Nephrotic syndrome

Nephrotic syndrome is a group of symptoms that include protein in the urine, low blood protein levels, high
cholesterol levels, high triglyceride levels, and swelling.
Causes
Nephrotic syndrome is caused by different disorders that damage the kidneys. This damage leads to the release of
too much protein in the urine.
The most common cause in children is minimal change disease. Membranous glomerulonephritis is the most
common cause in adults.
This condition can also occur from:

Cancer
Diseases such as diabetes, systemic lupus erythematosus, multiple myeloma, and amyloidosis
Genetic disorders
Immune disorders
Infections (such as strep throat, hepatitis, or mononucleosis)
Use of certain drugs

It can occur with kidney disorders such as:

Focal and segmental glomerulosclerosis

Glomerulonephritis
Mesangiocapillary glomerulonephritis

Nephrotic syndrome can affect all age groups. In children, it is most common between ages 2 and 6. This disorder
occurs slightly more often in males than females.
Symptoms
Swelling (edema) is the most common symptom. It may occur:

In the face and around the eyes (facial swelling)

In the arms and legs, especially in the feet and ankles
In the belly area (swollen abdomen)

Other symptoms include:

Foamy appearance of the urine

Poor appetite
Weight gain (unintentional) from fluid retention

Exams and Tests

The doctor will perform a physical exam. Laboratory tests will be done to see how well the kidneys are working.
They include:

Albumin blood test

Blood chemistry tests such as basic metabolic panel or comprehensive metabolic panel

Blood urea nitrogen (BUN)

Creatinine - blood test
Creatinine clearance - urine test
Urinalysis

Fats are often also present in the urine. Blood cholesterol and triglyceride levels may be high.
A kidney biopsy may be needed to find the cause of the disorder.
Tests to rule out various causes may include the following:

Antinuclear antibody
Cryoglobulins
Complement levels
Glucose tolerance test
Hepatitis B and C antibodies

HIV test
Rheumatoid factor
Serum protein electrophoresis (SPEP)
Syphilis serology
Urine protein electrophoresis (UPEP)

This disease may also change the results of the following tests:

Vitamin D level
Serum iron
Urinary casts

Treatment
The goals of treatment are to relieve symptoms, prevent complications, and delay kidney damage. To control
nephrotic syndrome, you must treat the disorder that is causing it. You may need treatment for life.
Treatments:

Keep blood pressure at or below 130/80 mmHg to delay kidney damage. Angiotensin-converting enzyme
(ACE) inhibitors or angiotensin receptor blockers (ARBs) are the medicines most often used. ACE
inhibitors may also help decrease the amount of protein lost in the urine.
You may take corticosteroids and other drugs that suppress or quiet the immune system.
Treat high cholesterol to reduce the risk of heart and blood vessel problems. A low-fat, low-cholesterol
diet is usually not very helpful for people with nephrotic syndrome. Medications to reduce cholesterol and
triglycerides (usually statins) may be needed.
A low-salt diet may help with swelling in the hands and legs. Water pills (diuretics) may also help with
this problem.
Low-protein diets may be helpful. Your health care provider may suggest eating a moderate-protein diet
(1 gram of protein per kilogram of body weight per day).
You may need vitamin D supplements if nephrotic syndrome is long-term and not responding to
treatment.
Blood thinners may be needed to treat or prevent blood clots.

Outlook (Prognosis)
The outcome varies. The condition may be acute and short-term or chronic and not respond to treatment. The
complications that occur can also affect the outcome.
Some people may eventually need dialysis and a kidney transplant.
Possible Complications

Acute kidney failure

Atherosclerosis and related heart diseases

Chronic kidney disease
Fluid overload, congestive heart failure, pulmonary edema
Infections, including pneumococcal pneumonia
Malnutrition
Renal vein thrombosis

When to Contact a Medical Professional

Call your health care provider if:

