C3 glomerulonephritis associated with monoclonal gammopathy: a case series.
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.
['Zand|Ladan|L|', 'Kattah|Andrea|A|', 'Fervenza|Fernando C|FC|', 'Smith|Richard J H|RJ|', 'Nasr|Samih H|SH|', 'Zhang|Yuzhou|Y|', 'Vrana|Julie A|JA|', 'Leung|Nelson|N|', 'Cornell|Lynn D|LD|', 'Sethi|Sanjeev|S|']
D000293:Adolescent D000328:Adult D000368:Aged D002648:Child D003176:Complement C3 D005260:Female D005500:Follow-Up Studies D005921:Glomerulonephritis D006801:Humans D008297:Male D008875:Middle Aged D010265:Paraproteinemias D055815:Young Adult
monoclonal gammopathy C3 Glomerulonephritis (C3 GN) membranoproliferative glomerulonephritis (MPGN) monoclonal gammopathy of undetermined significance (MGUS)