Abstract
Introduction
mRNA COVID-19 vaccine is more effective than traditional vaccines owing to superior immune activation. Nevertheless, the impact of mRNA COVID-19 vaccine on triggering de novo/relapsing glomerulonephritis (GN) is limited. We report a case series of patients who developed new or relapsing GN postvaccination.
Methods
We evaluated baseline characteristics, vaccine type, and clinical outcomes of 13 patients from our institution who had a new diagnosis or relapse of their GN post–mRNA COVID-19 vaccination.
Results
Of 13 patients, 8 patients were newly diagnosed with having GN and 5 patients had relapse. Median age was 62 years (range 19–83 years). Autoimmune disease (38%) was the most prevalent underlying disease followed by cancer (23%). Most patients were White males. IgA nephropathy (IgAN) was the most common GN in our series (5 patients, 38%) followed by membranous nephropathy (MN) (3 patients, 23%). There was 1 patient with IgAN who had evidence of IgA deposits before vaccination suggesting the immune activation after vaccination triggered a flare of the disease. Our case series also included the first case report of tip-variant focal segmental glomerulosclerosis (FSGS), NELL-1–associated MN, and atypical anti–glomerular basement membrane (GBM) nephritis. A total of 77% developed acute kidney injury (AKI) with most being Kidney Disease: Improving Global Outcomes stage 1 (67%). Outcomes are favorable with 80% responding to therapy.
Conclusion
New cases and relapse of GN can present shortly after mRNA COVID-19 vaccination. New cases of IgAN may result from unmasking of undiagnosed IgAN owing to robust immune activation rather than development of new deposits.
Keywords: COVID-19, glomerulonephritis, IgA nephropathy, minimal change disease, mRNA vaccine, SARS-CoV-2
Rapid and mass SARS-CoV-2 vaccination has been one of the pivotal strategies to curb the COVID-19 pandemic. The use of recently developed mRNA vaccine, such as BNT162b2 (Pfizer) and mRNA-1273 (Moderna), has provided effective protection against severe COVID-19 infection.1,2 mRNA vaccines use lipid nanoparticle as a vehicle to deliver genetically modified mRNA. Once injected, the mRNA is translated into target protein resulting in robust immune response.3 These vaccines thus far have been found to have excellent safety profile, and the most common immediate and short-term side effects for both mRNA vaccines have mostly involved injection site reaction. Severe reactions have been rare.1,2 Since mass-scale vaccination, however, several immune-mediated reactions, including cases of myocarditis and newly diagnosed or relapsed GN, have been reported.4,5 Most cases have been associated with mRNA vaccines (Pfizer and Moderna) and adenovirus vector deliveries.6, 7, 8, 9, 10, 11, 12, 13, 14 Nevertheless, rare cases of GN related to inactivated virus vaccine (CoronaVac from Sinovac) have also been reported.15 The most common reported GN thus far is IgAN. But whether COVID-19 vaccine results in an immune response that triggers IgA antibody (Ab) production and formation of new deposits in the kidneys or whether the immune response to the vaccine only unmasks the presence of previously formed deposits is unclear. In this case series, we report 13 cases of newly diagnosed or flares of GN post–COVID-19 mRNA vaccines and provide a literature review of all the reported GN cases thus far. We also provide evidence in 1 case of “new” IgAN wherein the deposits were present previously. We also report on 3 new diagnoses after COVID-19 vaccination, including a case of NELL-1–associated MN, a case of primary FSGS, and a case of atypical anti-GBM nephritis.
Method
Patient Selection
Patients who were either newly diagnosed or had a relapse of their GN after vaccination are reported in this case series. All patients had their kidney pathology results reviewed at the Mayo Clinic, Rochester, Minnesota. Clinical data and baseline characteristics, vaccine type, onset of symptoms, laboratories on presentation, treatments, and outcomes are based on review of medical records.
Literature Review
We searched all literature since the inception that reported newly diagnosed or relapse of GN after any type of COVID-19 vaccines through PubMed. We then extracted baseline characteristics, laboratories on presentation, treatments, and outcomes.
Statistical Analysis
We report continuous data with median and range. Categorical data are found with number and percentage. We used descriptive statistics in this report as the sample size is quite small and no analytical statistics were implemented.
Results
Baseline Demographic and Clinical Characteristics of Newly Diagnosed and Relapsed GNs
There were 13 patients reported in this case series. Of these, 8 of 13 cases (62%) were newly diagnosed with having GN whereas 5 of 13 cases (38%) were relapses. The median age was 62 (19–83) years. Most patients were White (12 of 13, 92%) and male (9 of 13, 69%). Autoimmune disease (38%) was the most common comorbidity in our series followed by cancer (23%). The autoimmune diseases included diabetes mellitus type 1, Crohn’s disease, ulcerative colitis, primary sclerosing cholangitis, and psoriatic arthritis. IgAN was the most common GN in our case series (5 of 13, 38%). The second most common GNs were MN (3 of 13, 23%) and primary podocytopathy (2 cases of minimal change disease [MCD] and 1 case of primary FSGS) (3 of 13, 23%). In addition, 54% of our patients received mRNA-1273 (Moderna) and the other 46% received BNT162b2 (Pfizer) vaccine. Most patients presented after the second dose (10 of 13, 77%). The median time of onset varied. Median time of onset in those newly diagnosed with having GN was 1 week after the first dose and 4 weeks after the second dose. In contrast, all of our relapse cases occurred after the second dose with median onset of 3 weeks. AKI, edema, and macroscopic hematuria were common presentations. Median serum creatinine level was 1.6 (0.6–2.5) mg/dl. Baseline clinical characteristics of each patient are found in Table 1.
Table 1.