You have symptoms of nephrotic syndrome

Nephrotic syndrome does not go away
New symptoms develop, including:
o Cough
o Decreased urine output
o Discomfort with urination
o Fever
o Severe headache
o Sores on the skin

Prevention
Treating conditions that can cause nephrotic syndrome may help prevent the syndrome.
Alternative Names
Nephrosis
References
Appel GB. Glomerular disorders and nephrotic syndromes. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd
ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 122.
Nachman PH, Jennette JC, Falk RJ. Primary glomerular disease. In: Brenner BM, ed. Brenner and Rector's The
Kidney. 8th ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 30.
Overview of Nephrotic Syndrome
Nephrotic syndrome (NS) is a condition that is often caused by any of a group of diseases that damage the
kidneys' filtering system, the glomeruli. The structure of the glomeruli prevents most protein from getting filtered
through into the urine. Normally, a person loses less than 150 mg of protein in the urine in a 24-hour period.
Nephrotic-range proteinuria, the urination of more than 3.5 grams of protein during a 24-hour period, or 25 times
the normal amount, is the primary indicator of NS.
Incidence and Prevalence of Nephrotic Syndrome
About two in every 10,000 people experience nephrotic syndrome. Nephrotic syndrome prevalence is difficult to
establish in adults because the condition is usually a result of an underlying disease. In children, it is diagnosed in
more boys than girls, usually between 2 and 3 years of age.
Nephrotic Syndrome Signs and Symptoms

In addition to proteinuria, there are three main symptoms of nephrotic syndrome associated with protein leaking
into the urine:

Hypoalbuminemia (low level of albumin in the blood)

Edema (swelling)
Hypercholesterolemia (high level of cholesterol in the blood)

Hypoalbuminemia is a low level of albumin (a protein) in the blood due to proteinuria. Low albumin in the
blood causes fluid to move from the blood into the tissue, causing swelling. The kidney perceives the decrease of
fluid in the blood and aggressively retains as much fluid and salt as it can. This contributes to the body's fluidoverload state.
Nephrotic-related swelling makes tissue puffy, soft, and impressionable to the touch. Edema is most common in
the legs and feet, especially after standing all day. It can cause feelings of tightness in the extremities and may
affect mobility. In later stages, swelling may occur in the abdomen (ascites), hands, and around the eyes in the
morning (called periorbital edema). In later stages, the whole body may swell (anasarca). Some people gain
weight after fluid builds up in their bodies for a long time.
Hypercholestrolemia, high blood cholesterol, is common in nephrotic syndrome). In addition to albumin, other
important enzymes involved in cholesterol metabolism slip through the glomeruli, which contribute to high blood
cholesterol.
Nephrotic Syndrome Complications
Nephrotic syndrome is associated with renal failure. The disease that causes NS can damage the glomeruli and
can interfere with their ability to clean the blood. The edema that is present in the legs may also be occurring in
the kidney tissue itself and can interfere with the kidneys' ability to clean the blood. Renal failure can either be
gradual (CRF) or acute (ARF).
A hypercoaguable state, in which the blood abnormally overclots, is also seen in some patients with NS. This
means that they are at risk for developing a blood clot in the legs or in the renal veins that transport blood from
the kidney. Some patients take blood thinners to prevent this complication.
Causes of Nephrotic Syndrome
There are a number of different disorders that can cause NS. Diabetes and, to a lesser extent, hypertension can
cause diffuse damage to the glomeruli and can ultimately lead to NS.
The following diseases can cause specific damage to the glomeruli and often result in the development of heavy
proteinuria and in many instances NS:

Amyloidosis (the stiffening and subsequent malfunction of the kidney due to fibrous protein deposit in the
tissue)
Congential nephrosis
Focal segmental glomerular sclerosis (FSGS) (creates scar tissue in the glomerulus, damaging its proteinrepellant membrane)
Glomerulonephritis (GN)
o Diffuse mesangial proliferative GN (affecting the messangium)
o Membranous (damages the protein-repellant membrane)
o Postinfectious (occurs after an infection)
IgA nephropathy (Berger's disease) (deposit of specific immunoglobulin A causing an inflammatory
reaction and leading to glomerulonephritis)
Minimal change disease (Nil's disease)
Pre-eclampsia (rarely associated with NS, more often associated with heavy proteinuria)

