Author: Dr Sharon Kang University of California San Francisco 2008-05-28
Introduction
A serious complication of kidney disease, the
nephrotic syndrome is a specific collection of signs and symptoms caused
by the loss of large amounts of protein from the blood into the urine
(more than 3.5 grams per day). The syndrome can occur in infants,
children, and adults, as well as in all racial and ethnic groups. Some
patients with the nephrotic syndrome are at high risk for end-stage
kidney failure. Once a kidney fails, survival is dependent upon either
dialysis or a kidney transplant.
Patients with nephrotic syndrome generally require the assistance of a kidney specialist (nephrologist) for diagnosis, therapy, and management. Early detection and treatment of the nephrotic syndrome may prevent progression of the kidney disease and loss of kidney function.
In this Google knol, we will discuss the clinical features of the nephrotic syndrome, the kidney diseases that cause the nephrotic syndrome, diagnosis, evaluation, prognosis, complications, and general therapy.
What is the nephrotic syndrome?
Nephrotic syndrome is a collection of signs and symptoms that occurs in people with kidney disease who have large amounts of protein in the urine. It results from abnormal loss of protein from the blood into the urine due to damage to the filtering units of the kidney. Normally, the filtering structures of the kidney (clusters of capillary blood vessels known as glomeruli) remove waste products and excess water from blood and excrete them into the urine. Normal glomeruli allow a very small amount of protein into the urine; normal kidneys excrete less than 150 mg per day into the urine. In patients with nephrotic syndrome, these glomeruli are damaged, resulting in significant loss of protein in the urine. A hallmark of the nephrotic syndrome is heavy proteinuria, more than 3500 mg (or 3.5 grams) of protein in the urine in 24 hours. The loss of large amounts of protein into the urine can be associated with the nephrotic syndrome, which includes the following signs and symptoms:- Significant proteinuria (high levels of protein in the urine, more than 3.5 grams/day)
- Hypoalbuminemia (low levels of the protein albumin in the blood)
- Peripheral edema (swelling of legs, ankles, abdomen, and tissues around the eyes due to abnormal fluid retention)
- Hyperlipidemia (high blood cholesterol levels)
Some
patients with severe proteinuria (protein in the urine more than 3.5
grams/day) will not have the associated signs and symptoms of the
nephrotic syndrome. Some patients with proteinuria will have some of
these features, but not the entire nephrotic syndrome. Doctors
occasionally describe proteinuria as nephrotic (“the patient has
nephrotic proteinuria” or “the proteinuria is nephrotic range”) if the
proteinuria exceeds 3.5 grams per day even if the patient does not have
the nephrotic syndrome. Some kidney diseases produce little or no
proteinuria.
Normal amounts of protein in the blood are needed to help regulate fluid throughout the body’s fluid compartments. Protein acts like a sponge, keeping fluid in the bloodstream. When levels of protein are low in the blood, fluid will leak out of the circulation and into the surrounding tissues causing swelling. Low levels of protein in the blood also promote salt and water retention by the kidneys, leading to fluid retention and swelling.
Patients with nephrotic syndrome can have normal kidney function early in the course of their disease. The kidneys may continue to clean the blood effectively, even if they leak protein into the urine. However, patients with proteinuria are at high risk for progressive loss of kidney function.
Normal amounts of protein in the blood are needed to help regulate fluid throughout the body’s fluid compartments. Protein acts like a sponge, keeping fluid in the bloodstream. When levels of protein are low in the blood, fluid will leak out of the circulation and into the surrounding tissues causing swelling. Low levels of protein in the blood also promote salt and water retention by the kidneys, leading to fluid retention and swelling.
Patients with nephrotic syndrome can have normal kidney function early in the course of their disease. The kidneys may continue to clean the blood effectively, even if they leak protein into the urine. However, patients with proteinuria are at high risk for progressive loss of kidney function.
Which kidney diseases cause the nephrotic syndrome?
While
many different types of kidney disease can cause the nephrotic
syndrome, the common target of these diseases is the glomerulus, the
filtering capillary unit of the kidney. Damage to the filter allows a
large amount of protein from the blood to enter the urine. Many
different terms are used to describe kidney diseases that primarily
affect the glomerulus: glomerular disease, glomerulonephritis
(inflammation in the kidney), glomerulosclerosis (scarring in the
kidney), and nephropathy (a general term for kidney disease). These
different terms confuse doctors and patients. Unfortunately, they are
often used interchangeably and imprecisely.
