Sex: F
Vaccine: COVID19
Symptoms: Hepatic enzyme, Hepatitis B virus test, Hepatitis C virus test, Immunology test, Intraocular pressure test
Clinical narrative: Tubulointerstitial nephritis and uveitis syndrome (TINU) following COVID-19 vaccination; The initial case was missing the following minimum criteria: (ICH-unidentifiable patients.). Upon receipt of follow-up information on [21jun2023], this case now contains all required information to be considered valid.  This is a literature report for the following literature source(s):   A 54-year-old female patient received BNT162b2 (BNT162B2), as dose 1, single (Batch/Lot number: unknown) for covid-19 immunisation. The patient's relevant medical history included: "chronic kidney disease" (ongoing); "contact lens user" (unspecified if ongoing); "hypertension" (ongoing); "acute kidney injury" (ongoing); "nephrotic range proteinuria" (unspecified if ongoing). Concomitant medication(s) included: PREDNISONE oral taken for acute kidney injury. The following information was reported: TUBULOINTERSTITIAL NEPHRITIS AND UVEITIS SYNDROME (hospitalization, medically significant), outcome "recovering", described as "Tubulointerstitial nephritis and uveitis syndrome (TINU) following COVID-19 vaccination". The patient underwent the following laboratory tests and procedures: Antineutrophil cytoplasmic antibody: Negative; Antinuclear antibody: Negative; Biopsy kidney: severe active collapsing glomerulopathy with, notes: active and healed lesions of moderate to advanced focal and segmental glomerulosclerosis (FSGS), deemed most likely secondary to prior episodes of collapsing glomerulopathy. She also had acute granulomatous interstitial nephritis noted on biopsy; Given granulomatous AIN findings on renal biopsy, notes: and anterior uveitis, there was concern about tubulointerstitial nephritis and uveitis syndrome (TINU); Blood creatinine: 2.36; Blood creatinine: 1.4 mg/dl, notes: At baseline; 2.8 mg/dl, notes: increase; Blood urea: 37, notes: Elevated; Complement factor C3: Negative; Complement factor C4: Negative; Double stranded DNA antibody: Negative; Negative; EGFR status assay: 23; Gene sequencing: two high risk APOL1 alleles (G1/G1), which have, notes: been associated with collapsing glomerulopathy. Interestingly she also had a homozygous variant of FAN1 (c2539T greater than A) which has been associated with a form of interstitial nephritis; Glomerular filtration rate: 50, notes: mL/min per 1.73 m2; Haematocrit: 34.2; Haemoglobin: 10.6, notes: mild anemia; Hepatic enzyme: within normal range; Hepatitis B virus test: Negative; Negative; Hepatitis C virus test: negative; negative; HIV test: Negative; Negative; HLA-B gene status assay: Negative; Immunology test: Negative; Intraocular pressure test: 10 mmHg, notes: in the right eye; 15 mmHg, notes: in the left eye; PLA2 antibody: Negative; 1 plus anterior chamber cell, notes: in the right eye; 0.5 plus anterior chamber cell, notes: in the left eye; Light chain analysis: 1.29; moderately elevated; moderately elevated; Lysozyme: 13.3, notes: elevated; Mycobacterium tuberculosis complex test: Negative; Protein urine: 5.2 g; Red blood cell sedimentation rate: 51, notes: elevated; Treponema test: Negative; Negative; Visual acuity tests: 20/25, notes: in the right eye; 20/25, notes: in the left eye; White blood cell count: elevated, notes: with left shift attributed to systemic steroid use. Therapeutic measures were taken as a result of tubulointerstitial nephritis and uveitis syndrome.  Case report: A 54-year-old female with past medical history of chronic kidney disease (with estimated glomerular filtration rate of 50 mL/min per 1.73 m2), acute kidney injury with nephrotic range proteinuria, and longstanding hypertension was referred with acute-onset bilateral eye pain and photophobia for two weeks. She was a previous contact lens user but had no history of ocular surgeries. At the time of ophthalmologic evaluation, the patient was on systemic prednisone for new-onset acute kidney injury and nephrotic range proteinuria that developed after the first dose of the Pfizer COVID-19 vaccine, for which the patient was admitted to the hospital one month prior. At that time, she presented with fever, malaise, and acute onset of lower extremity edema. She had an increase in her serum creatinine from a baseline of approximately 1.42.8 mg/dL. 24-hour urine protein was 5.2 g. Laboratory evaluation including HIV, HBV, PLA2 antibody, ANA, dsDNA, C3 and C4, was negative. Kappa and lambda light chains were moderately elevated but with a normal ratio of 1.29. Kidney biopsy at that time revealed severe active collapsing glomerulopathy with active and healed lesions of moderate to advanced focal and segmental glomerulosclerosis (FSGS), deemed most likely secondary to prior episodes of collapsing glomerulopathy. She also had acute granulomatous interstitial nephritis noted on biopsy. Genetic screen revealed two high risk APOL1 alleles (G1/G1), which have been associated with collapsing glomerulopathy. Interestingly she also had a homozygous variant of FAN1 (c2539T > A) which has been associated with a form of interstitial nephritis. She was started on oral glucocorticoids to treat both the collapsing glomerulopathy and granulomatous interstitial nephritis. Despite being on oral prednisone 40 mg daily, the patient was found to have 1+ anterior chamber cell in the right eye and 0.5+ anterior chamber cell in the left eye by Standardization of Uveitis Nomenclature (SUN) criteria. Visual acuity was 20/25 in each eye. Intraocular pressure was 10 mmHg in the right eye and 15 mmHg in the left eye by applanation tonometry. There was no inflammation in the vitreous or retina. Given acute onset of bilateral anterior uveitis, a full uveitis workup was sent. The serum RPR, FTA-antibody, quantiferon gold, Lyme western blot, HLA-B27, ANCA, double stranded DNA antibody, HIV, and hepatitis titers were repeated and negative. Liver enzymes were within normal range. The patient did exhibit mild anemia with hemoglobin of 10.6 and hematocrit of 34.2. There was an elevated white blood cell count with left shift attributed to systemic steroid use. Blood urea nitrogen (BUN) was elevated at 37, creatinine at 2.36 and eGFR was 23. ESR and lysozyme were elevated at 51 and 13.3 respectively. Given the active uveitis despite systemic corticosteroids, the patient was started on prednisolone acetate 1% every 2 hours while awake in both eyes and cyclopentolate 1% nightly in both eyes. The patient eventually tapered off oral prednisone. Cyclopentolate was discontinued. Prednisolone acetate 1% was tapered but continued at 1 drop in each eye daily for maintenance dose to maintain quiet disease. The patient eventually developed mild ocular hypertension from steroid response, so she was started on brimonidine 1 drop in each eye twice daily. Given granulomatous AIN findings on renal biopsy and anterior uveitis, there was concern about tubulointerstitial nephritis and uveitis syndrome (TINU). There was discussion with the patient about starting intravenous rituximab infusions to treat this condition; however, she was hesitant to proceed. Currently the patient is on the transplant list for stage 4 chronic kidney disease (CKD).; Sender's Comments: Based on the information provided, a causal relationship between suspect drug BNT162b2  and the reported event Tubulointerstitial nephritis and uveitis syndrome 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.