Age: 60.0
Sex: F
Vaccine: COVID19
Symptoms: Dyspnoea, Exercise tolerance decreased, Fatigue, Fluorescent in situ hybridisation, Glomerulonephritis
Clinical narrative: Acute kidney injury; exercise tolerance decreased; cough; dyspnoea; fatigue; Immune complex glomerulonephritis; acute tubulointerstitial nephritis; This literature-non-study case was reported in a literature article and describes the occurrence of ACUTE KIDNEY INJURY (Acute kidney injury), GLOMERULONEPHRITIS (Immune complex glomerulonephritis) and TUBULOINTERSTITIAL NEPHRITIS (acute tubulointerstitial nephritis) in a 60-year-old female patient who received mRNA-1273 (Moderna COVID-19 Vaccine) for COVID-19 vaccination. The occurrence of additional non-serious events is detailed below.      Concurrent medical conditions included Hypertension, Hypothyroidism and Diffuse large B-cell lymphoma (In remission) since 2019.   On 11-Jan-2021, the patient received first dose of mRNA-1273 (Moderna COVID-19 Vaccine) (unknown route) 1 dosage form. On 09-Feb-2021, received second dose of mRNA-1273 (Moderna COVID-19 Vaccine) (unknown route) dosage was changed to 1 dosage form. On 08-Mar-2021, the patient experienced ACUTE KIDNEY INJURY (Acute kidney injury) (seriousness criteria hospitalization and medically significant). On an unknown date, the patient experienced GLOMERULONEPHRITIS (Immune complex glomerulonephritis) (seriousness criterion medically significant), TUBULOINTERSTITIAL NEPHRITIS (acute tubulointerstitial nephritis) (seriousness criterion medically significant), EXERCISE TOLERANCE DECREASED (exercise tolerance decreased), FATIGUE (fatigue), COUGH (cough) and DYSPNOEA (dyspnoea). The patient was treated with METHYLPREDNISOLONE for Adverse event, at a dose of 125 milligram; PREDNISONE for Adverse event, at a dose of 60 milligram once a day and MYCOPHENOLATE MOFETIL in August 2021 for Adverse event, at an unspecified dose and frequency. At the time of the report, ACUTE KIDNEY INJURY (Acute kidney injury), GLOMERULONEPHRITIS (Immune complex glomerulonephritis), TUBULOINTERSTITIAL NEPHRITIS (acute tubulointerstitial nephritis), EXERCISE TOLERANCE DECREASED (exercise tolerance decreased), FATIGUE (fatigue), COUGH (cough) and DYSPNOEA (dyspnoea) outcome was unknown.      DIAGNOSTIC RESULTS (normal ranges are provided in parenthesis if available): In June 2020, Blood creatinine: 0.9 mg/dl increased to 0.9 mg/dL. On 12-Mar-2021, Biopsy kidney: severe atin Severe ATIN (acute tubulointerstitial nephritis) and immune complex GN (glomerulonephritis)with endocapillary hypercellularity. In October 2021, Blood creatinine: 4.92 mg/dl 4.92 mg/dL. In October 2021, Urine analysis: 200 mg/g at last follow-up in October 2021, it was down to 1.5 mg/dL with resolution of hematuria and decrease in proteinuria to 200 mg/gm. On an unknown date, Biopsy bone marrow: no evidence of lymphoma Bone marrow biopsy revealed no evidence of lymphoma.. On an unknown date, Biopsy kidney: focal mild segmental (abnormal) focal mild segmental  endocapillary hypercellularity. On an unknown date, Blood creatinine: 1.5 mg/dl Serum creatinine peaked at 4.92 mg/dL, and at her last follow-up in October 2021, it was down to 1.5 mg/dL with resolution of hematuria and decrease in proteinuria to 200 mg/gm. and 4.54  mg/dl 4.54  mg/dL, Admission serum. On an unknown date, Fluorescent in situ hybridisation: mixed t and b lymphocytes showed mixed T and B lymphocytes with abundant polyclonal plasma cells.. On an unknown date, Imaging procedure: unimpressive marginal lymphadenopathy Imaging showed an unimpressive marginal lymphadenopathy not warranting a biopsy.. On an unknown date, Immunohistochemistry: mixed t and b lymphocytes mixed T and B lymphocytes with abundant polyclonal plasma cells.. On an unknown date, Immunology test: full-house positive staining (Positive) full-house positive staining, characterized by diffuse, global mesangial and segmental capillary wall, granular positive staining by immunoglobulin IgG (3+), IgA (1+), IgM (2+), C1q (2+), C3 (1+), ? (3+), and ? (3+). Within tubular basement membranes, interstitium, and vascular walls, there was IgG, IgM, C1q, and C3 deposition. On an unknown date, Microscopy: sparse intramembranous sparse intramembranous and rare subendothelial electron-dense deposits (EDD). On an unknown date, Serology test: low c3 53 mg/dl Serological work-up was unremarkable, except for low C3 (53 mg/dL). On an unknown date, Urine analysis: urine dipstick negative Baseline proteinuria: No prior quantification; urine dipstick negative and 2,000 mg/g Peak proteinuria : 2,000 mg/g UPCR. On an unknown date, Urine protein/creatinine ratio: microscopic hematuria (abnormal) microscopic hematuria with 2-g proteinuria on spot.     For mRNA-1273 (Moderna COVID-19 Vaccine) (Unknown), the reporter considered ACUTE KIDNEY INJURY (Acute kidney injury), GLOMERULONEPHRITIS (Immune complex glomerulonephritis) and TUBULOINTERSTITIAL NEPHRITIS (acute tubulointerstitial nephritis) to be related. No further causality assessments were provided for EXERCISE TOLERANCE DECREASED (exercise tolerance decreased), FATIGUE (fatigue), COUGH (cough) and DYSPNOEA (dyspnoea).    