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Case Report

Tip Lesion Most Frequent FSGS Variant Related to COVID-19 Vaccine: Two Case Reports and Literature Review

by
Emmy Marjorie Carvalho de Araújo
1,
Marcos Adriano Garcia Campos
2,
Andressa Monteiro Sodré
1,
Maria Izabel de Holanda
3,
Rodrigo Hagemann
4,
Antonio Augusto Lima Teixeira Júnior
5,
Natalino Salgado Filho
1,
Precil Diego Miranda de Menezes Neves
6 and
Gyl Eanes Barros Silva
1,7,*
1
Faculty of Medicine, Federal University of Maranhão, Gonçalves Dias Square, São Luís 65020-240, Brazil
2
Clinical Hospital of Botucatu Medical School, São Paulo State University, Professor Mário Rubens Guimarães Montenegro Avenue, Botucatu 18618-687, Brazil
3
Bonsucesso Federal Hospital, Londres Avenue, Rio de Janeiro 21041-020, Brazil
4
Clinical Hospital Complex, Federal University of Paraná, General Carneiro Street, Curitiba 80060-900, Brazil
5
Departament of Genetics, Ribeirão Preto Medical School, University of São Paulo, Bandeirantes Avenue, Ribeirão Preto 14040-900, Brazil
6
Clinical Hospital, University of São Paulo, Dr. Ovídio Pires de Campos Street, São Paulo 05403-010, Brazil
7
Department of Pathology and Legal Medicine, Ribeirão Preto Medical School, University of São Paulo, Bandeirantes Avenue, Ribeirão Preto 14040-900, Brazil
*
Author to whom correspondence should be addressed.
Vaccines 2024, 12(1), 62; https://doi.org/10.3390/vaccines12010062
Submission received: 30 October 2023 / Revised: 3 January 2024 / Accepted: 5 January 2024 / Published: 8 January 2024
(This article belongs to the Special Issue Safety, Efficacy and Optimization of the COVID-19 Vaccines)
Browse Figure
Review Reports Versions Notes

Abstract

:
Large-scale COVID-19 vaccination has been one of the most effective strategies to control the spread of the SARS-CoV-2 virus. However, several cases of glomerular injury related to the COVID-19 vaccine have been described in the literature. We report two cases of a tip lesion variant of focal segmental glomerulosclerosis (FSGS), which presented with significant proteinuria and improved after immunosuppression. In our literature review, the tip lesion variant of FSGS is currently the most frequent variant associated with vaccination against COVID-19. Prognosis is favorable and without significant alterations in the tubulointerstitial or vascular compartments. Adverse effects of vaccines need to be recognized early and will help us to understand the immune and pathological mechanisms of kidney damage.

1. Introduction

Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, is highly contagious and can be fatal. One of the most effective public health strategies for containing this virus and minimizing the risk of contagion is large-scale vaccination [1]. The genetic sequencing of the virus allows researchers to study the development of live attenuated virus vaccines, inactivated virus vaccines, non-replicating viral vector vaccines, and mRNA vaccines using different technologies [2,3].
However, after the massive implementation of these vaccines, there have been several reports of new or reactivated glomerular diseases, especially in patients with exacerbated immune responses to immunization, such as those with immunoglobulin A nephropathy (IgAN), minimal change disease (MCD), and focal segmental glomerulosclerosis (FSGS), including FSGS tip lesion variant [4,5,6].
This study describes the development of FSGS tip lesion variant in patients who received a vaccine against COVID-19. We performed a literature review with articles related to post-COVID-19 FSGS by searching on PubMed and Google Scholar since 2020 for the following terms: “COVID-19 Vaccines” and “Glomerulonephritis” or “Nephrotic Syndrome” or “Glomerulosclerosis, Focal Segmental”.

2. Case Reports

2.1. Case 1

A 47-year-old, Caucasian man with hypertension and depression complained of progressive facial edema three weeks after receiving the first dose of the Oxford–AstraZeneca (AZ) vaccine. During hospitalization, the disease progressed to anasarca, which was associated with reduced diuresis, hypertension, hematuria, and progressive worsening of his renal function.
Upon admission, the patient’s creatinine was 2.6 mg/dL, urine protein was 12,673 mg/24 h, albumin was 1.7 mg/dL, C3 was 171 mg/dL, and C4 was 50 mg/dL. Antinuclear antibody (ANA) and antineutrophil cytoplasmic antibodies (ANCAs) were not measured. The patient’s serology was negative. Methylprednisolone pulse therapy was initiated. After three weeks of hospitalization, the patient was transferred to a tertiary service where he received oral prednisone (1 mg/kg/day), and a renal biopsy was performed after five days of pulse therapy. On that occasion, the patient had a negative reverse transcription polymerase chain reaction (RT-PCR) for COVID-19. But a new test was carried out after a week, and the patient presented a positive RT-PCR for COVID-19 during hospitalization.
The renal biopsy revealed six glomeruli that were normal except for the presence of a glomerulus with segmental sclerosis and synechia in the tubular pole. Only part of each glomerulus was damaged. The arterioles were normal. The tubulointerstitium was preserved. Immunofluorescence revealed moderately segmental deposition for C3 and immunoglobulin M in the vascular poles of some glomeruli. The patient was diagnosed with FSGS tip lesion variant. Genetic testing of high-risk alleles of the APOL1 gene revealed G0/G0.
The patient was treated with prednisone (1 mg/kg/day), furosemide, spironolactone, rivaroxaban, omeprazole, calcium carbonate, and cholecalciferol. After one year, the patient had a creatinine of 0.9 mg/dL, an albumin of 4.1 mg/dL, and a protein/creatinine ratio of 0.06. The prednisone was discontinued, and the patient was maintained on cyclosporine due to corticosteroid dependence.