Characteristics of initial presentation of patients with newly diagnosed and relapsed glomerulonephritis post–COVID-19 vaccination
| Case | Age | Sex | Race | Diagnosis | Vaccine | Onset after which dose | Onset time (wk) | Presenting symptoms | Baseline SCr (mg/dl) | Laboratories during presentation |
|||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SCr (g/dl) | Urine RBC (/HPF) | Urine protein (g/d) | SAlb (g/dl) | ||||||||||
| New cases | |||||||||||||
| 1 | 38 | M | W | IgAN | Pfizer | 2nd | 2 | Gross hematuria | 1.3 | 1.6 | 51–100 | 0.32 | NA |
| 2 | 44 | M | W | IgAN + acute interstitial nephritis | Moderna | 1st | 2 | AKI | 1.1 | 2.5 | 21–30 | 14 | 3.7 |
| 3 | 66 | M | W | IgAN | Moderna | 1st | 2 | Gross hematuria | 1.1 | 1.5a | 51–100 | 1.2 | 4.1 |
| 4 | 62 | M | W | IgAN | Pfizer | 2nd | 6 | AKI | 1 | 2.2 | 31–40 | 0.9 | 4.2 |
| 5 | 77 | M | W | Atypical anti-GBM nephritis | Pfizer | 1st | 1 | Hypertension | 1 | 1.8 | 51–100 | 1.6 | NA |
| 6 | 83 | M | W | MCD + ATN | Moderna | 2nd | 4 | AKI | 1.19 | 2.19 | <3 | 18 | 2.0 |
| 7 | 50 | F | W | NELL-1 MN | Pfizer | 2nd | 4 | Joint pain and proteinuria | 0.84 | 0.7 | 3–10 | 6.5 | 3.5 |
| 8 | 82 | F | W | MPO-ANCA | Moderna | 2nd | 4 | AKI, hematuria, proteinuria | 0.8 | 2.5b | 3–10 | 1.2 | NA |
| Relapsed cases | |||||||||||||
| 9 | 67 | F | W | MCD | Moderna | 2nd | 3 | Edema | 1 | 1.6 | <3 | 19 | 2.5 |
| 10 | 29 | F | A | FSGS (tip-variant) | Pfizer | 2nd | 3 | Edema | 0.6 | 0.6 | <3 | 10 | 2.2 |
| 11 | 39 | M | W | PLA2R MN | Pfizer | 2nd | 1 | Edema | 0.91 | 1.13 | 3–10 | 8.7 | 2 |
| 12 | 70 | M | W | PLA2R MN | Moderna | 2nd | 4 | Edema | 1.7 | 2.1 | <3 | 16.6 | 2.7 |
| 13 | 19 | M | W | IgAN | Moderna | 2nd | 1 | Gross hematuria | 0.96 | 0.76 | 11–20 | 0.61 | 4.5 |
A, Asian; AKI, acute kidney injury; ATN, acute tubular necrosis; F, female; FSGS, focal segmental glomerulosclerosis; GBM, glomerular basement membrane; HPF, high high-powered field; IgAN, IgA nephropathy; M, male; MCD, minimal change disease; MN, membranous nephropathy; MPO-ANCA, myeloperoxidase-antineutrophilic cytoplasmic antibody; NA, nonavailable; PLA2R: phospholipase A2 receptor; RBC, red blood cell; SAlb, serum albumin; SCr, serum creatinine; W, White.
Serum creatinine peaked at 2.2 mg/dl.
Serum creatinine peaked at 3.1 mg/dl.
Clinical Characteristics of Patients With Newly Diagnosed GNs
Of newly diagnosed cases (8 patients), there were 4 cases of IgAN, 1 case of MCD, 1 case of NELL-1–associated MN, 1 case of myeloperoxidase-antineutrophilic cytoplasmic Ab (ANCA) crescentic GN, and 1 case of atypical anti-GBM nephritis. The clinical characteristics of these patients are found in Table 1. There were 5 patients who presented after the second dose of the vaccine (range 2–6 weeks) and 3 patients who presented after the first dose (range 1–2 weeks). The main presenting symptom in patients with new diagnosis of IgAN included AKI and gross hematuria. Furthermore, 1 patient had a symptom of pericarditis in addition to gross hematuria at the time of presentation. There was also 1 patient who had a history of inflammatory bowel disease which raised possibility that he may have had IgA deposits in the kidney before undergoing vaccination and likely had asymptomatic IgAN. This patient also had history of renal cell carcinoma and had undergone partial nephrectomy 7 years before his vaccination. Results of his serum creatinine and urine studies had been normal at the time and in follow-up (last value from 1 year before vaccination). To evaluate for the presence of IgA deposits before vaccination, the nephrectomy sample was retrieved for further evaluation. Glomeruli were unremarkable on light microscopy. Immunofluorescence on pronase-digested, paraffin tissue was performed and revealed segmental mesangial staining of IgA, kappa, and lambda. Electron microscopy revealed presence of mesangial deposits. Therefore, the partial nephrectomy sample revealed evidence of subclinical IgAN. In addition, we had 1 case of atypical anti-GBM nephritis, characterized by bright diffuse linear GBM staining for IgG, kappa, and lambda on immunofluorescence and mesangial proliferation and basement membrane duplication on light microscopy, without the necrotizing and crescentic phenotype typically found in classic anti-GBM nephritis.16
Clinical Characteristics of Patients With Relapse of GN
Of the 5 patients who had a relapse, 2 patients had underlying phospholipase A2 receptor (PLA2R)-associated MN, 1 patient had relapse of MCD, and 1 patient originally had diagnosis of MCD but underwent a repeat kidney biopsy on relapse which revealed tip-variant lesion of primary FSGS, and 1 patient had underlying IgAN. All cases of relapse occurred after the second dose with onset ranging from 1 to 4 weeks. Detailed clinical characteristics of each patient are found in Table 1.
There was 1 patient with PLA2R-associated MN who was in complete remission with negative PLA2R Ab titer result and on no immunosuppression for 18 months before relapse. On relapse, the patient developed sudden-onset nephrotic syndrome and PLA2R Ab was elevated at 28 IU/ml. Another patient with PLA2R-associated MN who was in remission for 8 months presented with nephrotic syndrome, and PLA2R Ab titer result was positive at 3 IU/ml on enzyme-linked immunosorbent assay and positive by indirect immunofluorescence (they were both previously negative). The patient with primary FSGS was in complete remission and off immunosuppression for 24 months before relapse and presented with nephrotic syndrome. The patient with MCD was originally diagnosed with having MCD 3 months before vaccination. She went into complete remission within 4 weeks of starting therapy with high-dose steroids with proteinuria down to 200 mg per 24 hours. As a result, prednisone was tapered to 5 mg daily at which point she received her first dose of the vaccine. Nevertheless, 3 weeks after her second dose, she presented with worsening edema and was noted to have 19 g of protein in 24 hours. The patient with IgAN on last evaluation (2 months before vaccination) had serum creatinine level of 0.96 mg/dl, and urinalysis results revealed 50 to 100 red blood cells per high-powered field with 431 mg of protein per 24 hours. The patient also developed gross hematuria 24 hours after the second dose of COVID-19 vaccination. He had a similar reaction after influenza vaccination a year before.