The most common nephrotic diseases are membranous nephropathy, focal segmental glomerulosclerosis (FSGS), diabetic kidney disease, minimal change disease (MCD), and amyloidosis. (See below for explanations.) Other diseases that can be associated with nephrotic syndrome are IgA nephropathy and membranoproliferative glomerulonephritis (MPGN). There are many rare causes including light chain deposition disease and immunotactoid/fibrillary glomerulonephritis.
It is important to understand that nephrotic syndrome and nephrotic kidney disease differ from nephritic disease. Nephritic diseases typically present with blood in the urine (hematuria, which may be grossly visible), cylindrical clumps of red blood cells in the urine (called red blood cell casts), hypertension, and often rapid loss of kidney function. While nephrotic diseases may have hypertension and hematuria, these features are usually not as severe as with nephritic diseases. Unfortunately, some kidney diseases include the terms glomerulonephritis or nephritis in the name, although the disease may be either nephrotic or nephritic. Membranoproliferative glomerulonephritis and lupus nephritis are good examples of diseases that may be either nephrotic or nephritic.
Many of the kidney diseases that cause nephrotic syndrome can be either primary or secondary. Primary disease implies an unknown cause (idiopathic in medical terms), while secondary disease implies that another disease is causing the kidney disease. Membranous nephropathy, focal segmental glomerulosclerosis, IgA nephropathy, and membranoproliferative glomerulonephritis are kidney diseases that have primary and secondary forms. For example, primary membranous nephropathy is idiopathic (no known cause). Secondary membranous nephropathy may be caused by cancer, hepatitis B infection, chronic infections, systemic lupus erythematosus (lupus or SLE), and medications. Primary FSGS is idiopathic, while secondary FSGS may be caused by HIV infection, morbid obesity, heroin use, and chronic kidney disease.
A patient’s age, race, and family history will affect the likelihood of certain diseases causing the nephrotic syndrome.
The most common nephrotic diseases are membranous nephropathy, focal segmental glomerulosclerosis (FSGS), diabetic kidney disease, minimal change disease (MCD), and amyloidosis. (See below for explanations.) Other diseases that can be associated with nephrotic syndrome are IgA nephropathy and membranoproliferative glomerulonephritis (MPGN). There are many rare causes including light chain deposition disease and immunotactoid/fibrillary glomerulonephritis.
It is important to understand that nephrotic syndrome and nephrotic kidney disease differ from nephritic disease. Nephritic diseases typically present with blood in the urine (hematuria, which may be grossly visible), cylindrical clumps of red blood cells in the urine (called red blood cell casts), hypertension, and often rapid loss of kidney function. While nephrotic diseases may have hypertension and hematuria, these features are usually not as severe as with nephritic diseases. Unfortunately, some kidney diseases include the terms glomerulonephritis or nephritis in the name, although the disease may be either nephrotic or nephritic. Membranoproliferative glomerulonephritis and lupus nephritis are good examples of diseases that may be either nephrotic or nephritic.
Many of the kidney diseases that cause nephrotic syndrome can be either primary or secondary. Primary disease implies an unknown cause (idiopathic in medical terms), while secondary disease implies that another disease is causing the kidney disease. Membranous nephropathy, focal segmental glomerulosclerosis, IgA nephropathy, and membranoproliferative glomerulonephritis are kidney diseases that have primary and secondary forms. For example, primary membranous nephropathy is idiopathic (no known cause). Secondary membranous nephropathy may be caused by cancer, hepatitis B infection, chronic infections, systemic lupus erythematosus (lupus or SLE), and medications. Primary FSGS is idiopathic, while secondary FSGS may be caused by HIV infection, morbid obesity, heroin use, and chronic kidney disease.
A patient’s age, race, and family history will affect the likelihood of certain diseases causing the nephrotic syndrome.
