Introduction
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is considered safe in patients with kidney disease and is prioritized in this population due to increased mortality from coronavirus disease 2019 (COVID-19) (1). However, given the ability to activate the immune system, immunizations carry a risk of exacerbating disease or inducing flares in patients with glomerulonephritides. Prior to the onset of SARS-CoV-2 vaccinations, there were rare reports of immunizations temporally associated with glomerular disease. The incidence of these adverse events is unknown, although is likely exceedingly rare and is primarily described in single patient reports. Minimal change disease (MCD) has been reported in temporal association with influenza, hepatitis B, and tetanus-diphteria-poliomyelitis vaccinations. Additionally, crescentic glomerulonephritis (GN) has been triggered by influenza and pneumococcal immunizations (2).
The mechanism for which vaccines could elicit an autoimmune response resulting in GN is unknown, but it potentially could result from molecular mimicry of an antigen with host proteins in individuals with underlying genetic susceptibility or particular HLA haplotypes. Molecular mimicry has been described to induce autoimmune reactions in conjunction with influenza, hepatitis B, and human papillomavirus immunizations (3).
Currently, more individuals are being vaccinated than in any other time period before, and vaccinations include different vectors (nanoparticles or adenoviral-based replication-deficient virions). This worldwide vaccination program for SARS-CoV-2 during the COVID-19 pandemic provides an opportunity to investigate vaccine-related glomerular diseases. Here, we describe 29 cases of glomerular disease temporally associated with SARS-CoV-2 vaccination reviewed at a single center.
Materials and Methods
Patient Selection
Kidney biopsies from patients who developed AKI, nephritic syndrome, or nephrotic syndrome within 1 month of either the first or second dose of SARS-CoV-2 vaccination were included in the study, following approval by the Solutions Institutional Review Board. The guidelines of the Declaration of Helsinki for the protection of human subjects were followed. Native and allograft biopsies, as well as new-onset and recurrent kidney disease, were investigated. All kidney biopsies of patients with SARS-CoV-2 vaccine with close temporal association (within 1 month) to development of kidney disease were included to avoid selection bias. No patients in this study had known prior COVID-19. Kidney biopsies were reviewed at a single center, and clinical information was provided from nephrologists for clinicopathologic correlation.
Clinical Assessment and Follow-Up
Biopsies were reviewed at a single center, and clinical information was obtained (demographics, vaccine type, temporality to symptom onset, laboratory parameters, medical comorbidities, treatments, and follow-up). Clinical parameters included demographics, vaccine type, temporality of vaccine to onset of symptoms, laboratory parameters, medical history, treatments, and clinical follow-up. Patient demographics included age, race/ethnicity (which was physician-ascribed race), and sex. SARS-CoV-2 immunization types were recorded (Pfizer-BioNTech BNT162b2 mRNA, Moderna mRNA-1273, AstraZeneca adenoviral ChAdOx1 nCoV-19, or Johnson & Johnson/Janssen adenoviral JNJ-78436735). Documented medical comorbidities included preexisting chronic kidney disease (CKD; GFR <60 ml/min prior to disease onset), autoimmune disease, hypertension, diabetes, smoking, chronic obstructive pulmonary disease, and obesity. The number of weeks elapsed between the first and second vaccine doses to the time of biopsy and the number of days from vaccination to onset of symptoms were noted. Laboratory values included serum creatinine, proteinuria, hematuria, serologies (antinuclear antibodies, ANCA, hepatitis B, hepatitis C, and HIV), and serum albumin (grams per deciliter). Clinical follow-up parameters included the time interval between biopsy and last follow-up, treatment(s) provided prior to and after biopsy, requirement of kidney replacement therapy (KRT)/dialysis, clinical response, serum creatinine, and proteinuria.
Biopsy Database Comparisons
The frequencies of glomerular diseases during the period of mass vaccination (January 1, 2021–July 1, 2021) were compared with 2 years of biopsies evaluated by our laboratory prior to the pandemic (January 1, 2018–December 31, 2019) through searching a PowerPath kidney biopsy database by natural language searches and/or ICD10 codes. Within our database, the racial distribution includes 48.3% Whites, 15.4% Blacks, 4.7% Hispanics, 2.8% Asians, 1.9% Native Americans, and 27.0% patients of unknown descent (4). This is representative of the kidney biopsy database, although the demographics of each individual clinical practice submitting these biopsies are unknown.
Pathologic Assessment
Histopathologic review included evaluation of light, immunofluorescence, and electron microscopy processed by standard techniques. Light microscopy parameters included mesangial expansion, mesangial hypercellularity, endocapillary hypercellularity, fibrinoid necrosis, crescent formation, segmental sclerosis (including type according to the Columbia classification), and presence/absence of microangiopathic changes within glomeruli. Tubulointerstitial changes evaluated included acute tubular injury, interstitial edema, interstitial inflammation, lymphocytic tubulitis, interstitial fibrosis, and tubular atrophy. Vascular assessment included degree of arteriosclerosis and arteriolar hyalinosis. Immunofluorescence included IgA, IgG, IgM, C3, C1q, albumin, fibrinogen, and κ- and λ-light chain staining for all cases and was graded on a 0–3+ scale. Ultrastructural features recorded included the presence/absence of subepithelial, subendothelial, and mesangial electron dense deposits, as well as the degree of podocyte foot process effacement.
For biopsies with membranous nephropathy (MN), immunostaining for antigenic targets was performed using antibodies against phospholipase A2 receptor (PLA2R; Sigma-Aldrich; catalog no. HPA012657), neural epidermal growth factor like-1 (NELL1; Novus Biologicals; catalog no. H00004745), thrombospondin type 1 domain containing 7A (THSD7A; Atlas Antibodies; catalog no. AMA91234), and exostosin 1 (EXT1; Invitrogen; catalog no. PA5–27958). For all antigens, presence of granular capillary loop staining (1+ or greater) was considered a positive result.
APOL1 Genotyping
Genotyping for APOL1 G1 and G2 risk alleles was performed in patients with collapsing glomerulopathy (CG). Briefly, APOL1 genotyping was performed by nested multiplex PCR to amplify the regions of the APOL1 gene carrying the G1 single nucleotide polymorphism (rs73885319) and the G2 six–base pair insertion/deletion (rs71785313). A ViiA 7 real-time PCR system was used to perform TaqMan PCR. Data were evaluated on ViiA7 sequence detection software. Allelic discrimination plots were used to determine the call results.
Statistical Analyses
Means±SDs were used to compare patients’ ages. Other continuous variables were assessed by median±interquartile range (IQR). Frequency data were compared using chi-squared testing with GraphPad Prism software with a cutoff of P=0.01 for significance.
Literature Review
All patient reports and series describing glomerular disease in temporal association with SARS-CoV-2 vaccination were included in a review of the literature. PubMed and Google Scholar were used to identify articles, and only those written in the English language were included.
Results
Twenty-nine patients with kidney disease within 1 month of SARS-CoV-2 vaccination were identified; all had glomerular disease. Twenty-eight patients had native kidney biopsy (all of which were de novo GN), and there was one case of recurrent disease in a transplant recipient identified on allograft biopsy. Of the 29 patients, 27 received mRNA vaccines (11 Moderna, 12 Pfizer-BioNTech, and four unknown), and two received adenoviral vaccines (one Johnson & Johnson/Jensen and one AstraZeneca). Patients with an unknown vaccine type were vaccinated during a time period where only the Moderna and Pfizer-BioNTech vaccines were available under the Food and Drug Administration's emergency release authorization. Twenty-three patients who had mRNA vaccines received two vaccine doses. There were 12 men and 17 women, with a mean age of 55.2±19.3 years. Twenty patients were White, two were Black, three were Asian, one was Indian, and three were of Hispanic descent. Twenty-two patients had at least one comorbidity, including hypertension (n=16), diabetes mellitus (n=7), obesity (n=9), smoking (n=2), chronic obstructive pulmonary disease (n=4), autoimmune disease(s) (n=8), and CKD (n=7).