2.2. Case 2

A 17-year-old woman without comorbidities complained of moderate-intensity abdominal pain five days after receiving the Pfizer–BioNTech vaccine for COVID-19. The patient was initially diagnosed with a urinary tract infection. Levofloxacin was administered for five days, though the patient presented with lower limb edema with a progressive increase in eyelid edema after 10 days. No renal abnormalities were observed on ultrasound.
The patient had a creatinine of 2.2 mg/dL, urine protein of 9125 mg/24 h, hemoglobin of 12.7 g/dL, and hematocrit of 36.3%. A urinalysis revealed the absence of hematuria, leukocyturia, and casts. Serological test results for HIV, HCV, and HBV were negative. ANA and ANCA tests were not performed for this patient.
A renal biopsy revealed 18 glomeruli and five arteries. Twelve of the glomeruli were normal and six had segmental sclerosis, synechia, and hyaline deposits, all in the tubular pole. The damage was segmental because it affected only a part of the glomerulus. All of the arteries were within the normal limits. Interstitial tubules with mild degenerative changes were observed. Twelve glomeruli underwent immunofluorescence analysis, with segmental deposition for C3 and immunoglobulin M deposits in the vascular poles of some glomeruli. Transmission electron microscopy of the paraffin-embedded tissue shows diffuse effacement of foot processes as well as microvillous transformation but no immune-type deposits. The patient was diagnosed with FSGS tip lesion variant associated with mild acute tubular necrosis (Figure 1). The protocol used for histopathological analysis is available in the Supplementary Material.
Therefore, pulse therapy with prednisone (1 mg/kg) was initiated. The patient presented with a complete response in less than four weeks. The creatinine improved to 0.8 mg/dL and no proteins were detected in the urine. The prednisone treatment continued for approximately eight months, including the weaning period.

3. Discussion

3.1. Mechanisms of Post-Vaccine Glomerular Injury

The main coronavirus vaccines used during the pandemic were non-replicating viral vector and mRNA vaccines [3]. Non-replicating viral vector vaccines contain modified adenoviruses and are replication-defective. For example, the AZ vaccine uses a modified chimpanzee adenovirus. mRNA vaccines use lipid nanoparticles to transport genetically modified mRNA to the cell cytoplasm without entering the nucleus, which is a safe method with regard to the risk of adverse effects. The most commonly used mRNA vaccines are the BNT162b2 COVID-19 (Pfizer–BioNTech, Mainz, Germany) and mRNA-1273 (Moderna, Cambridge, MA, USA) vaccines [7].
However, the development of post-vaccination adverse effects is not new. Since the implementation of mass vaccination, several short-term adverse effects have been reported at the application site (pain, inflammation, and urticarial eruptions) or systemically (myocarditis, cognitive disorders, and kidney damage) [8,9,10]. Acute kidney injury (AKI) and glomerulopathies have been associated with COVID-19 vaccines in several reports [11]. A series of thirteen patients in whom glomerulonephritis was triggered after mRNA vaccination included eight patients who developed de novo glomerulonephritis and five who had relapses [12].
The immune response to the COVID-19 vaccine may be a trigger of nephropathies caused by T cell- and B cell-mediated podocyte damage, the humoral and cellular immune response mediated by the mRNA vaccine, and the genetic predisposition of the individual. Usually, renal involvement occurs in less than 20 days after the first injection, with the temporal relationship being smaller in subsequent injection doses [13]. Types of glomerulonephritis included IgAN, membranous nephropathy (MN), and primary podocytopathies, such as MCD and FSGS (mainly the tip lesion variant), and were related to ANCA [12,14,15].
Post-SARS-CoV-2 vaccination IgAN was reported in 48 patients, including 31 new cases and 17 relapses. Thirty of the patients had received the Pfizer vaccine, fifteen had received the Moderna vaccine, and three had received the AZ vaccine [5]. Currently, the most accepted theory related to the pathogenesis of IgAN is the multi-hit theory, in which triggering events, such as infectious or inflammatory conditions, precede the development of the disease [6]. There are several reports of adult and pediatric patients who developed IgA after vaccination, which may correspond to previously unrevealed glomerulonephritis or the vaccination triggering disease in patients with deposited IgA. However, the mechanisms associated with vaccination are not fully understood [16].
In addition to IgAN, MN has been associated with the COVID-19 vaccine, including new and recurrent cases [17,18]. In a study of 210 patients with a previous diagnosis of MN who were immunized with the Pfizer vaccine, 6 relapsed [19]. Immune dysregulation, which leads to non-identification and intolerance to podocyte antigens, is described as a possible cause of the onset or reappearance of nephropathy, although the mechanism has not yet been fully elucidated [20].