Common causes of nephrotic syndrome
- Minimal Change Disease (MCD, also called nil disease or lipoid nephrosis) is a kidney disease that causes 90% of cases of nephrotic syndrome in children under the age of 10 and more than 50% of cases in older children. The primary cause is unknown, but is thought to be due to an autoimmune process where the body’s immune system attacks the kidneys. It can also occur in adults, though less commonly than in children. Secondary forms of MCD may be caused by nonsteroidal anti-inflammatory drugs (NSAIDs) and Hodgkin’s lymphoma. As the name implies, MCD has only minimal abnormalities on kidney biopsy material examined under a normal light microscope. A powerful electron microscope is needed to see the slight damage to the glomerulus.
- Focal Segmental Glomerulosclerosis (FSGS) is the most common cause of primary nephrotic syndrome in adults, accounting for 35% of all cases and over 50% of cases in African American adults. Secondary forms of FSGS may be caused by HIV infection, reflux nephropathy (damage to the kidneys caused by backward flow of urine into the kidney), scarring from previous kidney, morbid obesity, and heroin use. Kidney biopsy can show collapse and scarring of glomeruli. Patients with primary FSGS often have very rapid onset of the nephrotic syndrome, whereas slowly increasing proteinuria and worsening kidney function are characteristic of secondary forms of FSGS.
- Membranous Nephropathy is the second most common cause of primary nephrotic syndrome in adults. It is the most common primary cause of nephrotic syndrome in Caucasian adults. Causes of secondary membranous nephropathy include hepatitis B infection, lupus, thyroid disease, cancer, chronic infections (syphilis, leprosy, schistosomiasis, and others), and medications such as gold, penicillamine, captopril, and NSAIDs.
- Amyloidosis is a disease with abnormal protein deposits in many different organs, including heart, kidney, blood vessels, liver, tongue, fat, and gastrointestinal tract. There are many causes of amyloidosis, but the primary form is caused by an abnormal antibody protein produced by white blood cells.
- Diabetes can cause kidney damage, called diabetic nephropathy, after several years. Many patients with diabetic nephropathy have proteinuria, but do not have the full blown nephrotic syndrome. Poorly controlled diabetes (chronically elevated blood sugar levels) increases the likelihood of diabetic kidney disease.
What are the symptoms of nephrotic syndrome?
Early symptoms include fatigue and a generalized feeling of illness (malaise). Edema or swelling in the legs and feet is a common complaint, especially after sitting or standing for a prolonged period of time. Puffiness around the eyes (periorbital edema) is often noted after waking up in the morning due to fluid accumulation around the eyes. Men may experience swelling of the scrotum. Abdominal fullness may develop due to the abnormal collection of fluid in the abdomen (ascites). Shortness of breath can occur if fluid builds up in the lungs. Nephrotic patients are in negative protein balance due to the protein losses in the urine and decreased production of protein by the liver. This protein malnutrition results in loss of muscle mass, which can be masked by weight gain due to fluid retention. Excess fluid in the gastrointestinal tract can lead to loss of appetite (anorexia), nausea, and vomiting. Patients may also notice foamy urine due to the large amount of protein in the urine. Rapid worsening of kidney function with decreased urine output can occur. Blood pressure can be low, normal, or high.The primary protein in the blood, albumin is usually the predominant protein lost in the urine in the nephrotic syndrome. Other proteins in the blood can be lost in the nephrotic syndrome, including proteins that prevent blood clots, regulate cholesterol levels, protect against infection, and regulate hormones. The loss of these proteins can cause the complications of nephrotic syndrome: blood clots, elevated cholesterol levels, increased infections, and altered hormone regulation.
How is nephrotic syndrome diagnosed?
The diagnosis of nephrotic syndrome is based on the combination of symptoms, physical exam findings, and laboratory tests of the blood and urine.Urine tests
The screening test for proteinuria is a urine dipstick analysis of a random urine sample. If this qualitative test is positive for protein, the physician should precisely measure or quantify the amount of protein in the urine. The gold standard method is a 24 hour urine collection. Unfortunately, collecting the urine for 24 hours is tedious, slow, and inconvenient. Doctors can estimate the amount of protein in a 24 hour urine sample using a single random urine sample. The spot urine protein:creatinine ratio is the urine protein concentration divided by the urine creatinine concentration in a small sample of urine. The ratio estimates the amount of protein in grams in a 24 hour urine sample. For example, a urine protein:creatinine ratio of five would estimate about five grams/day of proteinuria. The spot urine sample is easier to collect than a 24 hour urine sample and can be followed over time to track the proteinuria and its response to medical therapy.The nephrotic syndrome may produce classic findings in the patient’s urine. The doctor centrifuges a small sample of urine, discards the liquid portion, and examines the solid elements in the urine under the microscope. This procedure is urine microscopy or urine sediment examination. The classic findings include oval fat bodies (fat droplets inside kidney cells shed into the urine) and the Maltese cross (the oval fat body looks like a cross when examined with polarized light). These urinary findings are not specific or unique to any particular cause of nephrotic syndrome.