Treatment and Clinical Follow-Up
Of 13 patients, 9 (69%) received immunosuppression (5 of 8 [63%] had new diagnosis and 4 of 5 [80%] were recurrence). The other 4 patients were treated conservatively. There were 10 patients who have available follow-up data ranging from 1 to 5 months. Of these, 8 patients responded to the treatments (6 treated with immunosuppression and 2 treated conservatively with angiotensin-converting enzyme inhibitor). Patient number 3 who responded to therapy had developed symptoms after the first dose and had further elevation in creatinine after the second dose (peak creatinine 2.2 mg/dl) which then subsequently improved to 1.4 mg/dl. One patient with IgAN and acute interstitial nephritis and the patient with atypical anti-GBM nephritis were both treated with immunosuppressive therapy but have not yet responded and have had progression of their kidney disease. Both of these patients developed symptoms after the first dose of the vaccine but proceeded to receive the second dose. Additional treatment details and outcomes are outlined in Table 2.
Table 2.
Treatment and follow-up of patients with newly diagnosed and relapsed glomerulonephritis post–COVID-19 vaccination
| Case | Age | Sex | Diagnosis | Vaccine | Treatment | Response | F/U time (mo) | Laboratories during last follow-up |
Duration of remission before relapse (m) | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SCr (g/dl) | Urine RBC (/HPF) | Urine protein (g/d) | SAlb (g/dl) | |||||||||
| New cases | ||||||||||||
| 1 | 38 | M | IgAN | Pfizer | Conservative | Unknown | Unknown | Unknown | Unknown | Unknown | Unknown | NA |
| 2 | 44 | M | IgAN+ interstitial nephritis | Moderna | High-dose steroid | NR | 3 | 3.6 | 3–10 | 5.6 | 3.8 | NA |
| 3 | 66 | M | IgAN | Moderna | Prednisonea | R | 5 | 1.4 | 3–10 | 0.3 | NA | NA |
| 4 | 62 | M | IgAN | Pfizer | Conservative | R | 1.5 | 2.0 | <3 | 0.2 | NA | NA |
| 5 | 77 | M | Atypical anti-GBM | Pfizer | Prednisone + mycophenolate | NR | 1.5 | 2.9 | 51–100 | 0.3 | 4 | NA |
| 6 | 83 | M | MCD + ATN | Moderna | High-dose steroid | R | 1 | 1.2 | <3 | 2 | 2.7 | NA |
| 7 | 50 | F | NELL-1 MN | Pfizer | Conservative | R | 2 | 0.7 | <3 | 0.4 | 4.3 | NA |
| 8 | 82 | F | MPO-ANCA | Moderna | High-dose steroid + rituximab | R | 1 | 2.3 | NA | NA | NA | NA |
| Relapsed cases | ||||||||||||
| 9 | 67 | F | MCD | Moderna | High-dose steroid + rituximab | R | 2 | 1.5 | 0–2 | 0.07 | 4.4 | 1 |
| 10 | 29 | F | Primary FSGS | Pfizer | High-dose steroid + tacrolimus | R | 3.5 | 0.7 | <3 | 3.7 | 3.2 | 24 |
| 11 | 39 | M | PLA2R MN | Pfizer | Tacrolimus | R | 1 | 1.1 | 3–10 | 5.7 | 2.9 | 18 |
| 12 | 70 | M | PLA2R MN | Moderna | Obinutuzumab | Unknown | Unknown | Unknown | Unknown | Unknown | Unknown | 8 |
| 13 | 19 | M | IgAN | Moderna | Conservative | Unknown | Unknown | Unknown | Unknown | Unknown | Unknown | 6 |
ATN, acute tubular necrosis; F, female; F/U, follow-up; FSGS, focal segmental glomerulosclerosis; GBM, glomerular basement membrane; HPF, high high-powered field; IgAN, IgA nephropathy; M, male; MCD, minimal change disease; MN, membranous nephropathy; NA, nonapplicable; NR, no response; PLA2R, phospholipase A2 receptor; R, response; RBC, red blood cell; SAlb, serum albumin; SCr, serum creatinine.
Prednisone was initiated for treatment of pericarditis.
Clinical Characteristics of Patients From Published Literatures
We found a total of 20 articles related to COVID-19 vaccines and GN published since inception until July 25, 2021. There were 27 cases including 13 cases of newly diagnosed GNs (48%) and 14 cases of relapse (52%) (Table 3). IgAN was the most common pathology (11 cases [41%]: 4 new and 7 relapse) followed by MCD (10 cases [37%]: 4 new and 6 relapse). Other pathologies include 2 cases of anti-GBM (7%) (both new cases), 2 cases of ANCA vasculitis (7%) (both new cases, 1 case of myeloperoxidase-ANCA and 1 case of proteinase 3-ANCA), 1 case of ANCA-negative granulomatous vasculitis (4%) (relapse), and 1 case of PLA2R-associated MN (4%) (relapse). Median age was 41 years, and 48% were male. Nevertheless, patients tended to be younger in the relapse group (median age 38 years) compared with the newly diagnosed group (median age 56 years) (Table 4).
Table 3.
