FSGS and Complement Pathway

Sethi et al continue their important contributions to the AJKD Kidney Biopsy Teaching Case series. This month they report on case of focal segmental glomerulosclerosis with mutations in complement factor H and C3 proteins. Hitherto most mutations in this clinical setting have been localized to podocytes, with the exception of LAMB2, which is a glomerular basement membrane protein. The idea that secondary focal segmental glomerulosclerosis can be the result of multiple insults including chronic thrombotic microangiopathy is well recognized. Specifically, in the field of kidney transplantation, both cyclosporine and tacrolimus can cause endothelial injury leading to segmental sclerosis. Sethi et al stress that in some cases this vascular injury may be mild, associated with only segmental double contours, and reflect underlying genetic mutations in complement factor H or C3 genes. The frequency with which this happens, the potential role of environmental factors (such as infection, drug toxicity), and the familial pattern of disease transmission in such patients needs to be defined by further studies.

Parmjeet Randhawa, MD
Professor of Pathology, University of Pittsburgh Medical Center
AJKD Associate Editor

To view the article abstract or full-text (subscription required), please visit AJKD.org.

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