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Association of a Novel Complement Factor H Mutation With Severe Crescentic and Necrotizing Glomerulonephritis
Journal article   Peer reviewed

Association of a Novel Complement Factor H Mutation With Severe Crescentic and Necrotizing Glomerulonephritis

Fernando C Fervenza, Richard J.H Smith and Sanjeev Sethi
American journal of kidney diseases, Vol.60(1), pp.126-132
07/2012
DOI: 10.1053/j.ajkd.2012.03.007
PMCID: PMC4428583
PMID: 22542290

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Abstract

Severe crescentic and necrotizing glomerulonephritis typically is associated with anti–glomerular basement membrane or antineutrophil cytoplasmic antibodies. In this report, we describe a 23-year-old man with severe crescentic and necrotizing glomerulonephritis. Both anti–glomerular basement membrane and antineutrophil cytoplasmic antibody titers were negative. Kidney biopsy showed bright C3 staining in the mesangium and along capillary walls and no staining for immunoglobulins. Electron microscopy showed waxy deposits (many mesangial; few intramembranous or subendothelial), prompting evaluation of the alternative pathway of complement. Alternative pathway evaluation showed a novel mutation in short consensus repeat (SCR) 19 of complement factor H. In addition, the patient carried complement factor H and C3 risk alleles. Prompt treatment with intravenous steroids followed by oral steroids resulted in symptom alleviation and improved kidney function. This case shows what is to our knowledge a unique and previously unpublished cause of severe crescentic and necrotizing glomerulonephritis. Furthermore, the case demonstrates an expanding spectrum of complement-mediated glomerulonephritis and shows that crescentic and necrotizing glomerulonephritis with solely complement deposits should be evaluated for abnormalities in the alternative pathway of complement.
Crescentic glomerulonephritis alternative pathway of complement factor H mutation C3 glomerulonephritis

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