case report

New-onset Nephrotic Syndrome with Minimal Change Disease Following Pfizer-BioNTech COVID-19 Vaccine: A Case Report and Literature Review

Satoshi Mizuguchi1, Shinya Kawamoto1*, Masahiro Shimoyama1, Takehiko Yamaguch2, Takanori Yasu1

1Department of Cardiovascular Medicine and Nephrology, Dokkyo Medical University, Nikko Medical Center, Nikko, Tochigi, Japan

2Department of Pathology, Dokkyo Medical University, Nikko Medical Center, Nikko, Tochigi, Japan

*Corresponding author: Shinya Kawamoto, Department of Cardiovascular Medicine and Nephrology, Dokkyo Medical University, Nikko Medical Center, 632 Takatoku, Nikko, Tochigi 321-2593, Japan

Received Date: 01 March, 2023

Accepted Date: 16 March, 2023

Published Date: 20 March, 2023

Citation: Mizuguchi S, Kawamoto S, Shimoyama M, Yamaguch T, Yasu T (2023) New-onset Nephrotic Syndrome with Minimal Change Disease Following Pfizer-BioNTech COVID-19 Vaccine: A Case Report and Literature Review. J Vaccines Immunol 8: 186. DOI: https://doi.org/10.29011/2575-789X.000186

Abstract

Background: Vaccination is underway in tremendous numbers worldwide while COVID-19 infection remains serious. Relapse of nephrotic syndrome following vaccination during the remission phase has been reported, and a causal relationship has been considered. However, new-onset nephrotic syndrome in the background of large-scale vaccinations over a short period of time may be incidental and unrelated to the vaccine.

Case Presentatio: A 40-year-old Japanese woman with no history of kidney disease developed nephrotic syndrome following the first dose of Pfizer-BioNTech COVID-19 vaccine, which rapidly resolved with corticosteroid pulse therapy. She presented with a significant weight gain and anasarca 1 week after the vaccination. Laboratory examination revealed massive proteinuria (16.8 g/day) and severe hypoalbuminemia (1.2 g/dL). A renal biopsy revealed minimal change disease. She was treated with steroid pulse therapy and oral predonisolone (40 mg/day). She recovered completely 1 week after the steroid therapy. Throughout the course of her illness, no acute kidney injury or renal dysfunction were observed.

Conclusion: Nephrotic syndrome is an extremely rare side effect when compared to the number of vaccinations; and it does not warrant witholding the vaccination as long as it is recognized that it is steroid-responsive.

Keywords: Covid-19 vaccine; Minimal change disease; Nephrotic syndrome; Steroids

Abbreviations: MCD: Minimal Change Disease; COVID-19: Coronavirus 19

Background

The pandemic of coronavirus disease-2019 (COVID-19) poses a multi-faceted challenge for healthcare systems across the world. The emergence of new vaccines was seen as a game-changer in the battle against this pandemic. Vaccination is underway in tremendous numbers worldwide while COVID-19 infection remains serious. Relapse of nephrotic syndrome following vaccination during the remission phase has been reported, and a causal relationship has been considered [1-3]. However, new-onset nephrotic syndrome in the background of large-scale vaccinations over a short period of time may be incidental and unrelated to the vaccine. We report a case of new-onset nephrotic syndrome characterized by Minimal Change Disease (MCD) following the first dose of Pfizer-BioNTech COVID-19 vaccine.

