Causes and pathogenesis of focal segmental glomerulosclerosis

Abstract

Focal segmental glomerulosclerosis (FSGS) describes both a common lesion in progressive kidney disease, and a disease characterized by marked proteinuria and podocyte injury. The initial injuries vary widely. Monogenetic forms of FSGS are largely due to alterations in structural genes of the podocyte, many of which result in early onset of disease. Genetic risk alleles in apolipoprotein L1 are especially prevalent in African Americans, and are linked not only to adult-onset FSGS but also to progression of some other kidney diseases. The recurrence of FSGS in some transplant recipients whose end-stage renal disease was caused by FSGS points to circulating factors in disease pathogenesis, which remain incompletely understood. In addition, infection, drug use, and secondary maladaptive responses after loss of nephrons from any cause may also cause FSGS. Varying phenotypes of the sclerosis are also manifest, with varying prognosis. The so-called tip lesion has the best prognosis, whereas the collapsing type of FSGS has the worst prognosis. New insights into glomerular cell injury response and repair may pave the way for possible therapeutic strategies.

Focal Segmental Glomerulosclerosis

“…Critical is the elimination of other systemic diseases or primary renal diseases that may result in a similar presentation. Many reviews cover various aspects of FSGS and include comprehensive reviews (1)(2)(3)(4), disease mechanisms (5)(6)(7)(8), pediatric disease (9), immunologic aspects (10), treatment in children (11), and treatment in adults (12)(13)(14). We focus here on a practical approach to FSGS assessment on clinical and histopathologic grounds in the context of our current understanding of disease mechanisms and genetics.…”

Focal segmental glomerulosclerosis associated with cutaneous and systemic plasmacytosis

“…It is unknown whether CSP contributes to the development of FSGS. FSGS is a heterogeneous phenotype associated with various conditions, including neoplastic conditions, HIV infections, obesity, and so on [9]. Plasma cell proliferative disorders might also be linked with FSGS.…”

MicroRNA-206 and its down-regulation of Wilms’Tumor-1 dictate podocyte health in adriamycin-induced nephropathy

“…13 Podocyte loss and dysfunction in renal microenvironments are important features in the pathogenesis of FSGS. 2 Podocyte is a unique population of terminally-differentiated glomerular visceral epithelial cell that possess distinctive morphologic features exemplified by sophisticated foot processes. 14,15 Under pathologic conditions, injurious stimuli often cause podocyte dedifferentiation characterized by loss of podocyte-specific features, thereby leading to podocyte dysfunction and defective glomerular filtration.…”

“…Recent studies have revealed that FSGS is the result of mutations in crucial podocyte genes. 2 Wilms' tumor-1 (WT1) is a gene that is essential for the development and maintenance of normal podocyte and glomeruli. 3,4 Loss of WT1 in pathologic conditions is commonly interpreted as a result of podocyte depletion.…”