TY - JOUR
T1 - Membranoproliferative Glomerulonephritis
T2 - Pathogenetic Heterogeneity and Proposal for a New Classification
AU - Sethi, Sanjeev
AU - Fervenza, Fernando C.
N1 - Funding Information:
Supported in part by National Institutes of Health grant DK074409 and the Fulk Family Foundation Award (Mayo Clinic) (S.S.).
PY - 2011/7
Y1 - 2011/7
N2 - Membranoproliferative glomerulonephritis (MPGN) is a pattern of injury that results from subendothelial and mesangial deposition of Igs caused by persistent antigenemia and/or circulating immune complexes. The common causes of Ig-mediated MPGN include chronic infections, autoimmune diseases, and monoclonal gammopathy/dysproteinemias. On the other hand, MPGN also can result from subendothelial and mesangial deposition of complement owing to dysregulation of the alternative pathway (AP) of complement. Complement-mediated MPGN includes dense deposit disease and proliferative glomerulonephritis with C3 deposits. Dysregulation of the AP of complement can result from genetic mutations or development of autoantibodies to complement regulating proteins with ensuing dense deposit disease or glomerulonephritis with C3 deposits. We propose a new histologic classification of MPGN and classify MPGN into 2 major groups: Ig-mediated and complement-mediated. MPGN that is Ig-mediated should lead to work-up for infections, autoimmune diseases, and monoclonal gammopathy. On the other hand, complement-mediated MPGN should lead to work-up of the AP of complement. Initial AP screening tests should include serum membrane attack complex levels, an AP functional assay, and a hemolytic assay, followed by tests for mutations and autoantibodies to complement-regulating proteins.
AB - Membranoproliferative glomerulonephritis (MPGN) is a pattern of injury that results from subendothelial and mesangial deposition of Igs caused by persistent antigenemia and/or circulating immune complexes. The common causes of Ig-mediated MPGN include chronic infections, autoimmune diseases, and monoclonal gammopathy/dysproteinemias. On the other hand, MPGN also can result from subendothelial and mesangial deposition of complement owing to dysregulation of the alternative pathway (AP) of complement. Complement-mediated MPGN includes dense deposit disease and proliferative glomerulonephritis with C3 deposits. Dysregulation of the AP of complement can result from genetic mutations or development of autoantibodies to complement regulating proteins with ensuing dense deposit disease or glomerulonephritis with C3 deposits. We propose a new histologic classification of MPGN and classify MPGN into 2 major groups: Ig-mediated and complement-mediated. MPGN that is Ig-mediated should lead to work-up for infections, autoimmune diseases, and monoclonal gammopathy. On the other hand, complement-mediated MPGN should lead to work-up of the AP of complement. Initial AP screening tests should include serum membrane attack complex levels, an AP functional assay, and a hemolytic assay, followed by tests for mutations and autoantibodies to complement-regulating proteins.
KW - Alternative pathway of complement
KW - C3 glomerulopathy
KW - C3-GN
KW - MGUS
KW - MPGN
KW - Membranoproliferative glomerulonephritis
KW - Monoclonal gammopathy
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U2 - 10.1016/j.semnephrol.2011.06.005
DO - 10.1016/j.semnephrol.2011.06.005
M3 - Article
C2 - 21839367
AN - SCOPUS:79961214569
SN - 0270-9295
VL - 31
SP - 341
EP - 348
JO - Seminars in nephrology
JF - Seminars in nephrology
IS - 4
ER -