Summary of published cases of newly diagnosed and relapsed glomerulonephritis
| Authors | Case | Age | Sex | Underlying disease | Vaccine | Symptoms | Onset after which dose | Onset | Diagnosis | Treatments | Outcomes |
|---|---|---|---|---|---|---|---|---|---|---|---|
| New cases | |||||||||||
| Lebedev et al.10 | 1 | 50 | M | No | mRNA (Pfizer) | Nephrotic syndrome, AKI, HTN | 1st | D 10 | MCD | High-dose steroid | Proteinuria and AKI significantly improved at 2 wks |
| D’Agati et al.6 | 2 | 77 | M | DM type 2 | mRNA (Pfizer) | Nephrotic syndrome, AKI, HTN | 1st | 1 wk | MCD | High-dose steroid | Proteinuria and SCr not improved at 3 wks |
| Holzworth et al.7 | 3 | 63 | F | HTN, tobacco dependence | mRNA (Moderna) | Nephrotic syndrome, uncontrolled HTN | 1st | <1 wk | MCD | High-dose steroid | NA |
| Maas et al.35 | 4 | 80 | F | NA | mRNA (Pfizer) | Nephrotic syndrome, HTN | 1st | 1 wk | MCD | High-dose steroid | Proteinuria reduced from 15 g/d to >0.7 g/d at d 10 |
| Sekar et al.12 | 5 | 52 | M | HTN | mRNA (Moderna) | Headache, AKI, hematuria | 2nd | 2 wks | PR3-ANCA vasculitis | RTX (side effects) and then i.v. CyC + steroid was started | Dialysis was started. 2nd dose of i.v. CyC was planned |
| Shakoor et al.36 | 6 | 78 | F | HTN, DM type 2 | mRNA (Pfizer) | AKI, hematuria, proteinuria | 1st | 2 wks | MPO-ANCA vasculitis | High-dose steroid and RTX | SCr improved from 3.5 to 2.3 mg/dl |
| Gillion et al.13 | 7 | 77 | M | No | Adenovirus vector (AstraZeneca) | Fever, night sweat, and AKI | 1st | 4 wks | ANCA-negative granulomatous vasculitis | High-dose steroid | SCr was normalized at 4 wks |
| Kudose et al.37 | 8 | 50 | F | HTN, APS | mRNA (Moderna) | Gross hematuria | 2nd | D 2 | IgAN | Conservative | Hematuria resolved in 5 d |
| 9 | 19 | M | Microscopic hematuria | mRNA (Moderna) | Gross hematuria | 2nd | D 2 | IgAN | Conservative | Hematuria resolved in 2 d | |
| Tan et al.38 | 10 | 41 | F | GDM | mRNA (Pfizer) | Gross hematuria | 2nd | D 1 | IgAN | High-dose steroid + IV CyC | NA |
| 11 | 60 | M | Hyperlipidemia | mRNA (Pfizer) | Gross hematuria | 2nd | D 1 | Anti-GBM | High-dose steroid + oral CyC + PLEX | NA | |
| Hanna et al.17 | 12 | 17 | M | No | mRNA (Pfizer) | Gross hematuria, AKI, proteinuria | 2nd | <24 h | IgAN | High-dose steroid | SCr improved (duration not reported) |
| Sacker et al.39 | 13 | — | F | No | mRNA (Moderna) | AKI, hematuria, proteinuria | 2nd | 2 wks | Anti-GBM | High-dose steroid, CyC, PLEX | Remained dialysis dependent |
| Relapsed cases | |||||||||||
| Negrea et al.18 | 1 | 38 | F | IgAN in remission | mRNA (Moderna) | Macroscopic hematuria | 2nd | 8–24 h | IgAN | Conservative | Spontaneously resolved |
| 2 | 38 | F | IgAN in remission | mRNA (Moderna) | Macroscopic hematuria | 2nd | 8–24 h | IgAN | Conservative | Spontaneously resolved | |
| Perrin et al.11 | 3 | 22 | M | IgA vasculitis | mRNA (Moderna) | Macroscopic hematuria | 1st | D 2 | IgAN | Conservative | Spontaneously resolved |
| 4 | 41 | F | Kidney transplant | mRNA (Pfizer) | Macroscopic hematuria | 1st | D 2 | IgAN | Conservative | Spontaneously resolved | |
| 5 | 27 | F | On hemodialysis | mRNA (Pfizer) | Macroscopic hematuria | 2nd | D 2 | IgAN | Conservative | Spontaneously resolved | |
| Hanna et al.17 | 6 | 13 | M | DM type 1 | mRNA (Pfizer) | Gross hematuria, AKI | 2nd | <24 h | IgAN | Conservative | Hematuria and AKI resolved within 1 wk |
| Rahim et al.19 | 7 | 52 | F | IgAN treated with ACEi | mRNA (Pfizer) | Gross hematuria, worsening proteinuria | 2nd | <24 h | IgAN | Conservative | Hematuria resolved within 1 wk |
| Schwotzer et al.40 | 8 | 22 | M | Steroid-dependent MCD | mRNA (Pfizer) | Nephrotic syndrome | 1st | D 3 | MCD | High-dose steroid + TAC | Remission was achieved at d 17 after treatment |
| Kervella et al.8 | 9 | 34 | F | Steroid-dependent MCD | mRNA (Pfizer) | Nephrotic syndrome | 1st | D 10 | MCD | High-dose steroid | Remission was achieved shortly after treatment |
| Komaba et al.9 | 10 | 65 | M | MCD in remission | mRNA (Pfizer) | Nephrotic syndrome | 1st | D 19 | MCD | High-dose steroid + cyclosporine | Remission was achieved at 2 wks |
| Morlidge et al.14 | 11 | 30 | M | MCD previously treated with RTX, TAC, and prednisone | Adenovirus vector (AstraZeneca) | Foamy urine | 1st | D 2 | MCD | High-dose steroid | Remission was achieved at 10 d |
| 12 | 40 | F | MCD on prednisone and TAC maintenance | Adenovirus vector (AstraZeneca) | Foamy urine | 1st | D 2 | MCD | High-dose steroid | Remission was achieved at 2 wks | |
| Mancianti et al.41 | 13 | 39 | M | MCD in remission for 37 yr | mRNA (Pfizer) | Nephrotic syndrome | 1st | 1 wk | MCD | High-dose steroid | Remission was achieved at 4 wks |
| Aydin et al.15 | 14 | 66 | F | HTN; DM type 2; MN previously on cyclosporine and steroid but off 7 yr ago | Inactivated virus (Sinovac) | Nephrotic syndrome, AKI | 1st | 2 wks | PLA2R-associated MN | NA | NA |
ACEi, angiotensin angiotensin-converting enzyme inhibitor; AKI, acute kidney injury; ANCA, antineutrophil cytoplasmic antibodies; APS, antiphospholipid syndrome; CyC, cyclophosphamide; DM, diabetes mellitus; F, female; GBM, glomerular basement membrane; GDM, gestational diabetes; HTN, hypertension; IgAN, IgA nephropathy; M, male; MCD, minimal change disease; MN, membranous nephropathy; MPO, myeloperoxidase; NA, nonapplicable; PLA2R, phospholipase A2 receptor; PLEX, plasma exchange; PR3, proteinase 3; RTX, rituximab; SCr, serum creatinine; TAC, tacrolimus.
Table 4.