Blood tests
The blood should be tested for the characteristic findings and complications of the nephrotic syndrome, including a low blood albumin level (less than 3 g/dL). Elevated cholesterol and triglyceride levels occur because the liver increases production of lipids (fats) in response to decreased blood protein levels. The loss of proteins into the urine that regulate cholesterol levels can also increase lipid levels.The doctor may order other blood tests to help determine the cause of the nephrotic syndrome, because the first line of therapy is to treat the underlying disease. These blood tests may include tests for lupus, syphilis, hepatitis B, hepatitis C, HIV, and cryoglobulins since these diseases have been associated with the nephrotic syndrome. Blood and urine electrophoresis and immunofixation tests look for multiple myeloma and monoclonal gammopathies, diseases which produce abnormal antibodies and may cause the nephrotic syndrome. Patients with autoimmune diseases such as lupus may have low blood complement levels, indicating altered immune status or infection.
The patient’s kidney function can be measured with the blood creatinine level. Elevated blood creatinine levels indicate decreased kidney function. Some patients with the nephrotic syndrome will have normal kidney function and normal blood creatinine levels, while others will have decreased kidney function and markedly elevated creatinine levels.
Imaging tests (Radiology)
The nephrotic syndrome usually does not cause any gross abnormalities of the kidneys. Imaging of the kidneys with ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) is generally not required; the level of detail provided by these radiology studies is not sufficient to determine the cause of the nephrotic syndrome. The doctor may order a simple and safe ultrasound to make sure that there are no major abnormalities of the kidneys (such as urinary obstruction, a single kidney, or a small scarred kidney) especially prior to a kidney biopsy.Kidney biopsy
The
patient’s clinical history and laboratory tests may suggest a certain
cause of nephrotic syndrome, but they are not definitive or
confirmatory. For example, a patient with hepatitis B infection does
not necessarily have membranous nephropathy as the cause of nephrotic
syndrome. Determining the cause of the nephrotic syndrome usually
requires a kidney biopsy (see the Google knol on kidney biopsy for more
details).
Pediatric nephrologists generally start steroids in children with nephrotic syndrome since minimal change disease causes 90% of cases in children. Minimal change disease in children usually responds quickly and completely to steroids. The pediatric nephrologist will proceed to kidney biopsy if the proteinuria and nephrotic syndrome persist after several weeks of steroids.
In adults, no one kidney disease causes the majority of nephrotic syndrome cases. A kidney biopsy is often necessary to determine the exact cause of the nephrotic syndrome. By examining the kidney sample, the pathologist and nephrologist can diagnose the patient’s kidney disease, assess its severity, and help determine prognosis. With information provided by the kidney biopsy, the nephrologist can recommend a treatment plan (see below). Please see the Google knol on kidney biopsy for further details.
Pediatric nephrologists generally start steroids in children with nephrotic syndrome since minimal change disease causes 90% of cases in children. Minimal change disease in children usually responds quickly and completely to steroids. The pediatric nephrologist will proceed to kidney biopsy if the proteinuria and nephrotic syndrome persist after several weeks of steroids.
In adults, no one kidney disease causes the majority of nephrotic syndrome cases. A kidney biopsy is often necessary to determine the exact cause of the nephrotic syndrome. By examining the kidney sample, the pathologist and nephrologist can diagnose the patient’s kidney disease, assess its severity, and help determine prognosis. With information provided by the kidney biopsy, the nephrologist can recommend a treatment plan (see below). Please see the Google knol on kidney biopsy for further details.
What are potential complications of nephrotic syndrome?
The
nephrotic syndrome can lead to progressive loss of kidney function,
especially in adults. In some adult patients, nephrotic syndrome leads
to end-stage renal disease and dialysis. In children, the most common
cause of nephrotic syndrome is minimal change disease which generally
has an excellent prognosis and does not lead to permanent kidney disease
and dialysis.
