About FSGS

Focal Segmental Glomerulosclerosis (FSGS) is a type of Glomerular Disease, one of many diseases that affect kidney function by attacking the glomeruli, the tiny units within the kidney where blood is cleaned. Glomerulosclerosis (gloh-MAIR-yoo-loh-skleh-ROH-sis) describes the scarring or hardening of the tiny blood vessels within the kidney.

What are the kidneys and what do they do?
The two kidneys are bean-shaped organs located near the middle of the back, just below the rib cage to the left and right of the spine. Each about the size of a fist, these organs act as sophisticated filters for the body. They process about 400 quarts of blood a day to sift out about 2 quarts of waste products and extra water that eventually leave the body as urine.

Blood enters the kidneys through arteries that branch inside the kidneys into tiny clusters of looping blood vessels. Each cluster is called a glomerulus, which comes from the Greek word meaning filter. The plural form of the word is glomeruli. There are approximately 1 million glomeruli, or filters, in each kidney. The glomerulus is attached to the opening of a small fluid-collecting tube called a tubule. Blood is filtered in the glomerulus, and extra water and wastes pass into the tubule and become urine. Eventually, the urine drains from the kidneys into the bladder through larger tubes called ureters.

Each glomerulus-and-tubule unit is called a nephron. Each kidney is composed of about 1 million nephrons. In healthy nephrons, the glomerular membrane that separates the blood vessel from the tubule allows waste products and extra water to pass into the tubule while keeping blood cells and protein in the bloodstream.

How do glomerular diseases interfere with kidney function?
Glomerular diseases damage the glomeruli, letting protein and sometimes red blood cells leak into the urine. Sometimes a glomerular disease also interferes with the clearance of waste products by the kidney, so they begin to build up in the blood. Furthermore, loss of blood proteins like albumin in the urine can result in a fall in their level in the bloodstream. In normal blood, albumin acts like a sponge, drawing extra fluid from the body into the bloodstream, where it remains until the kidneys remove it. But when albumin leaks into the urine, the blood loses its capacity to absorb extra fluid from the body. Fluid can accumulate outside the circulatory system in the face, hands, feet, or ankles and cause swelling.

What are the symptoms of glomerular disease?
The signs and symptoms of glomerular disease include

• proteinuria: large amounts of protein in the urine
• hematuria: blood in the urine
• reduced glomerular filtration rate: inefficient filtering of wastes from the blood
• hypoproteinemia: low blood protein
• edema: swelling in parts of the body

One or more of these symptoms can be the first sign of kidney disease. But how would you know, for example, whether you have proteinuria? Before seeing a doctor, you may not. But some of these symptoms have signs, or visible manifestations:

• Proteinuria may cause foamy urine.
• Blood may cause the urine to be pink or cola-colored.
• Edema may be obvious in hands and ankles, especially at the end of the day, or around the eyes when awakening in the morning, for example.

How is glomerular disease diagnosed?
Patients with glomerular disease have significant amounts of protein in the urine, which may be referred to as "nephrotic range" if levels are very high. Red blood cells in the urine are a frequent finding as well, particularly in some forms of glomerular disease. Urinalysis provides information about kidney damage by indicating levels of protein and red blood cells in the urine. Blood tests measure the levels of waste products such as creatinine and urea nitrogen to determine whether the filtering capacity of the kidneys is impaired. If these lab tests indicate kidney damage, the doctor may recommend ultrasound or an xray to see whether the shape or size of the kidneys is abnormal. These tests are called renal imaging. But since glomerular disease causes problems at the cellular level, the doctor will probably also recommend a kidney biopsy--a procedure in which a needle is used to extract small pieces of tissue for examination under different types of microscopes, each of which shows a different aspect of the tissue. A biopsy may be helpful in confirming glomerular disease and identifying the cause.

What causes glomerular disease?
A number of different diseases can result in glomerular disease. It may be the direct result of an infection or a drug toxic to the kidneys, or it may result from a disease that affects the entire body, like diabetes or lupus. Many different kinds of diseases can cause swelling or scarring of the nephron or glomerulus. Sometimes glomerular disease is idiopathic, in that it occurs without an apparent associated disease.

Focal segmental glomerulosclerosis (FSGS) describes scarring in scattered regions of the kidney, typically limited to one part of the glomerulus and to a minority of glomeruli in the affected region. FSGS may result from a systemic disorder or it may develop as an idiopathic kidney disease, without a known cause. Proteinuria is the most common symptom of FSGS, but, since proteinuria is associated with several other kidney conditions, the doctor cannot diagnose FSGS on the basis of proteinuria alone. Biopsy may confirm the presence of glomerular scarring if the tissue is taken from the affected section of the kidney, but finding the affected section is a matter of chance, especially early in the disease process, when lesions may be scattered.

