.04 (eGFR 16 mL/min/1.73m2) approximately one week after vaccination. The urinalysis showed 1 + protein, 3 + blood, RBC 50/ HPF. The total urine protein to Cr ratio was 0.67. The renal ultrasound was unremarkable. Repeat kidney biopsy showed mild interstitial fibrosis and tubular atrophy without crescent formation (Fig. 1a). Immunofluorescence analysis showed weak IgA staining in mesangium (Fig. 1b). IgG staining was negative (Fig. 1c). Electron microscopy revealed some mesangial electron-dense deposits (Fig. 1d). Differential diagnosis included IgAN relapse, other de-novo glomerulonephropathies, urinary tract hemorrhage with obstruction, and urinary tract infection, among other causes of hematuria and AKI; however, given her history and kidney biopsy result, IgAN relapse was thought to be the most likely cause.

Fig. 1
figure 1

Histopathologic findings from renal biopsy. a Light microscopy shows no mesangial or endocapillary hypercellularity, or crescents. Fibrous adhesion to the Bowman capsule is identified focally (black arrow). There is mild interstitial fibrosis and tubular atrophy (original magnification × 10). b Immunofluorescence analysis demonstrates weak IgA staining in mesangium (original magnification × 20). c Immunofluorescence analysis demonstrates negative IgG staining in mesangium (original magnification × 20). d Electron microscopy reveals a small number of mesangial electron-dense deposits, especially underneath paramesangial basement membranes (white arrow). Bar = 1 μm

She was started on prednisone 60 mg daily. Cr level improved to 1.9 after 10 days, at which point prednisone was decreased to 40 mg daily. Thereafter prednisone was tapered down gradually over 2 months. Serum Cr recovered to 1.07 approximately 3 months after starting the steroid therapy. Patient tolerated the treatment without significant adverse effect.

Discussion

Here we report a case of IgAN relapse with significant AKI following COVID-19 vaccination that resolved after initiating steroid therapy. In accord with previously reported cases, gross hematuria occurred within a week after vaccination and resolved without intervention. The natural course of AKI due to IgAN following COVID-19 vaccination is unknown, but this case took a longer period for AKI to resolve compared to the case reported by Plasse et al. [11]. The efficacy of steroid therapy remains inconclusive; nevertheless, AKI seems to be reversible as in the cases thar are not related to COVID-19 vaccination. The previous retrospective study conducted by Kveder et al. in 2009, involving 584 adult patients, showed that all cases of AKI associated with IgAN and macroscopic hematuria resolved at a median follow-up of 15 months regardless of treatment status [12].

The pathogenesis of IgAN flare-up after COVID-19 vaccination is yet to be elucidated. The RNA vaccine has been shown to elicit antigen-specific, CD4+ and CD8+ T-cell responses producing multiple cytokines, including Interferon-ɣ, Tumor necrosis factor-α, and Interleukin-2 in animal studies [13]. A previous study showed early serum IgA rise after COVID-19 vaccination [14]. Hyperresponsiveness of IgA1 antibody was documented among those who developed IgAN flare following flu vaccine [15]. Similarly, COVID-19 vaccination may induce IgAN flare via IgA1 hyperresponsiveness to systemic cytokine.

Conclusion

IgAN relapse with significant AKI is associated with COVID-19 vaccination, and systemic steroid therapy is associated with recovery. IgAN exacerbation after COVID-19 vaccination should be closely monitored to elucidate any adverse effect related to the novel vaccine.

Availability of data and materials

Serum chemistry and urine study data used in this case report are available in the supplementary material.

Abbreviations

AKI:

Acute kidney injury

COVID-19:

Coronavirus disease of 2019

Cr:

Creatinine

eGFR:

Estimated glomerular filtration rate

HPF:

High-power field

IgAN:

IgA nephropathy

IMD:

Immune-mediated disease

RBC:

Red blood cell

SLE:

Systemic lupus erythematous

References

  1. Watad A, De Marco G, Mahajna H, Druyan A, Eltity M, Hijazi N, et al. Immune-mediated disease flares or new-onset disease in 27 subjects following mrna/dna sars-cov-2 vaccination. Vaccines. 2021;9:1–23.

    Article  Google Scholar 

  2. Lavery MJ, Nawimana S, Parslew R, Stewart L. A flare of pre-existing erythema multiforme following BNT162b2 (Pfizer–BioNTech) COVID-19 vaccine. Clin Exp Dermatol. 2021;46:0–2.