Case Presentation

A 40-year-old Japanese woman, who had no history of allergies or urinary abnormalities on her previous health examination, noticed foamy urine 5 days after receiving the first dose of Pfizer-BioNTech COVID-19 vaccine. On examination at the hospital 8 days after the vaccination, her blood pressure was 120/74 mmHg and pulse rate was 86/min; she was found to have anasarca and a significant weight gain of 4.4 kg. Laboratory examination revealed severe hypoalbuminemia, hypercholesterolemia, and massive proteinuria without hematuria (Table 1). A diagnostic workup for connective tissue disease was negative. Computed tomography images of her chest and abdomen did not show any significant abnormalities. Renal biopsy was performed the day after admission (9 days after the vaccination). The renal biopsy findings are shown in Figure 1. Light microscopy showed no obvious abnormalities, indicating the absence of tubulo-interstitial damage.(Figure 1a) Immunofluorescence staining was negative for immunoglobulins and complement factors (Figure 1b). Electron microscopy revealed epithelial foot process effacement (Figure 1c). These findings led to a diagnosis of MCD with nephrotic syndrome. Steroid pulse therapy (methylprednisolone 1000 mg/day administered intravenously for three days) was started with a diagnosis of nephrotic syndrome, following which prednisolone 40 mg/day was administered orally (Figure 2). Twelve days after steroid therapy, her urinary protein decreased to 0.4 g/day, and her edema resolved with a 5-kg reduction in body weight. She achieved complete remission of nephrotic syndrome 13 days after the treatment and was discharged after 4 weeks with continued oral steroid treatment. She has been maintaining complete remission of nephrotic syndrome with tapered doses of oral steroids for more than 6 months after discharge.


Table 1: Laboratory finding. 

Figure 1: Renal biopsy findings: Light mocroscopy PAS stain (a) and electron microscopy (b) demonstrating effacement of the epithelial foot process with no dense deposits.

 

Figure 2: Clinical course: Clinical events and trends in serum albumin (g/dL), urinary protein (g/gCr) and serum creatinine (mg/dl)

Discussion

Vaccination is underway in tremendous numbers worldwide while COVID-19 infection continues to remain serious. By September 2022, the number of vaccinations has exceeded 323 million in Japan alone, which is a huge number when compared to previous vaccines. Relapse of nephrotic syndrome after vaccination during the remission phase has been reported [1-4], and a causal relationship has been considered. However, regarding new-onset nephrotic syndrome in the background of large-scale vaccinations over a short period of time, the vaccination may have been coicidental with the spontaneous onset of nephrotic syndrome. Two cases of nephrotic syndrome have reportedly occured after administering the first dose of COVID-19 vaccine; a period of spontaneous remission was followed by a relapse after receiving the second dose of the vaccine [5,6]. These two cases were treated with steroids after the relapse of nephrotic syndrome and achieved complete remission [5,6]. Based on these cases, we believe that vaccination and new-onset of nephrotic syndrome may have a causal relationship, as in our case. The pathogenesis of COVID-19 vaccination-induced MCD and nephrotic syndrome remains unestablished. However, dysregulation of T-cell-mediated immunity is widely speculated to be the main cause. Increased production of permeability factors from enhanced type 2 T-helper cell activity causing cytokine release has been hypothesized as contributing to the development of MCD [7].

Recently, several cases of new-onset nephrotic syndrome after COVID-19 vaccination (Table 2) [8-22] have been reported from various countries. This indicates that the COVID-19 vaccine is used worldwide without regional differences; there is no gender or age difference with a wide age range (15-80 years). Apart from the messenger RNA vaccines (Pfizer-BioNTech, Moderna), adenovirus vector vaccines (Oxford AstraZeneca, Janssen, ChAdOx1) have also been used. The frequency by type of vaccine is proportional to the frequency of actual use. Mostly, the time to symptom-onset was about 1 week after the first vaccination as in our case, while IgA nephritis occurred one or a few days after the second dose [2]. It has been proposed that in “new onset of” IgA nephritis, IgA deposits were present before vaccination and that the vaccine only resulted in a “flare” [2]. Renal biopsy findings in all the cases were of MCD as in our case, except for one case of membranous nephropathy [10,23,24]. Although acute kidney injury was not present in our case, it was seen in 10 out of the 17 cases, and both nephrotic syndrome and acute kidney injury responded to steroid therapy.