Patients with nephrotic syndrome have an increased risk of blood clots in the veins (called deep vein thrombosis) due to urinary loss of proteins that prevent blood clots. Blood clots in the main vein in the kidney (the renal vein) can cause flank pain, blood in the urine, and worsening kidney function. However, renal vein thrombosis can also develop slowly without associated symptoms. Blood clots in the veins can travel or embolize to the lungs; a pulmonary embolus is a life-threatening condition requiring immediate medical attention.
Patients with nephrotic syndrome are more susceptible to infections than the general population due to the loss of antibodies in the urine. The elevated cholesterol levels in nephrotic patients increases the risk of heart attacks (myocardial infarction) and stroke (cerebrovascular accident).
Patients with nephrotic syndrome have an increased risk of blood clots in the veins (called deep vein thrombosis) due to urinary loss of proteins that prevent blood clots. Blood clots in the main vein in the kidney (the renal vein) can cause flank pain, blood in the urine, and worsening kidney function. However, renal vein thrombosis can also develop slowly without associated symptoms. Blood clots in the veins can travel or embolize to the lungs; a pulmonary embolus is a life-threatening condition requiring immediate medical attention.
Patients with nephrotic syndrome are more susceptible to infections than the general population due to the loss of antibodies in the urine. The elevated cholesterol levels in nephrotic patients increases the risk of heart attacks (myocardial infarction) and stroke (cerebrovascular accident).
What are the prognostic signs in the nephrotic syndrome?
In general, poorer prognosis is associated with decreased
kidney function at the time of presentation to a doctor’s care, severe
disease on kidney biopsy at the time of diagnosis, high blood pressure,
older age, and severity of proteinuria. These patients may respond less
optimally to therapy, may have worsening kidney function despite optimal
medical therapy, and may develop end stage kidney failure more rapidly.
How is the nephrotic syndrome treated?
The first line of therapy is to treat the underlying disease causing
the nephrotic syndrome. The various diseases that cause nephrotic
syndrome may have specific therapies. For example, diabetic kidney
disease requires tight control of blood sugars to prevent further damage
to the kidneys and other organs. Patients with minimal change disease
usually respond to steroids alone. Lupus kidney disease often requires
steroids and/or other immunosuppression drugs. Primary membranous
nephropathy and focal segmental glomerulosclerosis may also be treated
successfully with steroids and other immunosuppressive drugs.
Amyloidosis can respond to chemotherapy and steroids. More information
regarding treatment of these diseases can be found at http://kidney.niddk.nih.gov.
Management
of the nephrotic syndrome also focuses on reducing proteinuria, edema,
and high lipid levels. These adjuvant therapies can be used regardless
of the cause of the nephrotic syndrome. Nephrologists may treat milder
cases of nephrotic syndrome with these adjuvant therapies and close
monitoring, but no disease-specific therapy (steroids and other
immunosuppression drugs). Some diseases may resolve spontaneously
without disease-specific therapy. Membranous nephropathy is a good
example; roughly one third of cases will resolve spontaneously without
therapy. In other cases of nephrotic syndrome, patients are not good
candidates for disease-specific therapies because of other medical
conditions, contraindications to therapy, or markedly reduced kidney
function. However, even in these patients, adjuvant therapies can
effectively reduce symptoms and improve prognosis (see below for
details).
Proteinuria
A
cornerstone of nephrotic syndrome and proteinuria treatment is reducing
proteinuria. Proteinuria is toxic to the kidney itself and is
therefore both a marker of underlying kidney disease as well as a cause
of worsening kidney damage. The severity of proteinuria has been
associated with prognosis; more proteinuria predicts a worse prognosis.
Reductions in proteinuria have been associated with better outcomes and
improved kidney survival in many kidney diseases.
Angiotensin converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARB) are commonly used blood pressure medications that decrease pressure in the filtering units of the kidney (glomeruli), reducing proteinuria. ACE-I and ARB medications will help to prevent further kidney damage. They should be started in all patients with nephrotic syndrome who have persistent proteinuria, regardless of the underlying cause of their disease. Possible side effects of these medications include high potassium levels in the blood or temporary worsening of kidney function. These side effects may prevent the use of ACE-I and ARB medications in some patients.
