18 - Primary and Secondary (Non-Genetic) Causes of Focal and Segmental Glomerulosclerosis

Abstract

Focal segmental glomerulosclerosis (FSGS) is a histologic pattern of glomerular damage that may be primary (idiopathic) or secondary. FSGS is one of the most common causes of proteinuria and nephrotic syndrome in children and adults. Dysregulation and loss of podocytes underlie all forms of FSGS. Primary FSGS is mediated by one or more putative circulating permeability factors of unknown identity. Secondary forms of FSGS can be associated with familial/genetic disorders, viral diseases, medications, and adaptive structural-functional responses. Although monogenic disorders have been discovered in familial and sporadic FSGS, risk allele variants of APOL1 explain much of the predisposition to this lesion in patients of African descent. Histologic variants of FSGS help define pathogenesis, responsiveness to treatment, and risk for progression to renal failure. Some therapies have been effective in both primary and secondary forms of FSGS, but immunosuppressive medication use is restricted to the primary form. Corticosteroids, calcineurin inhibitors, and a variety of other medications have been effective in both reducing proteinuria and preventing end-stage renal disease in some FSGS patients.