Relapse of class V lupus nephritis after vaccination with COVID-19 mRNA vaccine
Authors: Katharina Tuschen, Jan Hinrich Bräsen, Jessica Schmitz, Martin Vischedyk, Alexander Weidemann
Journal: Kidney International (2021)

Several of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines use an mRNA lipid nanoparticle-encapsulated platform. In experimental models, the induced antibody titers are higher, and T- and B-cell responses are enhanced, compared to the level with traditional vaccines. Possibly, due to this higher efficacy, more and more kidney-specific side effects of mRNA vaccines related to immune-mediated glomerular disease are being reported.1Negrea L. Rovin B.H. Gross hematuria following vaccination for severe acute respiratory syndrome coronavirus 2 in 2 patients with IgA nephropathy.Kidney Int. 2021; 99: 1487Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar, 2Tan H.Z. Tan R.Y. Choo J.C.J. et al.Is COVID-19 vaccination unmasking glomerulonephritis?.Kidney Int. 2021; 100: 469-471Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar, 3Lebedev L. Sapojnikov M. Wechsler A. et al.Minimal change disease following the Pfizer-BioNTech COVID-19 vaccine.Am J Kidney Dis. 2021; 78: 142-145Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar Because of similar type I interferon and proinflammatory cytokine pathways in systemic lupus erythematodes and coronavirus disease 2019 (COVID-19), either potentiated or dysregulated immune responses to SARS-CoV-2 vaccines can be suspected to trigger disease activity in previously stable lupus.4Tang W. Askanase A.D. Khalili L. Merrill J.T. SARS-CoV-2 vaccines in patients with SLE.Lupus Sci Med. 2021; 8e000479Crossref PubMed Scopus (28) Google Scholar We present the case of a 42-year-old female patient who was diagnosed with lupus nephritis class V in 2016 on renal biopsy (Figure 1g and h) after she developed typical butterfly rash and nephrotic syndrome with proteinuria of 6 g/d (Figure 2a). At diagnosis, anti-dsDNA-IgG levels were 210 IU/ml, the antinuclear antibody (ANA) titer result was 1:640, and both complement C3 and C4 were slightly reduced (Figure 2b–d). Renal function was not impaired in 2016. She received induction treatment with cyclophosphamide and steroids and went into full remission (Figure 2a). Maintenance therapy consisted of hydroxychloroquine 200 mg qd until 2021. On April 21, 2021, she received the first dose of the COVID-19 mRNA vaccine BNT162b2, which she tolerated well. One week later, the proteinuria increased from 0.07 g/d to 6 g/d, and 5 weeks later it increased to 8.4 g/d (Figure 2a). She developed nephrotic syndrome with hyperlipoproteinemia and hypalbuminemia. Renal function was again not impaired. There were no other obvious triggers present. Complement was slightly below normal, as it had been in previous analyses (Figure 2d). ANA titers increased to 1:640, but there was no spike of anti-dsDNA-IgG (Figure 2b and c). Hematuria and skin abnormalities were absent, but she was feeling fatigued and complained about an unspecific weakness. Renal biopsy (Figure 1a–f) demonstrated lupus nephritis class V and II with slight focal and segmental mesangial hypercellularity (up to 5 cells per mesangial field) without any irregularities of the basement membranes (no spikes or double contours). The modified activity score (International Society of Nephrology/Renal Pathology Society/National Institutes of Health [ISN/RPS/NIH]) was 0/24, and the chronicity score was 0/12.5Bajema I.M. Wilhelmus S. Alpers C.E. et al.Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices.Kidney Int. 2018; 93: 789-796Abstract Full Text Full Text PDF PubMed Scopus (503) Google Scholar Spontaneous remission did not occur in follow-up measurements, and as nephrotic proteinuria persisted for 7 weeks, we initiated immunosuppressive therapy with mycophenolate mofetil (1 g bid) and prednisolone (60 mg qd). As can be seen in Figure 2a, proteinuria declined initially, and the patient reported substantial improvement of her general well-being and the absence of foamy urine. Proteinuria increased again the following week, but with a tendency toward improvement of the absolute amount in the next measurements. ANA titers, which increased after vaccination, also declined after the start of therapy. Anti-DNA-antibody levels did not increase after the vaccination, and the slightly-below-normal C3c-levels increased (Figure 2b–d).Figure 2(a) Time course of proteinuria with end of induction therapy (blue arrow), coronavirus disease 2019 (COVID-19) vaccination (red arrow), and start of immunosuppressive therapy (green arrow). ∗Time of biopsy and detection of spike-specific IgG antibody after the first vaccination with BNT162b2. Serological parameters (b) anti-dsDNA-IgG, (c) antinuclear antibody (ANA), and (d) complement C3c and C4 are plotted in relation to induction therapy, 2016 (blue); vaccination (red); and start of immunosuppression (green). Dotted lines mark normal limits. Note that the dates are different in the graphs because values were not obtained at each visit. MMF, mycophenolate mofetil.View Large Image Figure ViewerDownload Hi-res image Download (PPT) The patient had already developed an antibody response against the spike protein of SARS-CoV-2 (Figure 2); thus, we decided to postpone the second vaccination in light of declining incidence numbers. When to proceed with the second vaccination remains to be determined, as full remission of the proteinuria has not been achieved yet. To our knowledge, our case report is the first to describe a biopsy-proven relapse of lupus nephritis class V and II. New-onset minimal change glomerulopathies3Lebedev L. Sapojnikov M. Wechsler A. et al.Minimal