Study

Country

Age/Sex

Types of vaccine

1st or 2nd 

Symptom onset time after vaccination days

Renal pathology

AKI

Treatment

Response

8

Israel

50/M

Pfizer-BioNTech

1st

4 days

MCD

+

PSL

9

USA

63/F

Moderna

1st

7 days

MCD

+

mPSL + PSL

10

Singapore

70/M

Pfizer-BioNTech

1st

7 days

MN

+

ARB, Diuretics

×

11

India

19/F

ChAdOx1

1st

8 days

MCD

+

PSL

12

Canada

66/M

Pfizer-BioNTech

1st

10 days

MCD

+

Ramipril/PSL

13

Qatar

43/M

Moderna

1st

7 days

MCD

PSL

14

Qatar

45/F

Pfizer-BioNTech

1st

4 days

MCD

PSL/Furosemide

15

India

22/M

Oxford AstraZeneca

1st

14 days

MCD

PSL

16

Netherlands

61/F

Pfizer-BioNTech

1st

1 day

MCD

+

PSL

17

Japan

71/M

Pfizer-BioNTech

1st

7 days

MCD

PSL

18

Germany

31/F

Janssen

1st

3 days

MCD

mPSL + PSL

18

Germany

20/F

Pfizer-BioNTech

1st

5 days

MCD

PSL

19

Korea

51/M

Janssen

1st

7 days

MCD

+

PSL

20

USA

77/M

Pfizer-BioNTech

1st

7 days

MCD

+

PSL

×

21

Canada

71/M

Oxford AstraZeneca

1st

13 days

MCD

+

PSL

22

Netherlands

80/M

Pfizer-BioNTech

1st

7 days

MCD

+

PSL

23

Japan

22/M

Pfizer-BioNTech

1st

16 days

No data

 

PSL

24

Japan

15/M

Pfizer-BioNTech

1st

4 days

No data

PSL

25

Our case

40/F

Pfizer-BioNTech

1st

5 days

MCD

PSL

Table 2: Reported cases of new onset nephrotic syndrome after COVID-19 vaccination.

Conclusion

Nevertheless, nephrotic syndrome is an extremely rare side-effect when compared to the number of vaccinations; and it does not warrant witholding the vaccination as long as it is recognized that it is steroid-responsive. Rather, the risk of COVID-19 infection in the unvaccinated is more serious. However, caution must be exercised for the second dose of COVID-19 vaccine in patinets with new-onset nephrotic syndrome. Our case is also being carefully followed up with tapering corticosteroids until the second dose. Therefore, considering the risk of COVID-19, we recommend vaccination keeping in mind the possibility of this side-effect. Further studies should be conducted and more case reports of new-onset nephrotic syndrome following COVID-19 vaccination are needed for us to understand this phenomenon better.