Many of these diseases tend to occur more often in certain age groups:

Less than 1 year old

o Congenital nephrosis
Less than 15 years old
o Min change
o FSGS
o Other
Age 15 to 40 years
o Min change
o FSGS
o Other
Over age 40
o Membranous GN
o Diabetic nephropathy
Over 60
o Amyloidosis may account for up to 20% of cases

What is nephrotic syndrome?

Nephrotic syndrome is a sign that your kidneys are not working right. You have nephrotic syndrome if you have
high levels of protein in your urine, low levels of protein in the blood, and high cholesterol.
Nephrotic syndrome is not a disease. It is a warning that something is damaging your kidneys. Without treatment,
that problem could cause kidney failure. So its important to get treatment right away.
Nephrotic syndrome can occur at any age. But it is most common in children between the ages of 18 months and
8 years.
What causes nephrotic syndrome?
There are tiny blood vessels in the kidneys that filter waste and extra water from the blood. When these filters are
damaged, you get nephrotic syndrome. Protein helps move water from the tissues into the blood. Healthy kidneys
keep the right amount of protein in the blood. Damaged kidneys let protein slip from the blood into the urine.
Without enough protein in the blood, fluid builds up in the tissues. This can cause swelling.
Many things can cause this blood vessel damage, including diabetes, lupus, infection, certain cancers, and some
medicines. Sometimes doctors don't know what causes it.
A type of kidney disease called minimal change disease (also called nil disease) causes most of the cases of
nephrotic syndrome in children. Doctors don't know what causes minimal change disease.
Childhood nephrotic syndrome can occur at any age but is most common between the ages of 1-1/2 and 8 years. It
seems to affect boys more often than girls.
A child with the nephrotic syndrome has these signs:

High levels of protein in the urine

Low levels of protein in the blood
Swelling resulting from buildup of salt and water.

The nephrotic syndrome is not itself a disease. But it can be the first sign of a disease that damages the tiny bloodfiltering units (glomeruli) in the kidneys, where urine is made.

