Focal Segmental Glomerulosclerosis (FSGS)

Anatomy

The kidneys are paired organs responsible for filtering waste products and excess fluid from the blood. The structural and functional unit of the kidney is the nephron, and each kidney contains up to one million nephrons. Each nephron consists of a glomerulus—a network of tiny capillaries surrounded by Bowman’s capsule—and a system of renal tubules. Blood filtration occurs in the glomerulus, while the tubules are responsible for reabsorbing essential substances and secreting waste products into the urine.

Description of the Disease

Focal segmental glomerulosclerosis (FSGS) is a kidney disease characterized by scarring (sclerosis) affecting some (focal) glomeruli and only a portion (segmental) of each affected glomerulus. These scarred areas lose their ability to filter blood effectively, resulting in progressive kidney damage as more glomeruli become involved.

FSGS commonly presents with nephrotic syndrome, which is characterized by heavy proteinuria (more than 3.5 g of protein in the urine per day), low blood albumin levels (hypoalbuminemia), and generalized edema, particularly affecting the limbs and areas around the eyes.

FSGS is diagnosed in approximately 10% of patients who undergo kidney biopsy because of significant proteinuria. The disease occurs most frequently in adolescents and young adults.

Cause of the Disease

FSGS is classified as either primary (idiopathic) or secondary.

• Primary FSGS has no identifiable underlying cause.
• Secondary FSGS develops as a consequence of other kidney disorders or systemic diseases that place increased stress on the glomeruli.

Risk Factors

No specific risk factors have been identified for primary (idiopathic) FSGS.

Risk factors for secondary FSGS include:

• Human immunodeficiency virus (HIV) infection.
• Use of nephrotoxic medications or illicit drugs, particularly heroin.
• Obesity.
• Diabetes mellitus.
• A family history of kidney disease.
• Chronic kidney diseases, such as chronic pyelonephritis.

Symptoms

The most common clinical features of FSGS include:

• Generalized edema, particularly involving the legs, face, areas around the eyes, and abdomen, caused by fluid retention.
• High blood pressure (hypertension).

The disease often produces relatively few symptoms in its early stages, making laboratory testing important for early diagnosis.

Diagnosis

FSGS should be suspected in individuals with unexplained heavy proteinuria or clinical features of nephrotic syndrome. Kidney function is evaluated using blood and urine tests.

The diagnosis is confirmed by kidney biopsy. Microscopic examination demonstrates the characteristic pattern of focal and segmental glomerular scarring. Electron microscopy may also be performed to evaluate characteristic changes in the kidney’s filtering structures.

Treatment

Treatment aims to slow disease progression and reduce proteinuria, although complete recovery is uncommon. Without effective treatment, many patients develop chronic kidney failure, and some progress to end-stage kidney disease within approximately 10 years.

Primary FSGS is commonly treated with glucocorticosteroids, such as prednisolone. Additional immunosuppressive medications may be used in selected cases. In secondary FSGS, treatment focuses on managing the underlying disease. Supportive therapy, including medications to control blood pressure and reduce edema, is also an essential part of management.

Source | Author Doctor Nikas Samuolis, reviewed by Prof. Virginijus Šapoka | Vilnius University | Faculty of Medicine | Head of the Department of Internal Medicine, Family Medicine, and Oncology