3.2. Nephrotic Syndrome after COVID-19 Vaccine

The action of vaccines as triggers for the development or reactivation of nephrotic syndrome has been reported for vaccines against meningococcus C and B viruses, influenza, and diphtheria pertussis [21]. Some forms of podocytopathy have also been associated with COVID-19 vaccines. Kronbichler et al. suggested that there is a temporal and pathogenic association between vaccination and podocytopathies, especially MCD, after the first dose and between other podocytopathies after the second dose [22]. In a recent systematic review about nephrotic syndrome following COVID-19 immunization, pathogenesis was mainly attributed to the activation of angiotensin-converting enzyme-2 receptors, which leads to podocyte effacement [23].
The first description of the association between vaccination and the development of MCD was related to the influenza virus and highlighted the acute onset of the disease after vaccination [24,25]. More recently, prospective studies have reported a low rate of relapse in children who receive influenza vaccinations that is similar to the rate of relapse among unvaccinated children. Although external factors or coincidental events cannot be excluded, the short temporal relationship and the onset or reappearance of renal syndromes suggest a possible pathogenic correlation [26]. Several reports have reported the appearance of MCD soon after the administration of the Pfizer–BioNTech vaccine, including that in a previously healthy patient who developed MCD with nephrotic syndrome and AKI after the first dose of the vaccine [27,28]. The short temporal relationship and the exclusion of other previous factors suggests an association between the development of nephropathies and vaccination [27,29].
In addition to the vaccine, COVID-19 can affect the kidneys. Renal impairment is a potential symptom of SARS-CoV-2 infection, leading to increased morbidity and mortality. However, glomerular immunization reactions do not follow the same pattern as those related to infection [30]. Recently, a COVID-19-related podocyte lesion morphologically compatible with collapsing glomerulopathy (CG) was termed COVID-19-associated nephropathy (COVAN), though its etiology remains unclear [29,30,31]. A systematic review of 59 studies indicated that CG is the most prevalent glomerular histopathological finding related to SARS-CoV-2 [32,33], demonstrating that although viral infection favors the appearance of collapsing podocytopathy, patterns of changes after vaccination are different, as the development of MCD and other forms of FSGS are much more frequent than CG.
There are few reports of CG after vaccination, including post-vaccine CG, after Pfizer and AZ, in two patients who developed pulmonary congestion, dyspnea, massive edema, and chronic kidney disease (CKD) [34]. Another patient was diagnosed with CG after receiving the first dose of the Pfizer vaccine. The patient was healthy before receiving the vaccine and developed disease exactly seven days after vaccination, coinciding with the peak production of follicular T cells stimulated by the mRNA vaccine [35]. In kidney transplantation, a case of GC after mRNA (Moderna) COVID-19 vaccination was also found [36].

3.3. FSGS Tip Lesion Variant after COVID-19 Vaccine

Non-collapsing forms of FSGS are frequently associated with vaccination against SARS-CoV-2 [12,21]. The disease is morphologically classified into five variants according to the Columbia system: cellular, perihilar, collapsing, not otherwise specified (NOS), and tip lesion. The tip lesion variant presents as a sclerotic lesion at the tip of the glomerular tuft at the origin of the proximal tubule, with or without an excess of mesangial matrix and adhesion between the tuft and Bowman’s capsule (synechiae). It is characterized by higher levels of proteinuria and lower serum albumin levels than perihilar and NOS variants. Patients with the tip lesion variant typically have a good prognosis [37,38,39]. The frequency of the tip lesion variant is up to 17% and it may present with lower tubulointerstitial involvement [37,40,41]. However, among 14 patients with post-vaccine FSGS (Table 1), 7 were classified as having the tip lesion variant. The frequency may be higher as some described cases of FSGS are not classified.
FSGS has been characterized as one of the three main glomerulopathies associated with vaccination against COVID-19, and the tip lesion variant is the most common [12,51]. The patients presented in this report developed this variant after vaccination with the Pfizer or AZ vaccines. FSGS tip lesions are more commonly due to the Pfizer vaccine (Table 2). This may be due to the greater accessibility of the Pfizer vaccine and the greater efficiency in the synthesis of the COVID-19 spike protein [52]. However, factors such as sex, age, comorbidities, immunosuppressive status, and possible infection may also influence the appearance of these lesions [53].
The percentage of patients with adverse symptoms after vaccination with the Pfizer vaccine is 79% after the first dose and 84% after the second dose [54]. The development of renal complications, more specifically tip lesions, occurs after the second dose, with a greater number of new cases than relapses. This may be due to the increase in the response of the innate immune system after the second dose compared to the primary immunization, as the second dose of mRNA can induce a storm of cytokines including interferon-γ and CXCL10 [55,56].
Another important COVID-19 post-vaccine diagnosis is the development of autoimmune diseases like systematic lupus erythematous (SLE). The mechanism of the post-vaccine SLE-like syndrome may be due to an inactive viral component, vaccine adjuvants, or an attenuated microbe that generates molecular mimicry or bystander activation in genetically susceptible patients. Clinical manifestations, including renal involvement, and ANA can help with the diagnosis [57].
Most patients who develop the tip lesions variant are adult, Caucasian men between 20 and 45 years of age [58]. The mean age of patients with reported post-vaccination FSGS tip lesion variant is 36 years (range: 17–67 years), and the number of males and females is equal. Data regarding patient ethnicity have not been reported in most cases of post-vaccine FSGS tip lesion variant. Furthermore, no comorbidities were significantly associated with the development of post-immunization FSGS. One of the two patients presented in this study had a comorbidity (arterial hypertension).
According to the Kidney Disease Improving Global Outcomes guidelines for the management of patients with glomerulopathies, the treatment of FSGS is immunosuppressive therapy, including a combination of corticosteroids, calcineurin inhibitors, and cytotoxic agents [58,59]. In this study, the first patient was treated with prednisone and cyclosporine and experienced partial remission and slow evolution with the recurrence of nephrotic proteinuria. The second patient was treated with corticosteroids (prednisone) and experienced complete symptom remission within a few weeks. In previous studies, patients with post-vaccination tip lesion FSGS were also treated with immunosuppressants, such as cyclophosphamide, corticosteroids, and tacrolimus (Table 2). In addition to corticosteroid therapy, Janus kinase inhibitors appear to be a promising treatment for relapsing tip lesion variant FSGS [60]. One patient with FSGS non-tip variant was explicitly maintained on hemodialysis, confirming the low rate of progression to renal replacement therapy (RRT) among patients with the tip variant [59,60].
In general, the tip lesion variant presents with less severe hyalinosis and interstitial fibrosis or mild to moderate tubular atrophy when compared to other variants of FSGS, such as CG [41,61]. In addition, it is associated with significant renal survival. A retrospective study of 116 patients with primary FSGS reported that six of nine patients with the tip lesion variant had alterations in the tubulointerstitial compartment and none had fibrosis [41]. In our case report, the preservation of the tubulointerstitial compartment was observed in both patients. No vascular alterations or fibrosis were observed. Therefore, the patients in this study had a normal pattern of disease.