The most common presentation was AKI with concurrent nephritic or nephrotic syndrome (n=15), followed by nephritic syndrome (n=11) and nephrotic syndrome with preserved kidney function (n=3) (Table 1). A majority of patients had an elevated serum creatinine (median, 2.17±3.455 IQR, 1.195; 4.65), 28 had proteinuria (nephrotic range in 12 patients), 25 had hematuria, and 23 had hypoalbuminemia (of 27 with available data; median, 2.75±1.1 IQR, 2.3; 3.4). Five patients had hypocomplementemia (of 24 with available data). Twelve patients had antinuclear antibodies, and ten had a positive ANCA serology (Table 1). One patient had a positive hepatitis C serology (of 22 patients with data available), and one patient was HIV positive (of 18 patients with available data). There were no patients who were positive for hepatitis B sAg (n=22).
Table 1. -
Clinical and laboratory features of patients with severe acute respiratory syndrome coronavirus 2 vaccine–associated glomerular disease
Patient Number |
Age, yr |
Sex |
Race |
Vaccine Type |
1st/2nd Dose
a
|
Time |
Indication |
Diagnosis |
Creatinine |
Proteinuria |
Albumin |
Hematuria |
Antinuclear Antibodies |
ANCA |
Treatment before Biopsy |
Treatment after Biopsy |
Follow-Up |
Recovery |
Follow-Up Creatinine |
Follow-Up Proteinuria |
1 |
67 |
F |
B |
Moderna |
7 wk/3 wk |
<1 wk |
AKI, n.s. |
CG |
6.7 |
12 |
2.7 |
Pos |
Neg |
Neg |
D |
D; IS 1 |
12 wk |
Partial |
1.8 |
2.5 |
2 |
26 |
F |
B |
Moderna |
5 wk/1 wk |
<1 wk |
AKI, n.s. |
CG, MN |
7.7 |
6 |
2.4 |
Pos |
Pos |
Neg |
D; IS 1+IS 2 |
D; IS 3 |
1 wk |
No |
D* |
D* |
3 |
70 |
F |
W |
Pfizer |
7 wk/3 wk |
<1 wk |
AKI, n.s. |
MCD |
2.2 |
19.2 |
1.5 |
Neg |
Neg |
ND |
Diur |
IS 1 |
4 wk |
Yes |
1 |
Neg |
4 |
43 |
F |
Indian |
Pfizer |
11 wk/7 wk |
2 wk |
n.s. |
MCD |
Unk |
10 |
1.9 |
Neg |
Neg |
Neg |
None |
IS 1 |
4 wk |
Yes |
<1 |
Neg |
5 |
79 |
M |
Asian |
mRNA
a
|
2 wk |
<2 wk |
AKI, n.s. |
MCD |
2.1 |
4+ |
Low |
Pos |
Pos |
Neg |
IS 1; Diur |
IS 1 |
4 wk |
No |
2.5 |
UA 3+ |
6 |
72 |
M |
W |
Moderna |
9 wk/5 wk |
1 wk |
n.s. |
MCD |
0.7 |
16.1 |
2.7 |
Pos |
Pos |
Neg |
Diur; ARB |
IS 1, ACEI |
2 wk |
Yes |
0.9 |
UA Pos |
7 |
47 |
F |
W |
Pfizer |
5 wk/1 wk |
<2 wk |
AKI, n.s. |
MCD |
6.1 |
>600 mg/dl |
1.9 |
Neg |
Neg |
Neg |
D |
D; IS 1; ACEI |
4 wk |
No |
4.3; D* |
UA Pos; D* |
8 |
23 |
M |
W |
AstraZeneca |
2 wk |
2 wk |
AKI, n.s. |
MCD |
2.9 |
14 |
1.7 |
Pos |
Pos |
Neg |
None |
IS 1; Diur |
3 wk |
Yes |
1.0 |
0.07 |
9 |
45 |
F |
W |
Moderna |
<2 wk |
<2 wk |
n.s. |
MCD |
0.86 |
6 |
2.8 |
Pos |
Neg |
Neg |
Diur |
IS 1 |
NA |
NA |
NA |
NA |
10 |
33 |
F |
W |
Pfizer |
4 wk/<1 wk |
2 d |
Nephritic |
IgA N |
1.1 |
0.6 |
4.0 |
Pos |
Neg |
Neg |
None |
None |
None
a
|
Unk |
WNL |
Unk |
11 |
52 |
F |
W |
mRNA
a
|
5 wk/2 wk |
1 d, both |
Hem |
IgA N |
1.7 |
0 |
ND |
Pos |
Neg |
Neg |
None |
None |
6 wk |
Yes |
<1 |
Neg |
12 |
37 |
F |
W |
mRNA
a
|
5 wk/<2 wk |
12 d |
Nephritic |
IgA N |
1.4 |
3.5 |
3.1 |
Pos |
Neg |
Neg |
None |
IS 1; ACEI |
7 wk |
No |
Unk |
UA Pos |
13 |
35 |
M |
W |
Pfizer |
6 wk/3 wk |
1 d |
Nephritic |
IgA N |
1.4 |
>300 mg/dl |
4.2 |
Pos |
Neg |
Neg |
ARB |
IS 1; ARB |
2 wk |
No |
Unk |
Unk |
14 |
72 |
F |
Hisp |
Pfizer |
10 wk/7 wk |
2 d |
AKI, nephritic |
IgA N |
4.9 |
0.6 |
ND |
Pos |
Neg |
Pos |
IS 1 |
IS 1; IS 5 |
2 wk |
No |
4 |
UA Pos |
15 |
57 |
M |
W |
Moderna |
4 wk/ 3d |
1 d |
AKI, CKD, nephritic |
IgA N |
6.2 |
3+ |
2.5 |
Pos |
Neg |
Neg |
Diur |
IS 1; IS 5 |
4 wk |
No |
8; D* |
Pos; D* |
16 |
30 |
M |
W |
Pfizer |
4 wk/<1 wk |
1 d |
Nephritic |
IgA N |
1.1 |
2 |
4.2 |
Pos |
Neg |
Neg |
None |
None |
2 wk |
Yes |
1.1 |
UA Pos |
17 |
40 |
F |
W |
Moderna |
4 mo/3 mo |
<1 wk |
Nephritic |
IgA N |
1.3 |
30 mg/dl |
3.4 |
Pos |
Pos |
Pos |
None |
ARB |
2 wk |
No |
Unk |
Unk |
18 |
73 |
M |
W |
Pfizer |
3 mo/2 mo |
2 wk |
AKI, nephritic |
IgA N, AIN |
3.4 |
0.5 |
1.9 |
Pos |
Pos |
Neg |
None |
IS 1 |
2.5 wk |
Partial |
1 |
2.4 |
19 |
66 |
M |
Hisp |
mRNA
a
|
6 wk/3 wk |
3 d |
AKI, nephritic |
IgA N, DN |
9.77 |
3.3 |
2.4 |
Pos |
Neg |
Neg |
D |
D |
4 mo |
No |
D* |
D* |
20 |
76 |
M |
W |
Pfizer |
7 wk/<3 wk |
11 d |
AKI, nephritic |
Cres GN |
8.6 |
2+ |
2.3 |
Pos |
Pos |
Pos |
D |
D, IS 1, IS 4 |
3 wk |
No |
5.8 |
Unk |
21 |
81 |
F |
W |
Pfizer |
6 wk/3 wk |
2 d |
AKI, nephritic |
Cres GN |
3.1 |
1.8 |
3.4 |
Pos |
Pos |
Pos |
None |
IS 4, ARB |
3 wk |
No |
2.2 |
2.3 |
22 |
76 |
F |
W |
Moderna |
<1 wk |
5 d |
AKI, nephritic |
Cres GN |
3.0 |
2 |
3.1 |
Pos |
Pos |
Pos |
IS 1 |
IS 1, IS 4 |
5 wk |
Partial |
1.1 |
2+ |
23 |
71 |
F |
W |
Moderna |
4 mo/3 mo |
2 wk |
Nephritic |
Cres GN |
1.3 |
2.1 |
3.3 |
Pos |
Pos |
Pos |
IS 1 |
IS 1, IS 4 |
1 wk |
No |
NA |
NA |
24 |
65 |
F |
W |
Pfizer |
4 mo/3 mo |
2 wk |
AKI, nephritic |
Cres GN |
3.29 |
2.07 |
2.2 |
Pos |
Neg |
Pos |
None |
IS 1, IS 5 |
2 wk |
No |
4.83 |
2.9 |
25 |
79 |
F |
W |
Moderna |
8 wk/5 wk |
3 wk |
Nephritic |
Cres GN (recur) |
1.12 |
20 mg/dl |
4.0 |
Pos |
Neg |
Pos |
IS 1, IS 3, IS 6 |
IS 4 |
4 mo |
Yes |
0.82 |
None |
26 |
54 |
M |
Asian |
Moderna |
12 wk/9 wk |
1 d |
Nephritic |
MN |
1.3 |
3+ |
3.4 |
Pos |
Pos |
Pos |
None |
IS 1, IS 4 |
8 wk |
No |
0.86 |
3.5 |
27 |
68 |
M |
W |
J+J |
