BACKGROUND: C3 glomerulonephritis (GN) is a proliferative GN resulting from glomerular deposition of complement factors due to dysregulation of the alternative pathway of complement. Dysregulation of the alternative pathway of complement may occur as a result of mutations or functional inhibition of complement-regulating proteins. Functional inhibition of the complement-regulating proteins may result from a monoclonal gammopathy. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 32 Mayo Clinic patients with C3 GN, 10 (31%) of whom had evidence of a monoclonal immunoglobulin in serum. OUTCOMES: Clinical features, hematologic and bone marrow biopsy findings, kidney biopsy findings, kidney measures, complement pathway abnormalities, treatment, and follow-up of patients with C3 GN that was associated with a monoclonal gammopathy. RESULTS: Mean age of patients with C3 GN associated with monoclonal gammopathy was 54.5 years. Bone marrow biopsy done in 9 patients revealed monoclonal gammopathy of undetermined significance in 5 patients, small lymphocytic lymphoma/chronic lymphocytic leukemia in one patient, and no abnormal clones in the other 3 patients. Kidney biopsy showed membranoproliferative GN with bright capillary wall C3 staining in all 10 patients. Evaluation of the alternative pathway of complement showed abnormalities in 7 of 9 patients tested. No mutation in complement-regulating proteins was detected in any patient. As an index case, one patient with C3 GN and chronic lymphocytic leukemia was treated with rituximab, cyclophosphamide, vincristine, and prednisone, and one patient with C3 GN and monoclonal gammopathy of undetermined significance was treated with dexamethasone and bortezomib. Both patients showed significant decreases in hematuria and proteinuria and stabilization of kidney function. LIMITATIONS: Studies to show evidence of direct activation of the alternative pathway by monoclonal immunoglobulin were not done. CONCLUSIONS: The study highlights the association of C3 GN and monoclonal gammopathy, in particular in the older population, and the importance of targeting the underlying hematologic malignancy as an approach to treating C3 GN.
BACKGROUND:C3 glomerulonephritis (GN) is a proliferative GN resulting from glomerular deposition of complement factors due to dysregulation of the alternative pathway of complement. Dysregulation of the alternative pathway of complement may occur as a result of mutations or functional inhibition of complement-regulating proteins. Functional inhibition of the complement-regulating proteins may result from a monoclonal gammopathy. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 32 Mayo Clinic patients with C3 GN, 10 (31%) of whom had evidence of a monoclonal immunoglobulin in serum. OUTCOMES: Clinical features, hematologic and bone marrow biopsy findings, kidney biopsy findings, kidney measures, complement pathway abnormalities, treatment, and follow-up of patients with C3 GN that was associated with a monoclonal gammopathy. RESULTS: Mean age of patients with C3 GN associated with monoclonal gammopathy was 54.5 years. Bone marrow biopsy done in 9 patients revealed monoclonal gammopathy of undetermined significance in 5 patients, small lymphocytic lymphoma/chronic lymphocytic leukemia in one patient, and no abnormal clones in the other 3 patients. Kidney biopsy showed membranoproliferative GN with bright capillary wall C3 staining in all 10 patients. Evaluation of the alternative pathway of complement showed abnormalities in 7 of 9 patients tested. No mutation in complement-regulating proteins was detected in any patient. As an index case, one patient with C3 GN and chronic lymphocytic leukemia was treated with rituximab, cyclophosphamide, vincristine, and prednisone, and one patient with C3 GN and monoclonal gammopathy of undetermined significance was treated with dexamethasone and bortezomib. Both patients showed significant decreases in hematuria and proteinuria and stabilization of kidney function. LIMITATIONS: Studies to show evidence of direct activation of the alternative pathway by monoclonal immunoglobulin were not done. CONCLUSIONS: The study highlights the association of C3 GN and monoclonal gammopathy, in particular in the older population, and the importance of targeting the underlying hematologic malignancy as an approach to treating C3 GN.
Authors: M A Abrera-Abeleda; C Nishimura; J L H Smith; S Sethi; J L McRae; B F Murphy; G Silvestri; C Skerka; M Józsi; P F Zipfel; G S Hageman; R J H Smith Journal: J Med Genet Date: 2005-11-18 Impact factor: 6.318
Authors: Gerald B Appel; H Terence Cook; Gregory Hageman; J Charles Jennette; Michael Kashgarian; Michael Kirschfink; John D Lambris; Lynne Lanning; Hans U Lutz; Seppo Meri; Noel R Rose; David J Salant; Sanjeev Sethi; Richard J H Smith; William Smoyer; Hope F Tully; Sean P Tully; Patrick Walker; Michael Welsh; Reinhard Würzner; Peter F Zipfel Journal: J Am Soc Nephrol Date: 2005-03-30 Impact factor: 10.121
Authors: Robert A Kyle; Terry M Therneau; S Vincent Rajkumar; Dirk R Larson; Matthew F Plevak; Janice R Offord; Angela Dispenzieri; Jerry A Katzmann; L Joseph Melton Journal: N Engl J Med Date: 2006-03-30 Impact factor: 91.245
Authors: Julie Lin; Glen S Markowitz; Anthony M Valeri; Neeraja Kambham; William H Sherman; Gerald B Appel; Vivette D D'Agati Journal: J Am Soc Nephrol Date: 2001-07 Impact factor: 10.121
Authors: Richard J H Smith; Jessy Alexander; Paul N Barlow; Marina Botto; Thomas L Cassavant; H Terence Cook; Santiago Rodriguez de Córdoba; Gregory S Hageman; T Sakari Jokiranta; William J Kimberling; John D Lambris; Lynne D Lanning; Vicki Levidiotis; Christoph Licht; Hans U Lutz; Seppo Meri; Matthew C Pickering; Richard J Quigg; Angelique L Rops; David J Salant; Sanjeev Sethi; Joshua M Thurman; Hope F Tully; Sean P Tully; Johan van der Vlag; Patrick D Walker; Reinhard Würzner; Peter F Zipfel Journal: J Am Soc Nephrol Date: 2007-08-05 Impact factor: 10.121
Authors: Aishwarya Ravindran; Fernando C Fervenza; Richard J H Smith; An S De Vriese; Sanjeev Sethi Journal: Mayo Clin Proc Date: 2018-08 Impact factor: 7.616