Nephrotic Syndrome
• What increases my risk for nephrotic syndrome?
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 it’s 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.
What are the symptoms?
The most common early symptom of nephrotic syndrome, in both
children and adults, is swelling in the tissues around the eyes or in
the feet or ankles. They may also have swelling in the lungs that
can make it hard to breathe.
But many people who have nephrotic syndrome don't have
symptoms.
How is nephrotic syndrome diagnosed?
Doctors diagnose nephrotic syndrome using blood and urine tests.
You may have other tests to see what is causing nephrotic
syndrome. Adults may also have a kidney biopsy, in which the
doctor takes a sample of tissue to test for cancer.
How is it treated?
Treatment focuses on reversing, slowing, or preventing further
kidney damage. The treatment you need depends on whether you
are an adult or a child and what health problem caused nephrotic
syndrome. You may take medicine, and your doctor may suggest
a diet that is low in salt and protein.
With treatment, young children usually get better and have no
lasting problems. Often treatment is not as successful in older
children and adults. If the kidney damage is not stopped, it can
lead to chronic kidney disease.
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Learning about nephrotic syndrome:
• What causes it?
• What are the symptoms?
Cause
Nephrotic syndrome is caused by damage to the tiny blood
vessels in the kidney that filter waste and excess water from the
blood.
Many conditions and diseases can cause nephrotic syndrome,
including:
• Minimal change disease (also called nil disease), a type
of kidney disease. The cause of minimal change disease
is unknown, but it causes most of the cases of nephrotic
syndrome in children.1
• Membranous glomerulopathy and focal segmental
glomerulosclerosis, which are two other diseases of the
kidney. Both of these diseases affect the glomeruli. The
glomeruli help filter waste out of your blood. In focal
segmental glomerulosclerosis, some of the parts of the
glomeruli have scar tissue. This can affect how they
filter the blood. In membranous glomerulopathy, the
tissue wall (membrane) that separates blood and urine
and acts as a filter in your kidney becomes thickened
and damaged.
• Diabetes and lupus. Diabetes is the most common cause
of nephrotic syndrome in adults in the United States.2
• Infections, such as HIV, hepatitis B, hepatitis C,
syphilis, malaria, tuberculosis, or post-streptococcal
glomerulonephritis.
• Cancer, such as breast cancer, lung cancer, Hodgkin's
lymphoma, or multiple myeloma.
• Medicines, such as nonsteroidal anti-inflammatory
drugs, penicillamine, gold therapy, or captopril.
• Illegal drugs, such as heroin.
• Conditions such as preeclampsia, chronic graft rejection
following an organ transplant, and allergic reactions to
bee stings.
• Unknown (idiopathic) factors.
Symptoms
Many people who have nephrotic syndrome do not have any
noticeable physical symptoms. When symptoms are present, they
can include:
• Swelling in the tissues around the eyes (periorbital
edema) or in the feet or ankles (peripheral edema). This
is the most common early symptom of nephrotic
syndrome in both children and adults.
• Shortness of breath caused by fluid buildup in the lungs
(pulmonary edema).
o Adults older than 65 may be misdiagnosed
with heart failure.
o Children are often thought to have allergies.
• Dry skin.
• Swelling of the scrotum (scrotal edema), which may
cause a cord in the testicles to twist (testicular torsion).
Signs of nephrotic syndrome in blood and urine tests can include:
• Low protein (albumin) in the blood.
• High cholesterol and triglyceride levels.
• Low blood levels of iron and vitamin D.
• Protein in the urine (proteinuria).
What Increases Your Risk
Diabetes is the most common cause of nephrotic syndrome in
adults in the United States. About one-third of children who
develop nephrotic syndrome have diabetes.
You also have an increased risk of developing nephrotic
syndrome if you have a disease that results in an impaired
immune system, such as AIDS or lupus.
Nephrotic syndrome is a relatively rare disease that can occur at
any age. In the United States, it affects between 2 and 7 people
out of 100,000 each year. Children most commonly affected are
between the ages of 18 months and 8 years. Boys are affected
more often than girls.
