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Malignancy-Associated Membranous Nephropathy with Positive Anti-PLA2R Autoantibodies: Coincidence or Connection
Lyle W Baker1, Jaime Jimenez-Lopez2, Xochiquetzal J Geiger3
1Division of Nephrology and Hypertension, Mayo Clinic, Jacksonville, Florida, USA.
Abstract:
Membranous nephropathy (MN) is currently classified as either primary - often associated with positive anti-phospholipase-A2 receptor (PLA2R) autoantibodies - or as secondary - associated with malignancy, infection, medications, or autoimmune disease. We present a case of biopsy-proven MN with very high serum titer of anti-PLA2R autoantibodies in a patient with a synchronous diagnosis of poorly differentiated esophageal adenocarcinoma and renal cell carcinoma who presented with nephrotic syndrome. Based on the current classification, MN in the presence of active malignancy is diagnosed as secondary and unlikely to have positive anti-PLA2R autoantibodies. This raises several questions: whether this patient has secondary MN associated with malignancy and coincidentally discovered anti-PLA2R autoantibodies, primary MN due to anti-PLA2R autoantibodies with coincidentally discovered malignancy, or whether malignancy can induce the formation of anti-PLA2R autoantibodies that result in MN. This case report highlights the importance of age-appropriate cancer screening, even in patients with presumed primary MN and positive anti-PLA2R autoantibodies.
Insights
This case report details membranous nephropathy (MN) in a patient with simultaneous esophageal and kidney cancers. It questions whether malignancy can trigger anti-phospholipase-A2 receptor (PLA2R) antibodies in MN.
Area of Science:
- Nephrology
- Oncology
- Immunology
Background:
- Membranous nephropathy (MN) is categorized as primary (often anti-phospholipase-A2 receptor (PLA2R) antibody-associated) or secondary (linked to malignancy, infection, drugs, or autoimmune conditions).
- The presence of anti-PLA2R antibodies typically indicates primary MN.
Observation:
- A patient presented with nephrotic syndrome and biopsy-proven MN with high anti-PLA2R antibody titers.
- The patient was concurrently diagnosed with poorly differentiated esophageal adenocarcinoma and renal cell carcinoma.
Findings:
- This case challenges the typical classification of MN, as the patient had MN with high anti-PLA2R antibodies alongside active malignancy.
- It raises questions about the etiological relationship: secondary MN with coincident antibodies, primary MN with coincident malignancy, or malignancy-induced anti-PLA2R antibodies.
Implications:
- This case underscores the necessity of thorough cancer screening in patients diagnosed with MN, particularly those with positive anti-PLA2R antibodies.
- It suggests a potential, yet unconfirmed, role of malignancy in inducing anti-PLA2R antibodies, warranting further investigation into the interplay between cancer and autoimmune kidney disease.
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