    Google Scholar 

  3. Toom S, Wolf B, Avula A, Peeke S, Becker K. Familial thrombocytopenia flare-up following the first dose of mRNA-1273 Covid-19 vaccine. Am J Hematol. 2021;96:E134–5.

    Article  CAS  Google Scholar 

  4. Cohen SR, Prussick L, Kahn JS, Gao DX, Radfar A, Rosmarin D. Leukocytoclastic vasculitis flare following the COVID-19 vaccine. Int J Dermatol. 2021;60:1032–3.

    Article  CAS  Google Scholar 

  5. Negrea L, Rovin BH. Gross hematuria following vaccination for severe acute respiratory syndrome coronavirus 2 in 2 patients with IgA nephropathy. Kidney Int. 2021;99:1487. https://doi.org/10.1016/j.kint.2021.03.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kudose S, Friedmann P, Albajrami O, D’Agati VD. Histologic correlates of gross hematuria following Moderna COVID-19 vaccine in patients with IgA nephropathy. Kidney Int. 2021;100:468–9. https://doi.org/10.1016/j.kint.2021.06.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Perrin P, Bassand X, Benotmane I, Bouvier N. Gross hematuria following SARS-CoV-2 vaccination in patients with IgA nephropathy. Kidney Int. 2021;100:466–8. https://doi.org/10.1016/j.kint.2021.05.022.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Bomback AS, Kudose S, D’Agati VD. De novo and relapsing glomerular diseases after COVID-19 vaccination: what do we know so far? Am J Kidney Dis. 2021. https://doi.org/10.1053/j.ajkd.2021.06.004.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Anderegg MA, Liu M, Saganas C, Montani M, Vogt B, Huynh-Do U, et al. De novo vasculitis after mRNA-1273 (Moderna) vaccination. Kidney Int. 2021;100:474–6.

    Article  CAS  Google Scholar 

  10. Tan HZ, Tan RY, Choo JCJ, Lim CC, Tan CS, Loh AHL, et al. Is COVID-19 vaccination unmasking glomerulonephritis? Kidney Int. 2021;100:469–71. https://doi.org/10.1016/j.kint.2021.05.009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Plasse R, Nee R, Gao S, Olson S. Acute kidney injury with gross hematuria and IgA nephropathy after COVID-19 vaccination. Kidney Int. 2021;100:944–5.

    Article  CAS  Google Scholar 

  12. Kveder R, Lindič J, Aleš A, Kovač D, Vizjak A, Ferluga D. Acute kidney injury in immunoglobulin a nephropathy: Potential role of macroscopic hematuria and acute tubulointerstitial injury. Ther Apher Dial. 2009;13:273–7.

    Article  CAS  Google Scholar 

  13. Pardi N, Hogan MJ, Naradikian MS, Parkhouse K, Cain DW, Jones L, et al. Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses. J Exp Med. 2018;215:1571–88.

    Article  CAS  Google Scholar 

  14. Wisnewski AV, Luna JC, Redlich CA. Human IgG and IgA responses to COVID-19 mRNA vaccines. PLoS One. 2021;16(6):e0249499.

    Article  CAS  Google Scholar 

  15. Van Den Wall Bake AWL, Beyer WEP, Evers-Schouten JH, Hermans J, Daha MR, Masurel N, et al. Humoral immune response to influenza vaccination in patients with primary immunoglobulin A nephropathy. An analysis of isotype distribution and size of the influenza-specific antibodies. J Clin Invest. 1989;84:1070–5.

    Article  Google Scholar 

Download references

Acknowledgements

The part of this manuscript has been presented as a poster presentation during Kidney Week 2021 organized by American Society of Nephrology.

Funding

The authors declare that they have no sources of funding for the research.

Author information

Authors and Affiliations

Authors

Contributions

SW reviewed the data and wrote the manuscript. SZ performed the histological examination of the kidney.

AR saw, examined, and made clinical decisions for the patient. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Shota Watanabe.

Ethics declarations

Ethics approval and consent to participate

Ethics approval was waived as consent for publication was obtained from the patient in this case report.

Consent for publication

Written consent for publication has been obtained from the patient.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Watanabe, S., Zheng, S. & Rashidi, A. IgA nephropathy relapse following COVID-19 vaccination treated with corticosteroid therapy: case report. BMC Nephrol 23, 135 (2022). https://doi.org/10.1186/s12882-022-02769-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12882-022-02769-9

Keywords