4. Conclusions

The tip lesion variant of FSGS may be the most frequently reported variant described in the literature associated with vaccination against COVID-19, mainly mRNA vaccines and rarely non-replicating viral vector vaccines. In general, the prognosis is favorable, with rare reports of evolution to RRT and without significant alterations in the tubulointerstitial or vascular compartments. The epidemiological profile is similar to that of patients with tip lesions of primary origin. Physicians must be aware of the possible nephrological effects of vaccines to recognize and understand the immune and pathological mechanisms and potential effects on the body at an early stage.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/vaccines12010062/s1.

Author Contributions

Conceptualization, E.M.C.d.A., M.A.G.C. and G.E.B.S.; methodology, N.S.F.; data or sample collection or histopathological analysis, G.E.B.S., M.I.d.H. and R.H.; formal analysis, M.I.d.H.; investigation, R.H.; writing—original draft preparation, A.A.L.T.J. and E.M.C.d.A.; writing—review and editing, P.D.M.d.M.N. and A.M.S.; supervision, N.S.F. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the University Hospital of the Federal University of Maranhão (protocol code 4.101.862; date of approval 06/22/20).

Informed Consent Statement

Written informed consent has been obtained from the patient(s) to publish this paper.

Data Availability Statement

Data are contained within the article and Supplementary Materials.

Acknowledgments

The authors are grateful to the “Fapema Fundação de Amparo à Pesquisa e Desenvolvimento Científico e Tecnológico do Estado do Maranhão” (FAPEMA) for supporting our research.

Conflicts of Interest

The authors have no conflicts of interest to declare.

