|Year : 2019 | Volume
| Issue : 5 | Page : 1002-1009
|Vaccine-associated kidney diseases: A narrative review of the literature
Chinmay Patel1, Hitesh H Shah2
1 Division of Nephrology, Pikeville Medical Center, University of Pikeville-Kentucky College of Osteopathic Medicine, Pikeville, KY, USA
2 Division of Kidney Diseases and Hypertension, North Shore University Hospital and Long Island Jewish Medical Center, Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, USA
Click here for correspondence address and email
|Date of Submission||12-Dec-2018|
|Date of Decision||20-Jan-2019|
|Date of Acceptance||22-Jan-2019|
|Date of Web Publication||4-Nov-2019|
| Abstract|| |
Immunization is one of the greatest public health achievements of the 20th century. Vaccines have enabled the eradication of deadly diseases and decreased the morbidity and mortality associated with various infections. Most vaccines are safe to administer and cause only minor side effects. Although very rare, various glomerular diseases and acute kidney injury have been reported following immunization with certain vaccines including influenza, pneumococcal, and hepatitis B vaccines. This review summarizes these rare renal complications that have been published in the literature. Physicians and other health-care providers administrating vaccines should be aware of these very rare but possible renal side effects.
|How to cite this article:|
Patel C, Shah HH. Vaccine-associated kidney diseases: A narrative review of the literature. Saudi J Kidney Dis Transpl 2019;30:1002-9
|How to cite this URL:|
Patel C, Shah HH. Vaccine-associated kidney diseases: A narrative review of the literature. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2021 May 16];30:1002-9. Available from: https://www.sjkdt.org/text.asp?2019/30/5/1002/270254
| Introduction|| |
Immunization is an important public health tool. Any discussion of the adverse reactions to vaccines must begin by putting such events in the context of the overwhelming good that vaccines do. Immunization is one of the 10 great public health achievements of the 20th century and is considered “one of the greatest tools in the public health arsenal.” Vaccines have enabled tremendous decreases in infectious diseases, eradication of smallpox, saved lives, and remain among the most effective of our public health initiatives. Unfortunately, as result of this success, instead of the deadly diseases that they help prevent, the vaccines themselves have become a focus of anxiety for many. Most vaccines are safe to administer and cause only minor side effects. The common side effects of many vaccines and toxoids include fever, local reactions at the injection site injection site, or even serum sickness-like reaction. These side effects are not usually considered true contraindications to the vaccine. These adverse reactions can be caused by the immunogenic moiety in the vaccine or by trace amounts of antibiotics, preservatives, thiomersal, stabilizers, and residual animal proteins. The medical literature is full of claims and counterclaims with respect to the risk of autoimmune diseases as a consequence of vaccination. Although very rare, case reports published in the literature have associated vaccines to renal complications including different glomerular diseases and acute kidney injury (AKI). In this article, we review these published observations. The pathogenesis of the vaccine-related renal manifestations is beyond the scope of this article.
| Influenza Vaccine|| |
Influenza vaccination is known to be effective in lowering morbidity as well as preventing severe complications associated with seasonal influenza. The most common adverse reaction associated with the inactivated influenza vaccine includes injection site soreness or redness and mild constitutional symptoms such as malaise or fever. Influenza vaccine has been associated with rare autoimmune complications such as Guillain–Barre syndrome (GBS). The swine flu vaccine administered in 1976 was particularly associated with an increased risk for GBS. In subsequent years, influenza vaccines have been carefully monitored for this possible adverse effect and have shown a negligible risk. Influenza vaccine has been implicated in a number of renal complications [Table 1].
Influenza vaccine-associated nephrotic syndrome
The first case of influenza vaccine-related nephrotic syndrome secondary to minimal change disease (MCD) was reported by Kielstein et al. A 65-year-old female developed acute-onset nephrotic syndrome (NS) within one week of receiving the influenza vaccine. Proteinuria resolved spontaneously within three to four weeks of presentation. Kao et al reported a unique case of GBS coexisting with NS in a 72-year-old man within two weeks of receiving influenza vaccine. The underlying renal pathology, however, in this case was unknown. The patient responded well to steroid and plasmapheresis therapy. Gutiérrez et al have also reported a patient who developed NS and AKI, 18 days after receiving influenza vaccine. The kidney biopsy was consistent with MCD, ATN, and moderate active interstitial nephritis (AIN). Proteinuria and AKI resolved rapidly after treatment with oral prednisone.
