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Year : 2012  |  Volume : 55  |  Issue : 2  |  Page : 239-241
Can influenza H1N1 vaccination lead to the membranous glomerulonephritis?

1 Department of Internal Medicine, Duzce University, Faculty of Medicine, Duzce, Turkey
2 Department of Infectious Diseases, Duzce University, Faculty of Medicine, Duzce, Turkey
3 Department of Pathology, Duzce University, Faculty of Medicine, Duzce, Turkey

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Date of Web Publication3-Jul-2012


In 2009 winter, Influenza A (H1N1) monovalent split virus vaccine was used prevalently in the whole world as a result of the pandemic caused by Influenza (H1N1) virus. The vaccine's adverse effects were observed closely and vaccination has been found as safe in most studies. But some reports about immune response related diseases after influenza vaccinations are remarkable. The close relationship between membranous glomerulonephritis and antigens is known, particularly in seconder forms which occur after viral infections and vaccinations. So this case report is about a 56-year-old man, who developed membranous glomerulonephritis 23 days after the vaccination against Influenza A (H1N1) virus.

Keywords: Adverse effect, glomerulonephritis, H1N1 vaccination

How to cite this article:
Kutlucan A, Gonen I, Yildizhan E, Aydin Y, Sav T, Yildirim U. Can influenza H1N1 vaccination lead to the membranous glomerulonephritis?. Indian J Pathol Microbiol 2012;55:239-41

How to cite this URL:
Kutlucan A, Gonen I, Yildizhan E, Aydin Y, Sav T, Yildirim U. Can influenza H1N1 vaccination lead to the membranous glomerulonephritis?. Indian J Pathol Microbiol [serial online] 2012 [cited 2023 Mar 26];55:239-41. Available from:

   Introduction Top

Membranous glomerulonephritis (MGN) is one of the most common reasons for adult nephrotic syndrome (NS) and it is generally idiopathic. However, it may occasionally appear after viral infections such as influenza [1] and they are closely related with impaired immune response. The MGN which developed after the vaccination against influenza A (H1N1) virus that was brought to the agenda with pandemia in 2009 is presented in this report.

   Case Report Top

A 56-year-old male patient appealed to our clinic with the complaint of swelling on his feet and face. The patient developed influenza-like illness approximately 20 days after he was vaccinated with influenza vaccine that belonged to the year 2009. Following this, he had complained of pollakiuria, nocturia, and swelling on his feet and face. During this period, he had not received any kind of treatment before he came to our clinic.

There was no history of chronic illness, alcohol, drug or substance abuse except for 30 years' of smoking. His arterial blood pressure was 160/100 mmHg, pulse rate was 92 beats/min, and body temperature was 36.4°C. There were crackles at both of the lower lung fields and excessive pretibial edema bilaterally. There was no jugular venous distension. The other findings of physical examinations were normal. Serum creatinine and blood urea nitrogen levels were normal (0.9 mg/dl and 21 mg/dl, respectively), but the tests revealed hypoalbuminemia and proteinuria (serum albumin level was 2 gr/dl and urinary protein excretion was 7.3 gr/day) [Table 1]. Bilateral pleural effusion was present on chest X-ray. The kidneys looked normal in ultrasonography and minimal fluid was detected around his intestinal loops. There were not pathological findings in renal Doppler ultrasonography that was made as the patient had incipient and resistant hypertension. Renal biopsy was performed in order to find out NS etiology. As a result of the research that was carried out through histopathologic and immunofluorescence staining methods, some findings in relation to MGN were detected [Figure 1] and [Figure 2]. The predominant finding by light microscopy was the thickening of the glomerular capillary wall. With the silver stain mild spikes were seen in the basal membrane. Immunofluorescence revealed granular global subepithelial deposits that stained strongest for Ig G and C3. Staining for C1q, Ig M, Ig A, or fibrinogen was negative. Staining with Congo-Red was negative in terms of amyloidosis. A medical treatment was arranged consisting of 10 mg/day lysinopryl, 40 mg/day atorvastatin, and 100 mg/day acetylsalicylic acid, and 1 mg/kg/day methyl prednisolone. Following this, edema and proteinuria of the patient subsided and his clinical condition improved. The patient's steroid dose was decreased gradually and stopped completely in the following three months. Within this period, renal functions of the patient were stable. Examinations conducted on the patient intended for the seconder causes of MGN were not significant (malignancies, rheumatologic disorders, or infections). In light of anamnesis and laboratory results, we deduced that MGN was related to the influenza vaccine shot 23 days before the symptoms appeared.
Figure 1: Microphotograph show that thickining the basal membrane of glomerules (a, PAS ×200) and granular Ig G deposites (b, IF) identified along with basal membrane. Mild mesangial hypercellularity was seen in a few glomerules and there were not seen amiloid deposition in kidney biopsy

