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Treatment of primary focal segmental glomerulosclerosis

Daniel C Cattran, MD
Gerald B Appel, MD
Section Editors
Richard J Glassock, MD, MACP
Fernando C Fervenza, MD, PhD
Deputy Editor
Albert Q Lam, MD


Focal and segmental glomerulosclerosis (FSGS; often incorrectly abbreviated as focal sclerosis) is a morphologic pattern of glomerular injury primarily directed at the glomerular visceral epithelial cell (the podocyte) and defined by the presence of sclerosis in parts (segmental) of some (focal) glomeruli by light microscopy of a renal biopsy specimen. The lesion may be found either without an identifiable cause (in which case it is called "idiopathic" or "primary") or in response to previous glomerular injury, glomerular hypertension or hypertrophy, or to genetic defects, viral infections, or medications ("secondary") [1]. FSGS is distinct from focal and global glomerulosclerosis, which has a different prognosis and treatment. (See "Epidemiology, classification, and pathogenesis of focal segmental glomerulosclerosis".)

Primary FSGS can present acutely with overt nephrotic syndrome characterized by hypoalbuminemia and edema. However, primary FSGS can also present insidiously with less dramatic manifestations, possibly related to the underlying histologic variant. The diagnosis of primary FSGS is confirmed by a renal biopsy that reveals the morphologic features mentioned above as well as, in most cases, diffuse (greater than 80 percent) effacement of the foot processes by electron microscopy. By contrast, secondary FSGS most often presents as asymptomatic proteinuria without profound hypoalbuminemia or edema [2]. In addition, the kidney biopsy usually reveals glomerulomegaly, focal (rather than diffuse) foot process effacement, and, sometimes, evidence of a separate kidney disease that is responsible for the development of secondary FSGS. (See "Epidemiology, classification, and pathogenesis of focal segmental glomerulosclerosis".)

Distinguishing between primary and secondary disease is particularly important because of the markedly different approach to therapy in the two disorders. Primary FSGS is often responsive to immunosuppressive therapy, including glucocorticoids, cyclosporine, and other immunosuppressive agents. By contrast, immunosuppression is not indicated in secondary FSGS.

Renin-angiotensin-aldosterone system blockade (with angiotensin-converting enzyme [ACE] inhibitors or angiotensin receptor blockers [ARBs]) reduces proteinuria and slows progression in proteinuric kidney diseases. However, whether or not this is effective in primary FSGS is unknown.

This topic will review the prognosis and treatment of primary FSGS in adults, focusing on patients with nephrotic-range proteinuria. The causes of FSGS and the treatment of children with FSGS are discussed separately. (See "Epidemiology, classification, and pathogenesis of focal segmental glomerulosclerosis" and "Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults" and "Treatment of idiopathic nephrotic syndrome in children".)


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Literature review current through: May 2017. | This topic last updated: Nov 28, 2016.
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