4 wk |
< 4 wk |
AKI, CKD, nephritic |
MN |
3.3 |
0.6 |
3.2 |
Neg |
ND |
Neg |
Diur |
Diur |
3 wk |
Partial |
2.74 |
0.38 |
28 |
47 |
M |
Asian |
Moderna |
8 wk/5 wk |
6 d |
Nephritic |
MN |
0.7 |
2.7 |
2.3 |
Pos |
ND |
Neg |
None |
None |
2 wk |
Partial |
0.7 |
2.7 |
29 |
16 |
F |
Hisp |
Pfizer |
4 wk |
2 d |
Nephritic |
Diffuse LN |
0.7 |
0.8 |
3 |
Pos |
Pos |
Pos |
None |
IS 1 |
2 wk |
Yes |
0.48 |
0.53 |
F, woman; B, Black; n.s., nephrotic syndrome; CG, collapsing glomerulopathy; Pos, positive; Neg, negative; D, dialysis; I.S. 1, immunosuppression 1: steroid therapy (methylprednisolone or high-dose prednisone); MN, membranous nephropathy; I.S. 2, immunosuppression 2: plasmapheresis; I.S. 3, immunosuppression 3: mycophenolate mofetil; D*, measurement unknown or inaccurate due to patient on dialysis (creatinine and/or proteinuria value unreliable); W, White; MCD, minimal change disease; ND, not done; Diur, diuretics; Unk, unknown; M, man; UA, urinalysis; ARB, angiotensin receptor blocker; ACEI, angiotensin-converting enzyme inhibitor; NA, not applicable; IgA N, IgA nephropathy; WNL, within normal limits; Hem, hematuria; Hisp, Hispanic; I.S. 5, immunosuppression 5 (cyclophosphamide); AIN, acute interstitial nephritis; DN, diabetic nephropathy; Cres GN, crescentic GN; I.S. 4, immunosuppression 4 (rituximab); I.S. 6, immunosuppression 6 (calcineurin inhibitor); J+J, Johnson & Johnson; LN, lupus nephritis.
aPatient 10 had no impairment of kidney function, where clinical follow-up would not be required for months.
Prior to biopsy, six patients received immunosuppression, six had diuretic therapy, and five required dialysis. Three patients had oliguria. At follow-up (median, 20 days±IQR 43, 13; 56; n=27 patients), 22 patients received immunosuppression (most commonly corticosteroids). Eight patients had full recovery of kidney function, with return to baseline creatinine, proteinuria, and albumin levels and absence of blood and protein on urinalysis. Five patients showed partial recovery, with a reduction in serum creatinine but with persistent hematuria and/or proteinuria. Fourteen patients had no improvement in kidney function, and five required dialysis (Table 1).
Biopsy diagnoses included IgA nephropathy (IgAN; n=10), MCD (n=7), CG (n=2), crescentic GN (n=6), MN (n=3), and diffuse lupus nephritis (n=1). One of the patients with CG had concurrent exostosin-positive MN. One patient with MN was positive for PLA2R. The remaining MN cases were negative for PLA2R, THSD7A, NELL1, and EXT. All patients with crescentic GN had a positive ANCA serology (Table 1). Additionally, two patients with IgAN had a positive ANCA, and one of which had crescentic disease. Both patients with CG were of Black descent and were homozygous for APOL1 high-risk alleles (G1/G1 and G1/G2). Histopathologic features are shown in Table 2.
Table 2. -
Histopathology of severe acute respiratory syndrome coronavirus 2 vaccine–related glomerular disease biopsies
Patient Number |
Diagnosis |
Global Glomerulosclerosis |
Mesangial Matrix Expansion |
Mesangial Hyper cellularity |
Endocapillary Hyper cellularity |
Necrosis |
Crescents |
Segmental Sclerosis |
Acute Tubular Injury |
Interstitial Fibrosis/ Tubular Atrophy |
Arterio sclerosis |
Arteriolar Hyalinosis |
Immunofluorescence |
Mesangial Deposits |
Subend othelial Deposits |
Subepi thelial Deposits |
Foot Process Effacement |
1 |
CG |
0/24 |
No |
No |
No |
No |
No |
Yes |
Yes |
Mild |
No |
No |
No staining |
No |
No |
No |
Severe |
2 |
CG, MN |
0/45 |
No |
No |
No |
No |
No |
Yes |
Yes |
Mild |
Mild |
No |
3+IgG and C3, gr cap loop |
Yes |
No |
Yes |
Severe |
3 |
MCD |
1/31 |
No |
No |
No |
No |
No |
No |
Yes |
None |
No |
No |
No staining |
No |
No |
No |
Severe |
4 |
MCD |
0/35 |
No |
No |
No |
No |
No |
No |
Yes |
Mild |
Mod |
Mild |
No staining |
No |
No |
No |
Severe |
5 |
MCD |
3/33 |
Yes |
No |
No |
No |
No |
No |
Yes |
Mild |
Mod |
No |
No staining |
No |
No |
No |
Severe |
6 |
MCD |
0/20 |
Yes |
Yes |
No |
No |
No |
No |
No |
No |
No |
No |
No staining |
No |
No |
No |
Severe |
7 |
MCD |
6/30 |
No |
No |
No |
No |
No |
No |
Yes |
No |
Mod |
Mild |
No staining |
No |
No |
No |
Severe |
8 |
MCD |
0/40 |
No |
No |
No |
No |
No |
No |
Yes |
No |
No |
No |
No staining |
No |
No |
No |
Severe |
9 |
MCD |
0/60 |
No |
No |
No |
No |
No |
No |
No |
No |
No |
No |
No staining |
No |
No |
No |
Severe |
10 |
IgA N |
1/29 |
Yes |
Yes |
Yes |
No |
No |
Yes |
No |
No |
No |
No |
3+IgA and C3 gr mes |
Yes |
Yes |
No |
None |
11 |
IgA N |
3/27 |
No |
No |
No |
No |
No |
No |
No |
No |
No |
No |
3+IgA gr mes |
Yes |
No |
No |
Mild. |
12 |
IgA N |
1/16 |
Yes |
Yes |
Yes |
No |
No |
No |
Yes |
No |
Mild |
Mild |
3+IgA+C3, 1+IgG gr mes |
Yes |
No |
Yes |
Mod |
13 |
IgA N |
0/86 |
Yes |
Yes |
No |
No |
Yes |
No |
Yes |
No |
No |
No |
3+IgA gr mes |
Yes |
No |
No |
Mod |
14 |
IgA N |
10/40 |
Yes |
Yes |
No |
Yes |
Yes |
Yes |
Yes |
Mod |
Mod |
Mild |
2+IgA+IgM, 3+C3, trace IgG gr mes |
No |
No |
No |
Mild |
15 |
IgA N |
23/52 |
Yes |
Yes |
Yes |
Yes |
Yes |
Yes |
Yes |
Yes |
Severe |
Mod |
2+IgA, 1+C3 gr mes |
Yes |
No |
No |
Mod |
16 |
IgA N |
2/50 |
Yes |
Yes |
No |
No |
