Focal segmental glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) is a cause of nephrotic syndrome in children and adolescents, as well as an important cause of kidney failure in adults.

It is also known as "focal glomerular sclerosis" or "focal nodular glomerulosclerosis".

It accounts for about a sixth of the cases of nephrotic syndrome. (Minimal change disease (MCD) is by far the most common cause of nephrotic syndrome in children: MCD and primary FSGS may have a similar cause. )

Former NBA basketball players Sean Elliott and Alonzo Mourning have both survived bouts against FSGS. Alonzo Mourning is an Ambassador to The NephCure Foundation.

Appearance
The individual components of the name refer to the appearance of the kidney tissue on biopsy: focal—only some of the glomeruli are involved (as opposed to diffuse), segmental—only part of each glomerulus is involved (as opposed to global), glomerulosclerosis—refers to scarring of the glomerulus (a part of the nephron (the functional unit of the kidney)). The glomerulosclerosis is usually indicated by heavy PAS staining and findings of IgM and C3 in sclerotic segment.

Classification
Depending on the cause it is broadly classified as
 * Primary, when no underlying cause is found; usually presents as nephrotic syndrome
 * Secondary, when an underlying cause is identified; usually presents with kidney failure and proteinuria. This is actually a heterogeneous group including numerous causes such as
 * Infections such as HIV (known as HIV-Associated Nephropathy)
 * Toxins and drugs such as heroin and pamidronate
 * Familial forms
 * Secondary to nephron loss and hyperfiltration, such as with chronic pyelonephritis and reflux, morbid obesity, diabetes mellitus

There are many other classification schemes also.

Pathologic variants
Five mutually exclusive variants of focal segmental glomerulosclerosis may be distinguished by the pathologic findings seen on renal biopsy: Recognition of these variants may have prognostic value in individuals with primary focal segmental glomerulosclerosis (i.e. where no underlying cause is identified). The collapsing variant is associated with higher rate of progression to end-stage renal disease, whereas glomerular tip lesion variant has low rate of progression to end-stage renal disease in most patients. Cellular variant shows similar clinical presentation to collapsing and glomerular tip variant but has intermediate outcomes between these two variants. However, because collapsing and glomerular tip variant show overlapping pathologic features with cellular variant, this intermediate difference in clinical outcomes may reflect sampling bias in cases of cellular focal segmental glomerulosclerosis (i.e. unsampled collapsing variant or glomerular tip variant). The prognostic significance of perihilar and NOS variants has not yet been determined. The NOS variant is the most common subtype.
 * 1) Collapsing variant
 * 2) Glomerular tip lesion variant
 * 3) Cellular variant
 * 4) Perihilar variant
 * 5) Not otherwise specified (NOS) variant.

Causes
There are currently several known genetic causes of the hereditary forms of FSGS.

Symptoms and signs
In children and some adults, FSGS presents as a nephrotic syndrome, which is characterized by edema (associated with weight gain), hypoalbuminemia (low serum albumin, a protein in the blood), hyperlipidemia and hypertension (high blood pressure). In adults it may also present as kidney failure and proteinuria, without a full-blown nephrotic syndrome.

Tests

 * Urinalysis
 * Blood tests – cholesterol
 * Kidney biopsy

Differential diagnosis

 * Minimal change disease, especially in children
 * Several others

Treatment

 * Salt restriction and diuretics, such as furosemide, for edema
 * Antihypertensives (especially ACEIs) – if the blood pressure is too high
 * treat present hyperlipidemia (e.g. statins, fibrates)
 * Aldosterone antagonist to decrease proteinuria and thus offer a degree of reno-protection
 * Corticosteroids, such as prednisone – based on the clinical judgment of physician (no broad consensus/guideline)
 * Cytotoxics, such as cyclophosphamide may be used to induce remission in patients presenting with FSGS refractory to corticosteroids, or in patients who do not tolerate steroids.
 * Plasmapheresis – blood cleansing using a machine to remove the patient's blood plasma and replacing it with donor plasma.
 * Vitamin E
 * Immunosuppressive drugs
 * None – sometimes none of the above works and the patient will require dialysis with possibly later transplantation of a new kidney.