A case of membranous nephropathy (MN) following influenza vaccination was reported in a 56-year-old male who developed influenzalike illness and acute-onset NS approximately 20 days after receiving the 2009 H1N1 influenza vaccine. Both edema and proteinuria gradually subsided following a three-month therapy with angiotensin-converting enzyme inhibitor, a statin, acetylsalicylic acid, and methylprednisolone. We have previously reported a unique case of relapsing MN with AKI due to AIN following the 2009 H1N1 influenza vaccination. Our patient was a 60-year-old African-American female who presented with abrupt-onset NS and severe AKI, two weeks after receiving the 2009 H1N1 influenza vaccine. Kidney biopsy revealed MN and AIN. Soon after our patient was initiated on oral corticosteroid therapy, she had a complete resolution of NS and AKI. Her NS, however, relapsed soon after completing 2½ months of tapering oral corticosteroid therapy. The repeat kidney biopsy at the time of relapse showed MN and resolution of AIN. The patient responded well to an additional four-month course of tapering oral corticosteroid therapy with complete resolution of NS.
Influenza vaccine-associated pauci-immune glomerulonephritis/renal vasculitis
Many case reports and small series have noted an association between influenza vaccination and development of systemic vasculitis., Cases of leukocytoclastic vasculitis with pauci-immune crescentic glomerulonephritis (GN) and AKI, have also been described in literature. A case of necrotizing GN and vasculitis following influenza vaccination has also been reported. Uji et al described a case of microscopic polyangiitis (MPO) with renal involvement in an 83-year-old female after receiving influenza vaccine. The patient was successfully managed with corticosteroids and cyclophosphamide therapy. A unique case of MPO with giant cell arteritis (polyangitis overlap syndrome) and AKI was reported in a 65-year-old female following influenza vaccination. More recently, Duggal et al described two cases of anti-neutrophil cytoplasmic antibody (ANCA) -associated vasculitis with renal involvement following influenza vaccination. Both patients developed AKI, with one requiring dialysis. Kidney biopsy in the dialysis-dependent patient revealed necrotizing and crescentic pauciimmune GN, whereas the other patient, who had mild renal impairment, had focal necrotizing pauci-immune GN. Disease remission was achieved with cyclophosphamide and corticosteroids in the patient with focal necrotizing pauci-immune GN. The patient with crescentic GN remained dialysis dependent despite receiving immunosuppressive therapy and plasmapheresis.
Vaccination against influenza had been suggested to induce disease relapses in patients with ANCA-associated vasculitis; however, a retrospective study did not find any association between increases in relapse rate in patients with ANCA vasculitis vaccinated against influenza. Furthermore, in a prospective study in patients with granulomatosis with polyangiitis (GPA), no rise in disease activity following influenza vaccination with adequate antibody response to the vaccine was found.
Influenza vaccine-associated rhabdomyolysis and AKI
Cases of rhabdomyolysis and AKI following influenza vaccination have also been reported in literature. Plotkin et al reported a case of 68-year-old male who developed diffuse myalgia and muscle weakness within 24 h of being vaccinated for influenza. Laboratory data showed severe rhabdomyolysis and AKI. The patient was treated with forced alkaline diuresis and his renal function returned to normal within the following days. A similar case of rhabdomyolysis and AKI was reported in a 71-year-old patient within 24 h of receiving the seasonal flu vaccine. Of note, both the above patients were on concurrent statin therapy., A case of AKI due to possible AIN has also been reported in a patient, 12 days after influenza vaccination. This patient was also on statin therapy. The patient, however, recovered following corticosteroid therapy. Callado et al also reported a 58-year-old male patient who developed ascending weakness, intense myalgia with rhabdomyolysis, and AKI, five days after influenza A H1N1 vaccination. The patient required transient hemodialysis and recovered completely after two weeks. A case of rhabdomyolysis and AKI after influenza vaccination has also been reported in a kidney transplant recipient who had been on statin and cyclosporine therapy. A week after receiving the inactivated influenza vaccine, the patient developed diffuse myalgia, muscle weakness, and dark urine. Laboratory data were consistent with rhabdomyolysis and AKI. Muscle biopsy revealed toxic myositis, and transplant biopsy showed moderate tubular atrophy with tubulitis and presence of brown granular tubular casts consistent with myoglobin. The steroid dose was increased, and renal function gradually improved. The authors concluded that there is a risk of rhabdomyolysis in influenza-vaccinated patients who receive concomitant myotoxic drugs.
Of note, a small pilot study published in 2002 did not find any clinical and laboratory evidence to support influenza vaccination being associated with myopathy in patients taking statins.