No |
Yes |
Yes |
Mild |
Mod |
No |
3+IgA, 2+IgG, 3+C3 gr mes |
Yes |
Yes |
Yes |
Mild |
17 |
IgA N |
6/19 |
Yes |
No |
No |
No |
No |
No |
Yes |
Mild |
Mod |
No |
3+IgA, trace IgG, 2+C3 gr mes |
Yes |
No |
No |
Mod |
18 |
IgA N, AIN |
1/13 |
Yes |
No |
No |
No |
No |
No |
Yes |
No |
N/A |
Mild |
3+IgA, 1+IgG, 2+IgM, trace C3 gr mes |
Yes |
No |
No |
Mod |
19 |
IgA N, DN |
35/46 |
Yes |
Yes |
No |
No |
No |
Yes |
No |
Severe |
Severe |
Severe |
1+IgA, 1+IgG, 1+IgM gr mes |
No |
No |
No |
Mod |
20 |
Cres GN |
1/24 |
No |
No |
No |
Yes |
Yes |
No |
No |
Mild |
Severe |
No |
2+IgA, 1+C3 gr mes |
No |
No |
No |
Severe |
21 |
Cres GN |
4/13 |
Yes |
No |
No |
No |
Yes |
Yes |
Yes |
Mild |
Severe |
Mild |
1+IgM, trace C3 gr mes |
No |
No |
No |
Mild |
22 |
Cres GN |
9/36 |
No |
No |
No |
Yes |
Yes |
No |
Yes |
Mild |
Severe |
Mod |
3+C3 gr mes |
Yes |
No |
No |
Severe |
23 |
Cres GN |
20/29 |
No |
No |
No |
No |
No |
No |
Yes |
Mod |
Severe |
No |
3+IgM, 1+C3 gr mes |
Yes |
No |
No |
Mod |
24 |
Cres GN |
5/30 |
No |
No |
No |
Yes |
Yes |
No |
Yes |
Mod |
N/A |
No |
1+IgG, 1+C3 gr cap loop |
N/A |
N/A |
N/A |
N/A |
25 |
Cres GN |
13/51 |
No |
No |
No |
Yes |
Yes |
Yes |
Yes |
Mild |
No |
No |
No staining |
No |
No |
No |
None |
26 |
MN |
3/15 |
No |
No |
No |
No |
Yes |
Yes |
Yes |
No |
No |
Mod |
3+IgG, 2+C3 gr cap loop |
Yes |
No |
Yes |
Severe |
27 |
MN |
20/29 |
No |
No |
No |
No |
No |
Yes |
Yes |
Mild |
Severe |
No |
2+IgG, 2+IgM gr cap loop |
No |
No |
Yes |
Severe |
28 |
MN |
1/39 |
No |
No |
No |
No |
No |
No |
No |
Mild |
No |
No |
3+IgG, 2+C3 gr cap loop |
No |
No |
Yes |
Severe |
29 |
Diffuse LN |
0/55 |
Yes |
Yes |
Yes |
No |
No |
No |
No |
No |
No |
No |
3+IgA, 3+IgG, 3+IgM, 3+C3, 3+C1q gr mes +gr cap loop |
Yes |
No |
Yes |
Mod |
CG, collapsing glomerulopathy; MN, membranous nephropathy; gr cap loop, granular capillary loop; MCD, minimal change disease; Mod, moderate; IgA N, IgA nephropathy; gr mes, granular mesangial; AIN, acute interstitial nephritis; N/A, not applicable; DN, diabetic nephropathy; Cres GN, crescentic GN; LN, lupus nephritis.
In three patients, confounding factors were present that could represent additional or alternative antigenic triggers. These included long-term nonsteroidal anti-inflammatory drug use in a patient with MCD, although there was no recent increase or change in nonsteroidal anti-inflammatory drug use prior to vaccination. There was one patient with crescentic GN who had prior hydralazine use, although use was discontinued prior to the time of biopsy. One patient with IgAN had concurrent HIV infection, although IgAN is an unlikely cause of HIV-associated immune complex disease of the kidney.
There was no significant increase in kidney biopsy diagnoses of glomerular diseases during this period of mass vaccination. Although not an epidemiologic study, the frequency of diagnoses during this period (1/1/2021–7/1/2021; n=11,192 cases) was compared with each diagnosis 2 years prior to the COVID-19 pandemic and SARS-CoV-2 vaccination (1/1/2018–12/31/2019) through searching a biopsy database (n=36,389 cases). The overall frequencies of these glomerular diseases were not increased during this period of mass vaccination compared with prior to the pandemic for MCD (1.8% versus 2.2%; P=0.007), IgAN (7.0% versus 7.2%; P=0.70), pauci-immune crescentic GN (4.4% versus 4.4%; P>0.99), CG (2.6% versus 2.3%; P=0.06), and MN (5.6% versus 5.4%; P=0.41). The slight, nonsignificant increase in CG during this time period may be related to COVID-19–associated nephropathy cases (5). The true incidence of glomerular disease is unknown, as this is from a single center, and not all patients with glomerular disease (particularly those with recurrence) would undergo kidney biopsy.
Discussion
In the recent literature, multiple cases of kidney disease temporally related to SARS-CoV-2 vaccination have been reported (n=52 patients), including IgAN (n=20) (6789101112131415–16), MCD (n=17) (17181920212223242526272829–30), ANCA-associated pauci-immune crescentic GN (n=5) (313233–34), antiglomerular basement membrane antibody disease (n=2) (6,35), MN (n=3; of which one was PLA2R positive and one was THSD7A positive) (3637–38), membranous lupus nephritis (n=1) (39), IgG4-related kidney disease (n=1) (40), granulomatous interstitial nephritis (n=1) (41), thrombotic microangiopathy with sclerodermal renal crisis (n=1) (42), and T cell–mediated allograft rejection (n=1) (43) (Table 3). These reports included 27 cases of new-onset glomerular disease, with the remainder being relapses of patients with prior biopsy-proven GN (Table 3). Although we identified many of the same pathologic findings, unique to our series are cases of CG and proliferative lupus nephritis. Of note, there were no patients of African descent reported with vaccine-related glomerular disease in the literature, although race was not mentioned for all patients; only 12 of 52 patients had race mentioned, of which ten were White and two were of Asian descent. Although allograft rejection was reported in association with SARS-CoV-2 vaccination, we did not identify any cases of rejection at our institution.