Clinical characteristics of patients with GN post–COVID-19 vaccine from previously published literatures and current case series
| Characteristics | Current case series (n = 13) | Literatures (n = 27) | Total (n = 40) |
|---|---|---|---|
| Age (yr) | 62 (19–83) | 41 (13–80) | 50 (13–83) |
| Male sex, n (%) | 9 (69) | 13 (48) | 22 (55) |
| Underlying disease, n (%) | |||
| - Autoimmune disease | 5 (38) | NA | NA |
| - Diabetes | 2 (15) | NA | NA |
| - Cancer | 3 (23) | NA | NA |
| New vs. recurrent disease, n (%) | |||
| - New | 8 (62) | 13 (48) | 21 (53) |
| - Recurrent | 5 (38) | 14 (52) | 19 (47) |
| Diagnosis, n (%) | |||
| - IgA nephropathy | 5 (38) | 11 (41) | 16 (40) |
| - Minimal change disease | 2 (15) | 10 (37) | 12 (30) |
| - Membranous nephropathy | 3 (23) | 1 (4) | 4 (10) |
| - Anti-GBM disease | 1 (8) | 2 (7) | 3 (7) |
| - ANCA vasculitis | 1 (8) | 2 (7) | 3 (7) |
| - Focal segmental glomerulosclerosis | 1 (8) | — | 1 (3) |
| - ANCA-negative granulomatous vasculitis | — | 1 (4) | 1 (3) |
| Vaccine type, n (%) | |||
| - BNT162b2 (Pfizer) | 6 (46) | 15 (55) | 21 (53) |
| - mRNA-1273 (Moderna) | 7 (54) | 8 (30) | 15 (37) |
| - Adenovirus vector (AstraZeneca) | — | 3 (11) | 3 (7) |
| - Inactivated vaccine (CoronaVac by Sinovac) | — | 1 (4) | 1 (3) |
| Symptoms occur after 1st or 2nd dose, n (%) | |||
| - 1st dose | 3 (23) | 15 (56) | 18 (45) |
| - 2nd dose | 10 (77) | 12 (44) | 22 (55) |
| Onset | |||
| - New case s/p 1st dose | 1 (1, 2) | 1 (1, 4) | 1 (1, 4) |
| - New case s/p 2nd dose | 4 (2, 6) | 1 (1, 2) | 2 (1, 6) |
| - Relapse case s/p 1st dose | — | 1 (1, 2) | 1 (1, 2) |
| - Relapse case s/p 2nd dose | 3 (1, 4) | 1 (1, 1) | 1 (1, 4) |
| Laboratory on presentation | |||
| - Serum creatinine (mg/dl) | 1.6 (0.6, 2.5) | 1.7 (0.7, 8.4) | 1.7 (0.6, 8.4) |
| - Serum albumin (g/dl) | 3.1 (2, 4.5) | 2.7 (0.7, 4.7) | 2.9 (0.7, 4.7) |
| - Hematuria, n (%) | 9 (75) | 15 (58) | 24 (63) |
| - Urine protein (g/d) | 6.5 (0.3, 19) | 2.0 (0.3, 23.2) | 2.2 (0.3, 23.2) |
| Treatment, n (%) | |||
| - Conservative management | 4 (31) | 9 (33) | 13 (32) |
| - Immunosuppression | 9 (69) | 18 (67) | 27 (68) |
| Outcome,an (%) | |||
| - Response | 8 (80) | 21 (91) | 29 (88) |
| - Not response | 2 (20) | 2 (9) | 4 (12) |
ANCA, antineutrophil cytoplasmic antibodies; GBM, glomerular basement membrane; GN, glomerulonephritis; NA, nonavailable; s/p, status post.
There were only 10 patients in our case series and 23 patients from the literatures with follow-up outcome.
BNT162b2 (Pfizer) vaccine was the most common vaccine administered (15 of 27 patients, 55%) followed by mRNA-1273 (Moderna) (8 of 27 patients, 30%). There were 3 patients who received AstraZeneca vaccine (11%), and only a single patient who received inactivated vaccine (4%) (CoronaVac by Sinovac) (Table 4).
Of 27 patients, 15 patients (56%) developed symptoms after the first dose whereas the remaining (12 patients, 44%) developed symptoms after the second dose. Nevertheless, patients newly diagnosed with having GN tended to develop symptoms after the second dose (7 of 13 patients, 54%) and those with relapses tended to develop symptoms after the first dose (9 of 14 patients, 64%) (Table 4).
Clinical Characteristics and Follow-Up of Patients by Disease
IgA Nephropathy
In our case series, there were 5 cases of IgAN (4 new and 1 relapse). In the literatures, there were 11 cases of IgAN reported (4 new and 7 relapse). Gross hematuria was the most common presentation followed by AKI. Nevertheless, in most patients, gross hematuria was often self-limited and seldom required immunosuppression. Of the total of 16 patients, only 3 patients received immunosuppression and 1 patient had superimposed acute interstitial nephritis as well. All cases of relapsed IgA improved spontaneously within 1 to 2 weeks.
Primary Podocytopathy
In our case series, there were 2 cases of MCD (1 new and 1 relapse) and 1 case that was previously MCD but on repeat biopsy revealed a tip-variant FSGS lesion. In the literatures, there were 10 cases (4 new and 6 relapse). All cases in our series developed symptoms after the second dose, whereas all MCD cases in the literature developed symptoms after the first dose. All patients received immunosuppression. One patient with new MCD responded rapidly to therapy. One patient with relapse of MCD did not respond to high-dose steroids and received rituximab to which the patient responded. The patient with primary FSGS had partial response to prednisone in combination with tacrolimus.
Membranous Nephropathy
In our case series, there were 3 cases of MN in which 2 cases were associated with PLA2R (relapse) and 1 case with NELL-1 (new). The patient with NELL-1–associated MN had age-appropriate cancer screening completed with negative results. On the basis of literature review, there has been 1 case of PLA2R-associated MN after inactivated vaccine. All patients in our series developed nephrotic syndrome after the second dose. The patient with NELL-1–associated MN significantly improved after conservative management. Proteinuria improved from 6.5 g/d to 0.4 g/d within 3 months after angiotensin-converting enzyme inhibitor initiation. Of 2 patients with PLA2R-asociated MN, only 1 patient from our series has follow-up data. The patient was restarted on tacrolimus. At 1 month, proteinuria and serum albumin improved from 8.7 g/d to 5.7 g/d and 2.0 g/dl to 2.9 g/dl, respectively.