References

  1. Feikin, D.R.; Higdonet, M.M.; Abu-Raddadal, L.J.; Andrews, N.; Araos, R.; Goldberg, Y. Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease: Results of a systematic review and meta-regression. Lancet 2022, 399, 924–944. [Google Scholar] [CrossRef] [PubMed]
  2. Han, X.; Xu, P.; Sim, Q. Review of COVID-19 vaccines: Types, thoughts and application. J. Clin. Lab. Anal. 2021, 35, 23–37. [Google Scholar] [CrossRef]
  3. Angeli, F.; Reboldi, G.; Trapasso, M.; Santilli, G.; Zappa, M.; Verdecchia, P. Blood pressure increase following COVID-19 vaccination: A systematic overview and meta-analysis. J. Cardiovasc. Dev. Dis. 2022, 9, 5. [Google Scholar] [CrossRef] [PubMed]
  4. Timmermans, S.A.M.E.G.; Busch, M.H.; Abdul-Hamid, M.A.; Frenken, L.A.M.; Aarnoudse, A.; Paassen, P. Primary Podocytopathies After COVID-19 Vaccination. Kidney Int. Rep. 2022, 7, 892. [Google Scholar] [CrossRef] [PubMed]
  5. Yaohui, M.; Xu, G. New-Onset IgA nephropathy Following COVID-19 Vaccination. QJM Mon. J. Assoc. Physicians 2022, 116, 26–39. [Google Scholar]
  6. Farooqf, H.; Rehman, M.A.U.; Asmar, A.; Asif, S.; Mushtaq, A.; Qureshi, M.A. The pathogenesis of COVID-19-induced IgA nephropathy and IgA vasculitis: A systematic review. J. Taibah Univ. Med. Sci. 2022, 17, 1–13. [Google Scholar]
  7. Pardi, N.; Hogan, M.J.; Weissman, D. Recent advances in mRNA vaccine technology. Curr. Opin. Immunol. 2020, 65, 14–20. [Google Scholar] [CrossRef]
  8. Albert, E.; Aurigemma, G.; Saucedo, J.; Gerson, D.S. Myocarditis following COVID-19 vaccination. Radiol. Case Rep. 2021, 16, 2142–2145. [Google Scholar] [CrossRef]
  9. Goss, A.; Samudralwar, L.D.; Das, R.R.; Nath, A. ANA investigates: Neurological complications of COVID-19 vaccines. Ann. Neurol. 2021, 89, 856. [Google Scholar] [CrossRef]
  10. Zhang, J.; Jiajia, C.; Ye, Q. Renal Side Effects of COVID-19 Vaccination. Vaccines 2022, 10, 1783. [Google Scholar] [CrossRef]
  11. Luo, H.; Li, X.; Ren, Q.; Zhou, Y.; Chen, G.; Zhao, B.; Li, X. Acute kidney injury after COVID-19 vaccines: A real-world study. Ren. Fail. 2022, 44, 958–965. [Google Scholar] [CrossRef] [PubMed]
  12. Klomjit, N.; Alexander, M.P.; Fervenza, F.C.; Zoghby, Z.; Garg, A.; Hogan, M.C.; Nasr, S.H.; Minshar, M.A.; Zand, L. COVID-19 vaccination and glomerulonephritis. Kidney Int. Rep. 2021, 6, 2969–2978. [Google Scholar] [CrossRef] [PubMed]
  13. Fenoglio, R.; Lalloni, S.; Marchisio, M.; Oddone, V.; Simone, E.D.; Vecchio, G.D.; Sciascia, S.; Roccatello, D. New Onset Biopsy-Proven Nephropathies after COVID Vaccination. Am. J. Nephrol. 2022, 53, 325–330. [Google Scholar] [CrossRef] [PubMed]
  14. Mancianti, N.; Guarnieri, A.; Tripodi, S.; Salvo, D.P.; Garosi, G. Minimal change disease following vaccination for SARS-CoV-2. J. Nephrol. 2021, 34, 1039–1040. [Google Scholar] [CrossRef] [PubMed]
  15. Hassanzadeh, S.; Djamali, A.; Mostafavi, L.; Pezeshgi, A. Renal complications after vaccination against COVID-19; A literature review. J. Nephropharmacology 2022, 11, e01-11. [Google Scholar]
  16. Hanna, C.; Hernandez, L.P.H.; Bu, L.; Kizilbash, S.; Najera, L.; Rheault, M.N.; Czyzyk, J.; Kouri, A.M. IgA nephropathy presenting as macroscopic hematuria in 2 pediatric patients after receiving the Pfizer COVID-19 vaccine. Kidney Int. 2021, 100, 705. [Google Scholar] [CrossRef] [PubMed]
  17. Rashid, W.; Mousa, H.; Khan, J.; Ijaz, F.; Ezell, G.D. A case of membranous nephropathy hypothetically associated with the COVID-19 vaccine. Cureus 2022, 14, e24245. [Google Scholar] [PubMed]
  18. Aydin, M.F.; Yildiz, A.; Oruç, A.; Sezen, M.; Dilek, K.; Gullulu, M.; Yavuz, M.; Ersoy, A. Relapse of primary membranous nephropathy after inactivated SARS-CoV-2 virus vaccination. Kidney Int. 2021, 100, 464–465. [Google Scholar] [CrossRef]
  19. Visch, R.; Wetzsel, J.; Vink, C.; Logt, A.E.V. Vaccination against COVID-19 in patients with membranous nephropathy. Kidney Int. Rep. 2022, 7, 1922–1923. [Google Scholar] [CrossRef]
  20. Da, Y.; Goh, G.H.; Khatri, P. A case of membranous nephropathy following Pfizer–BioNTech mRNA vaccination against COVID. Kidney Int. 2021, 100, 938–939. [Google Scholar] [CrossRef]
  21. Li, N.L.; Coates, P.T.; Rovin, B.H. COVID-19 vaccination followed by activation of glomerular diseases: Does association equal causation? Kidney Int. 2021, 100, 959–965. [Google Scholar] [CrossRef]
  22. Kronbichler, A.; Hans-Joachim, A. mRNA COVID-19 Vaccines and Their Risk to Induce a Relapse of Glomerular Diseases. J. Am. Soc. Nephrol. 2022, 33, 2128–2131. [Google Scholar] [CrossRef] [PubMed]
  23. Parikh, C.; Upadhyay, H.; Patel, S.; Sundararajan, R.; Shah, D.; Anand, A.; Baraskar, B.; Bhatt, T.; Verma, D.; Agrawal, S.; et al. Nephrotic syndrome following COVID-19 vaccination: A systematic review. J. Nephrol. 2023, 36, 2431–2440. [Google Scholar] [CrossRef] [PubMed]