Table 3. -
Severe acute respiratory syndrome coronavirus 2 vaccine–associated glomerular disease cases reported in the literature
Patient Number |
N
|
Diagnosis |
Age, yr |
Sex |
Type |
1st/2nd |
Time |
Indication |
Serum Creatinine |
Proteinuria |
Hematuria |
Serum Albumin |
Antinuclear Antibodies |
ANCA |
Treatment |
Follow-Up |
Recovery |
Follow-Up Creatinine |
6 (new) |
2 |
IgAN; anti-GBM |
41; 60 |
F; F |
Pfi; Toz |
2nd |
1 d |
Nephritic; AKI+n.s. |
1.73; 6.12 |
2.03; 7.58 |
Yes; Yes |
Unk |
Pos; Neg |
Unk |
I.S. 1+I.S. 5; I.S. 1+I.S. 2 |
NA |
NA |
NA |
7 (new) |
2 |
IgAN; Cres GN |
39; 81 |
M; M |
Mod |
1st |
Unk |
Nephritic; AKI |
Inc; Inc |
Pos; Pos |
Yes |
Unk |
Unk |
Unk; Pos |
I.S. 1+I.S. 5; I.S. 1+I.S. 2+I.S. 5 |
NA |
No; Yes |
Unk |
8 (recur) |
3 |
IgAN |
22; 41; 27 |
M; F; F |
Mod; Pfi; Pfi |
1st; 2nd; 2nd |
2 d |
Nephritic |
Unk |
0.34; 0.47; 1.9 |
Yes |
Unk |
Unk |
Unk |
I.S. 1+RAASi; I.S. 1+I.S. 3+I.S. 6; I.S. 1+I.S. 3+I.S. 6 |
Unk |
Yes; Yes; Yes |
Unk |
9 (new) |
2 |
IgAN |
50; 19 |
F; M |
Mod |
2nd |
2 d |
Nephritic |
1.7; 2.1 |
2.0; None |
Yes |
Unk |
Neg; Unk |
Neg; Unk |
None |
5 d; 2 d |
Yes; Yes |
Unk |
10 (1 new, 1 recur) |
2 |
IgAN |
13; 17 |
M; M |
Pfi |
2nd |
1 d |
AKI+ nephritic |
1.31; 1.78 |
1.1; 1.8 |
Yes; Yes |
3.4; 3.8 |
Unk |
Unk |
ACEI; I.S. 1 |
1 wk; Unk |
Yes; No |
Unk |
11 (recur) |
2 |
IgAN |
38 |
F; F |
Mod |
2nd |
1 d |
Nephritic |
Unk |
0.82; 0.59 |
Yes; Yes |
Unk |
Unk |
Unk |
None |
21 d |
Yes |
Unk |
12 (recur) |
1 |
IgAN |
52 |
F |
Pfi |
2nd |
1 d |
Nephritic |
Unk |
2.4 |
Yes |
Unk |
Unk |
Unk |
Unk |
1 wk |
Partial |
Unk |
13 (recur) |
4 |
IgAN |
22; 39; 50; 67 |
F; F; M; M |
Mod; Mod; Mod; Mod |
2nd |
2 d; 2 d; 1 d; 4 wk |
Nephritic |
Unk; Unk; Unk; Unk |
0.4; 0.9; 3.56; 2.10 |
Yes; Yes; Yes; Yes |
Unk |
Unk |
Unk |
None; None; RAASi; I.S. 1 |
4 wk; 4 wk; 4 wk; 4 wk |
Yes; Yes; Yes; Yes |
Unk; Unk; Unk; Unk |
14 (new) |
1 |
IgAN |
30 |
M |
Pfi |
2nd |
1 d |
Nephritic |
1.02 |
4+ |
Yes |
Unk |
Neg |
Neg |
RAASi |
6 wk |
Partial |
1.03 |
15 (recur) |
1 |
IgAN |
78 |
F |
Mod |
1st |
7 d |
Nephritic |
1.18 |
Unk |
Yes |
Unk |
Neg |
Neg |
I.S. 1 |
Unk |
Yes |
Unk |
16 (recur) |
2 |
IgAN |
Unk |
Unk |
Pfi |
2nd |
5 d |
AKI+nephritic |
3.53; 1.16 |
4.97;0.61 |
Yes |
Unk |
Unk |
Unk |
I.S. 1 |
2 mo |
Yes |
Unk |
17 (new) |
1 |
MCD |
77 |
M |
Pfi |
1st |
7 d |
n.s. |
2.33 |
4+ |
Unk |
3.0 |
Unk |
Unk |
I.S. 1 |
21 d |
No |
3.74 |
18 (new) |
1 |
MCD |
50 |
M |
Pfi |
1st |
4 d |
AKI+n.s. |
2.31 |
6.9 |
Unk |
1.93 |
Neg |
Neg |
I.S. 1 |
17 d |
Yes |
0.97 |
19 (recur) |
1 |
MCD |
34 |
F |
Pfi |
1st |
10 d |
n.s. |
Unk |
2.4 |
Unk |
Unk |
Unk |
Unk |
I.S. 1 |
Unk |
Partial |
Unk |
20 (recur) |
2 |
MCD |
30; 40 |
M; F |
AZ |
1st |
2 d; 1 d |
Nephritic; n.s. |
0.931.19 |
0.21; 3+ |
Unk |
4.7; Unk |
Unk |
Unk |
I.S. 1; I.S. 1+I.S. 6 |
10 d; 14 d |
Yes; Yes |
Unk |
21 (new) |
1 |
MCD |
63 |
F |
Pfi |
1st |
7 d |
n.s. |
1.48 |
3+ |
Yes |
0.7 |
Unk |
Unk |
ARB; I.S. 1 |
Unk |
Unk |
Unk |
22 (new) |
1 |
MCD |
80s |
M |
Pfi |
1st |
7 d |
n.s. |
1.43 |
15.3 |
Unk |
1.0 |
Unk |
Unk |
I.S. 1 |
10 d |
Yes |
Unk |
23 (recur) |
1 |
MCD |
60s |
M |
Pfi |
1st |
8 d |
n.s. |
0.99 |
11.5 |
Unk |
2.8 |
Unk |
Unk |
I.S. 1+I.S. 6 |
14 d |
Yes |
Unk |
24 (recur) |
1 |
MCD |
22 |
M |
Pfi |
1st |
3 d |
n.s. |
0.8 |
3+ |
Unk |
2.3 |
Unk |
Unk |
I.S. 1+I.S. 6 |
17 d |
Yes |
Unk |
25 (recur) |
1 |
MCD |
39 |
M |
Pfi |
1st |
3 d |
AKI+n.s. |
1.8 |
8 |
Unk |
2.7 |
Unk |
Unk |
I.S. 1 |
4 wk |
Yes |
Unk |
26 (new) |
1 |
MCD |
61 |
F |
Pfi |
1st |
8 d |
n.s. |
1.47 |
12 |
Unk |
2.1 |
Neg |
Neg |
D; I.S. 1 |
21 d |
Partial |
Unk |
27 (1 new, 2 recur) |
3 |
MCD |
33;41; 34 |
F; F; F |
Mod; Pfi; Pfi |
2nd |
3 wk; 5 d; 4 wk |
n.s.; n.s.; n.s. |
Unk; Unk; Unk |
6.4;14.4;12.9 |
Unk; Yes; Unk |
2.3;2.6;2.8 |
Unk; Unk; Unk |
Unk; Unk; Unk |
Unk |
Unk |
Unk |
Unk |
28 (new) |
1 |
MCD |
51 |
M |
J+J |
1st |
28 d |
n.s. |
1.54 |
8.6 |
Yes |
1.6 |
Neg |
Neg |
I.S. 1 |
2 wk |
Yes |
0.95 |
29 (new) |
1 |
MCD |
71 |
M |
AZ |
1st |
13 d |
AKI+n.s. |
10.6 |
20.5 |
Yes |
2.6 |
Neg |
Neg |
I.S. 1; D |
38 d |
Yes |
1.4 |
30 (new) |
1 |
MCD |
19 |
F |
AZ |
1st |
8 d |
n.s. |
1.09 |
3.18 |
Unk |
2.15 |
Unk |
Unk |
I.S. 1 |
Unk |
Yes |
Unk |
31 (new) |
1 |
Cres GN, ANCA |
29 |
F |
Pfi |
2nd |
7 wk |
Nephritic; AKI |
1.91 |
0.633 |
Yes |
4.4 |
Unk |
Pos |
I.S. 1; I.S. 4; I.S. 5 |
10 wk |
Yes |
1.01 |
32 (new) |
1 |
Cres GN, ANCA |
52 |
M |
Mod |
2nd |
14 d |
Nephritic; AKI |
8.41 |
1+ |
Yes |
Unk |
Unk |
Pos |
D; I.S. 5 |
Unk |
No |
Unk; D |
33 (new) |
1 |
Cres GN, ANCA |
78 |
F |
Pfi |
2nd |
8 d |
Nephritic; AKI |
3.54 |
2.05 |
3+ |
Unk |
Unk |
Pos, MPO |
I.S. 1; I.S. 4 |
1 mo |
Partial |
1.71 |
34 (new) |
1 |
Cres GN, ANCA |
63 |
M |
AZ |
1st |
2 d |
Nephritic; AKI |
2.91 |
2+ |
Yes |
Unk |
Unk |
Pos |
I.S. 1; I.S. 5 |
6 wk |
Partial |
2.09 |
35 (new) |
1 |
Cres GN, anti-GBM |
NA |
F |
Mod |
2nd |
14 d |
AKI |
7.8 |
1.9 |
Yes |
Unk |
Neg |
Neg |
D; I.S. 1+I.S. 2+I.S. 5 |
Unk |
No |
Unk |
36 (new) |
1 |
MN |
66 |
F |
Sino |
1st |
14 d |
n.s. |
2.78 |
9.42 |
Unk |
2.6 |
Unk |
Unk |
Unk |
NA |
NA |
NA |
37 (recur) |
1 |
MN. THSD7A Pos |
70 |
M |
Pfi |
2nd |
1 d |
n.s. |
1.29 |
4.4 |
Yes |
1.7 |
Unk |
Unk |
ARB; diuretics |
2 mo |
No |
Unk |
38 (new) |
1 |
MN, PLA2R Pos (no biopsy) |
76 |
M |
Pfi; Mod (2nd) |
1st |
4 d |
n.s. |
0.86 |
6.5 |
Yes |
1.6 |
Unk |
Unk |
I.S. 4 |
2 mo |
Partial |
1.15 |
39 (recur) |
1 |
MLN |
42 |
F |
Pfi |
1st |
1 wk |
n.s. |
wnl |
8.4 |
Neg |
Low |
Pos |
Unk |
I.S. 1; I.S. 3 |
3 wk |
Partial |
Unk |
40 (recur) |
1 |
IgG4 KD |
66 |
M |
Pfi |
2nd |
14 d |
AKI |
2.38 |
Unk |
Unk |
Unk |
Neg |
Unk |
I.S. 1+I.S. 4 |
Unk |
Yes |
0.57 |
41 (new) |
1 |
Gran TIN |
77 |
M |
AZ |
1st |
4 wk |
AKI |
2.78 |
Neg |
Neg |
Unk |
Neg |
Neg |
I.S. 1 |
4 wk |
Yes |
Unk |
42 (new) |
1 |
TMA/SRC |
34 |
F |
Pfi |
1st |
<1 wk |
AKI |
2.07 |
0.8 |
Neg |
Unk |
Neg |
Unk |
ACEi |
1 wk |
Yes |
Unk |
43 (new) |
1 |
TCMR |
23 |
F |
Pfi |
2nd |
8 d |
AKI |
4.07 |
Unk |
Unk |
Unk |
Pos |
Unk |
I.S. 1+I.S. 3+I.S. 6 |
10 d |
Partial |
2.6 |
