Focal and segmental glomerulosclerosis: multiple pathways are involved

Abstract

Focal segmental glomerulosclerosis (FSGS) is not a disease but a clinicopathologic entity. The term FSGS itself is a misnomer because its lesions are not always focal, segmental, or sclerotic. Its clinical expression also widely varies and is nonspecific. Confronted with such diversity, one cannot but translate the title of this contribution into a unifying version focusing on the podocyte, initial culprit, or victim of multiple processes leading to FSGS. Some have been identified in human glomerulopathies and/or in animal or cell culture models, and are classified as secondary. Genetic forms, nonsyndromic or syndromic, have adduced a wealth of knowledge on the slit diaphragm architecture and explain the reason for their steroid resistance. Others, mostly expressed by a nephrotic syndrome, will be considered as idiopathic until the offending factor(s) that affect the molecular array of the slit diaphragm filtration barrier are identified and counteracted. Recent research has lead to suggesting that FSGS is not a T-cell-driven autoimmune glomerulopathy. Thus, treatments considered as etiologic, including glucocorticoids and calcineurin inhibitors, are in fact endowed with a mode of action on podocytes that suggests that drugs used such as immunosuppressors also might be considered as antiproteinuric agents.