To the editor:
Anecdotal reports linking minimal change disease (MCD) to vaccinations possibly due to immune dysregulation,1 including influenza vaccine,2 pneumococcal,3 meningococcal C vaccines,4 and BNT162b2 coronavirus disease 2019 (COVID-19) vaccine (Pfizer-BioNTech)5 , 6 have been published. We report 2 cases of biopsy-proven MCD relapsing within 2 days of receiving an AstraZeneca COVID-19 vaccine.
A 30-year-old man had received 1 g of rituximab in August 2020, having experienced annual relapses on tacrolimus. His prednisolone had been weaned to 1 mg/day by January and discontinued altogether by February 2021. Two days after his COVID-19 vaccine, he developed a headache and frothy urine. Urine protein-to-creatinine ratio 1 week later was 213 mg/mmol; albumin was preserved at 47 g/l; creatinine was stable at 82 μmol/l. At that time, lymphocyte subsets showed complete B-cell depletion; CD19 was 0.00. He did not seek medical attention until 2 months after receiving the vaccine when his urine protein-to-creatinine ratio was 142 mg/mmol. Repeat lymphocyte subsets then revealed B-cell return; CD19 was 0.06. Complete remission was achieved with 10 days of starting prednisolone 20 mg daily.
A 40-year-old woman was maintained on prednisolone 5 mg daily and tacrolimus (Adoport); trough level was 4.6 μg/l before vaccination. One day after receiving her first COVID-19 vaccine, she developed a headache, frothy urine, and ankle swelling. After 1 week, her general practitioner recorded 3+ dipstick proteinuria. Unfortunately, no laboratory samples were sent. Prednisolone was increased to 30 mg daily, and complete remission was achieved within 2 weeks. Creatinine was unchanged at 105 μmol/l.
The association with various vaccines has been described, occurring between 4 days to several weeks later.1 , 5 , 6 , 7 The timing of COVID-19 vaccination and the very early development of relapse of MCD in our cases raises questions as to the mechanisms involved. At 2 days after vaccination, one would assume the vaccine triggered a more generalized cytokine-mediated response.7 Others have postulated that symptoms after 4 days represent a rapid T cell–mediated response to viral mRNA.2 , 5 , 6
We administered the second dose of a different COVID vaccine, and neither patient suffered an adverse effect. However, both patients were taking 15 mg prednisolone daily at the time. This may prove a useful strategy in similar cases.
We await further reports to evaluate the true incidence.
References
- 1.Clajus C., Spiegel J., Brocker V. Minimal change nephrotic syndrome in an 82 year old patient following a tetanus-diphtheria-poliomyelitis-vaccination. BMC Nephrol. 2009;10:21. doi: 10.1186/1471-2369-10-21. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Kielstein J.T., Termuhlen L., Sohn J. Minimal change nephrotic syndrome in a 65-year-old patient following influenza vaccination. Clin Nephrol. 2000;54:246–248. [PubMed] [Google Scholar]
- 3.Kikuchi Y., Imakiire T., Hyodo T. Minimal change nephrotic syndrome, lymphadenopathy and hyperimmunoglobulinemia after immunization with a pneumococcal vaccine. Clin Nephrol. 2002;58:68–72. doi: 10.5414/cnp58068. [DOI] [PubMed] [Google Scholar]
- 4.Abeyagunawardena A., Goldblatt D., Andrews N., Trompeter R. Risk of relapse after meningococcal C conjugate vaccine in nephrotic syndrome. Lancet. 2003;362:449–450. doi: 10.1016/s0140-6736(03)14072-x. [DOI] [PubMed] [Google Scholar]
- 5.Lebedev L., Sapojnikov M., Wechsler A. Minimal change disease following the Pfizer-BioNTech COVID-19 vaccine. Am J Kidney Dis. 2021;78:142–145. doi: 10.1053/j.ajkd.2021.03.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.D’Agati V.D., Kudose S., Bomback A.S. Minimal change disease and acute kidney injury following the Pfizer-BioNTech COVID-19 vaccine. Kidney Int. 2021;100:461–463. doi: 10.1016/j.kint.2021.04.035. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Sette A., Crotty S. Adaptive immunity to SARS-CoV-2 and COVID-19. Cell. 2021;184:861–880. doi: 10.1016/j.cell.2021.01.007. [DOI] [PMC free article] [PubMed] [Google Scholar]