Confirming a diagnosis of FSGS may require repeat kidney biopsies. Arriving at a diagnosis of idiopathic FSGS requires the identification of focal scarring and the elimination of possible systemic causes such as diabetes or an immune response to infection. Since idiopathic FSGS is, by definition, of unknown cause, it is difficult to treat. No universal remedy has been found, and most patients with FSGS progress to ESRD over 5 to 20 years. Some patients with an aggressive form of FSGS proceed to ESRD in 2 to 3 years. Treatments involving steroids or other immunosuppressive drugs appear to help some patients by decreasing proteinuria and improving kidney function. But these treatments are beneficial only to a minority of those in whom they are tried, and some patients experience even poorer kidney function as a result of therapy. ACE inhibitors may also be used in FSGS to decrease proteinuria. Treatment should focus on controlling blood pressure and blood cholesterol levels, factors that may contribute to kidney scarring.

Minimal Change Disease (MCD) is the diagnosis given when a patient has Nephrotic Syndrome and the kidney biopsy reveals little or no change to the structure of glomeruli or surrounding tissues when examined by a light microscope. Tiny drops of a fatty substance called a lipid may be present, but no scarring has taken place within the kidney. MCD may occur at any age, but it is most common in childhood. A small percentage of patients with idiopathic nephrotic syndrome do not respond to steroid therapy. For these patients, the doctor may recommend a low-sodium diet and prescribe a diuretic to control edema. The doctor may recommend the use of nonsteroidal anti-inflammatory drugs to reduce proteinuria. ACE inhibitors have also been used to reduce proteinuria in patients with steroid-resistant MCD. These patients may respond to larger doses of steroids, more prolonged use of steroids, or steroids in combination with immunosuppressant drugs, such as chlorambucil, cyclophosphamide, or cyclosporine.

What are renal failure and end-stage renal disease?
Renal failure is any acute or chronic loss of kidney function and is the term used when some kidney function remains. ESRD is total, or nearly total, permanent kidney failure. Depending on the form of glomerular disease, renal function may be lost in a matter of days or weeks or may deteriorate slowly and gradually over the course of decades.

Acute Renal Failure
A few forms of glomerular disease cause very rapid deterioration of kidney function. For example, PSGN can cause severe symptoms (hematuria, proteinuria, edema) within 2 to 3 weeks after a sore throat or skin infection develops. The patient may temporarily require dialysis to replace renal function. This rapid loss of kidney function is called acute renal failure (ARF). Although ARF can be life-threatening while it lasts, kidney function usually returns after the cause of the kidney failure has been treated. In many patients, ARF is not associated with any permanent damage. However, some patients may recover from ARF and subsequently develop chronic renal failure (CRF).

Chronic Renal Failure
Most forms of glomerular disease develop gradually, often causing no symptoms for many years. CRF is the slow, gradual loss of kidney function. Some forms of CRF can be controlled or slowed down. For example, diabetic nephropathy can be delayed by tightly controlling blood glucose levels and using ACE inhibitors to reduce proteinuria and control blood pressure, but CRF cannot be cured. Partial loss of renal function means that some portion of the patient's nephrons have been scarred, and scarred nephrons cannot be repaired. In most cases, CRF leads to End-Stage Renal Disease.

End-Stage Renal Disease
To stay alive, a patient with ESRD must go on dialysis--hemodialysis or peritoneal dialysis--or receive a new kidney through transplantation. Patients with CRF who are approaching ESRD should learn as much about their treatment options as possible so they can make an informed decision when the time comes. With the help of dialysis or transplantation, many people continue to lead full, productive lives after reaching ESRD.

Points to Remember

• The kidneys filter waste and extra fluid from the blood.
• The filtering process takes place in the nephron, where microscopic blood vessel filters, called glomeruli, are attached to fluid-collecting tubules.
• A number of different disease processes can damage the glomeruli and thereby cause kidney failure. Glomerulosclerosis is a broad term that includes many forms of damage to the glomeruli.
• Some forms of kidney failure can be slowed down, but scarred glomeruli can never be repaired.
• Treatment for the early stages of kidney failure depends on the disease causing the damage.
• Early signs of kidney failure include blood or protein in the urine and swelling in the hands, feet, abdomen, or face. Kidney failure may be silent for many years.
  

Source: National Kidney and Urologic Diseases Information Clearinghouse
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The National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC) is a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The NIDDK is part of the National Institutes of Health under the U.S. Department of Health and Human Services. Established in 1987, the clearinghouse provides information about diseases of the kidneys and urologic system to people with kidney and urologic disorders and to their families, health care professionals, and the public. NKUDIC answers inquiries, develops and distributes publications, and works closely with professional and patient organizations and Government agencies to coordinate resources about kidney and urologic diseases.
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NIH Publication No. 03-4358
March 2003