Many patients with nephrotic syndrome ask if reducing dietary protein intake will help reduce proteinuria and protect kidney function. The logic is undeniable: reducing protein in the diet should reduce the amount of protein in the urine. Unfortunately, it is unclear if dietary protein restriction reduces proteinuria and protects kidney function. A large clinical trial of dietary protein restriction (called the Modification of Diet in Renal Disease Study) was inconclusive, and its findings are still debated among nephrologists. Some nephrologists will recommend dietary protein restriction, especially if patients have significant proteinuria despite ACE/ARB medications or if they cannot tolerate ACE/ARB medications. Other nephrologists do not routinely recommend dietary protein restriction in the absence of conclusive evidence from clinical trials. Dietary protein restriction should be done carefully and with the assistance of a nutritionist if possible to avoid malnutrition and inadequate amounts of other nutrients. Most nephrologists would agree that high protein diets such as the Atkins diet should be avoided.
Angiotensin converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARB) are commonly used blood pressure medications that decrease pressure in the filtering units of the kidney (glomeruli), reducing proteinuria. ACE-I and ARB medications will help to prevent further kidney damage. They should be started in all patients with nephrotic syndrome who have persistent proteinuria, regardless of the underlying cause of their disease. Possible side effects of these medications include high potassium levels in the blood or temporary worsening of kidney function. These side effects may prevent the use of ACE-I and ARB medications in some patients.
Many patients with nephrotic syndrome ask if reducing dietary protein intake will help reduce proteinuria and protect kidney function. The logic is undeniable: reducing protein in the diet should reduce the amount of protein in the urine. Unfortunately, it is unclear if dietary protein restriction reduces proteinuria and protects kidney function. A large clinical trial of dietary protein restriction (called the Modification of Diet in Renal Disease Study) was inconclusive, and its findings are still debated among nephrologists. Some nephrologists will recommend dietary protein restriction, especially if patients have significant proteinuria despite ACE/ARB medications or if they cannot tolerate ACE/ARB medications. Other nephrologists do not routinely recommend dietary protein restriction in the absence of conclusive evidence from clinical trials. Dietary protein restriction should be done carefully and with the assistance of a nutritionist if possible to avoid malnutrition and inadequate amounts of other nutrients. Most nephrologists would agree that high protein diets such as the Atkins diet should be avoided.
Edema
Swelling
can be prevented or reduced with dietary salt restriction and fluid
restriction. Medications that increase urine output (diuretics) may
also be necessary. Conservative measures such as leg elevation and
compression stockings around the legs may help reduce edema. Patients
should weigh themselves frequently to help monitor fluid gain or loss.
Hyperlipidemia
Dietary
modification alone is rarely effective at reducing high blood
cholesterol levels in the nephrotic syndrome. Most patients require
lipid lowering medications called statins (for example, atorvastatin or
simvastatin). The lipid abnormalities usually improve with successful
treatment of the underlying cause of the nephrotic syndrome. However,
doctors may start statin therapy to reduce cholesterol levels while
waiting for the nephrotic syndrome to resolve (either spontaneously or
with directed therapy). Patients may be able to discontinue statin
therapy if their lipid abnormalities resolve with successful treatment
of their nephrotic syndrome.
Blood clots, deep vein thrombosis, pulmonary embolus
Patients with nephrotic syndrome are at higher risk for blood clots.
However, blood thinning medications such as warfarin are not recommended
to prevent blood clots in patients who have never had a blood clot.
However, if a patient has had a blood clot as a complication of the
nephrotic syndrome, the doctor should use blood thinning medications to
dissolve the clot and prevent further clot formation. Heparin can be
used for short term anticoagulation for hours to days, while warfarin is
used for long term anticoagulation over weeks to months. Warfarin
therapy should be used as long as the nephrotic syndrome persists. Some
patients may have reasons why blood thinners should not be used, such
as excessive bleeding risk and risk of falling.
References:
American Kidney Fund: http://www.kidneyfund.org/kf_nephrotic_syndrome.aspNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): http://kidney.niddk.nih.gov/kudiseases/pubs/nephrotic/
National Kidney Foundation: http://www.kidney.org/ATOZ/atozItem.cfm?id=93
The Nephcure Foundation: http://www.nephcure.org/Info_aboutneph.html