Influenza vaccine-associated Henoch–Schonlein purpura
In 1979, Damjanov and Amato reported the first adult case of Henoch–Schonlein purpura (HSP) whose renal disease progressed irreversibly after influenza vaccination. In 2010, Watanabe reported four pediatric cases of HSP which developed soon after receiving the 2009 H1N1 influenza vaccine. In addition to their four cases, Watanabe also reviewed seven previously reported cases of HSP following influenza vaccination. Eight of 11 patients were children. The time of vaccination to the onset of symptoms averaged nearly 12 days. Of these 11 patients, only three had renal involvement. While the outcome was favorable in most patients, one patient developed chronic GN and another progressed to end-stage renal disease. More recently, McNally et al reported a unique case of HSP in a kidney transplant recipient following influenza vaccination. The patient had prior history of end-stage renal disease due to IgA nephropathy (IgAN). However, there was no clinical evidence of IgAN recurrence in the allograft.
Influenza vaccine-associated kidney allograft rejection
Fischer et al recently reported three cases of AKI causing graft loss in kidney transplant recipients within two months of seasonal influenza vaccination. These three patients had different native kidney diseases but were vaccinated in the same season of 2009–2010. Kidney biopsy findings revealed signs of acute and chronic humoral rejection (Type 1A per Banff classification) with peritubular capillaritis, positive C4d staining, and transplant glomerulopathy in the first case. The second case showed acute cellular rejection, severe interstitial edema, interstitial inflammation (i2), and focal moderate tubulitis (t2). Biopsy findings in the third case were consistent with relapse of native IgAN.
In contrast to the above-mentioned cases, influenza vaccine has also been shown to protect against AKI. A recent nested case–control study found that vaccination against influenza is associated with a 37% reduced risk of AKI among adults aged >65 years.
| Hepatitis B Vaccine|| |
In 1995, Macário et al reported the first case of NS associated with hepatitis B vaccination. A 41-year-old patient presented with sudden-onset NS after receiving the second dose of recombinant hepatitis B vaccine. Kidney biopsy revealed MCD with mild mesangial expansion. A complete remission of the NS was observed with two weeks of corticosteroid therapy. However, two relapses occurred during the phase of corticosteroid taper requiring increase in dose of the corticosteroids.
The first pediatric case of NS following hepatitis B vaccine was reported in 1998 by Ozdemir et al. A 3-year-old boy presented with generalized edema and facial swelling after the second dose of recombinant hepatitis B vaccine. Kidney biopsy was not performed due to the patient’s age. Complete clinical remission was achieved following corticosteroid therapy, and the patient was diagnosed as possible MCD. Two other pediatric cases of steroid-responsive NS following recombinant hepatitis B vaccination have been reported. Both patients were diagnosed with MCD.
A unique case of lupus nephritis (LN) following hepatitis B vaccination has also been reported. One week after receiving the recombinant hepatitis B vaccine, a 27-year-old female patient presented with asthenia, edema, and nephritic syndrome with laboratory data showing AKI, hypocomplementemia, positive lupus serology, and nephrotic-range proteinuria with red cell and granular casts. A renal biopsy showed diffuse proliferative GN (Class IV LN). The patient achieved complete remis-sion with cyclophosphamide and prednisone therapy.
| Pneumococcal Vaccine|| |
A unique case of crescentic GN from antiglomerular basement membrane (GBM) disease occurring soon after pneumococcal vaccination has been reported. This 30-year-old male with a previous history of splenectomy received pneumococcal vaccine for secondary prophylaxis of pneumococcal sepsis. Two weeks after receiving pneumococcal vaccination, the patient was hospitalized with oliguric AKI. Kidney biopsy showed crescentic GN with linear deposits of anti-GBM antibodies on immunofluorescence. Anti-GBM antibody titer was elevated, and testing for ANCA was negative. The patient was successfully treated with plasma exchange, cyclophosphamide, corticosteroids, and short-term hemodialysis.
Kikuchi et al reported the occurrence of NS and renal failure in a 67-year-old female following pneumococcal vaccination. A kidney biopsy showed MCD with mild AIN. The patient responded well to intensive corticosteroid therapy.
| Pertussis Vaccine|| |
In 1966, Bishop et al reported a unique case of diffuse vasculitis with AKI following multiple doses of pertussis vaccine. This 45-year-old Caucasian male inmate had volunteered as a subject for production of hyper-immune pertussis globulin. The patient received a dose of tetanus toxoid followed by seven injections of pertussis vaccine over a 6-week period, and the 8th injection was administered two months later. A week after the 8th injection, the patient developed fever, arthralgia, adenopathy, generalized edema, proteinuria, and oliguric AKI and subsequently died of multiorgan failure secondary to a disseminated vasculitis involving the small- and medium-vessel arteries and arterioles.