The designations of (new) or (recur) represent de novo glomerular disease or recurrent glomerular disease for each report. IgAN, IgA nephropathy; GBM, glomerular basement membrane antibody disease; F, woman; Pfi, Pfizer-BioNTec BNT162b vaccine; Toz, BioNTech Tozinameran mRNA vaccine; n.s., nephrotic syndrome; Unk, unknown; Pos, positive; Neg, negative; I.S. 1, immunosuppression 1: steroid therapy (methylprednisolone or high-dose prednisone); I.S. 5, immunosuppression 5 (cyclophosphamide); I.S. 2, immunosuppression 2: plasmapheresis; NA, not applicable (lack of follow-up data); Cres GN, crescentic GN; M, man; Mod, Moderna mRNA-1273 vaccine; Inc, XXX; RAASi; renin-angiotensin-aldosterone system inhibitor; I.S. 3, immunosuppression 3: mycophenolate mofetil; I.S. 6, immunosuppression 6 (calcineurin inhibitor); ACEI, angiotensin-converting enzyme inhibitor; MCD, minimal change disease; AZ, AstraZeneca AZD1222/ChAdOx1-nCoV-19 vaccine; D, dialysis; J+J, Johnson & Johnson; I.S. 4, immunosuppression 4 (rituximab); MPO, myeloperoxidase; MN, membranous nephropathy; Sino, Sinovac-Coronovac vaccine; THSD7A, thrombospondin type 1 domain containing 7A; ARB, angiotensin receptor blocker; PLA2R, phospholipase A2 receptor; MLN, membranous lupus nephritis; wnl, within normal limits; IgG4 KD, IgG4-related kidney disease; Gran TIN, granulomatous tubulointerstitial nephritis; TMA, thrombotic microangiopathy; SRC, scleroderma renal crisis; ACEi, angiotensin converting enzyme inhibitor; TCMR, acute T cell-mediated rejection.
Both mRNA and adenoviral vaccines have been associated with induction of glomerular disease in patients vaccinated against SARS-CoV-2. Although the vector varies (lipid nanoparticles versus replication-deficient adenovirus), the antigenic target is common between these—the SARS-CoV-2 spike protein. The mechanism for this phenomenon is unknown but potentially, could result from molecular mimicry of the spike protein with host peptides.
The most common disease manifestation in our series and in the literature is IgAN (44). An IgA immune response against SARS-CoV-2 spike protein (45) could trigger IgAN in patients who produce galactose-deficient IgA antibodies, as previously reported with influenza vaccine (46). In a study of 89 patients with IgAN who received at least one dose of SARS-CoV-2 vaccine, no patients had gross hematuria or impaired kidney function at follow-up (47). In 29 patients examined in a shorter time interval (mean=11 days), two patients had a mild increase in serum creatinine with mild hematuria and proteinuria. This suggests that although IgA flare is possible, the incidence is <10% of individuals who had self-resolved in this series (47).
CG, although a common cause of AKI in COVID-19, has not been previously described in the setting of vaccination. CG is well described in association with COVID-19 infection, in which the pathogenesis is thought to be related the inflammatory response against the virus acting as a “second hit” to APOL1 risk alleles (48) rather than resulting from direct viral infection of the renal parenchyma. Likewise, the immune response to the SARS-CoV-2 spike protein from immunization may induce a similar “second hit” in susceptible individuals. Similarly, in patients with lupus, the immune response to COVID-19 disease or vaccination could be a trigger for disease flares (49).
Limitations
Given that there is only a temporal relationship between the onset of symptoms and vaccination, causality is unclear. It is possible that immunization did not trigger the onset of glomerular disease within all of these patients. The study was restricted to patients developing glomerular disease within 1 month of SARS-CoV-2 vaccination and did not compare with other time frames. This 1-month cutoff, although arbitrary, is similar to that of cases reported in the literature (Table 2).
Although there was no overall increase in glomerular disease diagnosed on biopsies during the time of mass SARS-CoV-2 vaccinations in our practice, there was no control group for comparison for a patient-control design, and we did not conduct an epidemiologic study. We are thus unable to determine the frequency of glomerular injury after vaccination. Further data are required to determine the true risk of induction or flare of glomerular disease in response to SARS-CoV-2 vaccination.
Conclusion
The current mass vaccination against the SARS-CoV-2 virus provides the ability to observe the association of glomerular disease with vaccination. Although there are cases of glomerular disease in temporal association with vaccination, we do not know the true incidence or prevalence of disease. Within clinical trials, patients who were immunosuppressed (including those with glomerular disease) were excluded. This results in a lack of safety and efficacy data for SARS-CoV-2 vaccines within this population (50). As patients with kidney disease have an increased risk of morbidity and mortality from COVID-19, it is a priority to immunize these individuals against SARS-CoV-2. Additionally, as poorer immune responses are generated in response to vaccination, more potent vaccines (i.e., mRNA) and booster doses are recommended (1). Further data are required to determine the incidence of glomerular disease induction or recurrence in response to vaccination, response to therapy, and long-term clinical outcomes. To examine this, a registry has been created at the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases to examine these outcomes (International Registry of COVID infection in Glomerulonephritis-2). We suggest that new-onset or recurrent glomerular disease should be monitored as a potential adverse event.
Disclosures
J.T. Henry reports ownership interest in Fort Smith Regional Dialysis. G. Schlessinger reports consultancy agreements with Medtronic and ownership interest in US Renal Care. Z. Karam reports honoraria from Spherix. R.M. Seipp reports honoraria from M3 Global Research and Spherix Global Insights. P.D. Walker reports consultancy agreements with Apellis and Travere and honoraria from Apellis and Travere. All remaining authors have nothing to disclose.
Funding
None.
Acknowledgments
A portion of this work was accepted as an abstract at the 2021 American Society of Nephrology annual meeting held virtually on November 4, 2021.
