key: cord-0923177-82hl5ee5
authors: Leclerc, Simon; Royal, Virginie; Lamarche, Caroline; Laurin, Louis-Philippe
title: Minimal Change Disease With Severe Acute Kidney Injury Following the Oxford-AstraZeneca COVID-19 Vaccine: A CASE Report
date: 2021-07-07
journal: Am J Kidney Dis
DOI: 10.1053/j.ajkd.2021.06.008
sha: 616088a444496fc36e1ad0d74c92c4115d76f219
doc_id: 923177
cord_uid: 82hl5ee5

We report a CASE of minimal change disease (MCD) with severe acute kidney injury (AKI) following the first injection of the ChAdOx1 nCoV-19/AZD1222 vaccine (Oxford-AstraZeneca). A 71-year-old man with history of dyslipidemia and a baseline serum creatinine of 0.7 mg/dl presented with nephrotic syndrome, AKI, and severe hypertension 13 days after receiving the Oxford-AstraZeneca vaccine. Refractory hyperkalemia and hypervolemia with oligoanuria prompted initiation of hemodialysis. His serum albumin was 2.6 g/dL and his urinary protein-creatinine ratio was 2321 mg/mmol. Given a high suspicion for rapidly progressive glomerulonephritis, empirical glucocorticoid treatment was initiated (3 methylprednisolone pulses followed by high-dose prednisone). A kidney biopsy showed minimal change disease (MCD) and acute tubular injury. Kidney function and proteinuria subsequently improved, and hemodialysis was discontinued 38 days after the start of therapy. This case describes de novo MCD after the Oxford-AstraZeneca vaccine. It adds to the few published case reports of MCD after the Pfizer-BioNTech vaccine. Further reports and studies will be needed to elucidate whether MCD is truly associated to COVID-19 vaccination.

The coronavirus 2019 (COVID-19) pandemic has been associated with an increased mortality worldwide. New vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were thus developed to limit contagion and mortality. Major side effects of these vaccines are uncommon. However, de novo minimal change disease (MCD) following the Pfizer-BioNTech COVID-19 vaccine has been reported (1, 2, 3) .

We report the case of a 71-year-old man with nephrotic syndrome and acute kidney injury (AKI) following the administration of the ChAdOx1 nCoV-19/AZD1222 vaccine (University of Oxford, AstraZeneca, and the Serum Institute of India), based on a replication-incompetent chimpanzee adenovirus vector that expresses the SARS-CoV-2 spike protein. His kidney biopsy demonstrated MCD and acute tubular injury.

A 71-year-old man presented to the emergency room with anasarca, AKI, and severe hypertension. He was only known to have dyslipidemia, which was treated with rosuvastatin 20 mg daily. His usual blood pressure was 130/80 mm Hg. He had no prior history of SARS-CoV-2 infection or chronic kidney disease. His baseline serum creatinine was 0.7 mg/dl. He was not taking any other medications including nonsteroidal anti-inflammatory drugs. Thirteen days before presentation, he received the first injection of the Oxford-AstraZeneca COVID-19 vaccine. One day after vaccination, and 12 days before presentation, he developed new-onset hypertension (>190/>100 mmHg) and progressive facial and upper extremity edema.

J o u r n a l P r e -p r o o f On admission, blood pressure was 204/102 mmHg. Physical examination revealed bilateral pitting edema in all extremities. His serum albumin and creatinine were 2.8 g/dL and 10.6 mg/dL, respectively. Serum urea nitrogen was 103.8 mg/dL. Serum sodium (138 mmol/L), calcium (9 mg/dL), and bicarbonate (25 mmol/L) were within reference ranges but serum magnesium (2.9 mg/dL), potassium (5.5 mmol/L), and phosphorus (9.6 mg/dL) were elevated. Hemoglobin (13.4 g/L) and bilirubin (0.18 mg/dL) were within reference ranges and haptoglobin was not decreased (3.05 g/L).

The initial urinary protein-creatinine ratio was 2321 mg/mmol. Six to ten red blood cells per high power field and granular casts were seen on urine microscopy. Polymerase chain reaction for SARS-CoV-2 was negative. The clinical course and important laboratory studies are summarized in Figure 1 .

To exclude infection and neoplasm, an abdominal ultrasound, thoracic computed tomography, and blood cultures were done and were unremarkable. Antinuclear and anti-double stranded DNA antibodies were negative. Antineutrophil cytoplasmic autoantibodies as well as anti-glomerular basement membrane and M-type phospholipase A2 receptor antibodies were negative. Levels of complement factors C3 and C4 were normal. Tests for human immunodeficiency virus, and hepatitis B and C virus were negative. Serum free light chains levels and protein electrophoresis with immunofixation were normal.

