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Focal Segmental Glomerulosclerosis
Focal segmental glomerulosclerosis (FSGS), also known as “focal glomerular sclerosis” or “focal nodular glomerulosclerosis,” is a histopathologic finding of sclerosis of glomeruli and damage to renal podocytes. FSGS is a leading cause of nephrotic syndrome in children and adults. Signs and symptoms include proteinuria, water retention, and edema. Other symptoms include immune compromise and hypercoagulability. Kidney failure is a common long-term complication of disease. FSGS can be classified as primary versus secondary. Primary FSGS is caused by a permeability factor that injures podocytes. Secondary FSGS is an adaptation to hyperfiltration due to other causes or due to toxic injury. Diagnosis is established by renal biopsy. Treatment consists of glucocorticoids and other immune-modulatory drugs. Response to therapy is variable, with a significant portion of patients progressing to end-stage kidney failure. FSGS is estimated to occur in 2-3 persons per million. FSGS is found more frequently among males and individuals of African descent.

Signs and Symptoms
The most common symptoms include :


 * Frothy urine (due to excess protein)
 * Pitting edema (due to loss of serum albumin)
 * Susceptibility to infection (due to loss of serum immunoglobulin)

Common signs secondary to excess glomerular protein loss, including  :


 * Proteinuria (often in the nephrotic range of >3.5 g/day)
 * Hypoalbuminemia (<3.5 g/dl)
 * Hypogammaglobulinemia
 * Hypercholesterolemia (compensatory by the liver to compensate for serum oncotic pressure)
 * Fatty casts in the urine (secondary to hypercholesterolemia)

Causes and Pathophysiology
Primary FSGS is caused by a putative unidentified set of circulatory factors that damage podocytes, leading to podocyte effacement. Podocyte effacement, in turn, diminishes the integrity of the filtration barrier of the renal glomerulus, leading to filtration of proteins.

Secondary FSGS is caused by some stress or toxin that directly injures podocytes. Toxins that may damage podocytes include steroids and heroin. Added stress secondary to hyperfiltration can induce podocyte damage. This may be caused by a number of factors, such as obesity or gross renal hypertrophy.

Genetics also play a contribution to the development of FSGS.

'''***NOTE: Table below taken from original article. Not sure if I want to include this section or not - seems a bit too large and detailed.***'''

Diagnosis
Diagnosis of FSGS is made by renal biopsy that includes at least 15 serial cuts with at least 8 glomeruli. Histologic features include sclerosis of a portion (average: 15%) of the glomerular space, with a portion of glomeruli manifesting any sclerosis.

Other tests helpful in the diagnosis include urine protein, urinalysis, serum albumin, and serum lipids.

Management
First-line treatment for primary FSGS consists of anti-inflammatory drugs. Specifically, glucocorticoids are begun in patients manifesting with nephrotic-range proteinuria (>3.5 g/day). For patients who maintain nephrotic-range proteinuria despite glucocorticoids, or for patients who demonstrate glucocorticoid intolerance, calcineurin inhibitors (e.g., tacrolimus) are initiated. Successful treatment is defined as a drop in proteinuria to sub-nephrotic ranges.

The treatment of secondary FSGS involves addressing the particular toxic or stress agent.

Prognosis
The majority of untreated cases of FSGS will progress to end-stage kidney disease. Important prognostic factors include the degree of proteinuria and initial response to therapy.

Patients with nephrotic-range (>3.5 g/day) proteinuria have over a 50% rate of progression to end-stage kidney disease at 10 years. Only 15% of patients with sub-nephrotic ranges of proteinuria progress to end-stage renal failure at 10 years.

Initial response to therapy also dictates long-term outcomes. Those defined as having a "complete response" typically manifest a proteinuria of <300 mg/day; those with a "partial response" manifest a sub-nephrotic range of proteinuria, <3.5 g/day. Either complete or partial response is associated with 80% kidney survival at 10-years, compared with about 50% among non-responsive patients.