key: cord-0988309-hj4qfp0f
authors: Abramson, Matthew; Mon-Wei Yu, Samuel; Campbell, Kirk N.; Chung, Miriam; Salem, Fadi
title: IgA Nephropathy After SARS-CoV-2 Vaccination
date: 2021-07-14
journal: Kidney Med
DOI: 10.1016/j.xkme.2021.05.002
sha: 118902456192a2fe8266e641f6d3be31fdfb8292
doc_id: 988309
cord_uid: hj4qfp0f

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.

While IgA Nephropathy (IgAN) typically triggered by upper respiratory infections, relapse of IgAN has been reported in patients receiving vaccinations. More recently, there have been three case reports of patients who presented with IgAN relapse following SARS-CoV-2 mRNA vaccination. 1, 2 Here, we present the first case of newly diagnosed IgAN after receiving the Moderna SARS-CoV-2 mRNA vaccine.

A 30-year-old-man of Western European and South American ancestry presented with new-onset hematuria and proteinuria. He had no known past medical history and had never been tested for COVID-19 infection. He did not report any known COVID Immunofluorescence revealed 3+ diffuse granular mesangial staining for IgA (Fig. 1B) .

Staining was weakly positive for C3 and negative for IgG and other immunoglobulins/complement antibodies. Ultrastructural examination revealed scattered immune-type electron-dense deposits in the mesangium and mild podocyte foot process effacement (Fig. 1C) . Pathological features were consistent with IgA nephropathy (IgAN) with Oxford MEST-C Classification as M1-E0-S1-T0-C0, 3 and his risk of a 50% decline in eGFR or progression to kidney failure within 5 years is approximately 3.9%, as per a recent risk prediction model by the International IgA Nephropathy Network. 4 He J o u r n a l P r e -p r o o f was started on losartan 25mg daily, which was well tolerated. After six weeks of therapy, UPCR improved to 0.43g/g and creatinine remained stable at 1.03mg/dL.

To our knowledge, this is the first reported case of newly diagnosed IgAN in a kidney biopsy related to a COVID-19 vaccine, after a very recent report of exacerbated IgAN in two patients who received the second dose of mRNA-1273 SARS-CoV-2 vaccine. 5 While correlation does not inherently imply causation, the timing of symptom onset shortly after the vaccine should be considered as the inciting event.

IgAN is an immune-complex disease characterized by mesangial IgA1 deposition with or without concurrent IgG and C3 deposits. Despite IgAN being the most common primary glomerulonephritis worldwide 6 , its underlying pathogenesis was unclear until the recognition of circulating poorly-galactosylated IgA1 in serum and direct deposit in glomeruli by mass spectrometry analysis. 7 It is noteworthy that the existence of poorlygalactosylated IgA1 alone is not sufficient to trigger IgAN. Immune complexes formed by pathogenic IgA1 and glycan-specific IgG or IgA targeted at these aberrantly galactosylated areas are usually required, followed by impaired liver removal and an increased affinity for mesangial cells. 8 Thus, IgAN is proposed as a multi-hit disease. It According to Centers of Disease Control and Prevention (CDC) data, there was no reported hematuria/proteinuria except for one patient who developed acute kidney injury (AKI) due to obstructive nephrolithiasis resulting in death. 19 It is beyond the scope of the discussion on the causality of IgAN in our patient. Still, emerging data suggest the importance of analyzing pre-existing antibodies to self-carbohydrates in either infected or vaccinated persons. 20 Another intranasal vaccine candidate against SARS-CoV-2 is currently under investigation 21 , which might directly perturb dysregulated mucosal immune system in genetically predisposed persons. Of note, local mucosal responses to natural SARS-CoV-2 in the nasopharynx are shown to be dominated by early IgA neutralizing antibodies compared to IgG and IgM and were associated with a peripheral expansion of IgA-secreting plasmablasts. 22 It is therefore essential to monitor any de novo IgAN or exacerbations of pre-existing IgAN following intranasal vaccinations.

Lastly, in the first published mRNA-1273 trial data, there were only 4.6% Asians among all participants. Since IgAN is more common in the Asian population, larger clinical trial data, particularly with more diverse participants, are urgently needed to fully assess the possible correlation between IgAN and vaccination against SARS-CoV-2. While providers and patients should be aware of this adverse effect, it should be emphasized that this is likely a rare occurrence and should not deter others from seeking SARS-CoV-

A case of gross hematuria and IgA nephropathy