One day after admission, the patient was oligoanuric and his hyperkalemia and hypervolemia became refractory to intravenous diuretics, prompting hemodialysis to be initiated. Given the presence of AKI, proteinuria, hematuria, edema, and hypertension, a rapidly progressive glomerular disease could not be excluded. Empirical steroid therapy J o u r n a l P r e -p r o o f was thus initiated 1 day after admission, starting with 3 daily pulses of methylprednisolone 1 g followed by prednisone 60 mg per day. A kidney biopsy was performed 4 days after admission and 17 days after vaccination. There were 24 glomeruli sampled for light microscopy, including 2 globally sclerotic. Viable glomeruli showed a normal morphology. In the cortex, diffuse acute tubular epithelial injury was observed, with epithelial flattening, loss of brush border, and cell sloughing. Interstitial fibrosis was mild, accompanied by mild mononuclear interstitial infiltrate. Arteriolar hyalinosis was moderate, and arterial sclerosis was mild. Immunofluorescence for IgA, IgG, IgM, kappa and lambda light chain, C3, C1q, fibrin, and albumin was performed on 10 glomeruli and did not show any specific glomerular staining. Segmental linear staining along the tubular basement membranes was noted with IgG and kappa light chain (1+ on a scale of 0 to 3+). The electron microscopy report showed diffuse podocyte foot-process effacement (>80%) with focal microvillous transformation. No glomerular or tubular immune-complex type deposits or organized deposits were seen ( Figure 2 ). There were no tubuloreticular inclusions. Together, these findings were compatible with a diagnosis of MCD with acute tubular injury. Hemodialysis therapy was stopped after 38 days of therapy. At dialysis cessation, serum creatinine went down to 1.4 mg/dL. At the last follow-up, 30 days after the end of hemodialysis, the urinary protein-creatinine ratio decreased to 28 mg/mmol and serum creatinine was 1.2 mg/dL.

We described the case of a 71-year-old man who presented with nephrotic syndrome, new-onset hypertension, and AKI 13 days after receiving his first dose of the Oxford-AstraZeneca COVID-19 vaccine. We diagnosed MCD with acute tubular injury. vaccine. Both cases responded to prednisolone therapy.

MCD has also been previously described following vaccination against other pathogens. There are several case reports of MCD in the literature after vaccination for influenza (7, 8) , tetanus-diphtheria-poliomyelitis (9) and hepatitis B virus (10, 11) .

Classically, MCD presents with nephrotic syndrome and a preserved kidney function. AKI has been described in the setting of MCD (12) , but this is not a usual presentation. Moreover, hypertension and hematuria are not classically associated with MCD. Our patient required dialysis, which is rare in the context of newly diagnosed MCD. Interestingly, AKI has been reported so far in all published MCD cases suspected to be in relation to the Pfizer-BioNTech COVID-19 vaccine.

It is obviously difficult to prove definite causality in the case we present here as well as in other previously published cases. Even if secondary causes of MCD were excluded and the presentation was atypical for primary MCD, de novo MCD after vaccination might only be coincidental.

Several hypotheses can be formulated on how a vaccine could trigger MCD.

Considering that it is now described with both mRNA-based (Pfizer BioNTech) and adenovirus vector-based (Oxford-AstraZeneca) vaccines points to a potential mechanism that probably does not implicate a direct effect of the vaccine itself. Instead, J o u r n a l P r e -p r o o f a T cell process ignited by the vaccine might lead to podocyte injury. Furthermore, there are at least 3 reported cases of MCD that occurred after SARS-CoV-2 infection (13, 14, 15) , suggesting a molecular mimicry mechanism between SARS-CoV-2 spike protein and self-antigens on the podocytes. Another hypothesis includes an aberrant activation of the immune system in predisposed individuals. Further reports and studies will be needed to elucidate whether MCD is truly associated with COVID-19 vaccination.

In conclusion, we describe a 71-year-old man diagnosed with MCD and AKI after the first dose of the Oxford-AstraZeneca COVID-19 vaccine. He needed short-term hemodialysis and responded well to high-dose steroids. This case adds to the few published cases that associate the Pfizer-BioNTech COVID-19 vaccine with MCD. Our report suggests a potential relationship between MCD and the Oxford-AstraZeneca COVID-19 vaccine. Since vaccination seems to be the most promising way out of the current COVID-19 global pandemic, millions of doses of different COVID-19 vaccines will be administered around the world in a near future. Thus, adult and pediatric nephrologists should be aware of this rare but generally reversible potential complication of COVID-19 vaccination.

Support: There were no expenses related to this study. LPL is a Fonds de recherche du Québec-Santé Junior 2 Scholar. The funders had absolutely no role in the preparation of this manuscript. 

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