  24. Kielstein, J.T.; Termuhlen, L.; Sohn, J.; Kliem, V. Minimal change nephrotic syndrome in a 65-year-old patient following influenza vaccination. Clin. Nephrol. 2000, 54, 246–248. [Google Scholar] [PubMed]
  25. Clajus, C.; Spiegel, J.; Brocker, V.; Chatzikyrkou, C.; Kielstein, J.T. Minimal change nephrotic syndrome in an 82-year-old patient after tetanus-diphtheria-polio vaccination. BMC Nefrol. 2009, 10, 1–5. [Google Scholar]
  26. Bomback, A.S.; Kudose, S.; D’agati, V.D. De novo and relapsing glomerular diseases after COVID-19 vaccination: What do we know so far? Am. J. Kidney Dis. 2021, 78, 477–480. [Google Scholar] [CrossRef]
  27. Lebedev, L.; Sapojnikov, M.; Wechsler, A.; Varadi-Levi, R.; Zamir, D.; Tobaret, A.; Levin-Iaina MD, N.; Fytlovich, S.; Yagil, Y. Minimal change disease following the Pfizer-BioNTech COVID-19 vaccine. Am. J. Kidney Dis. 2021, 78, 142–145. [Google Scholar] [CrossRef]
  28. Salem, F.; Rein, J.L.; Yu, S.M.W.; Abramson, M.; Cravedi, P.; Chung, M. Report of three cases of minimal change disease after the second dose of the mRNA vaccine SARS-CoV-2 COVID-Kidney. Int. Rep. 2021, 6, 2523–2524. [Google Scholar]
  29. Teragaki, M.; Tanaka, M.; Yamamoto, H.; Watanabe, T.; Takeoka, J.; Fukumi, A.; Maeda, K.; Takami, Y.; Saita, H.; Iwanari, S. Relapse of minimal change disease following the third mRNA COVID-19 vaccination: A case report and literature review. CEN Case Rep. 2023, 27, 1–6. [Google Scholar] [CrossRef]
  30. Pacheco, I.C.R.; Costa, D.M.N.; Sousa, D.S.; Filho, N.S.; Silva, G.E.B.; Neves, P.D.M.M. Kidney injury associated with COVID-19 infection and vaccine: A narrative review. Front. Med. 2022, 9, 956158. [Google Scholar] [CrossRef]
  31. Velez, J.C.Q.; Caza, T.; Larsen, C.P. COVAN is the new HIVAN: The resurgence of glomerulopathy collapsing with COVID. Nat. Rev. Nephrol. 2020, 16, 565–567. [Google Scholar] [CrossRef] [PubMed]
  32. Cutrim, M.M.; Neves, P.D.M.d.M.; Campos, M.A.G.; Wanderley, D.C.; Teixeira-Júnior, A.A.L.; Muniz, M.P.R.; Ladchumananandasivam, F.R.; Gomes, O.V.; Vasco, R.F.V.; Brito, D.J.d.A.; et al. Collapsing Glomerulopathy: A Review by the Collapsing Brazilian Consortium. Front. Med. 2022, 9, 846173. [Google Scholar] [CrossRef] [PubMed]
  33. Klomjit, N.; Zand, L.; Cornell, L.D.; Alexander, M.P. COVID-19 and Glomerular Diseases. Kidney Int. Rep. 2023, 8, 1137–1150. [Google Scholar] [CrossRef] [PubMed]
  34. Neves, P.D.M.M.; Caires, R.A.; Guimarães, M.P.; Costalonga, E.C.; Cavalcante, L.B.; Silva, V.T.C.; Mattedi, F.Z.; Santana, L.F.; Teixeira-Júnior, A.A.; Gomes, O.V.; et al. Collapsing glomerulopathy following SARS-CoV-2 adenovirus-vector–based vaccine: Report of 2 cases. Kidney Int. 2022, 101, 637–639. [Google Scholar] [CrossRef]
  35. Lim, C.A.; Lee, H.S.; Yoon, S.; Kim, E.J.; Seo, J.W.; Koo, J.R.; Baek, S.H. Focal segmental glomerulosclerosis following the Pfizer-BioNTech COVID-19 vaccine. Kidney Res. Clin. Pract. 2022, 41, 263. [Google Scholar] [CrossRef]
  36. Chen, S.; Kowalewska, J.; McCune, T.R. COVID-19 Associated Collapsing FSGS in an APOL1 Homozygous Transplant Recipient After Successful COVID Vaccination: A Case Report. Transplant. Proc. 2022, 54, 1543–1546. [Google Scholar] [CrossRef] [PubMed]
  37. Thomas, D.B.; Franceschini, N.; Hogan, S.L.; Holder, S.T.; Jennette, C.E.; Falk, R.J.; Jennette, J.C. Clinical and pathologic characteristics of focal segmental glomerulosclerosis pathologic variants. Kidney Int. 2006, 69, 920–926. [Google Scholar] [CrossRef] [PubMed]
  38. Stokes, M.B.; Valeri, A.M.; Markowitz1, G.S.; D’Agati1, V.D. Cellular focal segmental glomerulosclerosis: Clinical and pathologic features. Kidney Int. 2006, 70, 1783–1792. [Google Scholar] [CrossRef]
  39. Paassen, P.V.; Vriesman, P.J.C.B.; Rie, H.V.; Tervaert, J.W.C. Signs and symptoms of thin basement membrane nephropathy: A prospective regional study in primary glomerular disease—The Limburg Renal Registry. Kidney Int. 2004, 66, 909–913. [Google Scholar] [CrossRef]
  40. Shakeel, S.; Mubarak, M.; Kazy, J.I.; Jafry, N.; Ahmed, E. Frequency and clinicopathological features of primary focal segmental glomerulosclerosis variants in adults with nephrotic syndrome. J. Nephropathol. 2013, 2, 28. [Google Scholar] [CrossRef]
  41. Swarnalatha, G.; Ram, R.; Ismal, K.M.; Vali, S.; Sahay, M.; Dakshinamurty, K.V. Focal and segmental glomerulosclerosis: Does prognosis vary with the variants? Saudi J. Kidney Dis. Transplant. 2015, 26, 173. [Google Scholar] [CrossRef]
  42. Hummel, A.; Oniszczuk, J.; Kervella, D.; Charbit, M.; Guerrot, D.; Testa, A.; Philipponnet, C.; Chauvet, C.; Guincestre, T.; Brochard, K.; et al. Idiopathic nephrotic syndrome relapse following COVID-19 vaccination: A series of 25 cases. Clin. Kidney J. 2022, 15, 1574–1582. [Google Scholar] [CrossRef] [PubMed]