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Being diagnosed:
• Who can diagnose and treat nephrotic syndrome?
• How will my doctor diagnose nephrotic syndrome?
• Can it be prevented?
When To Call a Doctor
Call 911 or other emergency services if you have nephrotic
syndrome and you develop:
• Chest pain.
• Severe shortness of breath or difficulty breathing.
• Sudden and severe abdominal or one-sided (flank) pain.
Call your doctor immediately if you have:
• Bloody urine (gross hematuria).
• Sudden, severe swelling in your legs, and pain when
you flex your feet.
• Swelling of the scrotum.
• Sudden, severe increase in swelling around the eyes or
in the hands, legs, or feet.
• Sudden weight gain, such as 2 lb (0.9 kg) in 24 hours or
5 lb (2.3 kg) in a week.
Watchful Waiting
If you think your child or you may have nephrotic syndrome, or if
your child or you have the condition and the symptoms are
getting worse, don't wait to get treatment. Call your doctor right
away.
Exams and Tests
In addition to a medical history and physical exam, other tests to
diagnose nephrotic syndrome include:
• A 24-hour urine collection, which measures the total
amount of protein in the urine collected over 24 hours.
You will be diagnosed with nephrotic syndrome if you
have more than 3500 mg of protein in your urine.
• Urine test for albumin. Lower levels of albumin in the
blood can cause fluid to collect in the ankles, lungs, or
abdomen.
• Creatinine and creatinine clearance. Results of these
tests give information on how well your kidneys are
working.
• Blood profile tests to measure the amount of protein,
cholesterol, and sugar (glucose) in the blood.
• Kidney ultrasound to look at the kidneys. This exam can
rule out other causes of your symptoms.
You may need other tests before treatment for nephrotic
syndrome begins, including:
• A test for varicella (chickenpox) antibodies.
• A bone density scan.
In adults, additional testing usually includes:
• Serum protein electrophoresis (SPEP).
• Antinuclear antibodies (ANA).
• Antibody tests for systemic lupus erythematosus.
• C3 and C4 complement, proteins normally found in the
blood.
• Tests for hepatitis B and hepatitis C.
Unless nephrotic syndrome is clearly caused by diabetes, a kidney
biopsy is usually done to find the cause. Children do not usually
have a biopsy.
Prevention
Avoiding situations or controlling the other diseases that can
contribute to kidney disease can sometimes prevent nephrotic
syndrome. The earlier a person changes factors that damage the
kidneys, the better. You can help prevent kidney damage by:
• Keeping your blood pressure at less than 125/75 mm Hg
with medication, diet, and exercise. For more
information, see the topic High Blood Pressure
(Hypertension).
• Keeping strict control over your blood glucose level if
you have diabetes. For more information, see the topic
Type 1 Diabetes or Type 2 Diabetes.
• Maintaining healthy levels of fats (lipids), such as
cholesterol and triglycerides. For more information, see
the topic High Cholesterol.
• Not smoking or using other tobacco products. For more
information, see the topic Quitting Tobacco Use.
If you were diagnosed with nephrotic syndrome in the past:
• Avoid dehydration. For more information, see the topic
Dehydration.
o Promptly treat illnesses that cause dehydration,
such as diarrhea, vomiting, or fever.
o Prevent dehydration during hot weather and
when you exercise. Drink 8 to 10 glasses of
fluids (water or rehydration drinks) each day.
Drink extra water before, during, and after
exercise. Take a container of water or sports
drink with you when you exercise, and try to
drink at least every 15 to 20 minutes. Use a
sports drink if you will be exercising for longer
than 1 hour.
o Avoid caffeine drinks, such as coffee and
colas. They increase urine output, which
increases dehydration.
o Avoid alcoholic beverages. They increase
urine output, which increases dehydration.
o Do not take salt tablets. Most people get plenty
of salt in their diets. Use a sports drink if you
are worried about replacing minerals lost
through sweating. Do not use a sports drink if
you have heart failure unless you are instructed
to do so by your doctor.
o Stop working outdoors or exercising at the first
sign of dizziness, lightheadedness, or fatigue.
o Wear one layer of lightweight, light-colored
clothing when you are working or exercising
outdoors. Replace sweaty clothing with dry
clothing as soon as you can.
