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  • Review Article
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Pathogenesis, diagnosis and management of paraneoplastic glomerulonephritis

Nature Reviews Nephrology volume 7, pages 85–95 (2011)Cite this article

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

  • 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

  • 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

  • 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

  • Severe thrombocytosis may induce focal segmental glomerulosclerosis in patients with polycythemia vera, essential thrombocythemia or primary myelofibrosis

  • Autoimmunity in myelodysplastic syndromes may cause a variety of glomerulonephritides

  • Presence of glomerular inflammatory cells, IgG1 and IgG2 may aid diagnosis of paraneoplastic membranous nephropathy

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Figure 1: Paraneoplastic glomerulonephritis associated with solid tumors.
Figure 2: Paraneoplastic glomerulonephritis associated with lymphoid malignancies.
Figure 3: Paraneoplastic glomerulonephritis associated with myeloid malignancies.
Figure 4: Paraneoplastic glomerulonephritis associated with thymoma.

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Acknowledgements

The authors' research is currently supported by NIH grant R01DK082718.

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Authors and Affiliations

  1. Arizona Kidney Disease and Hypertension Center, 4511 North Campbell Avenue, Suite 100, Tucson, 85718, AZ, USA

    Yeong-Hau H. Lien

  2. University of Arizona, College of Pharmacy, 1703 East Mabel Street, Tucson, 85721, AZ, USA

    Li-Wen Lai

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Both authors contributed equally to researching data for the article, discussing content, writing, and reviewing/editing the article before submission.

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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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