key: cord-0802484-5y1dtfhg
authors: Czerlau, Cecilia; Bocchi, Federica; Saganas, Charalampos; Vogt, Bruno
title: Acute interstitial nephritis after messenger RNA-based vaccination
date: 2021-09-28
journal: Clin Kidney J
DOI: 10.1093/ckj/sfab180
sha: 77d1a0bec97ba422449af420cac9e0c06bb622fb
doc_id: 802484
cord_uid: 5y1dtfhg

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Patient 2 was a 54-year-old man, known for a history of myocardial infarction, who presented with glomerular erythrocyturia and nephrotic syndrome 3 days after the second dose of Moderna vaccine. The kidney biopsy showed AIN with granulomas and tubular destruction. Subsequent electron microscopic examination revealed evidence of focal segmental glomerulosclerosis (FSGS) with fusion of podocyte extensions, two segmental scleroses and prominent ischemoid changes. Because the patient was not under regular medical care and had no complaints, it remains unknown whether he had pre-existing FSGS and additionally developed interstitial nephritis after SARS-CoV-2 vaccination or whether both entities occurred after vaccination.

Patient 3 was a 58-year-old man with primary FSGS diagnosed in 2013 and refractory to treatment with several recurrences in the past. The patient reported increased oedema a few days after the second dose of Moderna vaccine. Laboratory examination revealed AKI with a picture of nephrotic syndrome. A renal biopsy revealed extensive AIN. Focal and segmental involvement with sclerosis in 5 of 25 glomeruli was also described, with no evidence of disease recurrence. Electron microscopic examination revealed a high degree of fusion of podocyte extensions, consistent with the known FSGS.

Patient 4 was a 38-year-old woman who was under regular medical care due to ulcerative colitis. One month after the second dose of Moderna vaccine, a routine examination revealed active urine sediment and proteinuria of 0.5 g/day. Renal biopsy showed AIN and immunofluorescence demonstrated mesangial immunoglobulin A (IgA) deposits. This was confirmed by electron microscopy. The cause of the interstitial nephritis may be related to chronic inflammatory bowel disease. However, the bowel disease was well controlled with ustekinumab for several years before the SARS-CoV-2 vaccination. Based on the temporal correlation, and with wellcontrolled underlying disease, vaccine-induced AIN is most likely. Patient 5 was a 35-year-old woman who has been taking certolizumab since 2016 for rheumatoid arthritis. At the end of March she received the second dose of Pfizer-BioNTech vaccine, after which she felt unwell and tired. Laboratory chemistry showed a 50% increase in creatinine compared with the previous values from last year. Renal biopsy showed evidence of IgA nephropathy with crescents and hypercellularity as well as AIN. Interstitial nephritis may occur in the setting of IgA nephropathy, but it is usually less severe. It remains unclear whether the interstitial nephritis occurred in the setting of certolizumab therapy or after vaccination. The temporal correlation suggests vaccination-caused interstitial nephritis.

To the best of our knowledge, these are the first described cases of AIN after vaccination with an mRNA-based vaccine. AIN is an inflammatory pathology of renal interstitium and tubules that occurs on an allergic basis with oedema and acute damage and can potentially heal with interstitial fibrosis [4] . The exact mechanism of allergic reactions associated with mRNA vaccines is unclear. The systematic review and meta-analysis by Chen et al. [5] found that the incidence of anaphylaxis associated with the Pfizer-BioNTech vaccine was approximately 10 times higher than that associated with all previous vaccines. One possible explanation is that some individuals are at higher risk for non-IgEmediated mast cell activation or complement activation. This is related to the lipid or polyethylene glycol lipid component of the vaccine. Early evaluation for AIN in patients with pre-existing renal disease or without pre-existing nephropathy is warranted if renal function worsens after vaccination with mRNA-based SARS-CoV-2 vaccines. In some cases it is not easy to differentiate whether worsening renal function is a recurrence of the previously known nephropathy (patient 3), a previously undiagnosed underlying disease (eventually patient 2) or a new

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Acute interstitial nephritis after mRNA-based vaccination disease. Steroid therapy was used in all patients with good effect, except patient 2, and might be the treatment of choice.

We obtained informed consent from the patients to publish their case.

C.C., F.B., C.S. and B.V. designed the study. C.C. and F.B. performed the literature search. All authors contributed to the data interpretation. C.C., F.B. and C.S. wrote the first draft of the manuscript, which was subsequently revised by B.V.

None declared.