• Avoid medications that may harm the kidney.
• Avoid X-ray tests that use contrast material.
• Prevent heart disease. Lifestyle changes—eating a low-
fat diet, quitting smoking, and getting regular exercise—
can help reduce your overall risk of developing heart
disease and stroke. For more information, see the topic
Coronary Artery Disease.
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Getting treatment:
• How is nephrotic syndrome treated?
• Will I need to take medicines?
• Is surgery used to treat nephrotic syndrome?
Treatment Overview
Treatment for nephrotic syndrome depends on the cause and the
age of the person who has the condition. Medicines, changes in
diet, and care for other conditions, such as diabetes or high blood
pressure, are all possible treatments for this syndrome. These
treatments may reverse, slow or prevent further kidney damage.
Most children who have nephrotic syndrome do well with
treatment and have a normal life expectancy. Children older than
age 12 at the time of diagnosis and adults who also have diabetes
or high blood pressure do not respond as well to treatment as do
children younger than 12.
Doctors define complete recovery as living without symptoms or
treatment for more than 2 years.1
Initial treatment
Treatment of nephrotic syndrome depends on the cause of the
disease and may include:
• Corticosteroids, such as prednisone or prednisolone, to
reduce swelling.
• Diuretics, such as bumetanide (Bumex) or furosemide
(Lasix), to reduce fluid buildup in the body (edema) and
help with reducing sodium, potassium, and water. Fluid
reduction should occur slowly to avoid further kidney
damage and low blood pressure.
• Medications, such as angiotensin-converting enzyme
(ACE) inhibitors and angiotensin II receptor blockers
(ARBs), to reduce the amount of protein lost in the
urine, lower blood pressure, and slow the progress of the
disease.
• In rare cases, salt-free albumin given through a vein
(IV). Albumin helps remove extra fluid from the tissues.
You may need emotional support during treatment for nephrotic
syndrome. If you or your child has nephrotic syndrome and you
are having a hard time handling treatment or the severity of your
child's condition, talking with a doctor or seeking counseling may
help.
First treatments can last from 6 to 15 weeks, often longer in
adults.4 Depending on how severe your symptoms are or whether
they return, ongoing treatment may be necessary for months to
years, or even the rest of your life.
Ongoing treatment
Ongoing treatment for nephrotic syndrome and complications of
the disease include:
• Daily or alternate-day prednisone, if nephrotic
syndrome returns.
• Cyclophosphamide, cyclosporine, or CellCept, when
treatment with corticosteroids is not successful.
• Steps to lower blood pressure, including medication, a
healthier diet, and exercise. Untreated high blood
pressure increases your risk for stroke or heart attack.
For more information, see the topics High Blood
Pressure (Hypertension), Coronary Artery Disease, and
Stroke.
• Changes in diet to replace nutrients lost through the
urine, reduce fluid buildup in the body, and reduce the
risk of complications. Some doctors prescribe a diet that
limits protein, salt (sodium), and fats but is high in
carbohydrates. The amount of protein allowed may vary,
depending on your condition.
• Anticoagulants, such as warfarin (Coumadin) or
heparin, to treat blood clots if they form.
• Early treatment of infections with antibiotics.
• Vaccinations with a pneumococcal vaccine (What is
a PDF document?), such as Pneumovax, to prevent
infections; chickenpox (varicella) vaccines; and a yearly
flu shot. Vaccination is not recommended until nephrotic
syndrome has responded to treatment with
corticosteroids.5, 6
• Calcium and vitamin D supplements to protect your
bones and help prevent osteoporosis during long-term
corticosteroid treatment (for example, prednisone).
You can help slow the progression of kidney damage caused by
nephrotic syndrome by:
• Keeping blood pressure at less than 125/75 mm Hg with
medication, diet, and exercise. For more information,
see the topic High Blood Pressure (Hypertension).