Anti-GBM and ANCA–Associated Vasculitis
In our case series, there was 1 case of atypical anti-GBM nephritis. In the literatures, there have been 2 cases of classic anti-GBM nephritis. The patient from our series presented 1 week after the first dose with symptom of uncontrolled hypertension (systolic blood pressure level >200 mm Hg), whereas the other 2 cases from literatures presented within 2 weeks after the second dose. Outcome data were available in 2 patients (one from our series and another from the literature). Our patient did not respond to mycophenolate and high-dose steroid, and his serum creatinine level continued to rise. He has now been initiated on cyclophosphamide, but it is too early to know the response. Another patient received cyclophosphamide, plasmapheresis, and high-dose steroid, but the patient did not respond and has remained on dialysis.
We had 1 patient with myeloperoxidase-ANCA–associated vasculitis, and in the literature, there were 2 cases of ANCA–associated vasculitis, one associated with myeloperoxidase and another with proteinase 3. In addition, there was a single case report of ANCA-negative granulomatous vasculitis post adenoviral vector vaccine. Our patient presented with shortness of breath and fatigue 4 weeks after the second dose. The patient was found to have AKI, serum creatinine level of 2.5, with microscopic hematuria and subnephrotic range proteinuria. Subsequently, serum creatinine level increased to 3.1, and a kidney biopsy was done which revealed pauci-immune crescentic GN. The patient was treated with rituximab and high-dose prednisone, and serum creatinine level 1 month post-treatment improved at 2.3 mg/dl. From the literature, patients with myeloperoxidase-ANCA and ANCA-negative granulomatous vasculitis responded to therapy with improvement in serum creatinine. In contrast, the patient with proteinase 3-ANCA–associated vasculitis required initiation of dialysis.
Discussion
Our case series is the largest series to report on both newly diagnosed and relapsed cases of GN post–COVID-19 vaccination. All patients in our series received mRNA vaccines. The BNT162b (Pfizer) and mRNA-1273 (Moderna) are the 2 most widely used vaccines in the United States after their use was approved under emergency use authorization by the US Food and Drug Administration. Most patients in our series developed kidney-related symptoms after the second dose, but the onset of symptoms varied from 1 week after the first dose to 6 weeks after the second dose. Taking into account cases reported in the literature, the onset of symptoms has been reported as early as few hours after the first dose.17, 18, 19 It is possible that some patients in our series may have had signs of kidney injury (e.g., elevated creatinine, proteinuria, or microscopic hematuria) between the first and second doses but had not been medically evaluated in that interim. In addition, the 3 patients who had developed symptoms after the first dose proceeded to receive the second dose as their presentations at the time were not attributed to the COVID-19 vaccine. Even though the median age was 62 years, the range varied from 19 to 83 years of age. This wide range of presentation has also been noted in the other recent reports in the literature ranging from 13 to 80 years of age (Table 4).
The mRNA vaccine has been developed and refined for nearly 2 decades, but it was not used clinically until only recently.20 The vaccine contains purified modified mRNA and a vehicle that helps deliver mRNA into host cells.20 After injection, mRNA will be translated into target protein which in turn results in immune system activation. Growing evidence from several large phase 3 randomized controlled trials and real-world data have revealed superiority of mRNA vaccine over inactivated vaccine.1,2,21,22 This may be partly due to their ability to induce robust cell-mediated and Ab-mediated immune responses.3 Indeed, they have been found to induce neutralizing Ab to the level far beyond convalescent serum.23 Moreover, the neutralizing Ab after mRNA vaccine seems to be higher than that of adenoviral vector COVID-19 vaccine.23 The cell-mediated response results from up-regulation of CD4+ and CD8+ T cells accompanied by increasing interferon γ secretion.3 The CD4+ T cell response from mRNA vaccine has been found to confer partial protection to nonancestral strain of SARS-CoV-2 and endemic coronavirus suggesting immune crossover.24 Similarly, another study was found to have cross-reactivity of Ab to SARS-CoV-2 spike protein and nucleocapsid to other self-human antigens, such as transglutaminase 3, extractable nuclear antigen, myelin basic protein, mitochondria, α-myosin, thyroid peroxidase, collagen, and claudin.25 Therefore, it is conceivable that this higher immunogenicity and cross-reactivity could lead to unexpected and perhaps nonspecific immune activation that may aggravate, unmask, or incite autoimmune processes. Similar to the cases of GN, this immune activation after mRNA COVID-19 vaccination has been associated with cases of myocarditis, particularly in young males.5 A detailed investigation in a single patient with myocarditis revealed up-regulated specific natural killer cells but absence of Th17 and certain cytokines that are often associated with myocarditis suggesting underlying host-related factors can play a role in development of autoimmunity.4 Indeed, we observed a high prevalence of autoimmune diseases in our series, and it is likely that this underlying immune dysregulation is a risk factor for development of GN or relapse of the disease.
It is noteworthy that many of the reported GNs in association with COVID-19 vaccination have also been noted with the COVID-19 infection itself. Podocytopathy and collapsing glomerulopathy in addition to cases of anti-GBM disease and ANCA–associated vasculitis have all been reported.26, 27, 28, 29 The pathophysiology of GNs in association with COVID-19 infection is complex and may include direct cytotoxicity to the podocytes in addition to immune dysregulation.27,28 It is possible that the immune response to COVID-19 vaccine mimics what happens in response to natural infection thus resulting in GN in susceptible patients.
