Sex: F
Vaccine: COVID19
Symptoms: Complement factor C3, Complement factor C4, Glomerulonephritis membranous, HIV test, Hepatitis B virus test
Clinical narrative: de novo NELL-1 (Neural epidermal growth factor-like 1) Membranous nephropathy; This is a literature report.  A 50-year-old female patient received BNT162b2 (BNT162B2), as dose 2, single (Batch/Lot number: unknown) for covid-19 immunisation. The patient had no relevant medical history. The patient's concomitant medications were not reported. Vaccination history included: Covid-19 vaccine (DOSE 1, SINGLE; MANUFACTURER UNKNOWN), for COVID-19 immunisation. The following information was reported: GLOMERULONEPHRITIS MEMBRANOUS (medically significant), 5 weeks after the suspect product(s) administration, outcome "recovering", described as "de novo NELL-1 (Neural epidermal growth factor-like 1) Membranous nephropathy". The patient underwent the following laboratory tests and procedures: Biopsy kidney: was consistent with Membranous nephropathy, PLA2R, notes: negative, THSD7A negative, NELL-1 positive; Blood albumin (3.5-5): 3.5 g/dl, notes: normal; Blood creatinine (0.59-1.04): 0.69 mg/dl; Cancer screening: Negative, notes: for any malignancy; Cell marker: Negative; Negative; Complement factor C3: normal; Complement factor C4: normal; Hepatitis B virus test: Negative; Hepatitis C virus test: Negative; HIV test: Negative; Examination: was benign except for bilateral upper and, notes: lower extremity edema; Positive, notes: Neural epidermal growth factor-like 1; Negative; Negative; Monoclonal immunoglobulin: Negative; Protein urine: 6458, notes: Units: mg/day with accompanying dyslipidemia; Protein urine (normal high range 180): 8720 mg/g, notes: proteinuria on random estimation; 370 mg/g, notes: improved at 4 months after initial clinical presentation; Renal function test: normal; continued to be normal; Serology test: Negative, notes: for lupus, hepatitis B, hepatitis C, monoclonal paraproteins, phospholipase A2 receptor antibody (PLA2R), thrombospondin type 1 domain containing 7A antibody (THSD7A), human immunodeficiency virus; Urine analysis: was without hematuria or pyuria.  Clinical course: COVID-19 pandemic has upended our lives in ways that we had never imagined. Healthcare providers are learning more about the disease process and its effects both in short-and long-term as the available data is evolving. We as nephrologists have been in unique position since we take care of these patients in multiple settings ranging from intensive care units to our clinics and dialysis units. With more recent data, there have been reports of COVID-19 vaccinations causing de novo or recurrence of glomerulonephritis. We present a case of de novo NELL-1 (Neural epidermal growth factor-like 1) Membranous nephropathy developing after second dose of COVID-19 vaccination (Pfizer-BioNTech) followed by spontaneous remission. Method(s): 50-year-old female with no past medical history, no prescription or over the counter medication, non-smoker, non-contributory family history was referred to nephrology clinic for evaluation of new onset edema and proteinuria. Age-appropriate cancer screening was negative for any malignancy. Examination was benign except for bilateral upper and lower extremity edema. Laboratory parameters showed normal renal function with creatinine 0.69 mg/dl (0.59-1.04 mg/dl). Urinalysis was without hematuria or pyuria. She had proteinuria at 8,720 mg/g (<180 mg/g) on random estimation, 6,458 mg/day on 24-hour collection with accompanying dyslipidemia and normal serum albumin at 3.5 g/dl (3.5-5 g/dl). Serological testing was negative for lupus, hepatitis B, hepatitis C, monoclonal paraproteins, phospholipase A2 receptor antibody (PLA2R), thrombospondin type 1 domain containing 7A antibody (THSD7A), human immunodeficiency virus and had normal complement i.e., C3 and C4 levels. She had received her second dose of COVID-19 vaccination (Pfizer-BioNTech) approximately 8 weeks prior to clinical evaluation and her symptoms started around 5 weeks after vaccination. Kidney biopsy was consistent with Membranous nephropathy, PLA2R negative, THSD7A negative, NELL-1 positive. Based on the clinical presentation, there was concern if new onset membranous nephropathy is somehow related to COVID-19 vaccination. It was decided to manage patient conservatively without any immunosuppressive therapy. Angiotensin converting enzyme inhibitors were prescribed but had to be discontinued because of hypotension. Patient did have spontaneous clinical remission and her proteinuria improved at 370 mg/g at 4 months after initial clinical presentation and kidney function continued to be normal. Result(s): [Formula presented] Conclusion(s): Our patient did not have any underlying risk factors for membranous nephropathy. Considering the timeline of COVID-19 Vaccination and development of proteinuria, it does point towards vaccination likely mounting a polyclonal antibody response precipitating NELL-1 + membranous nephropathy which went into spontaneous clinical remission as the vaccination effect waned. Though, based on this causality cannot be proven. At this point, we are still contemplating whether our patient should get third booster or not. No conflict of interest.; Sender's Comments: Based on available information and the temporal association, a possible contributory role of Comirnaty vaccine cannot be excluded for the reported events of "GLOMERULONEPHRITIS MEMBRANOUS ". The impact of this report on the benefit/risk profile of the Pfizer drug 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.