• Keeping strict blood glucose control if you have
diabetes. For more information, see the topics Type 1
Diabetes and Type 2 Diabetes.
• Maintaining healthy levels of fats (lipids), such as
cholesterol and triglycerides. For more information, see
the topic High Cholesterol.
• Not smoking or using other tobacco products. For more
information, see the topic Quitting Tobacco Use.
• Avoiding medications that may harm the kidneys.
• Avoiding X-ray tests that use contrast material.
• Preventing coronary artery disease. Lifestyle changes
such as eating a low-fat diet, quitting smoking, and
getting regular exercise can help reduce your overall
risk of developing heart disease and stroke. For more
information, see the topic Coronary Artery Disease.
• Weighing yourself daily so that you are aware of any
rapid weight gain.
You may need emotional support during treatment for nephrotic
syndrome. If you or your child has nephrotic syndrome and you
are having a hard time handling treatment or the severity of your
child's condition, talking with a doctor or seeking counseling may
help.
Treatment if the condition gets worse
Sometimes treatment for nephrotic syndrome is unsuccessful. If
this occurs, you may develop chronic kidney disease. Your doctor
may recommend that you begin hemodialysis, peritoneal dialysis,
or consider a kidney transplant. For more information, see the
topic Chronic Kidney Disease.
Clinical trials are ongoing to test more effective medicines for the
treatment of steroid-resistant (relapsing) nephrotic syndrome. Ask
your doctor about clinical trials if treatment has not successfully
controlled your nephrotic syndrome. To participate in a clinical
trial, you may need to travel to a large treatment center.
Medications
Nephrotic syndrome is usually successfully treated with a
combination of medicines.
Medication Choices
Medicines to treat nephrotic syndrome include:
 • Corticosteroids, such as prednisone or prednisolone, to
reduce swelling.
• Albumin, to restore blood volume.
• Diuretics, such as bumetanide or furosemide, to help
maintain fluid balance.
• Cyclophosphamide, cyclosporine, or CellCept, when
treatment with corticosteroids is not successful.
Most children are successfully treated with corticosteroids,
though relapses are common.7
Clinical trials are ongoing to test more effective medicines for the
treatment of steroid-resistant (relapsing) nephrotic syndrome. Ask
your doctor about information on clinical trials if treatment has
not successfully controlled your nephrotic syndrome. To
participate in a clinical trial, you may need to travel to a large
treatment center.
What To Think About
Most children who have nephrotic syndrome do well with
treatment and have a normal life expectancy. Children older than
age 12 at the time of diagnosis and adults who also have diabetes
or high blood pressure do not respond as well to treatment as do
children younger than 12.
Surgery
Surgery is not used to treat nephrotic syndrome. But if treatment
is not controlling your condition and you have developed chronic
kidney disease, your doctor may recommend a kidney transplant.
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Living with nephrotic syndrome:
• Should I reduce my salt intake?
• What can I do about my dry skin?
• What medicines should I avoid if I have nephrotic
syndrome?
Reducing your salt intake
It's often a good idea to reduce the amount of salt (sodium) in
your diet if you are diagnosed with certain conditions, such as
nephrotic syndrome, Cushing's syndrome, or heart failure.
Exactly how much daily salt is needed varies from person to
person.
Try some of these tips for lowering your salt intake:
• Flavor your foods with herbs and spices such as basil,
tarragon, or mint, or use salt-free sauces or lemon juice.
Try plain or flavored vinegar to flavor soups and stews.
Use about 1 tsp (4.9 mL) of vinegar for every 2 qt (1.9
L) of soup or stew.
• Choose fresh or frozen vegetables and fruits.
• Include more grains and beans in your diet.
• Choose foods marked “low-salt” or “low-sodium.”
Foods labeled this way must contain less than 140 mg of
sodium per serving.
• Do not use salt during cooking or at the table. Talk to
your health professional before using a salt substitute. It
may not be recommended, because most salt substitutes
contain potassium. Potassium can build up in the bodies
of people with kidney disease and cause severe illnesses
and even death.