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Figure 2: PAS and silver stains show that mild spikes and marked thick capillary wall in glomerule(C, PAS-M ×400)

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Table 1: Laboratory findings

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   Discussion Top

MGN, or membranous nephropathy as it is sometimes called, accounts for approximately 30% of cases of NS in adults, with a peak incidence between the ages of 30-50 years. Membranous nephritis is typically associated with immune deposits along the glomerular basement membrane. The main pathology in MGN is diffuse granular accumulation of IgG and C3 deposits and uniform thickening of the basement membrane that can be demonstrated by biopsy. In 25-30% of cases, MGN is secondary to malignancy (solid tumors of the breast, lung, and colon), rheumatologic disorders like lupus or rarely rheumatoid arthritis, or infection. [1]

The close relationship between this disease and antigens comes into prominence in their secondary forms, especially the ones that develop after viral infections. There are some cases of NS, acute glomerulonephritis, post-infectious glomerulonephritis that developed after viral infections such as Influenza A in the literature. [1] Besides, it has been accepted that after vaccinations, the risk of encountering immune response related diseases increases. For instance, Influenza vaccine is a risk for Guillain-Barré syndrome (GBS), which is an immunity related disease. [2] In recent years, NS cases have been reported to have developed after HBV, pneumococcus, and Influenza vaccinations. [3],[4] While the reason for some of these cases was minimal change disease, the pathology of the others could not be defined. In 2000, Kielstein et al, [5] reported NS connected with minimal change disease after Influenza vaccination, and in 2002, Yanai-Berar et al, [6] presented leukocytoclastic vasculitis accompanied with pauci-immune crescentic glomerulonephritis. In 2004, Kao et al, [7] presented GBS accompanied with NS, and in 2005, Hyla-Klekot et al, [8] presented necrotizing glomerulonephritis cases which developed after Influenza vaccination. But a MGN case after Influenza vaccination as we presented was not reported in the literature before.

In 2009 winter, Influenza A (H1N1) monovalent split virus was used prevalently in the whole world as a result of the pandemic caused by Influenza (H1N1) virus. A lot of researches have been carried out on the safety and immunogenicity of this vaccine and in many of them the vaccine has been found to be safe. One dose of vaccine was highly immunogenic in adults, suggesting that it afforded sufficient protection against this pandemic influenza A H1N1 virus. These studies also revealed that the immunogenic response to the vaccine develops on 23 th day after vaccination. [9] In surveillance studies, some serious side effects such as GBS and anaphylaxis that are no different from seasonal Influenza vaccine were reported. However, nephropathy or related case was not reported. [9],[10]

The MGN diagnosis that appeared with NS clinic and was confirmed through renal biopsy has been thought to be associated with 15 mg dose swine Influenza vaccine (each 0.5 ml dose of 7.5 micrograms (H1N1) virus-like (X -181) strains and adjuvant MF59C) inoculated to the patient 23 days before, since emergence of the illness and development of immunogenic effect of the vaccine occurred simultaneously. Watanabe et al,[11] reported that four patients exhibited purpura, three complained of arthralgias, and one had both abdominal pain and renal involvement after H1N1 vaccination. Reviewing the literature, 11 patients with HSP following influenza vaccination have been reported. Five of those 11 patients had past history of immunologically mediated disease including HSP, drug eruptions, and food allergy. While a favorable outcome was noted in most patients, one patient developed end-stage renal failure and another exhibited chronic glomerulonephritis. [11] Precise reason for MGN and renal involvement following H1N1 vaccination was unclear, but possible disposition to autoimmune renal disease appears to be the cause of MGN.