Author Contributions
T.N. Caza, C.P. Larsen, N. Messias, and P.D. Walker conceptualized the study; H. Amin, S.Y. Bae, E.J. Betchick, J. Brandt, C.A. Cassol, T.N. Caza, K.K. Chouhan, M.J. Diamond, J. Edwu-okwuwa, E.B. Elashi, S.L. Fabian, J.A. Flaxenburg, A. Frome, M. Haderlie, A. Hannoudi, R.S. Haun, J.T. Henry, E.T. Hoerschgen, B. Iqbal, Z. Karam, S. Khalillullah, E.H. Kim, C.P. Larsen, R.M. May, N. Messias, G. Schlessinger, M. Seek, R.M. Seipp, G. Shenoy, E. Ulozas, I. Vancea, P.D. Walker, J.L. Weatherspoon, and M.S. Ziadie were responsible for data curation; T.N. Caza, A. Hannoudi, R.S. Haun, and C.P. Larsen were responsible for investigation; T.N. Caza, A. Hannoudi, R.S. Haun, C.P. Larsen, and R.M. May were responsible for formal analysis; T.N. Caza and R.S. Haun were responsible for methodology; C.P. Larsen was responsible for project administration; C.P. Larsen was responsible for resources; T.N. Caza, C.P. Larsen, and N. Messias were responsible for visualization; C.P. Larsen provided supervision; T.N. Caza and A. Hannoudi wrote the original draft; and C.A. Cassol, T.N. Caza, C.P. Larsen, and R.M. May reviewed and edited the manuscript.
References
1. Windpessl M, Bruchfeld A, Anders HJ, Kramer H, Waldman M, Renia L, Ng LFP, Xing Z, Kronbichler A:
COVID-19 vaccines and kidney disease. Nat Rev Nephrol 17: 291–293, 2021
https://doi.org/10.1038/s41581-021-00406-6
2. Patel C, Shah HH: Vaccine-associated kidney diseases: A narrative review of the literature. Saudi J Kidney Dis Transpl 30: 1002–1009, 2019
https://doi.org/10.4103/1319-2442.270254
3. Segal Y, Shoenfeld Y: Vaccine-induced autoimmunity: The role of molecular mimicry and immune crossreaction. Cell Mol Immunol 15: 586–594, 2018
https://doi.org/10.1038/cmi.2017.151
4. May RM, Cassol C, Hannoudi A, Larsen CP, Lerma E, Haun RS, Braga JR, Hassen SI, Wilson J, VanBeek C, Vankalakunti M, Barnum L, Walker PD, Bourne TD, Messias NC, Ambruzs JM, Boils CL, Sharma SS, Cossey LN, Baxi PV, Palmer M, Zuckerman J, Walavalkar V, Urisman A, Gallan A, Al-Rabadi LF, Rodby R, Luyckx V, Espino G, Santhana-Krishnan S, Alper B, Lam SG, Hannoudi GN, Matthew D, Belz M, Singer G, Kunaparaju S, Price D, Chawla S, Rondla C, Abdalla MA, Britton ML, Paul S, Ranjit U, Bichu P, Williamson SR, Sharma Y, Gaspert A, Grosse P, Meyer I, Vasudev B, El Kassem M, Velez JCQ, Caza TN: A multi-center retrospective cohort study defines the spectrum of kidney pathology in Coronavirus 2019 Disease (
COVID-19) [published online ahead of print August 3, 2021]. Kidney Int 10.1016/j.kint.2021.07.015
5. Velez JCQ, Caza T, Larsen CP: COVAN is the new HIVAN: The re-emergence of
collapsing glomerulopathy with
COVID-19 [published correction appears in
Nat Rev Nephrol 16: 614, 2020]. Nat Rev Nephrol 16: 565–567, 2020
6. Tan HZ, Tan RY, Choo JCJ, Lim CC, Tan CS, Loh AHL, Tien CS, Tan PH, Woo KT: Is
COVID-19 vaccination unmasking glomerulonephritis? Kidney Int 100: 469–471, 2021
https://doi.org/10.1016/j.kint.2021.05.009
7. Anderegg MA, Liu M, Saganas C, Montani M, Vogt B, Huynh-Do U, Fuster DG: De novo vasculitis after mRNA-1273 (Moderna) vaccination. Kidney Int 100: 474–476, 2021
https://doi.org/10.1016/j.kint.2021.05.016
8. Perrin P, Bassand X, Benotmane I, Bouvier N: Gross hematuria following SARS-CoV-2 vaccination in patients with
IgA nephropathy. Kidney Int 100: 466–468, 2021
https://doi.org/10.1016/j.kint.2021.05.022
9. Kudose S, Friedmann P, Albajrami O, D’Agati VD: Histologic correlates of gross hematuria following Moderna
COVID-19 vaccine in patients with
IgA nephropathy. Kidney Int 100: 468–469, 2021
https://doi.org/10.1016/j.kint.2021.06.011
10. Hanna C, Herrera Hernandez LP, Bu L, Kizilbash S, Najera L, Rheault MN, Czyzyk J, Kouri AM:
IgA nephropathy presenting as macroscopic hematuria in 2 pediatric patients after receiving the Pfizer
COVID-19 vaccine. Kidney Int 100: 705–706, 2021
https://doi.org/10.1016/j.kint.2021.06.032
11. Negrea L, Rovin BH: Gross hematuria following vaccination for severe acute respiratory syndrome coronavirus 2 in 2 patients with
IgA nephropathy. Kidney Int 99: 1487, 2021
https://doi.org/10.1016/j.kint.2021.03.002
12. Rahim SEG, Lin JT, Wang JC: A case of gross hematuria and
IgA nephropathy flare-up following SARS-CoV-2 vaccination. Kidney Int 100: 238, 2021
https://doi.org/10.1016/j.kint.2021.04.024
13. Park K, Miyake S, Tai C, Tseng M, Andeen NK, Kung VL: Letter regarding: “A case of gross hematuria and
IgA nephropathy flare-up following SARS-CoV-2 vaccination.” Kidney Int Rep 6: 2246–2247, 2021
https://doi.org/10.1016/j.ekir.2021.06.007
14. Abramson M, Mon-Wei Yu S, Campbell KN, Chung M, Salem F:
IgA nephropathy after SARS-CoV-2 vaccination [published online ahead of print July 14, 2021]. Kidney Med 10.1016/j.xkme.2021.05.002
https://doi.org/10.1016/j.xkme.2021.05.002
15. Obeid M, Fenwick C, Pantaleo G: Reactivation of IgA vasculitis after
COVID-19 vaccination. Lancet Rheumatol 3: e617, 2021
https://doi.org/10.1016/S2665-9913(21)00211-3
16. Plasse R, Nee R, Gao S, Olson S: Acute kidney injury with gross hematuria and
IgA nephropathy after
COVID-19 vaccination. Kidney Int 100: 944–945, 2021
https://doi.org/10.1016/j.kint.2021.07.020
17. D’Agati VD, Kudose S, Bomback AS, Adamidis A, Tartini A:
Minimal change disease and acute kidney injury following the Pfizer-BioNTech
COVID-19 vaccine. Kidney Int 100: 461–463, 2021
https://doi.org/10.1016/j.kint.2021.04.035
18. Lebedev L, Sapojnikov M, Wechsler A, Varadi-Levi R, Zamir D, Tobar A, Levin-Iaina N, Fytlovich S, Yagil Y:
Minimal change disease following the Pfizer-BioNTech
COVID-19 vaccine. Am J Kidney Dis 78: 142–145, 2021
https://doi.org/10.1053/j.ajkd.2021.03.010
19. Kervella D, Jacquemont L, Chapelet-Debout A, Deltombe C, Ville S:
Minimal change disease relapse following SARS-CoV-2 mRNA vaccine. Kidney Int 100: 457–458, 2021
https://doi.org/10.1016/j.kint.2021.04.033
20. Morlidge C, El-Kateb S, Jeevaratnam P, Thompson B: Relapse of
minimal change disease following the AstraZeneca
COVID-19 vaccine. Kidney Int 100: 459, 2021
https://doi.org/10.1016/j.kint.2021.06.005
21. Holzworth A, Couchot P, Cruz-Knight W, Brucculeri M:
Minimal change disease following the Moderna mRNA-1273
SARS-CoV-2 vaccine. Kidney Int 100: 463–464, 2021
https://doi.org/10.1016/j.kint.2021.05.007