• Avoid fast foods, prepackaged foods (such as TV
dinners and frozen entrees), and processed foods (such
as lunch meats and cheeses). Always check the serving
size on processed food. Eating more than the single
serving size may increase your sodium beyond a healthy
level.
• Avoid foods that contain monosodium glutamate (MSG)
and disodium phosphate.
• Avoid canned foods.
• Avoid salted ham, potato chips, pretzels, salted nuts, and
other salty snack foods.
Skin care when you have nephrotic syndrome
Nephrotic syndrome may cause your skin to become dry and
fragile, break open easily, bleed, and become infected. You can
prevent or reduce additional skin problems by using these tips:
• Check for areas that are red, warm to the touch, or
bleeding. Use a mirror or ask someone else to look at
your feet, back, or buttocks if you have trouble seeing
these areas.
• Avoid excessive bathing. Soap and water deplete your
skin of the essential oils that hold in moisture.
o Limit showers or baths to 10 minutes.
o Do not use hot water to bathe.
o Use bath oils in the tub. (Be careful, because
bath oil will make the tub slippery.)
o Use mild soaps, such as Dove or Cetaphil,
especially under the arms and in the genital
area.
• Use a moisturizing lotion after you bathe, or more
frequently if your skin tends to become dry easily. Avoid
products that contain alcohol, because they can dry your
skin.
• Avoid scratching your skin or rubbing it vigorously with
towels. If itching is a problem, see relief from itching.
• Avoid chemicals that may irritate the skin, such as
rubbing alcohol, soaps, detergents, or solvents.
• Use baking soda or cornstarch powders on areas of your
skin that become irritated. Avoid powders that contain
talc. Breathing in talc can irritate your lungs.
• Avoid tight-fitting clothes and shoes. Wear natural-fiber
clothes that allow moisture to evaporate from your skin.
Avoid wearing wool and acrylic fabrics next to your
skin.
Medications that can cause acute renal failure
Many medications can cause acute renal failure. Examples
include:
• Antibiotics, such as aminoglycosides, cephalosporins,
amphotericin B, bacitracin, acyclovir, and vancomycin.
• Blood pressure medicines called ACE inhibitors (such
as captopril and ramipril) and angiotensin receptor
blockers (ARBs).
• Medicines used for cancer treatment (chemotherapy),
such as cisplatin, carboplatin, and methotrexate.
• Dyes (contrast media) used in medical imaging tests.
• Illegal drugs, such as heroin and methamphetamine.
• Medicines used to treat HIV (protease inhibitors), such
as indinavir and ritonavir.
• Nonsteroidal anti-inflammatory drugs, such as
ibuprofen, ketoprofen, or aspirin.
• Ulcer medicines such as cimetidine (Tagamet).
Other chemicals, such as insecticides, herbicides, and ethylene
glycol, can also cause acute renal failure.
http://health.yahoo.com/urinary-overview/nephrotic-syndrome-
topic-overview/healthwise--aa124985.html
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Childhood Nephrotic Syndrome
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 blood-filtering 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.
Hope Through Research
The National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) conducts and supports research to help many
kinds of people with kidney disease, including children. NIDDK's
Division of Kidney, Urologic, and Hematologic Diseases
maintains the Pediatric Nephrology Program, which supports
research into the causes, treatment, and prevention of kidney
diseases in children, including minimal change disease,
congenital nephrotic syndrome, primary glomerular disease, and
postinfection glomerulonephritis.
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http://www.patient.co.uk/showdoc/27000748/
Nephrotic Syndrome
Nephrotic syndrome is a condition where the 'filters' in the
kidney become 'leaky' and large amounts of protein leak from
your blood into your urine. The main symptom is oedema
(fluid retention) which is mainly due to the low protein level
in the blood. Various diseases can cause nephrotic syndrome,
some more serious than others. Treatment and outcome
(prognosis) vary, depending on the cause. The common cause
in children (minimal change disease) usually responds very
well to treatment.
