Focal segmental glomerulosclerosis: towards a better understanding for the practicing nephrologist

Focal and segmental glomerulosclerosis (FSGS) is a common histopathological lesion that can represent a primary podocytopathy, or occur as an adaptive phenomenon consequent to nephron mass reduction, a scar from a healing vasculitic lesion, direct drug toxicity or viral infection among other secondary causes. Thus, the presence of an FSGS lesion in a renal biopsy does not confer a disease diagnosis, but rather represents the beginning of an exploratory process, hopefully leading ultimately to identification of a specific etiology and its appropriate treatment. We define primary FSGS as a 'primary' podocytopathy characterized clinically by the presence of nephrotic syndrome in a patient with an FSGS lesion on light microscopy and widespread foot process effacement on electron microscopy (EM). Secondary FSGS is commonly characterized by the absence of nephrotic syndrome and the presence of segmental foot process effacement on EM. Failure to accurately differentiate between the primary and secondary forms of FSGS has resulted in many patients undergoing unnecessary immunosuppressive treatment. Here, we review some key points that may assist the practicing nephrologist to distinguish between primary and secondary FSGS.