No concomitant information were provided. The patient received her first dose of Moderna vaccine in January 2021, following which, she experienced fatigue and decreased exercise tolerance, and subsequently dyspnea and cough. While still symptomatic, she received the second dose in February 2021. Four weeks after second dose, the patient presented with shortness of breath and fatigue and was admitted due to acute kidney injury (AKI) noted on routine tests. Admission serum creatinine was 4.54 mg/dL, which had increased from 0.9 mg/dL in June 2020. No identifiable cause of AKI was recognized on history. Urine analysis showed microscopic hematuria with 2-g proteinuria on spot urine protein-creatinine ratio (UPCR). Serological work-up was unremarkable, except for low C3 (53 mg/dL). Imaging showed an unimpressive marginal lymphadenopathy not warranting a biopsy. Bone marrow biopsy revealed no evidence of lymphoma. Kidney biopsy showed focal mild segmental endocapillary hypercellularity. There was diffuse, dense interstitial lymphoplasmacytic infiltrate with focal germinal center formation, associated with numerous foci of moderate to severe tubulitis. Immunohistochemical stain and in situ hybridization showed mixed T and B lymphocytes with abundant polyclonal plasma cells. Biopsy findings were consistent with severe acute tubulointerstitial nephritis (ATIN) and immune complex mediated glomerulonephritis with focal endocapillary hypercellularity. She was treated with methylprednisolone 125 mg for 3 days and then prednisone 60 mg daily. Prednisone was tapered off and mycophenolate mofetil (MMF) was added in August 2021. Serum creatinine peaked at 4.92 mg/dL, and at her last follow-up in October 2021, it was down to 1.5  Company comment: This literature case concerns a 60-year-old female patient, with medical history of Hypertension, Hypothyroidism and Diffuse large B-cell lymphoma in remission and no prior renal disease, who experienced the unexpected event of acute kidney injury which required hospitalization and medically significant events of glomerulonephritis and tubulointerstitial nephritis. The patient also experienced non serious events of fatigue and decreased exercise tolerance, and subsequently dyspnea and cough which started following first dose of mRNA-1273. The events of acute kidney injury, glomerulonephritis and tubulointerstitial nephritis occurred approximately 27 days after the second dose of mRNA-1273. As reported, after acute kidney injury was noted on routine tests the patient was admitted to hospital with serum creatinine was 4.54 mg/dL, which had increased from 0.9 mg/dL 10 months prior. No identifiable cause of AKI was recognized on history, as reported. Urine analysis showed microscopic hematuria with 2-g proteinuria on spot urine protein-creatinine ratio (UPCR). Biopsy findings were consistent with severe acute tubulointerstitial nephritis (ATIN) and immune complex mediated glomerulonephritis with focal endocapillary hypercellularity and the patient was treated with methylprednisolone for 3 days and then prednisone daily. Prednisone was tapered off and mycophenolate mofetil (MMF) was added. It is unclear if above mentioned non serious events following first dose were symptoms of unrecognised serious events which were diagnosed after second dose. Above mentioned medical history remains a confounder. The benefit-risk relationship of mRNA-1273 is not affected by this report.  This case was linked to MOD-2022-485478, MOD-2022-485479 (Patient Link).   Most recent FOLLOW-UP information incorporated above includes: On 16-Feb-2022: Follow up received by safety 17-Feb-2022 has Email with FTA received from team and  significant Patient information, Lab data, Medical history, treatment information and events.; Sender's Comments: This literature case concerns a 60-year-old female patient, with medical history of Hypertension, Hypothyroidism and Diffuse large B-cell lymphoma in remission and no prior renal disease, who experienced the unexpected event of acute kidney injury which required hospitalization and medically significant events of glomerulonephritis and tubulointerstitial nephritis. The patient also experienced non serious events of fatigue and decreased exercise tolerance, and subsequently dyspnea and cough which started following first dose of mRNA-1273. The events of acute kidney injury, glomerulonephritis and tubulointerstitial nephritis occurred approximately 27 days after the second dose of mRNA-1273. As reported, after acute kidney injury was noted on routine tests the patient was admitted to hospital with serum creatinine was 4.54 mg/dL, which had increased from 0.9 mg/dL 10 months prior. No identifiable cause of AKI was recognized on history, as reported. Urine analysis showed microscopic hematuria with 2-g proteinuria on spot urine protein-creatinine ratio (UPCR). Biopsy findings were consistent with severe acute tubulointerstitial nephritis (ATIN) and immune complex mediated glomerulonephritis with focal endocapillary hypercellularity and the patient was treated with methylprednisolone for 3 days and then prednisone daily. Prednisone was tapered off and mycophenolate mofetil (MMF) was added. It is unclear if above mentioned non serious events following first dose were symptoms of unrecognised serious events which were diagnosed after second dose. Above mentioned medical history remains a confounder. The benefit-risk relationship of mRNA-1273 is not affected by this report.