Relapse of GN after vaccination when there is up-regulation of both cell-mediated (e.g., in cases of relapse of MCD)30 and Ab-mediated immunity (e.g., relapse of PLA2R-associated MN) is conceivable. But why do some patients develop new GN? One possibility is that they have underlying immune dysregulation which in turn makes them predisposed to development of GN. As noted previously, 38% of the individuals in our series had altered autoimmunity at baseline. Another possibility is that the disease perhaps was present before the vaccination, but patient was clinically asymptomatic. This may be the case in patients with new IgAN. We were able to reveal for the first time that in at least 1 patient with “new” diagnosis of IgAN, the IgA deposits were indeed present before the vaccination. This patient had a previous partial nephrectomy sample available from 7 years before, and review of this sample confirmed IgA deposits. This case provides proof that in some individuals, the vaccine only results in a “flare” of the already present disease rather than development of new IgA antibodies that are deposited in the kidney. Although we cannot confirm this finding in other cases of IgAN owing to lack of prevaccination kidney specimen, it is likely that cases with earlier onset of symptoms postvaccination have already had IgA deposits. IgAN was the most often noted GN post–COVID-19 vaccination both in our series and based on review of the literature. This finding might be explained by the fact that IgA comprises the major Ab response early after mRNA COVID-19 vaccination.31
The development of GN (e.g., IgAN and MCD) after vaccination is not new and has been reported in humans and animal models.34, 33, 32 It is likely that the mRNA vaccine results in a more potent immune response and therefore associated with a higher rate of GN compared with other types of vaccine (inactivated virus). It is important to also note that this unwanted immune activation occurs in only a very small percentage of vaccinated patients. The exact incidence is unknown as some cases may not have been reported in the literature or may not have been recognized. The rarity of GNs post–COVID-19 vaccine may be similar to the cases of myocarditis in association with the mRNA vaccines, and thus far, the Centers for Disease Control and Prevention endorses continuation of COVID-19 vaccination owing to benefit over risk profile.5
At this point in time, outcome of newly diagnosed and relapsed GNs post–COVID-19 vaccine seems favorable in patients with nephrotic syndrome and IgAN. Most IgAN cases who presented with gross hematuria spontaneously remitted without specific intervention. Approximately 69% of the patients in our case series developed AKI, but most of them developed AKI stage 1. Of the 10 patients with available follow-up data, 8 have responded to therapy (conservative and immunosuppression). One case of IgAN has had a progressive course. This patient, however, also had features of acute interstitial nephritis on his kidney biopsy results which may have contributed to progression of the disease. In contrast, patients with anti-GBM and ANCA–associated vasculitis particularly seem to have fewer desirable outcomes. One patient with atypical anti-GBM nephritis has had progressive disease after treatment with high-dose steroids and mycophenolate mofetil. His treatment has been changed to cyclophosphamide, and additional follow-up at this point is not available. None of the patient from our case series required dialysis. Nevertheless, there were 2 patients from the literature including anti-GBM and proteinase 3-ANCA vasculitis who did not respond to therapy and thus required dialysis initiation. Taken together, of 40 reported cases, only 2 patients (5%) have been reported to require dialysis. Longer term follow-up is needed to better understand the trajectory and kidney outcome of these patients.
Our case series has limitations. Even though it is the largest series reported thus far, the sample size is still limited. This is likely in part due to the fact that the incidence is low, but we cannot exclude the possibility that some cases may have been missed. Another limitation is lack of long-term data on these patients. Even though in short-term outcomes seem favorable we need longer term follow-up of these patients. Finally, we cannot prove with certainty that the vaccine resulted in development of new or relapse of the GN, but certainly the temporal association is compelling.
In summary, this case series in combination with cases published thus far in the literature provides data on 40 patients with new and relapsed GN post–mRNA COVID-19 vaccine. As mass vaccination efforts continue, and recognizing the overwhelming benefits of vaccination for individuals with chronic kidney disease who are at increased risk of devastating COVID-19 complications (including death, dialysis, long COVID-19 infection), nephrologists and other physicians should be aware of this association and remain vigilant when evaluating patients postvaccination especially when there are symptoms of kidney-related injury present.
Disclosure
All the authors declared no competing interests.
References
- 1.Polack F.P., Thomas S.J., Kitchin N., et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N Engl J Med. 2020;383:2603–2615. doi: 10.1056/NEJMoa2034577. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Baden L.R., El Sahly H.M., Essink B., et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384:403–416. doi: 10.1056/NEJMoa2035389. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Sahin U, Muik A, Vogler I, et al. BNT162b2 induces SARS-CoV-2-neutralising antibodies and T cells in humans. medRxiv. Published December 11, 2020. Accessed July 7, 2021. https://www.medrxiv.org/content/10.1101/2020.12.09.20245175v1.full.pdf
- 4.Muthukumar A., Narasimhan M., Li Q.Z., et al. In depth evaluation of a case of presumed myocarditis following the second dose of COVID-19 mRNA vaccine. Circulation. 2021;144:487–498. doi: 10.1161/CIRCULATIONAHA.121.056038. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Gargano J.W., Wallace M., Hadler S.C., et al. Use of mRNA COVID-19 vaccine after reports of myocarditis among vaccine recipients: update from the Advisory Committee on Immunization Practices-United States, June 2021. MMWR Morb Mortal Wkly Rep. 2021;70:977–982. doi: 10.15585/mmwr.mm7027e2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.D’Agati V.D., Kudose S., Bomback A.S., et al. 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.Holzworth A., Couchot P., Cruz-Knight W., Brucculeri M. Minimal change disease following the Moderna mRNA-1273 SARS-CoV-2 vaccine. Kidney Int. 2021;100:463–464. doi: 10.1016/j.kint.2021.05.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Kervella D., Jacquemont L., Chapelet-Debout A., et al. Minimal change disease relapse following SARS-CoV-2 mRNA vaccine. Kidney Int. 2021;100:457–458. doi: 10.1016/j.kint.2021.04.033. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Komaba H., Wada T., Fukagawa M. Relapse of minimal change disease following the Pfizer-BioNTech COVID-19 vaccine. Am J Kidney Dis. 2021;78:469–470. doi: 10.1053/j.ajkd.2021.05.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Lebedev L., Sapojnikov M., Wechsler A., et al. 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]
