Age: 60.0
Sex: F
Vaccine: FLUX(H1N1)
Symptoms: Blood triglycerides increased, Blood urea increased, Chest X-ray normal, Complement factor normal, Computerised tomogram abdomen abnormal
Clinical narrative: Initial unsolicited report received from the literature on 23 November 2015. This case is linked to 2015SA196261 (same literature). The following is verbatim from the article: ABSTRACT. Immunization with influenza vaccine remains an important global health strategy to prevent outbreaks and epidemics of seasonal influenza. Influenza vaccine has rarely been associated with vasculitis, acute kidney injury (AKI) and nephrotic syndrome (NS). Glomerular diseases following influenza vaccination have also been rarely reported. We report a patient who developed acute-onset massive proteinuria with NS and severe AKI soon after receiving the 2009 H1N1 influenza vaccine. Kidney biopsy showed membranous nephropathy (MN) and acute interstitial nephritis (AIN). Optimal management of glomerular diseases or AIN following influenza vaccination is not known. Our 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. A repeat kidney biopsy revealed MN and resolved AIN. A subsequent prolonged course of oral corticosteroids resulted in complete clinical remission of the NS as well as normalization of renal function. Long-term response to corticosteroid therapy in such cases is not known. However, our patient continued to remain in clinical remission with normal renal function, five years after the initial treatment. This case involves a 60-year-old female patient who was vaccinated with a dose of Influenza vaccine (batch number, expiration date, dose, dose number, route and site of administration were not reported) on an unspecified date. The patient received influenza vaccine two weeks before her ER presentation. The patient had medical history of bronchial asthma. The patient had refused influenza vaccination in the past as her father died from Guillain-Barre (GB) syndrome after receiving influenza vaccine. The patient did not have history of drug allergy, diabetes, hypertension, hepatitis or blood transfusion. The patient denies smoking, alcohol or intravenous drug use. The patient received a dose of Montelukast, Albuterol and ADVAIR as concomitant medications. On an unspecified date, following the vaccination, the patient experienced worsening bilateral lower extremity edema, lower extremity edema, intermittent nausea, vomiting, fever, nephrotic syndrome, hypertension, acute interstitial nephritis, relapse of the NS which later diagnosed with acute kidney injury. The patient required emergency room visit. On an unspecified date, the patient was hospitalized for management of worsening edema. Laboratory investigation includes, on physical examination, her blood pressure was elevated at 220/100 mmHg and there was 3+ pitting edema of the lower extremities. She was afebrile in the ER. The rest of the examination was unremarkable. 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 plus proteinuria. Her random urine total protein to creatinine (TP/CR) ratio was significantly elevated at 22. A 24-h 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 perinephric inflammatory changes. Chest X-ray was normal. Workup for secondary causes of the NS and 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 includes eight glomeruli were identified on light microscopic examination of the kidney biopsy specimen. The glomeruli showed patent 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 processes was seen. The kidney biopsy findings were consistent with (stage 1) MN and AIN. 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. 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 our patient was responding well to the diuretic therapy and had no uremic symptoms, she was not dialyzed. 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. The serum creatinine normalized (1.04 mg/dL) 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. However, one week after completion of prednisone therapy, the patient presented to the office with bilateral lower extremity swelling and 30 pounds weight gain. Laboratory tests performed during that office 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 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. Since then, the patient has refused further influenza vaccinations. At the five-year follow-up, our 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). The outcome of the event was not reported. List of documents held by sender: none.