  43. Huang, Y.T.; Chang, F.P.; Hung, S.C.; Wang, Y.C. Relapsed focal segmental glomerulosclerosis and severe acute kidney injury after Oxford-AstraZeneca (AZ) COVID-19 vaccine. Arch. Med. Sci. 2022, 18, 1693–1695. [Google Scholar] [CrossRef]
  44. Sirpal, V.; Fichadiya, H.; Al-Alwan, A.; Ashok, M.; Sirpal, V. A case of FSGS in a previously healthy male after the second dose of COVID-19 mRNA vaccine. J. Investig. Med. 2022, 70, 1041–1042. [Google Scholar]
  45. Jha, V.K.; Akal, R.S.; Sharma, A.; Mahapatra, D. Post covishield (ChAdOx1 nCoV-19) vaccination: New onset focal segmental glomerulosclerosis resistant to steroid and calcineurin inhibitor. Indian J. Nephrol. 2022, 32, 378. [Google Scholar] [CrossRef] [PubMed]
  46. Horinouchi, T.; Ueda, C.; Kitakado, H.; Yoshikawa, N.; Nozu, K. Steroid resistant nephrotic syndrome with collapsing focal segmental glomerulosclerosis in a 12-year-old Japanese female after SARS-CoV-2 vaccination. J. Nephrol. 2023, 36, 1435–1438. [Google Scholar] [CrossRef] [PubMed]
  47. Marega, A.; Pizzolitto, S.; Pian, M.; Biasi, C.; Giacomini, A.; Bertoni, M.; Romano, G.; Boscutti, G. De novo double glomerulopathy (membranous nephropathy, MN and collapsing focal segmental glomerulosclerosis, CFSGS) associated to positive myeloperoxidase-o (MPO) antibody following pfizer - biontech MRNA vaccination COVID-19. Nephrol. Dial. Transplant. 2022, 37, i156–i157. [Google Scholar] [CrossRef]
  48. Khan, S.; Caberto, S.C. A Case of Collapsing Focal Segmental Glomerulosclerosis in Post-mRNA COVID-19 Vaccination. J. Am. Soc. Nephrol. 2022, 33, 339. [Google Scholar]
  49. Rajarathinam, V.D.; Gopalakrishnan, N.; Senthilkumaran, G.; Vs, J.; Murugesan, C.M.; Balasubramanian, C.M.; Devaraju, P.K.; Thanigachalam, D.; Solomon, D.; Moses Lamech, T.; et al. POS-021 COVID vaccine associated glomerular diseases—A case series. Kidney Int. Rep. 2022, 7, S471. [Google Scholar] [CrossRef]
  50. Roy, S.; Behera, M.R.; Kaul, A.; Prasad, N.; Patel, M.R.; Kushwaha, R.S. A Case Series on Glomerular Disease Manifesting for the First Time after COVID 19 Vaccination. Indian J. Nephrol. 2022, 32, S15–S16. [Google Scholar]
  51. Perea-Ortega, L.; Criado, P.C.; Guzman, P.H.; Sanchez, M.L.F.; Rojas, R.T. MO221: Glomerulopathies After COVID-19 Vaccination. Report of Cases in Our Centre. Nephrol. Dial. Transplant. 2022, 37, gfac067-020. [Google Scholar] [CrossRef]
  52. Cortés-Sarabia, K.; Gutiérrez-Torres, M.; Mendoza-Renteria, E.M.; Leyva-Vázquez, M.A.; Vences-Velázquez, A.; Hernández-Sotelo, D.; Beltrán-Anaya, F.O.; Moral-Hernández, O.D.; Illades-Aguiar, B. Variation in the humoral immune response induced by administration of the Pfizer/BioNTech BNT162b2 vaccine: A systematic review. Vacinnes 2022, 10, 909. [Google Scholar] [CrossRef] [PubMed]
  53. Dighriri, I.M.; Alhusayni, K.M.; Mobarki, A.Y.; Aljerary, I.S.; Alqurashi, K.A.; Aljuaid, F.A.; Alamri, K.A.; Mutwalli, A.A.; Maashi, N.A.; Aljohani, A.M.; et al. Pfizer-BioNTech COVID-19 Vaccine (BNT162b2) Side Effects: A Systematic Review. Cureus 2022, 14, e23526. [Google Scholar] [CrossRef] [PubMed]
  54. Arunachalam, P.S.; Scott, M.K.D.; Hagan, T.; Li, C.; Feng, Y.; Wimmers, F.; Grigoryan, L.; Trisal, M.; Edara, V.V.; Lai, L.; et al. Systems vaccinology of the BNT162b2 mRNA vaccine in humans. Nature 2021, 596, 410–416. [Google Scholar] [CrossRef] [PubMed]
  55. Li, Y.; Rao, M.; Xu, G. New-onset acute kidney disease post COVID-19 vaccination. Vaccines 2022, 10, 742. [Google Scholar] [CrossRef]
  56. Chun, M.J.; Korbet, S.M.; Schwartz, M.M.; Lewis, E.J. Focal segmental glomerulosclerosis in nephrotic adults: Presentation, prognosis, and response to therapy of the histologic variants. J. Am. Soc. Nephrol. 2004, 15, 2169–2177. [Google Scholar] [CrossRef] [PubMed]
  57. Khatri, G.; Priya; Shaikh, S.; Aashish; Rai, A.; Cheema, H.A.; Essar, M.Y. Systematic lupus erythematous patients following COVID-19 vaccination: Its flares up and precautions. Ann. Med. Surg. 2022, 80, 104282. [Google Scholar] [CrossRef] [PubMed]
  58. Floege, J.; Barbour, S.J.; Cattran, D.C.; Hogan, J.J.; Nachman, P.H.; Tang, S.C.; Wetzels, J.F.; Cheung, M.; Wheeler, D.C.; Winkelmayer, W.C.; et al. Management and treatment of glomerular diseases (part 1): Conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2019, 95, 268–280. [Google Scholar] [CrossRef]
  59. Rovin, B.H.; Caster, D.J.; Cattran, D.C.; Gibson, K.L.; Hogan, J.J.; Moeller, M.J.; Roccatello, D.; Cheung, M.; Wheeler, D.C.; Winkelmayer, W.C.; et al. Management and treatment of glomerular diseases (part 2): Conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2019, 95, 281–295. [Google Scholar] [CrossRef]
  60. Sedlacek, M.; Pettus, J.R. Complete remission of tip lesion variant focal segmental glomerulosclerosis (FSGS) with the Janus Kinase (JAK) inhibitor tofacitinib. CEN Case Rep. 2022, 11, 225–230. [Google Scholar] [CrossRef]
