Age: 60.0
Sex: F
Vaccine: FLUX(H1N1)
Symptoms: Blood pressure increased, Blood triglycerides increased, Blood urea increased, Chest X-ray normal, Complement factor normal
Clinical narrative: Case number PHHY2016US023093, is an initial literature case report received on 18 Feb 2016 and from Vaccine Adverse Event Reporting System (VAERS, reference number: 612763) on 19 Feb 2016 (combined report). The author in the article discussed about membranes nephropathy (MN) and severe acute kidney injury (AKI) following influenza vaccination. This report refers to a 60 years old female patient. Past medical history included bronchial asthma for which she was referred to the emergency room (ER) by her primary medical doctor (PMD) for evaluation of elevated serum creatinine level (10.3 mg/dL). She did not have history of drug allergy, diabetes, hypertension, hepatitis or blood transfusion. She denies smoking, alcohol or intravenous drug use. She had refused influenza vaccine (manufacturer and batch number: not reported) in the past as her father died from Guillain-Barre syndrome after receiving influenza vaccine (see case: PHHY2016US023178). Concomitant medications included Albuterol, ADVAIR and montelukast. She had received 2009 H1N1 influenza vaccine (manufacturer and batch number: not reported) on an unknown date. The patient said that she developed fever, intermittent nausea, vomiting, lower extremity edema, acute-onset massive proteinuria with nephrotic syndrome (NS) and severe AKI soon after being immunized with the influenza vaccine. Two weeks after the vaccination she went to ER (emergency room). The patient was seen by her PMD one day before her ER visit for evaluation of worsening bilateral lower extremity edema. Review of systems was negative for sore throat, dyspnea, gross hematuria, arthralgias or rash. On physical examination, her blood pressure was elevated at 220/100 mm Hg and there was 3+ pitting edema of the lower extremities. She was afebrile in the ER. The rest of the examination was unremarkable. The patient was initially started on furosemide and metolazone for management of edema. She was also started on amlodipine and clonidine for management of hypertension. The BP was well controlled with the above medications. As the patient was responding well to the diuretic therapy and had no uremic symptoms, she was not dialyzed. At the time of ER presentation, the serum creatinine was elevated at 9.93 mg/dL and blood urea nitrogen was 77 mg/dL. The serum creatinine checked three months before presentation to the ER was 0.9 mg/dL. The serum total protein was 7.8 g/dL and serum albumin was low (2.3 g/dL). Because of the high globulin fraction, serum immunofixation was performed, which revealed polyclonal gammopathy but no monoclonal immunoglobulin was seen. Repeat laboratory testing performed subsequently revealed a total protein level of 4.5 g/dL and serum albumin of 2.2 g/dL. Aspartate aminotransferase was mildly elevated (49 U/L). Other liver enzymes were within normal limits. Complete blood count was normal. Urinalysis was significant for 20-30 WBC/hpf, 10-20 RBC/hpf and 3+ proteinuria. Her random urine total protein to creatinine (TP/CR) ratio was significantly elevated at 22. A 24-hour urine collection revealed 20.5 g of protein. A non-contrast computed tomography (CT) scan of the abdomen and pelvis in the ER revealed no hydronephrosis or peri-nephric inflammatory changes. Chest x-ray was normal. Workup for secondary causes of the nephrotic syndrome (NS) and acute kidney injury (AKI) revealed non-reactive hepatitis C virus antibody and hepatitis B surface antigen. The antinuclear antibody, anti-neutrophil cytoplasmic antibodies (ANCA), cryoglobulins, anti-glomerular basement membrane antibody and human immunodeficiency virus (HIV) antibody were all negative. The serum complement levels were normal. A CT scan-guided kidney biopsy was subsequently performed. Kidney biopsy findings: eight glomeruli were identified on light microscopic examination of the kidney biopsy specimen. The glomeruli showed patient capillary loops and urinary spaces. The interstitium showed patchy edema and mild to moderate inflammatory cell infiltrate composed of mononuclear cells with many eosinophils. The arteries showed mild intimal sclerosis without vasculitis. Immunofluorescence showed scattered fine granular staining for IgG, C3, kappa and lambda light chains in the outer aspect of the glomerular capillary wall. Electron microscopy showed scattered electron-dense deposits in the subepithelial and intramembranous locations. Extensive effacement of the epithelial cell foot processed was seen. The kidney biopsy findings were consistent with (stage 1) MN an acute interstitial nephritis (AIN). After reviewing the results of the kidney biopsy, the patient was initiated on daily oral prednisone (0.75 mg/kg) with tapering doses over the next 2.5 months. However, one week after completion of prednisone therapy, the patient presented to the hospital for a visit with bilateral lower extremity swelling and 30 pounds weight gain. Laboratory tests performed during that visit revealed a low serum albumin level of 2.1 g/dL and an elevated serum creatinine level of 2.3 mg/dL. The total cholesterol (417 mg/dL) and triglyceride (608 mg/dL) levels were also elevated. Her spot urine TP/Cr increased significantly to 28. The patient was hospitalized for management of worsening edema. Repeat kidney biopsy performed during her hospital stay revealed rare subepithelial deposits on electron microscopy with a varied degree of translucency suggestive of resorption of previous deposits. There was no evidence of AIN on repeat kidney biopsy (resolved). The patient was reinitiated on daily oral prednisone (0.75 mg/kg) soon after reviewing the biopsy results. Prednisone was gradually tapered over the next four months. Two weeks after reinitiation of corticosteroids, her serum creatinine decreased to the normal range (0.88 mg/dL), her serum albumin increased to 3.5 g/dL and spot urine TP/CR decreased to 2.2. Serum albumin improved further to 4.1 g/dL after one month of oral prednisone therapy. Proteinuria continued to decline and spot urine TP/CR normalized (0.2) two weeks after completion of the second course of oral corticosteroid therapy. The patient responded well to an initial course of oral corticosteroid therapy with normalization of serum creatinine level but had a relapse of NS with AKI soon after completion of corticosteroid therapy. Since then, the patient has refused further influenza vaccinations. The serum creatinine normalized (1.04 mg/dL0 five weeks after initiation of oral prednisone. The serum albumin normalized (3.7 g/dL) after seven weeks, while spot urine TP/CR decreased dramatically to 1.3 after nine weeks of oral corticosteroid therapy. At the five-year follow-up, the patient continues to remain in complete clinical remission of the NS (spot urine TP/CR of 0.1) with normal renal function (serum creatinine: 0.9 mg/dL). A subsequent prolonged course of oral corticosteroids resulted in complete clinical remission of the NS as well as normalization of renal function. Outcome of the events was recovered. The author concluded that based on the experience one can consider corticosteroid therapy in patients with MN and AIN following influenza vaccination. However, further studies are required to investigate the exact pathogenesis of influenza vaccine-induced MN.