References

  1. Hummel A, Oniszczuk J, Kervella D, Charbit M, Guerrot D, et al. (2022) Idiopathic nephrotic syndrome relapse following COVID-19 vaccination: a series of 25 cases. Clin Kidney J 15: 1574-1582.
  2. Klomjit N, Alexander MP, Fervenza FC, et al. (2021) COVID-19 vaccination and glomerulonephritis. Kidney Int Rep 6: 2969-2978.
  3. Bomback AS, Kudose S. D’Agati VD (2021) De novo and relapsing glomerular disease after COVID-19 vaccination: What do we know so far? Am J Kidney Dis 78: 477-480.
  4. Komaba H, Wada T, Fukagawa M (2021) Relapse of minimal change disease following the Pfizer-Biontech COVID-19 vaccine. Am J Kidney Dis 78: 469-470.
  5. Marinaki S, Kolovou K, Liapis G et al. (2021) De novo minimal change disease following vaccination with the Pfizer/BioNTech SARS-CoV-2 vaccine in a living kidney donor. Medicina (Kaunas) 58: 37.
  6. Unver S, Haholu A, Yildirim S (2021) Nephrotic syndrome and acute kidney injury following Corona Vac anti-SARS-CoV-2 vaccine.Clin Kidney J 14: 2608-2611.
  7. Sette A, Crotty S (2021) Adaptive immunity to SARS-COV-2 and COVID-19. Cell 184: 861-880.
  8. Lebedev L, Sapojnikov M, Wechsler A, et al. (2021) Minimal change disease following the Pfizer-BioNTech COVID-19 vaccine. Am J Kidney Dis 78:142-145.
  9. Holzworth A, Couchot P, Cruz-Knight W, Brucculeri M (2021) Minimal change disease following the Moderna mRNA-1273 SARS-CoV-2 vaccine. Kidney Int 100: 463-464.
  10. Da Y, Goh GH, Khatri P (2021) A case of membranous nephropathy following Pfizer-BioNTech mRNA vaccination against COVID-19. Kidney Int 100: 938-939.
  11. Anupama YJ, Patel RGN (2021) Vankalakunti M. Nephrotic syndrome following ChAdOx1 nCoV-19 vaccine Against SARScoV-2. Kidney Int Rep 6: 2248.
  12. Hanna J, Ingram A, Shao T (2021) Minimal change disease After first dose of Pfizer-BioNTech COVID-19 vaccine: A case report and review of minimal change disease related to COVID-19 vaccine. Can J Kidney Health Dis 8: 2021.
  1. Thappy S, Thalappil SR, Abbarh S, et al. (2021) Minimal change disease following the Moderna COVID-19 vaccine: first case report. BMC Nephrol 22: 376.
  2. Abdulgayoom M, Albuni MK, Abdelmahmuod E, et al. (2021) Minimal change nephrotic syndrome four days after the administration of Pfizer-BioNTech COVID-19 vaccine—a new side effect or coincidence? [rep.]. Clin Case Rep 9: 2021.
  3. Biradar V, Konnur A, Gang S, et al. (2022) Adult-onset nephrotic syndrome following coronavirus disease vaccination. Clin Kidney J 15: 168-170.
  4. Weijers J, Alvarez C, Hermans MMH (2021) Post-vaccinal minimal change disease. Kidney Int 100: 459-461.
  5. Kobayashi S, Fugo K, Yamazaki K, Terawaki H (2021) Minimal change disease soon after Pfizer-BioNTech COVID-19 vaccination. Clin Kidney J 14: 2606-2607.
  6. Dormann H, Knüppel-Ruppert A, Amann K, Erley C (2021) Nephrotic syndrome After vaccination Against COVID-19: three new cases From Germany. Dtsch Arztebl Int 118: 662-663.
  7. Maas RJ,Gianotten S, van der Meijden WAG (2021) An additional case of minimal change disease following the Pfizer-BioNTech COVID-19 vaccine. Am J Kidney Dis 78: 312.
  8. D’Agati VD, Kudose S, et al. (2021) Minimal change disease and acute kidney injury following the Pfizer-BioNTech COVID-19 vaccine.Kidney Int 100: 461-463.
  9. Leclerc S, Royal V, Lamarche C, Laurin LP (2021) Minimal change disease With severe acute kidney injury following the Oxford-AstraZeneca COVID-19 vaccine: A case report. Am J Kidney Dis 78: 607-610.
  10. Salem F , Rein JL , Yu SM-W, et al. (2021) Report of three cases of minimal change disease following the second dose of mRNA SARS-CoV-2 COVID-19 vaccine. Kidney Int Rep 6: 2523-2524.
  11. Nagai K , Kageyama M , Iwase M, et al. (2022) A young adult with nephrotic syndrome following COVID-19 vaccination. CEN Case Rep 11: 397-398.
  12. Nakazawa E , Uchiyama T , Hirai Y, et al. (2022) New-onset pediatric nephrotic syndrome following Pfizer-BioNTech SARS-COV-2 vaccination: a case report and literature review. CEN Case Rep 11: 242-246.

© by the Authors & Gavin Publishers. This is an Open Access Journal Article Published Under Attribution-Share Alike CC BY-SA: Creative Commons Attribution-Share Alike 4.0 International License. With this license, readers can share, distribute, download, even commercially, as long as the original source is properly cited. Read More.

Journal of Vaccines, Immunology and Immunopathology