Overview
mRNA vaccines have played a central role in global control of COVID-19. Their safety profile is strong, yet rare immune mediated renal events continue to appear in case literature. Primary Sjögren’s syndrome can involve the kidneys, most often as tubulointerstitial nephritis. Glomerular disease is less common but clinically significant when it occurs.
This report describes a patient with primary Sjögren’s syndrome who developed rapidly progressive glomerulonephritis and nephrotic syndrome one month after receiving a fourth COVID-19 vaccine dose. Renal biopsy demonstrated features of primary membranous nephropathy with anti-PLA2R positivity. The temporal pattern, combined with biopsy findings, supports a vaccine related trigger. The patient responded to aggressive immunosuppression, dialysis support, and plasma exchange, and achieved complete remission within three months.
This case highlights the importance of timely recognition and management of vaccine related renal complications in patients with autoimmune backgrounds.
Introduction
COVID-19 mRNA vaccines have been administered worldwide and have provided strong protection against severe infection. Although adverse effects are uncommon, recent reports describe new-onset glomerular disease following vaccination, including minimal change disease, IgA nephropathy, and membranous nephropathy.
Primary membranous nephropathy is an immune mediated glomerular disease defined by subepithelial immune deposits and is frequently associated with anti-PLA2R antibodies. Vaccine associated MN is uncommon, which makes each case important to understand.
Primary Sjögren’s syndrome is a chronic autoimmune disease that affects exocrine glands and can involve multiple organs. Renal disease is typically tubulointerstitial. Glomerular involvement is rare, but when present it can lead to significant morbidity. Familial clustering of Sjögren’s syndrome and related autoimmune disorders is well documented and may increase susceptibility to immune mediated renal injury.
Case Summary
A 52-year-old woman with primary Sjögren’s syndrome, hypertension, hyperlipidemia, and hyperuricemia presented with shortness of breath, edema, and oliguria. Her pSS had been stable for three years with hydroxychloroquine. Her family history included rheumatoid arthritis in her mother and sister, and Sjögren’s syndrome in her elder sister.
She had received four COVID-19 vaccinations, including two mRNA based doses. One month after the final dose she developed flank pain and progressive edema. Prior urinalysis had been normal, and baseline serum creatinine was 0.55 mg/dL.
At presentation, she had gained eight kilograms and had signs of systemic fluid overload. Laboratory results showed acute kidney injury, hypoalbuminemia, and nephrotic range proteinuria of 14 g per day. Urinalysis showed 4+ proteinuria and microscopic hematuria. ANA and anti-Ro/SSA were positive. Imaging showed bilateral pleural effusion, pulmonary congestion, and mild pericardial effusion.
Renal biopsy revealed membranous nephropathy with mesangial expansion, focal crescents, and pronounced tubulointerstitial nephritis. Immunofluorescence showed granular IgG and C3. Electron microscopy showed subepithelial deposits with focal mesangial deposits. PLA2R staining was positive. Serum anti-PLA2R antibody was low but detectable. These findings confirmed new-onset primary membranous nephropathy presenting with rapidly progressive glomerulonephritis.
The patient required haemodialysis and plasma exchange, along with methylprednisolone pulse therapy followed by tapering prednisone, mycophenolate mofetil, and a calcineurin inhibitor. Proteinuria resolved within three months. Serum creatinine returned to baseline. Over the next year she experienced intermittent microalbuminuria but remained clinically stable.
Discussion
This case illustrates a temporal link between mRNA COVID-19 vaccination and new-onset primary membranous nephropathy in a patient with primary Sjögren’s syndrome. Although causation cannot be definitively established, the timeline, immune profile, and biopsy findings support the possibility of an immune trigger induced by the vaccine.
Proposed mechanisms for vaccine associated nephropathy include:
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Strong spike protein driven immune activation
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Cross reactivity between viral antigens and podocyte or glomerular antigens through molecular mimicry
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Innate immune stimulation by lipid nanoparticles that enhances autoantibody production in predisposed individuals
Reports of new-onset MN following mRNA vaccination typically appear within two to four weeks of administration, often after later doses. This timeline matches the current case. Importantly, the absolute risk remains low, and the protective benefits of vaccination against COVID-19 continue to outweigh these rare adverse events.
Renal involvement in pSS is usually tubulointerstitial, but glomerular disease occurs in a subset of patients and can be influenced by genetic and immune backgrounds. Familial clustering of pSS and related autoimmune disorders in this case suggests a predisposition to glomerular injury. The combination of underlying autoimmune susceptibility and an external immune stimulus could act as a catalyst for disease onset.
Management of MN in this setting requires careful attention to renal function, degree of proteinuria, and antibody profiles. Aggressive early therapy is crucial in the presence of rapidly progressive glomerulonephritis. Combination immunosuppression, dialysis support, and plasma exchange can induce remission in severe cases, as demonstrated here.
Clinical Implications
For clinicians caring for autoimmune patients:
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Recent mRNA vaccination should be considered when new nephrotic syndrome or rapidly progressive glomerulonephritis emerges.
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Early urinalysis and renal function monitoring after vaccination may help identify complications in high risk individuals, especially those with autoimmune disease or strong family history.
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Prompt biopsy and aggressive intervention can prevent irreversible renal injury.
The rarity of these events does not diminish the overall benefit of vaccination, but it underscores the need for vigilance.
Conclusion
This case highlights new-onset primary membranous nephropathy triggered shortly after COVID-19 mRNA vaccination in a patient with primary Sjögren’s syndrome. The clinical course, biopsy findings, and timing support an immune mediated mechanism. Early recognition and timely treatment enabled complete remission. Clinicians should maintain awareness of vaccine related renal complications in autoimmune populations and intervene quickly when symptoms appear.