Pathogenesis, diagnosis and management of paraneoplastic glomerulonephritis

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 (T(H)2) profile has an important role in the development of thymoma-associated glomerular lesions. Furthermore, overexpression of the T(H)2 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.

Figure 1

Paraneoplastic glomerulonephritis associated with solid tumors. Data are taken from several sources.– and are presented as number of reported cases of specific types of paraneoplastic glomerulonephritides associated with each type of cancer. Specific numbers of lung cancer types for each glomerulonephritis type are: for membranous nephropathy: non-small cell lung cancer (NSCLC): 15, small cell lung cancer (SCLC):6, carcinoid: 2, mesothelioma: 2, lymphoepithelioma: 1; for MCD: NSCLC: 8, SCLC: 1, mesothelioma: 1; for MPGN: NSCLC: 4, SCLC:1; carcinoid: 2; for RPGN: NSCLC: 4, SCLC: 1; for IgAN: NSCLC: 1, SCLC: 1. Specific numbers of renal cancer types for each glomerulonephritis type are: for membranous nephropathy: renal cell carcinoma (RCC): 11, justaglomerular cell tumor: 1; for MCD: RCC: 6, oncocytoma:1; for MPGN: RCC: 3, Wilm’s tumor:1; for IgAN: RCC: 18, oncocytoma: 1. Abbreviations: IgAN: IgA nephropathy; MCD: minimal change disease; MN: membranous nephropathy; MPGN: membranoproliferative glomerulonephritis; RPGN: rapidly progressive glomerulonephritis.

Figure 2

Paraneoplastic glomerulonephritis associated with lymphoid malignancies. Data are taken from several sources.,,– Paraneoplastic glomerulonephritis associated with HCL,, and CTCL,,– are also included. Numbers are reported cases of specific types of paraneoplastic glomerulonephritis associated with each malignancy. Abbreviations: ALL: acute lymphocytic leukemia, CLL: chronic lymphocytic leukemia; CTCL, cutaneous T-cell lymphoma; FSGS, focal segmental glomerulosclerosis; HCL, hairy cell leukemia; IgAN: IgA nephropathy; MCD: minimal change disease; MN: membranous nephropathy; MPGN: membranoproliferative glomerulonephritis.

Figure 3

Paraneoplastic glomerulonephritis associated with myeloid malignancies. Data are taken from several sources–,–,–,–,,– and are presented as numbers of specific types of paraneoplastic glomerulonephritis associated with different myeloid malignancies. Abbreviations: AML, acute myeloid leukemia; CML, chronic myelogenous leukemia; CMML, chronic myelomonocytic leukemia; ET, essential thrombocythemia; FibGN: fibrillary glomerulonephritis; FSGS, focal segmental glomerulosclerosis; IgAN: IgA nephropathy; MDS, myelodysplastic syndrome; MesPGN: mesangial proliferative glomerulonephritis; MCD, minimal change disease; MN, membranous nephropathy; MPGN: membranoproliferative glomerulonephritis; PMF, primary myelofibrosis; PV, polycythemia vera; RPGN, rapidly progressive glomerulonephritis.

Figure 4

Paraneoplastic glomerulonephritis associated with thymoma. Data are from several sources,– and are presented as number of reported cases of specific types of paraneoplastic glomerulonephritis associated with thymoma. Abbreviations: FSGS, focal segmental glomerulosclerosis; MCD, minimal change disease; MN, membranous nephropathy; RPGN: rapidly progressive glomerulonephritis; TMA, thrombotic microangiopathy.