IgA Nephropathy After SARS-CoV-2 Vaccination

Abstract

Here we present the first case of newly diagnosed IgA nephropathy (IgAN) after a SARS-CoV-2 vaccination. A 30-year-old man with no known past medical history presented with gross hematuria and subnephrotic proteinuria 24 hours after the second dose of the mRNA-1273 SARS-CoV-2 vaccine. A kidney biopsy showed IgAN. He was started on an angiotensin receptor blocker resulting in proteinuria reduction. Similar to natural infection of SARS-CoV2, persons who receive two mRNA-based vaccines demonstrate robust antibodies against the receptor-binding domain (RBD) of the S1 protein. Given the uniqueness of glycosylation of RBD and potent stimulation of immune response from mRNA-based vaccine compared to other vaccines, we hypothesize that our patient developed de novo antibodies leading to IgA-containing immune-complex deposits. This case highlights the urgency of understanding the immunological responses to novel mRNA-based SARS-CoV-2 vaccines in more diverse populations. Despite the lack of clear causality, nephrologists should be alerted if any new-onset hematuria or proteinuria is observed.

Kidney complications following COVID-19 vaccination; a review of the literature

“…36 articles were identified including a total of 49 reported cases (Table 1). These included MCD (n = 17) (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25), IgA nephropathy (IgAN) (n = 15) (26)(27)(28)(29)(30)(31)(32)(33)(34), IgA nephritis/vasculitis (n = 5) (10,30,35,36), ANCA glomerulonephritis/vasculitis (n = 5) (7,8,35,37,38), anti-GBM nephritis (n = 2) (28, 39), 1 case of each granulomatous vasculitis (40), acute tubulointerstitial nephritis (ATIN) (41), scleroderma renal crisis (42), IgG4-related disease nephritis (43), and primary MN (11).…”

“…They suggested that mRNA vaccines, similar to COVID-19 infection, produce strong antibodies against the RBD of the S1 protein. Therefore, the glycosylation of RBD and the immune response from the mRNA vaccine may be the underlying cause of the production of antibodies that resulted in the deposition of IgA immune-complexes in this patient (34). Moreover, severe COVID-19 infection is associated with a strong IgA response that may be triggered in the bronchial mucosa (55).…”

“…In addition, there are increased affinity for mesangial cells and deposition in the glomeruli. It is possible that, other factors are also involved in the pathogenesis of IgAN such as gene variants that are triggered with infections or other environmental factors that lead to the production of anti-glycan IgG or IgA (34). Furthermore, it has been reported that severe COVID-19 infection is associated with increased levels of IgA and antiphospholipid IgA (IgA-aPL) antibodies.…”

“…Among the cases, 14 individuals were IgAN relapses following Pfizer-BioNTech and Moderna vaccinations in adult patients (26)(27)(28)(29)(30)32). Two of the other case were IgAN relapse following Pfizer-BioNTech vaccinations in pediatric patients (31) There has only been one report of a new-onset IgAN following Moderna vaccination (34).…”

Canagliflozin Markedly Decreased Proteinuria in a Patient With IgA Nephropathy

“…Huang et al report increased proteinuria and gross hematuria as a consequence of exacerbation of a patient's biopsy-proven IgAN concurrent with a COVID-19 infection [6]. Abramson et al report newly diagnosed IgAN in a kidney biopsy after a man presented with gross hematuria and proteinuria 24 hours after a COVID-19 vaccine [7]. In addition, there are two recent reports [8,9] of three patients with prior biopsy-proven IgAN presenting with gross hematuria usually with increased proteinuria within 24 hours of the second dose of SARS-CoV-2 vaccine.…”