key: cord-0941137-cc5ce2y5
authors: Jefferis, Julia; Kassianos, Andrew J.; Grivei, Anca; Doucet, Brian; Healy, Helen; Francis, Leo; Yu Mon, Saw; John, George T.
title: SARS-CoV-2 vaccination-associated collapsing glomerulopathy in a kidney transplant recipient.
date: 2022-01-04
journal: Kidney Int
DOI: 10.1016/j.kint.2021.12.018
sha: e3851c48f134c14271c819caa463912858d5909b
doc_id: 941137
cord_uid: cc5ce2y5

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A stable kidney transplant recipient (KTR) of 14 years received the SARS-CoV-2 ChAdOx1 (AZD1222) vaccine and, within a fortnight, presented with severe acute kidney injury (AKI)creatinine 533µmol/L (baseline 125-187µmol/L) and nephrotic range proteinuria (urine PCR=2000g/mol, no hematuria). The allograft, her first, was from a deceased Caucasian donor, following kidney failure from IgA vasculitis, and stable for many years (Fig1A). Initial kidney biopsy showed glomerulomegaly, glomerulitis, podocyte enlargement with protein droplets and collapse of the glomerular tufts along with glomerular and interstitial immune infiltrates (Banff score i3 t0 v0 g3 ptc0 ci1 ct1 cv0 cg1b mm0 ah3 ti3 i-IFTA3) (Fig1B-C); EM unavailable. Immunofluorescence for immunoglobulins and C4d immunohistochemistry, antibodies against donor-specific HLA and Angiotensin 2R1 were absent. Treatment response for suspected antibody-mediated rejection with methylprednisolone, intravenous immunoglobulin and plasma exchange was poor. Repeat kidney biopsy showed absence of immune cell infiltration and features consistent with collapsing glomerulopathy (CG) with acute tubular injury and mild glomerulitis (Banff score i0 t1 v0 g1 ptc0 ci1 ct1 cv0 cg3 mm0 ah3 ti0 i-IFTA3) (Fig1D-E). EM revealed detachment of podocytes with extensive foot process effacement, microvillous hyperplasia, protein droplets in some podocytes, normal glomerular basement membranes, with no evidence of immune complex deposition. Secondary causes of CG including CMV, BK, HIV, parvovirus and SARS-CoV-2 infection were excluded. The patient required haemodialysis at three months with persisting proteinuria (15g/day). Further immunohistochemistry confirmed: (1) expression of Ki67, a marker of glomerular expansion/proliferation in CG, detected in biopsy 1, with epithelial cell reactivity in Bowman's space (Fig1F); (2) reduced glomerular expression of synaptopodin and podocalyxin, evidence of podocyte dedifferentiation previously associated with CG, on biopsy 1 (Supplementary Fig1); and (3) significantly increased levels of inflammatory subpopulations on initial biopsy to be significantly attenuated following intervention (Supplementary Fig2). 1, 2 SARS-CoV-2 vaccination has been associated with many glomerular diseases, minimal change and membranous nephropathy, whilst SARS-CoV-2 infection has been associated with CG including in a KTR. [3] [4] [5] We report the first case of a KTR developing CG after SARS-CoV-2 ChAdOx1 vaccination, with no identifiable cause besides temporal association with vaccination. 

The Dysregulated Podocyte Phenotype

AJKD Atlas of Renal Pathology: Collapsing Glomerulopathy

Nephrotic syndrome and vasculitis following SARS-CoV-2 vaccine: true association or circumstantial? Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association

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COVID-19-Related Collapsing Glomerulopathy in a Kidney Transplant Recipient. American journal of kidney diseases : the official journal of the National Kidney Foundation

The authors would like to thank the tissue donors for provision of renal bio-specimens. The authors also gratefully acknowledge the staff of QIMR Berghofer Core Histology and Australian Cancer Research Foundation Centre for Comprehensive Biomedical Imaging (QIMR Berghofer) for expert technical assistance with staining and image analysis and Dr Kim

All the authors declared no competing interests.