Understanding kidneys and urine
The kidneys clear waste materials from the body and maintain a
normal balance of fluids and chemicals in the body. The two
kidneys lie to the sides of the upper abdomen, behind the
intestines, and either side of the spine. Each kidney is about the
size of a large orange, but bean-shaped.
A large renal artery takes blood to each kidney. The artery divides
into many tiny blood vessels (capillaries) throughout the kidney.
In the outer part of the kidneys tiny blood vessels cluster together
to form structures called glomeruli.
Each glomerulus is like a filter. The structure of the glomerulus
allows waste products and some water and salt to pass from the
blood into a tiny channel called a tubule, while keeping blood
cells and protein in the bloodstream. Each glomerulus and tubule
is called a 'nephron'. There are about one million nephrons in each
kidney.
As the waste products, water and salts pass along the tubule there
is a complex adjustment of the content. For example, some water
and salts may be absorbed back into the bloodstream, depending
on the current level of water and salt in your blood. Tiny blood
vessels next to each tubule enable this 'fine tuning' of the transfer
of water and salts between the tubules and the blood.
The liquid that remains at the end of each tubule is called urine.
This drains into larger channels (ducts) which drain into the renal
pelvis (the inner part of the kidney). From the renal pelvis the
urine passes down a tube called a ureter which goes from each
kidney to the bladder. Urine is stored in the bladder until it is
passed out through the urethra when we go to the toilet. The
'cleaned' (filtered) blood from each kidney collects into a large
renal vein which takes the blood back towards the heart.
What is nephrotic syndrome?
Nephrotic syndrome is not a single disease - it is a syndrome. A
syndrome is a set of symptoms and signs that tend to occur
together, and which can be caused by one or more different
diseases. Nephrotic syndrome can be caused by many different
diseases, some more serious than others.
The 'hallmark' or main feature of nephrotic syndrome is that the
kidneys leak a lot of protein. Normally, urine contains virtually no
protein. In nephrotic syndrome the urine contains large amounts
of protein. What happens is that filters in the kidneys (the
glomeruli) become 'leaky' and protein, instead of remaining in the
blood, leaks out into the urine. Protein in the urine is called
'proteinuria.'
The other key features of nephrotic syndrome are:
• A low level of protein in the blood as a result of protein
loss in the urine. Although there is a drop in many of the
proteins normally found in the bloodstream, the main
protein that leaks from the blood into the urine is called
albumin. A low blood level of albumin is a main feature
of nephrotic syndrome.
• Fluid retention (oedema). This is a consequence of the
low level of albumin in the bloodstream, and other
complex factors not fully understood.
• A high blood level of cholesterol and other lipids (fats).
This is due to the change in the balance of various
protein levels in the blood due to the protein leakage.
• Normal kidney function, at least initially. This means
that the 'waste clearing' function of the kidneys is not
affected - at least not at first. However, some of the
conditions that cause nephrotic syndrome can progress
to cause kidney failure.
Other typical symptoms and signs of nephrotic syndrome are
discussed later.
What are the causes of nephrotic syndrome?
Various diseases can affect the glomeruli and can result in
nephrotic syndrome. The following gives a brief description of
the main ones.
Minimal change disease
The name 'minimal change' comes from the fact that there is
virtually no change detectable in the glomeruli if a sample of
kidney is looked at under the microscope. Although the glomeruli
look normal under the microscope, there seems to be some minor
change in the glomeruli that allows leakage of protein. The cause
of minimal change disease is not clear. It probably has something
to do with a slight change in the immune system, or perhaps a
'reaction' of parts of the immune system to some unidentified
factor.
Minimal change disease causes about 9 in 10 cases of nephrotic
syndrome in children under the age of five years. It causes about
1 in 5 cases of nephrotic syndrome in adults. It usually responds
well to treatment with steroid medication and does not cause
kidney failure in most cases.
Membranous nephropathy
This is sometimes called membranous nephritis or membranous
glomerulonephritis. It is a common cause of nephrotic syndrome
in adults. It is an uncommon cause in children. In this condition
there is some thickening of the membrane in the glomeruli (the
'filter' of the glomeruli) which makes the glomeruli 'leaky' to
protein. The thickening can be seen under a microscope if a
sample of kidney is taken for testing. In many cases, the cause or
reason for this change to occur in the glomeruli is not known.
