FsGs

Focal segmental glomerulosclerosis (FSGS) is a pattern of kidney disease characterized by scarring (sclerosis) in some glomeruli (focal) and only part of each affected glomerulus (segmental). It is a common cause of nephrotic-range proteinuria and a leading cause of chronic kidney disease and end-stage kidney disease in adults and children.

FSGS can be classified as primary (idiopathic) or secondary to other conditions that injure nephrons. Secondary forms occur with adaptive responses to reduced nephron number or increased workload (for example obesity, hypertension, or unilateral renal hypoplasia), viral infections (notably HIV), drugs (heroin, pamidronate), immune disorders, or systemic diseases. Genetic forms associated with mutations in podocyte or slit diaphragm genes (such as NPHS2, ACTN4, TRPC6, INF2) are increasingly recognized and may present in childhood or adulthood. Histologic variants include perihilar, cellular, tip lesion, and collapsing forms, with the latter often linked to HIV or APOL1 risk alleles.

Pathophysiology largely involves podocyte injury and detachment, leading to focal scarring and progression to glomerulosclerosis. Immunofluorescence is typically negative or shows nonspecific trapping of IgM and C3, and electron microscopy reveals extensive foot process effacement. Diagnosis rests on renal biopsy, in the context of proteinuria, often nephrotic in primary disease.

Treatment focuses on managing proteinuria and preserving renal function. Primary FSGS is usually treated with corticosteroids; nonresponders or relapsing cases may require calcineurin inhibitors or rituximab. Secondary forms are managed by addressing underlying conditions and using renin–angiotensin system blockade, blood pressure control, and lifestyle measures. Prognosis varies; factors such as degree of proteinuria, baseline kidney function, and genetic form influence outcomes, with many cases progressing to chronic kidney disease or ESRD. Transplantation is possible, though recurrence risk is higher in certain genetic or APOL1-associated cases.