22. Maas RJ, Gianotten S, van der Meijden WAG: An additional case of
minimal change disease following the Pfizer-BioNTech
COVID-19 vaccine. Am J Kidney Dis 78: 312, 2021
https://doi.org/10.1053/j.ajkd.2021.05.003
23. Komaba H, Wada T, Fukagawa M: Relapse of
minimal change disease following the Pfizer-BioNTech
COVID-19 vaccine. Am J Kidney Dis 78: 469–470, 2021
https://doi.org/10.1053/j.ajkd.2021.05.006
24. Schwotzer N, Kissling S, Fakhouri F: Letter regarding “
Minimal change disease relapse following SARS-CoV-2 mRNA vaccine.” Kidney Int 100: 458–459, 2021
https://doi.org/10.1016/j.kint.2021.05.006
25. Mancianti N, Guarnieri A, Tripodi S, Salvo DP, Garosi G:
Minimal change disease following vaccination for SARS-CoV-2. J Nephrol 34: 1039–1040, 2021
https://doi.org/10.1007/s40620-021-01091-1
26. Weijers J, Alvarez C, Hermans MMH: Post-vaccinal
minimal change disease. Kidney Int 100: 459–461, 2021
https://doi.org/10.1016/j.kint.2021.06.004
27. Salem F, Rein JL, Yu SM, Abramson M, Cravedi P, Chung M: Report of three cases of
minimal change disease following the second dose of mRNA SARS-CoV-2
COVID-19 vaccine. Kidney Int Rep 6: 2523–2524, 2021
https://doi.org/10.1016/j.ekir.2021.07.017
28. Lim JH, Han MH, Kim YJ, Kim MS, Jung HY, Choi JY, Cho JH, Kim CD, Kim YL, Park SH: New-onset nephrotic syndrome after Janssen
COVID-19 vaccination: A case report and literature review. J Korean Med Sci 36: e218, 2021
https://doi.org/10.3346/jkms.2021.36.e218
29. Leclerc S, Royal V, Lamarche C, Laurin LP:
Minimal change disease with severe acute kidney injury following the Oxford-AstraZeneca
COVID-19 vaccine: A case report. Am J Kidney Dis 78: 607–610, 2021
30. Anupama YJ, Patel RGN, Vankalakunti M: Nephrotic syndrome following ChAdOx1 nCoV-19 vaccine against SARScoV-2. Kidney Int Rep 6: 2248, 2021
https://doi.org/10.1016/j.ekir.2021.06.024
31. Dube GK, Benvenuto LJ, Batal I:
ANCA-associated glomerulonephritis following the Pfizer-BioNTech
COVID-19 vaccine [published online ahead of print August 17, 2021]. Kidney Int Rep 10.1016/j.ekir.2021.08.012
https://doi.org/10.1016/j.ekir.2021.08.012
32. Sekar A, Campbell R, Tabbara J, Rastogi P:
ANCA glomerulonephritis after Moderna
COVID-19 vaccination. Kidney Int 100: 473–474, 2021
https://doi.org/10.1016/j.kint.2021.05.017
33. Shakoor MT, Birkenbach MP, Lynch M:
ANCA-associated vasculitis following Pfizer-BioNTech
COVID-19 vaccine. Am J Kidney Dis 78: 611–613, 2021
34. Villa M, Díaz-Crespo F, Pérez de José A, Verdalles U, Verde E, Ruiz FA, Acosta A, Mijaylova A, Goicoechea M: A case of
ANCA-associated vasculitis after AZD1222 (Oxford-AstraZeneca) SARS-CoV-2 vaccination: Casualty or causality? Kidney Int 100: 937–938, 2021
35. Sacker A, Kung V, Andeen N: Anti-GBM nephritis with mesangial IgA deposits after SARS-CoV-2 mRNA vaccination. Kidney Int 100: 471–472, 2021
https://doi.org/10.1016/j.kint.2021.06.006
36. Aydın MF, Yıldız A, Oruç A, Sezen M, Dilek K, Güllülü M, Yavuz M, Ersoy A: Relapse of primary
membranous nephropathy after inactivated SARS-CoV-2 virus vaccination. Kidney Int 100: 464–465, 2021
https://doi.org/10.1016/j.kint.2021.05.001
37. Da Y, Goh GH, Khatri P: A case of
membranous nephropathy following Pfizer-BioNTech mRNA vaccine against coronavirus 2019. Kidney Int 100: 938–939, 2021
38. Gueguen L, Loheac C, Saidani N, Khatchatourian L:
Membranous nephropathy following anti-
Covid-19 mRNA vaccination [published online ahead of print August 20, 2021]. Kidney Int 10.1016/j.kint.2021.08.006
39. Tuschen K, Bräsen JH, Schmitz J, Vischedyk M, Weidemann A: Relapse of class V
lupus nephritis after vaccination with
COVID-19 mRNA vaccine. Kidney Int 100: 941–944, 2021
40. Masset C, Kervella D, Kandel-Aznar C, Fantou A, Blancho G, Hamidou M: Relapse of IgG4-related nephritis following mRNA
COVID-19 vaccine. Kidney Int 100: 465–466, 2021
https://doi.org/10.1016/j.kint.2021.06.002
41. Gillion V, Jadoul M, Demoulin N, Aydin S, Devresse A: Granulomatous vasculitis after the AstraZeneca anti-
SARS-CoV-2 vaccine. Kidney Int 100: 706–707, 2021
https://doi.org/10.1016/j.kint.2021.06.033
42. Oniszczuk J, Pagot E, Limal N, Hüe S, Audard V, Moktefi A, El Karoui K: Scleroderma renal crisis following mRNA vaccination against SARS-CoV-2. Kidney Int 100: 940–941, 2021
43. Del Bello A, Marion O, Delas A, Congy-Jolivet N, Colombat M, Kamar N: Acute rejection after anti-SARS-CoV-2 mRNA vaccination in a patient who underwent a kidney transplant. Kidney Int 100: 238–239, 2021
https://doi.org/10.1016/j.kint.2021.04.025
44. Bomback AS, Kudose S, D’Agati VD: De novo and relapsing glomerular diseases after
COVID-19 vaccination: What do we know so far? Am J Kidney Dis 78: 477–480, 2021
45. Sterlin D, Mathian A, Miyara M, Mohr A, Anna F, Claër L, Quentric P, Fadlallah J, Devilliers H, Ghillani P, Gunn C, Hockett R, Mudumba S, Guihot A, Luyt CE, Mayaux J, Beurton A, Fourati S, Bruel T, Schwartz O, Lacorte JM, Yssel H, Parizot C, Dorgham K, Charneau P, Amoura Z, Gorochov G: IgA dominates the early neutralizing antibody response to SARS-CoV-2. Sci Transl Med 13: eabd2223, 2021
https://doi.org/10.1126/scitranslmed.abd2223
46. van den Wall Bake AW, Beyer WE, Evers-Schouten JH, Hermans J, Daha MR, Masurel N, van Es LA: Humoral immune response to influenza vaccination in patients with primary immunoglobulin A nephropathy. An analysis of isotype distribution and size of the influenza-specific antibodies. J Clin Invest 84: 1070–1075, 1989
https://doi.org/10.1172/JCI114269
47. Lim CC, Choo J, Tan CS:
COVID-19 vaccination in immunoglobulin A nephropathy. Am J Kidney Dis 78: 617, 2021
48. Wu H, Larsen C, Hernandez-Arroyo C, Mohamed MMB, Caza T, Sharshir M, Chughtai A, Xie L, Gimenez JM, Sandow TA, Lusco MA, Yang H, Acheampong E, Rosales IA, Colvin RB, Fogo AB, Velez JCQ: AKI and
collapsing glomerulopathy associated with
COVID-19 and
APOL 1 high-risk genotype. J Am Soc Nephrol 31: 1688–1695, 2020
49. Horisberger A, Moi L, Ribi C, Comte D: Impact of
COVID-19 pandemic on SLE: Beyond the risk of infection. Lupus Sci Med 7: e000408, 2020
https://doi.org/10.1136/lupus-2020-000408
50. Glenn DA, Hegde A, Kotzen E, Walter EB, Kshirsagar AV, Falk R, Mottl A: Systematic review of safety and efficacy of
COVID-19 vaccines in patients with kidney disease. Kidney Int Rep 6: 1407–1410, 2021
https://doi.org/10.1016/j.ekir.2021.02.011