- 11.Perrin P., Bassand X., Benotmane I., Bouvier N. Gross hematuria following SARS-CoV-2 vaccination in patients with IgA nephropathy. Kidney Int. 2021;100:466–468. doi: 10.1016/j.kint.2021.05.022. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Sekar A., Campbell R., Tabbara J., Rastogi P. ANCA glomerulonephritis after the Moderna COVID-19 vaccination. Kidney Int. 2021;100:473–474. doi: 10.1016/j.kint.2021.05.017. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Gillion V., Jadoul M., Demoulin N., et al. Granulomatous vasculitis after the AstraZeneca anti-SARS-CoV-2 vaccine. Kidney Int. 2021;100:706–707. doi: 10.1016/j.kint.2021.06.033. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Morlidge C., El-Kateb S., Jeevaratnam P., Thompson B. Relapse of minimal change disease following the AstraZeneca COVID-19 vaccine. Kidney Int. 2021;100:459. doi: 10.1016/j.kint.2021.06.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Aydın M.F., Yıldız A., Oruç A., et al. Relapse of primary membranous nephropathy after inactivated SARS-CoV-2 virus vaccination. Kidney Int. 2021;100:464–465. doi: 10.1016/j.kint.2021.05.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Nasr S.H., Collins A.B., Alexander M.P., et al. The clinicopathologic characteristics and outcome of atypical anti-glomerular basement membrane nephritis. Kidney Int. 2016;89:897–908. doi: 10.1016/j.kint.2016.02.001. [DOI] [PubMed] [Google Scholar]
- 17.Hanna C., Herrera Hernandez L.P., Bu L., et al. IgA nephropathy presenting as macroscopic hematuria in 2 pediatric patients after receiving the Pfizer COVID-19 vaccine. Kidney Int. 2021;100:705–706. doi: 10.1016/j.kint.2021.06.032. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Negrea L., Rovin B.H. Gross hematuria following vaccination for severe acute respiratory syndrome coronavirus 2 in 2 patients with IgA nephropathy. Kidney Int. 2021;99:1487. doi: 10.1016/j.kint.2021.03.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Rahim S.E.G., Lin J.T., Wang J.C. A case of gross hematuria and IgA nephropathy flare-up following SARS-CoV-2 vaccination. Kidney Int. 2021;100:238. doi: 10.1016/j.kint.2021.04.024. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Pardi N., Hogan M.J., Weissman D. Recent advances in mRNA vaccine technology. Curr Opin Immunol. 2020;65:14–20. doi: 10.1016/j.coi.2020.01.008. [DOI] [PubMed] [Google Scholar]
- 21.Jara A., Undurraga E.A., González C., et al. Effectiveness of an inactivated SARS-CoV-2 vaccine in Chile. N Engl J Med. 2021;385:875–884. doi: 10.1056/NEJMoa2107715. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Thompson M.G., Burgess J.L., Naleway A.L., et al. Prevention and attenuation of COVID-19 with the BNT162b2 and mRNA-1273 vaccines. N Engl J Med. 2021;385:320–329. doi: 10.1056/NEJMoa2107058. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Tada T, Zhou H, Samanovic MI, et al. Comparison of neutralizing antibody titers elicited by mRNA and adenoviral vector vaccine against SARS-CoV-2 variants. bioRxiv. Published August 6, 2021. Accessed July 23, 2021. https://www.biorxiv.org/content/10.1101/2021.07.19.452771v3.full.pdf
- 24.Woldemeskel B.A., Garliss C.C., Blankson J.N. SARS-CoV-2 mRNA vaccines induce broad CD4+ T cell responses that recognize SARS-CoV-2 variants and HCoV-NL63. J Clin Invest. 2021;131 doi: 10.1172/JCI149335. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Vojdani A., Kharrazian D. Potential antigenic cross-reactivity between SARS-CoV-2 and human tissue with a possible link to an increase in autoimmune diseases. Clin Immunol. 2020;217:108480. doi: 10.1016/j.clim.2020.108480. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Gupta R.K., Bhargava R., Shaukat A.A., et al. Spectrum of podocytopathies in new-onset nephrotic syndrome following COVID-19 disease: a report of 2 cases. BMC Nephrol. 2020;21:326. doi: 10.1186/s12882-020-01970-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Prendecki M., Clarke C., Cairns T., et al. Anti-glomerular basement membrane disease during the COVID-19 pandemic. Kidney Int. 2020;98:780–781. doi: 10.1016/j.kint.2020.06.009. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Shetty A.A., Tawhari I., Safar-Boueri L., et al. COVID-19-associated glomerular disease. J Am Soc Nephrol. 2021;32:33–40. doi: 10.1681/ASN.2020060804. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Uppal N.N., Kello N., Shah H.H., et al. De novo ANCA-associated vasculitis with glomerulonephritis in COVID-19. Kidney Int Rep. 2020;5:2079–2083. doi: 10.1016/j.ekir.2020.08.012. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Ishimoto T., Shimada M., Araya C.E., et al. Minimal change disease: a CD80 podocytopathy? Semin Nephrol. 2011;31:320–325. doi: 10.1016/j.semnephrol.2011.06.002. [DOI] [PubMed] [Google Scholar]
- 31.Wisnewski A.V., Campillo Luna J., Redlich C.A. Human IgG and IgA responses to COVID-19 mRNA vaccines. PLoS One. 2021;16 doi: 10.1371/journal.pone.0249499. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Kavukçu S., Soylu A., Sarioğlu S., et al. IgA nephropathy in mice following repeated administration of conjugated Haemophilus influenzae type B vaccine (PRP-T) Tokai J Exp Clin Med. 1997;22:167–174. [PubMed] [Google Scholar]
- 33.Kielstein J.T., Termühlen L., Sohn J., Kliem V. Minimal change nephrotic syndrome in a 65-year-old patient following influenza vaccination. Clin Nephrol. 2000;54:246–248. [PubMed] [Google Scholar]
- 34.Gutiérrez S., Dotto B., Petiti J.P., et al. Minimal change disease following influenza vaccination and acute renal failure: just a coincidence? Nefrologia. 2012;32:414–415. doi: 10.3265/Nefrologia.pre2012.Feb.11370. [DOI] [PubMed] [Google Scholar]
- 35.Maas 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;78:312. doi: 10.1053/j.ajkd.2021.05.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Shakoor M.T., Birkenbach M.P., Lynch M. ANCA-associated vasculitis following the Pfizer-BioNTech COVID-19 vaccine. Am J Kidney Dis. 2021;78:611–613. doi: 10.1053/j.ajkd.2021.06.016. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Kudose S., Friedmann P., Albajrami O., D’Agati V.D. Histologic correlates of gross hematuria following Moderna COVID-19 vaccine in patients with IgA nephropathy. Kidney Int. 2021;100:468–469. doi: 10.1016/j.kint.2021.06.011. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.Tan H.Z., Tan R.Y., Choo J.C.J., et al. Is COVID-19 vaccination unmasking glomerulonephritis? Kidney Int. 2021;100:469–471. doi: 10.1016/j.kint.2021.05.009. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39.Sacker A., Kung V., Andeen N. Anti-GBM nephritis with mesangial IgA deposits after SARS-CoV-2 mRNA vaccination. Kidney Int. 2021;100:471–472. doi: 10.1016/j.kint.2021.06.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40.Schwotzer N., Kissling S., Fakhouri F. Letter regarding “Minimal change disease relapse following SARS-CoV-2 mRNA vaccine”. Kidney Int. 2021;100:458–459. doi: 10.1016/j.kint.2021.05.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41.Mancianti N., Guarnieri A., Tripodi S., et al. Minimal change disease following vaccination for SARS-CoV-2. J Nephrol. 2021;34:1039–1040. doi: 10.1007/s40620-021-01091-1. [DOI] [PMC free article] [PubMed] [Google Scholar]