Sex: F
Vaccine: COVID19
Symptoms: Complement factor, Complement factor C3, Complement factor C4, Computerised tomogram kidney, Glomerulonephritis rapidly progressive
Clinical narrative: P-ANCA-associated pauci-immune glomerulonephritis; This is a literature report for the following literature source(s):   A 62-year-old female patient received BNT162b2 (BNT162B2), as dose 2, single (Batch/Lot number: unknown) for COVID-19 immunization. The patient's relevant medical history included: "limited systemic sclerosis" (unspecified if ongoing); "pulmonary arterial hypertension" (unspecified if ongoing); "interstitial lung disease" (unspecified if ongoing); "diabetes mellitus type 2" (unspecified if ongoing); "admitted to the hospital" (unspecified if ongoing); "acute kidney injury" (ongoing). Concomitant medication(s) included: SILDENAFIL taken for pulmonary hypertension; MACITENTAN taken for pulmonary hypertension; DULAGLUTIDE taken for gastrooesophageal reflux disease; PANTOPRAZOLE taken for gastrooesophageal reflux disease. Vaccination history included: Bnt162b2 (DOSE 1, SINGLE), for COVID-19 immunization. The following information was reported: GLOMERULONEPHRITIS RAPIDLY PROGRESSIVE (medically significant), 4 weeks after the suspect product(s) administration, outcome "recovering", described as "P-ANCA-associated pauci-immune glomerulonephritis". The patient underwent the following laboratory tests and procedures: Antineutrophil cytoplasmic antibody: 335.8 iU, notes: elevated; 12.0 iU, notes: Decreased; Antineutrophil cytoplasmic antibody: positive, notes: titer of greater than 1:640; Antinuclear antibody: positive, notes: titer of 1:640; Blood creatinine: improved from 6.70 to 2.5, notes: eight months after presentation; Blood creatinine: 1.0 mg/dl, notes: Baseline; two months before presentation; 5.18 mg/dl, notes: Elevated; two months before presentation; 2.6 mg/dl, notes: improved; 2.5 mg/dl, notes: stabilized; Blood pressure measurement: 150/90 mmHg, notes: on admission; Blood urine: negative; Complement factor: were within the normal range; Complement factor C3: 80 mg/dl, notes: mildly low; Complement factor C4: normal; Computerised tomogram kidney: showed crescentic glomerulonephritis with five out, notes: of 57 glomeruli manifesting cellular crescent formation; Hepatitis B virus test: negative; Hepatitis C virus test: Negative; Immunology test: negative; Microscopy: was abnormal, notes: with 20 isomorphic red blood cells/high-power field; Pathology test: LM - crescentic glomerulonephritis, notes: IF - negative. EM - not available; physical examination: remarkable, notes: only for a 2+ lower-extremity edema; Protein urine: negative; Red blood cells urine: 3+, notes: RBC; Ultrasound scan: showed a normal kidney size and echotexture, notes: without hydronephrosis; Urine analysis: 1+, notes: protein; Urine protein/creatinine ratio: 0.8, notes: Unit: g/g; of creatinine; Vital signs measurement: remarkable, notes: only for a 2+ lower-extremity edema. Therapeutic measures were taken as a result of glomerulonephritis rapidly progressive.  Clinical course: Case presentation: The patient with a history of limited systemic sclerosis complicated by pulmonary arterial hypertension, interstitial lung disease, and diabetes mellitus type 2 was admitted to the hospital for elevated serum creatinine of 5.18 mg/dL from a baseline of less than 1.0 mg/dL two months before presentation. The patient was asymptomatic except for increased urinary frequency, which she attributed to a recently increased dose of diuretics to manage worsening lower-extremity edema. The patient was on sildenafil 20 mg and macitetan 10 mg daily for pulmonary hypertension, dulaglutide, and pantoprazole 40 mg daily for gastroesophageal reflux disease due to esophageal dysmotility. She had received two doses of the Pfizer-BioNTech mRNA SARS-CoV-2 vaccine four and seven weeks prior to admission and reported no previous infection by SARS-CoV-2. Her blood pressure on admission was 150/90 mmHg. The rest of her vitals and physical examination were remarkable, only for a 2+ lower-extremity edema. Her acute kidney injury (AKI) did not resolve after stopping diuretics and administering normal saline. Renal ultrasound showed a normal kidney size and echotexture without hydronephrosis. Urine microscopy was abnormal, with 20 isomorphic red blood cells/high-power field (HPF). The urine protein-to-creatinine ratio by spot analysis was 0.8 g/g of creatinine. Complements were within the normal range except for a mildly low C3 at 80 mg/dL. Hepatitis B and C serologies were negative. The antinuclear antibody was positive with a titer of 1:640, and the perinuclear form of ANCA (P-ANCA) was positive with a titer of more than 1:640. Myeloperoxidase (MPO) antibody was elevated at 335.8 IU. A CT-guided kidney biopsy was performed, which showed crescentic glomerulonephritis with five out of 57 glomeruli manifesting cellular crescent formation. No endocapillary hypercellularity, fibrinoid necrosis, or segmental sclerosis was seen within the glomeruli. There was no arterial inflammation, necrosis, or thrombosis. Moderate-to-severe interstitial fibrosis and tubular atrophy were present. Immunofluorescence (IF) was negative. There was no evidence of a scleroderma renal crisis. Hence, the diagnosis of P-ANCA-associated pauci-immune glomerulonephritis was made. Due to the recent administration of the BNT162b2 mRNA (Pfizer/BioNTech) vaccine, it was thought that the vaccine triggered her P-ANCA-associated pauci-immune glomerulonephritis. The patient was treated with intravenous methylprednisolone 500 mg for three doses, followed by a tapering dose of oral prednisone and six cycles of cyclophosphamide 750 mg each. After completing the cyclophosphamide regimen, she was started on maintenance of mycophenolate 1 g twice daily and prednisone tapered to 5 mg daily. Eight months following her presentation, her serum creatinine improved to 2.6 mg/dL, the urine dipstick became negative for protein, and hematuria and the MPO antibody decreased to 12.0 IU.  No follow-up attempts are needed. No further information is expected.; Sender's Comments: Based on the available information in the case, the causal association between the reported events and the suspect drug BNT162B2 cannot be excluded.  The impact of this report on the benefit/risk profile of the Pfizer product is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to regulatory authorities, Ethics Committees, and Investigators, as appropriate.