   Conclusion Top

Although vaccines are some kind of divine efforts to prevent infections that may reach to pandemic level, they are also significant because of their side effects on mostly healthy people. The Influenza virus against which the human beings have been struggling for years came into prominence in 2009 because of the pandemic it caused. Fortunately, the disaster was avoided thanks to the vaccine. However, as in the presented case, the number of the cases of immune response related illnesses and renal diseases such as NS developing after the vaccine is gradually increasing. The growing role of the vaccines in NS and glomerulonephritis etiology is also striking.

   References Top

1.Lewis JB, Neilson EG. Glomerular diseases. In: Fauci AS, Kasper DL, Longo DL, Braunwald E, Hauser SL, Jameson JL, et al., editors. Harrison's principles of internal medicine. 17 th ed. New York: McGraw Hill; 2008. p. 1782-97.  Back to cited text no. 1
2.Lehmann HC, Hartung HP, Kieseier BC, Hughes RA. Guillain-Barré syndrome after exposure to influenza virus. Lancet Infect Dis 2010;10:643-51.  Back to cited text no. 2
3.Islek I, Cengiz K, Cakir M, Kucukoduk S. Nephrotic syndrome following hepatitis B vaccination. Pediatr Nephrol 2000;14:89-90.  Back to cited text no. 3
4.Kikuchi Y, Imakiire T, Hyodo T, Higashi K, Henmi N, Suzuki S, et al. Minimal change nephrotic syndrome, lymphadenopathy and hyperimmunoglobulinemia after immunization with a pneumococcal vaccine. Clin Nephrol 2002;58:68-72.  Back to cited text no. 4
5.Kielstein JT, Termühlen L, Sohn J, Kliem V. Minimal change NS in a 65-year-old patient following influenza vaccination. Clin Nephrol 2000;54:246-8.  Back to cited text no. 5
6.Yanai-Berar N, Ben-Itzhak O, Gree J, Nakhoul F. Influenza vaccination induced leukocytoclastic vasculitis and pauci-immune crescentic glomerulonephritis. Clin Nephrol 2002;58:220-3.  Back to cited text no. 6
7.Kao CD, Chen JT, Lin KP, Shan DE, Wu ZA, Liao KK. Guillain-Barré syndrome coexisting with pericarditis or nephrotic syndrome after influenza vaccination. Clin Neurol Neurosurg 2004;106:136-8.  Back to cited text no. 7
8.Hyla-Klekot L, Kucharska G, Cieslak W. Necrotizing glomerulonephritis in decursu vasculitis after vaccination against influenza. Pol Merkur Lekarski 2005;19:75-7.  Back to cited text no. 8
9.Greenberg ME, Lai MH, Hartel GF, Wichems CH, Gittleson C, Bennet J, et al. Response to a monovalent 2009 influenza A (H1N1) vaccine. N Engl J Med 2009;361:2405-13.  Back to cited text no. 9
10.Vellozzi C, Broder KR, Haber P, Guh A, Nguyen M, Cano M, et al. Adverse events following influenza A (H1N1) 2009 monovalent vaccines reported to the Vaccine Adverse Event Reporting System, United States, October 1, 2009-January 31, 2010. Vaccine 2010;28:7248-55.  Back to cited text no. 10
11.Watanabe T. Henoch-Schönlein purpura following influenza vaccinations during the pandemic of influenza A (H1N1). Pediatr Nephrol 2011;26:795-8.  Back to cited text no. 11

Correspondence Address:
Ibak Gonen
Duzce University, Department of Infectious Diseases, Faculty of Medicine, Duzce
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.97893

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