change disease following the Pfizer-BioNTech COVID-19 vaccine.Am J Kidney Dis. 2021; 78: 142-145Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar,6Maas R.J. Gianotten S. van der Meijden W.A.G. An additional case of minimal change disease following the Pfizer-BioNTech COVID-19 vaccine.Am J Kidney Dis. 2021; 78: 312Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar and other forms of glomerulonephritis (e.g., de novo IgAN,2Tan H.Z. Tan R.Y. Choo J.C.J. et al.Is COVID-19 vaccination unmasking glomerulonephritis?.Kidney Int. 2021; 100: 469-471Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar relapse IgA nephropathy,1Negrea L. Rovin B.H. Gross hematuria following vaccination for severe acute respiratory syndrome coronavirus 2 in 2 patients with IgA nephropathy.Kidney Int. 2021; 99: 1487Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar and even anti–glomerular basement membrane glomerulonephritis)7Sacker A. Kung V. Andeen N. Anti-GBM nephritis with mesangial IgA deposits after SARS-CoV-2 mRNA vaccination.Kidney Int. 2021; 100: 471-472Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar have been described as sequelae of mRNA COVID-19 vaccination. This case adds yet another piece of evidence that relapse in immune-mediated disease might be induced by COVID-19 mRNA vaccine. Although the mechanisms triggering these relapses are still elusive, stringent postvaccination surveillance for renal function, proteinuria, and serologic markers for immune disease is essential in this vulnerable patient population. Anti-GBM nephritis with mesangial IgA deposits after SARS-CoV-2 mRNA vaccinationKidney InternationalVol. 100Issue 2PreviewWe read with interest recent reports of minimal change disease and glomerulonephritis following receipt of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine, including 1 case of anti–glomerular basement membrane (anti-GBM) antibody disease.1 Full-Text PDF Gross hematuria following vaccination for severe acute respiratory syndrome coronavirus 2 in 2 patients with IgA nephropathyKidney InternationalVol. 99Issue 6PreviewSeveral of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines use a nucleoside-modified, purified mRNA lipid nanoparticle-encapsulated platform. Compared with traditional inactivated viral and adjuvanted protein vaccines, this RNA platform elicits far higher neutralizing antibody titers, stronger antigen-specific cluster of differentiation (CD) 4+ and CD8+ T-cell responses, and stronger germinal center B and TFH cell activation in experimental animals.1 The activated CD4+ and CD8+ T cells produce several proinflammatory cytokines, including interferon-γ and tumor necrosis factor-α. Full-Text PDF Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indicesKidney InternationalVol. 93Issue 4PreviewWe present a consensus report pertaining to the improved clarity of definitions and classification of glomerular lesions in lupus nephritis that derived from a meeting of 18 members of an international nephropathology working group in Leiden, Netherlands, in 2016. Here we report detailed recommendations on issues for which we can propose adjustments based on existing evidence and current consensus opinion (phase 1). New definitions are provided for mesangial hypercellularity and for cellular, fibrocellular, and fibrous crescents. Full-Text PDF Open ArchiveIs COVID-19 vaccination unmasking glomerulonephritis?Kidney InternationalVol. 100Issue 2PreviewWe read with great interest the reports of macroscopic hematuria occurring hours following coronavirus disease 2019 (COVID-19) vaccination in patients with known IgA nephropathy (IgAN).1,2 We report 2 previously healthy individuals who presented with macroscopic hematuria shortly after COVID-19 vaccination and were diagnosed with IgAN and crescentic glomerulonephritis, respectively. Full-Text PDF New-onset class III lupus nephritis with multi-organ involvement after COVID-19 vaccinationKidney InternationalVol. 101Issue 4PreviewVaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can trigger an autoimmune response. Two cases of lupus nephritis after the administration of the mRNA vaccine (BNT162b2, Pfizer–BioNTech) and the adenoviral vector vaccine (AZD1222 [ChAdOx1-S], AstraZeneca) have been reported.1,2 We present a case of lupus nephritis with multi-organ involvement after the administration of the AZD1222 vaccine. Full-Text PDF New-onset systemic lupus erythematosus beginning as class V lupus nephritis after COVID-19 vaccinationKidney InternationalVol. 100Issue 6PreviewWe read the report by Tuschen et al. of a 42-year-old woman with a previous diagnosis of systemic lupus erythematosus (SLE) and class V lupus nephritis (LN) that developed a flare 1 week after vaccination with the mRNA coronavirus disease 2019 (COVID-19) vaccine BNT162b2 (Pfizer–BioNTech).1 Here, we report a case of a 23-year-old woman who presented with nephrotic syndrome 1 week after vaccination with the first dose of the AZD1222 (ChAdOx1-S) nCoV-19 vaccine (AstraZeneca). Full-Text PDF COVID-19 vaccination followed by activation of glomerular diseases: does association equal causation?Kidney InternationalVol. 100Issue 5PreviewTo date, >4 billion doses of the various severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been administered worldwide in response to the coronavirus disease 2019 (COVID-19) pandemic. Even as widespread vaccination campaigns have contributed to declining case rates, adverse events are appearing beyond those originally reported in the clinical trials of vaccine efficacy and safety. Of particular relevance to the kidney is the increasing number of reports of de novo or reactivation of glomerular diseases (Table 11–25). Full-Text PDF