  61. Mungan, S.; Turkmen, E.; Aydin, M.C.; Saglam, A.E.; Baydar, D.E. Tip lesion variant of primary focal and segmental glomerulosclerosis: Clinicopathological analysis of 20 cases. Ren. Fail. 2015, 37, 858–865. [Google Scholar] [CrossRef] [PubMed]
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Figure 1. Histopathological findings in renal biopsy. (A) Glomerulus with segmental sclerosis at the tubular pole (black arrow) surrounded by normal tubulointerstitial compartment. (B) Segmental sclerosis with adherence and herniated into the tubular lumen (black arrow). (C) Normal glomerulus in the same patient (black arrow indicating vascular pole). (A–C) Masson’s trichrome stain. (D,E) C3 and IgM deposits in tubular pole observed via immunofluorescence (white arrow). (F) Electron microscopy showing diffuse podocytes foot process effacement (black arrow) and microvillous transformation (black head arrow).
Figure 1. Histopathological findings in renal biopsy. (A) Glomerulus with segmental sclerosis at the tubular pole (black arrow) surrounded by normal tubulointerstitial compartment. (B) Segmental sclerosis with adherence and herniated into the tubular lumen (black arrow). (C) Normal glomerulus in the same patient (black arrow indicating vascular pole). (A–C) Masson’s trichrome stain. (D,E) C3 and IgM deposits in tubular pole observed via immunofluorescence (white arrow). (F) Electron microscopy showing diffuse podocytes foot process effacement (black arrow) and microvillous transformation (black head arrow).
Vaccines 12 00062 g001
Table 1. Segmental and focal glomerulosclerosis after vaccination against COVID-19.
Table 1. Segmental and focal glomerulosclerosis after vaccination against COVID-19.
AuthorNVariant
Hummel et al. (2022) [42]2Tip lesion
Fenoglio et al. (2022) [13]1Tip lesion
Klomjit et al. (2021) [12]1Tip lesion
Timmermans et al. (2022) [4]1Tip lesion
Huang et al. (2022) [43]1Not specified
Sirpal et al. (2022) [44]1Tip lesion
Vijoy Kumar Jha et al. (2022) [45]1Tip lesion
Cho A Lim et al. (2022) [35]1Cellular
Horinouchi et al. 2023 [46]1Collapsing
Marega et al. (2022) [47]1Collapsing
Khan et al. (2022) [48]1Collapsing
Rajarathinam et al. (2022) [49]2Not specified
Roy et al. (2022) [50]1Not specified
Table 2. Characteristics of patients with segmental and focal glomerulosclerosis tip lesion variant after COVID-19 vaccination.
Table 2. Characteristics of patients with segmental and focal glomerulosclerosis tip lesion variant after COVID-19 vaccination.
AuthorSexAge (Years)VaccineDoseDays until SymptomsProteinuria (Initial/Final)Creatinine (Initial/Final)Albumin (Initial/Final)Type of CaseTreatmentRRT
Hummel et al. (2022) [42]Female46Pfizer2200.1 g/g/9 g/g2.1 mg/dL/-3.9 g/dL/2.2 g/dL RelapseCTX-
Hummel et al. (2022) [42]Female67Pfizer1180.3 g/g/9.2 g/g3.7 mg/dL/-4.0 g/dL/1.9 g/dLRelapseCsA + MMF-
Fenoglio et al. (2022) [13]Female24Pfizer288-/--/--/-De novoGCNo
Klomjit et al. (2021) [12]Female29Pfizer221-/10 g/dL0.6 mg/dL/0.7 mg/dL2.2 g/dL/3.2 g/dLRelapseGC + FKNo
Timmermans et al. (2022) [4]Male47Pfizer214-/4.5 g/d0.8 mg/dL/-2.0 g/dL/-De novo -
Sirpal et al. (2022) [44]Male26Moderna221-/3.2 g (24 h) 5 g/dL/2.7 g/dLDe novoFK-
Vijoy Kumar Jha et al. (2022) [45]Male21AZ11223.87 g (24 h)/20.7 g (24 h)1.06 mg/dL/1.02 mg/dL0.9 g/dL/-De novoGC + FK-
Patient 1 *Male47AZ13012.6 g (24 h)/normal2.6 mg/dL/0.91 mg/dL1.7 g/dL/4.1 g/dLDe novoGC + CsANo
Patient 2 *Female17Pfizer359.125 g/dL/normal2.2 mg/dL/0.8 mg/dL-/-
AZ: Oxford AstraZeneca vaccine; CTX: Cyclophosphamide; CsA: Cyclosporine; MMF: Mycophenolate mofetil; GC: Glucocorticoid; FK: Tacrolimus; RRT: renal replacement therapy; * Patient described in the current study.
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Araújo, E.M.C.d.; Campos, M.A.G.; Sodré, A.M.; Holanda, M.I.d.; Hagemann, R.; Teixeira Júnior, A.A.L.; Salgado Filho, N.; Neves, P.D.M.d.M.; Silva, G.E.B. Tip Lesion Most Frequent FSGS Variant Related to COVID-19 Vaccine: Two Case Reports and Literature Review. Vaccines 2024, 12, 62. https://doi.org/10.3390/vaccines12010062

AMA Style

Araújo EMCd, Campos MAG, Sodré AM, Holanda MId, Hagemann R, Teixeira Júnior AAL, Salgado Filho N, Neves PDMdM, Silva GEB. Tip Lesion Most Frequent FSGS Variant Related to COVID-19 Vaccine: Two Case Reports and Literature Review. Vaccines. 2024; 12(1):62. https://doi.org/10.3390/vaccines12010062

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Araújo, Emmy Marjorie Carvalho de, Marcos Adriano Garcia Campos, Andressa Monteiro Sodré, Maria Izabel de Holanda, Rodrigo Hagemann, Antonio Augusto Lima Teixeira Júnior, Natalino Salgado Filho, Precil Diego Miranda de Menezes Neves, and Gyl Eanes Barros Silva. 2024. "Tip Lesion Most Frequent FSGS Variant Related to COVID-19 Vaccine: Two Case Reports and Literature Review" Vaccines 12, no. 1: 62. https://doi.org/10.3390/vaccines12010062

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