Abstract
Paraneoplastic glomerulonephritis is a rare complication of malignancy that is frequently mistaken for idiopathic glomerulonephritis. Failure to recognize paraneoplastic glomerulonephritis can subject patients to ineffective and potentially harmful therapy. The pathology of paraneoplastic glomerulonephritis varies between different types of malignancies. This Review discusses the association of glomerulonephritis with both solid tumors and hematological malignancies. The pathogenetic mechanisms of many glomerular lesions seem to relate to altered immune responses in the presence of a malignancy. Studies in the Buffalo/Mna rat model of spontaneous thymoma and nephrotic syndrome indicate that polarization of the immune response toward a T-helper-2 (TH2) profile has an important role in the development of thymoma-associated glomerular lesions. Furthermore, overexpression of the TH2 cytokine interleukin 13 in rats induces minimal change disease. Such findings from experimental studies might facilitate the identification of biomarkers that can distinguish paraneoplastic glomerulonephritis from idiopathic and other secondary glomerulonephritides. This Review describes potential pathogenetic mechanisms for paraneoplastic glomerulonephritides associated with different malignancies and highlights the need for a multidisciplinary approach to the management of patients with paraneoplastic glomerulonephritis.
Key Points
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The pathogenesis of paraneoplastic glomerulonephritis differs according to whether the disease is associated with a solid tumor, a lymphoid or myeloid malignancy, or a thymoma
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Polarization of the immune response toward a T-helper-2 profile may lead to the development of minimal change disease or focal segmental glomerulosclerosis in patients with thymoma or Hodgkin lymphoma
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Membranoproliferative glomerulonephritis and membranous nephropathy associated with B-cell lymphoma and leukemia are related to the presence of monoclonal immunoglobulin, cryoglobulin, and possibly hepatitis C virus infection
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Severe thrombocytosis may induce focal segmental glomerulosclerosis in patients with polycythemia vera, essential thrombocythemia or primary myelofibrosis
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Autoimmunity in myelodysplastic syndromes may cause a variety of glomerulonephritides
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Presence of glomerular inflammatory cells, IgG1 and IgG2 may aid diagnosis of paraneoplastic membranous nephropathy
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Lien, YH., Lai, LW. Pathogenesis, diagnosis and management of paraneoplastic glomerulonephritis. Nat Rev Nephrol 7, 85–95 (2011). https://doi.org/10.1038/nrneph.2010.171
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DOI: https://doi.org/10.1038/nrneph.2010.171
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