The kidneys are two bean-shaped organs found in the lower back. They are about the size of a fist. They clean the
blood by filtering out excess water and salt and waste products from food. Healthy kidneys keep protein in the
blood, which helps the blood soak up water from tissues. But kidneys with damaged filters may let protein leak
into the urine. As a result, not enough protein is left in the blood to soak up the water. The water then moves from
the blood into body tissues and causes swelling. You may see swelling around your child's eyes, belly, and legs.
Your child may urinate less often than usual and may gain weight from the excess water.
To diagnose childhood nephrotic syndrome, the doctor may ask for a urine sample to check for protein. The
doctor will dip a strip of chemically treated paper into the urine sample.
Too much protein in the urine will make the paper change color. Or the doctor may ask for a 24-hour collection of
urine for a more precise measurement of the protein and other substances in the urine.
The doctor may take a blood sample to see how well the kidneys are removing wastes. Healthy kidneys remove
creatinine and urea nitrogen from the blood. If the blood contains high levels of these waste products, some
kidney damage may have already occurred. But most children with the nephrotic syndrome do not have
permanent kidney damage.
In some cases, the doctor may want to examine a small piece of the child's kidney under a microscope to see if
substances there are causing the syndrome. The procedure of collecting a small tissue sample from the kidney is
called a biopsy, and it is usually performed with a long needle passed through the skin. The child will be awake
during the procedure and receive calming drugs and a local painkiller at the site of the needle entry. General
anesthesia is used in the very rare cases where open surgery is required. The child will stay overnight in the
hospital to rest and allow the health care team to ensure that no problems occur.
Minimal Change Disease
The most common form of the nephrotic syndrome in children is called minimal change disease. Doctors do not
know what causes it. The condition is called minimal change disease because children with this form of the
nephrotic syndrome have normal or nearly normal biopsies. If your child is diagnosed with minimal change
disease, the doctor will probably prescribe prednisone, which belongs to a class of drugs called corticosteroids.
Prednisone stops the movement of protein from the blood into the urine, but it does have side effects that the
doctor will explain. Following the doctor's directions exactly is essential to protect your child's health. The doctor
may also prescribe another type of drug called a diuretic, which reduces the swelling by helping the child urinate.
When protein is no longer present in the urine, the doctor will begin to reduce the dosage of prednisone. This
process takes several weeks. Some children never get sick again, but most do develop swelling and protein in the
urine again, usually following a viral illness. However, as long as the child continues to respond to prednisone and
the urine becomes protein free, he or she has an excellent long-term outlook without kidney damage.
Children who relapse frequently, or who seem to be dependent on prednisone or have side effects from it, may be
given a second type of drug called a cytotoxic agent. The agents most frequently used are cyclophosphamide,
chlorambucil, and cyclosporine. After reducing protein in the urine with prednisone, the doctor may prescribe the
cytotoxic agent for a while. Treatment with cyclophosphamide and chlorambucil usually lasts for 8 to 12 weeks,
while treatment with cyclosporine frequently takes longer. The good news is that most children "outgrow" this
disease by their late teens with no permanent damage to their kidneys.
Other Conditions That Involve the Childhood Nephrotic Syndrome
In about 20 percent of children with the nephrotic syndrome, the kidney biopsy reveals scarring or deposits in the
glomeruli. The two most common diseases that damage these tiny filtering units are focal segmental
glomerulosclerosis (FSGS) and membranoproliferative glomerulonephritis (MPGN). Very rarely, a child may be
born with a condition that causes the nephrotic syndrome (congenital nephropathy).

Since prednisone is less effective in treating these diseases than it is in treating minimal change disease, the doctor
may use additional therapies, including cytotoxic agents. Recent experience with a class of drugs called ACE
inhibitors (a type of blood pressure drug) indicates that these drugs help prevent protein from leaking into the
urine and keep the kidneys from being damaged in children with the nephrotic syndrome.
Classification
Nephrotic syndrome can be primary, being a disease specific to the kidneys, or it can be secondary, being a renal
manifestation of a systemic general illness. In all cases, injury to glomeruli is an essential feature.
Primary causes of nephrotic syndrome include the following, in approximate order of frequency:

Minimal-change nephropathy
Focal glomerulosclerosis
Membranous nephropathy
Hereditary nephropathies

Secondary causes include the following, again in order of approximate frequency:

Diabetes mellitus
Lupus erythematosus
Amyloidosis and paraproteinemias
Viral infections (eg, hepatitis B, hepatitis C, human immunodeficiency virus [HIV] )
Preeclampsia

Nephrotic-range proteinuria may occur in other kidney diseases, such as IgA nephropathy. In that common
glomerular disease, one third of patients may have nephrotic-range proteinuria.
Nephrotic syndrome may occur in persons with sickle cell disease and evolve to renal failure. Membranous
nephropathy may complicate bone marrow transplantation, in association with graft versus host disease.
Kidney diseases that affect tubules and interstitium, such as interstitial nephritis, will not cause nephrotic
syndrome.
The above causes of nephrotic syndrome are largely those for adults, and this article will concentrate primarily on
adult nephrotic syndrome. However, nephrotic syndrome in infancy and childhood is an important entity. For
discussion of this topic, see the Medscape Reference article Pediatric Nephrotic Syndrome.
From a therapeutic perspective, nephrotic syndrome may be classified as steroid sensitive, steroid resistant,
steroid dependent, or frequently relapsing.
Corticosteroids (prednisone), cyclophosphamide, and cyclosporine are used to induce remission in nephrotic
syndrome. Diuretics are used to reduce edema. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin
II receptor blockers are administered to reduce proteinuria.