Focal Segmental Glomerulosclerosis, Adult

Abstract

Focal and segmental glomerulosclerosis (FSGS) is the histological manifestation of a variety of clinicopathological entities. The hallmark pathologic finding is the presence of segmental glomerular scars in some but not all the glomeruli. Clinically, it presents with varying degrees of proteinuria and progression to end-stage renal disease if untreated. FSGS is the leading cause of primary glomerular disease in adults who present with nephrotic syndrome, occurring at higher rates in black patients. Morphologic variants of FSGS, which include the classic or not otherwise specified (NOS), collapsing, tip, perihilar, and cellular lesions, have prognostic importance with the collapsing lesion having the lowest response to glucocorticoids and thus worst outcomes, whereas the tip lesion is the most glucocorticoid-responsive variant with the best outcomes, resembling minimal change disease. Primary FSGS, often presenting with nephrotic syndrome, is primarily a podocytopathy. Circulating permeability factors are thought to play a central role in podocyte foot process effacement in primary FSSG. Secondary FSGS is a result of irreversible podocyte injury from a diverse group of insults such as viruses and drugs or an adaptive glomerular hyperfiltration in such cases as obesity or loss of nephron mass. Unlike primary FSGS, secondary forms of FSGS tend not to recur after kidney transplantation. Treatment of primary FSGS ranges from conservative management to glucocorticoids to immunosuppressive medications depending on the clinical presentation. Response to therapy is the strongest predictor of long-term renal survival. Treatment of secondary FSGS focuses on identifying and eliminating the underlying culprit.