| Diphtheria–Pertussis–Tetanus Vaccine|| |
Severe proliferative GN with hypocomplementemia and cryoglobulinemia was reported in a 30-year-old female nurse who repeatedly injected herself with a combination diphtheria, pertussis, and tetanus (DPT) vaccine. The patient claimed that she had injected herself with 2 mL of DPT vaccine every two months for the last four years. Before this fact was known, she was given a variety of therapeutic regimens including anticoagulation, steroids, cyclophosphamide, azathioprine, and plasma exchange, all without demonstrable benefit. Discontinuation of the repeated vaccine injections led to striking clinical remission. A psychiatric assessment later revealed features of hysterical and depressive illness.
| Tetanus–Diphtheria–Poliomyelitis Vaccine|| |
Nephrotic syndrome from MCD has been reported in an 82-year-old Caucasian female after receiving a combi-nation vaccination for tetanus, diphtheria, and poliomyelitis. The patient responded well to angiotensin-converting enzyme inhibitor and steroid therapy with improvement in her proteinuria.
| Smallpox Vaccine|| |
A case of NS following smallpox vaccination was first reported by Chamberlain et al in 1966. Ten days after receiving the smallpox vaccine, a 49-year-old female became unwell with development of facial puffiness, lower extremity swelling, elevated blood pressure, oliguria, and anasarca. Laboratory data showed AKI and nephrotic-range proteinuria. The patient died later due to complications related to lower extremity deep-venous thrombosis, cellulitis, and bronchopneumonia. A kidney biopsy performed at autopsy showed slight GBM thickening, suggestive of possible MN. Tubules were preserved with slight interstitial edema.
| Measles Vaccine|| |
In 1972, Kuzemko reported two pediatric cases of sudden-onset NS after measles vaccination. Complete remission of NS was achieved with oral corticosteroids, suggestive of possible MCD.
| Rabies Vaccine|| |
In 1979, Singhal et al reported a case of GN in a 45-year-old female after immunization with rabies vaccine. After a rabid dog bite, the patient received a dose of tetanus toxoid along with rabies vaccine daily for 15 days followed by a booster dose at one month. Two weeks after the booster dose, the patient developed fever, arthritis, maculo-papular rash, diffuse edema, and nephrotic-range proteinuria. The patient responded well to corticosteroid therapy with resolution of rash and arthritis in two weeks and proteinuria by four weeks. Kidney biopsy performed at four weeks revealed normal-looking glomeruli, tubular eosinophilic casts, and mild interstitial fibrosis on light microscopy. Immunofluorescence showed faint deposits of IgG in the mesangium. According to the authors, as there was delay in performing the kidney biopsy, the irregular immune deposits of faint IgG could be remnant of an immune complex deposition which might have been cleared by phagocytic activity. The authors also inferred that the decrease in proteinuria following steroid therapy suggested a steroid-responsive NS.
| Meningococcal Vaccine|| |
A study published in 2003 suggested an increased risk of relapse of NS after administration of meningococcal C conjugate vaccine (MCCV) in children less than 18 years of age. A subsequent study, however, invalidated this finding and found no association between MCCV and relapse of NS.
| Bacillus Calmette–Guerin Vaccine|| |
Bacillus Calmette–Guerin (BCG) vaccine is used to protect against tuberculosis (TB). BCG is used in many countries with a high prevalence of TB to prevent childhood tuberculous meningitis and miliary disease. However, BCG is not generally recommended for use in the United States because of the low risk of infection with Mycobacterium tuberculosis, the variable effectiveness of the vaccine against adult pulmonary TB, and the vaccine’s potential interference with tuberculin skin test reactivity. BCG vaccine when administered into the bladder is thought to provoke an immune response. Intravesical BCG is one of the most commonly used immunotherapies used in bladder cancer treatment. Although rare, intravesical BCG immunotherapy has been associated with few kidney diseases including asymptomatic renal granuloma formation, AKI due to interstitial nephritis (with or without granulomas), acute GN, and NS from MN.
| Conclusion|| |
Vaccines play an important role in protecting individuals from various infectious diseases and are generally considered safe. Although very rare, different kidney diseases have been associated with certain vaccines [Table 1]. The exact pathogenesis of this occurrence remains unknown. All the above-mentioned observations support the need for close monitoring and continued registration of vaccine-related side effects. Physicians and other health-care providers administrating vaccines should also be aware of these possible renal side effects. We, however, suggest no change in the current vaccination guidelines based on these sporadic case reports.
Conflict of interest: None declared.
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Division of Nephrology, Pikeville Medical Center, University of Pikeville-Kentucky College of Osteopathic Medicine, Pikeville, KY
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