However, there are various conditions that can result in
membranous nephropathy developing. For example, an abnormal
reaction of the immune system to some infections or drugs can
cause this disease.
Focal segmental glomerulosclerosis (FSGS)
This is a condition where small 'scars' (sclerosis) develop on
some glomeruli. The cause is unknown in most cases. However, a
reaction of the immune system to 'something' or to various
different things is thought to be the cause. FSGS accounts for up
to 1 in 10 cases of nephrotic syndrome in children but a higher
percentage of cases in adults.
Other disorders of the glomeruli
There are various other uncommon kidney disorders which
primarily affect the glomeruli that can result in nephrotic
syndrome. For example, membranoproliferative
glomerulonephritis, mesangial proliferative glomerulonephritis,
fibrillary glomerulosclerosis, diffuse mesangial sclerosis, IgM
mesangial nephropathy. The cause of some of these conditions is
not clear. However, some are probably caused by reactions of the
immune system that cause damage to specific parts of the
glomeruli or nearby cells.
Other general conditions
A complication of some other more generalised conditions can
cause damage to glomeruli resulting in nephrotic syndrome. For
example, nephrotic syndrome is a possible complication of
diabetes, SLE (systemic lupus erythematosus), rheumatoid
arthritis, polyarteritis nodosa, Henoch-Schönlein purpura, various
infections, various cancers, amyloidosis. It can also occur as a
side effect of certain drugs, and as a consequence of various
poisons or toxins.
What are the symptoms of nephrotic syndrome?
Oedema ('fluid retention') is a main symptom
Oedema occurs when fluid leaks out of blood vessels into the
body tissues. This causes swelling and 'puffiness' of the affected
tissues. The swelling is usually painless, but the swollen tissues
may feel 'tight'. With children, the face is often affected first and
the face becomes 'puffy'. With adults, the ankles often become
swollen at first (as gravity helps fluid to pool in the lower legs).
As oedema becomes worse, the calves, then the thighs may
become swollen.
In severe cases of nephrotic syndrome, the oedema can become
extensive. Fluid may accumulate in the lower back, the arms, in
the abdominal cavity (ascites) or in the chest between the lungs
and the chest wall (pleural effusion).
The main reason why fluid leaks out from the blood vessels and
into the body's tissues with nephrotic syndrome is because of a
low level of protein in the blood. As protein is lost from the body
in the urine, the body makes more protein in the liver which
passes into the bloodstream. However, in time the amount made
by the liver cannot keep up with the amount lost by the leaky
kidneys, and so the blood level of protein goes down. If the blood
level of protein is low then fluid tends to leak out of the blood
vessels into the body tissues. (Protein and other chemicals in the
blood exert an 'osmotic pressure' which tends to pull fluid into the
blood vessels. If the concentration of protein reduces, the osmotic
pressure reduces, and fluid leaks out.)
Note: nephrotic syndrome is just one cause of oedema. There are
other causes of oedema. For example, heart failure is the most
common cause of oedema, especially in older people.
Other symptoms
Other symptoms that may develop include:
• Your urine may appear frothy.
• Tiredness, lethargy and being off your food.
• If the nephrotic syndrome persists for a long time then
you may develop wasting of your muscles, and your
nails may become white.
• Depending on the cause of the nephrotic syndrome, you
may also have other symptoms. For example, if you
have nephrotic syndrome as a complication of
rheumatoid arthritis you may have a range of other
symptoms caused by the arthritis. Some conditions of
the kidney can cause high blood pressure and/or kidney
failure.
What are the possible complications?
Possible complications from nephrotic syndrome itself
Complications can be caused by nephrotic syndrome itself due to
the loss of normal proteins from the blood. These include:
• An increased risk of developing infections. This is
because you can lose antibodies in the urine.
(Antibodies are proteins that help to defend the body
from infection.) Any signs of infection (sore throat,
fever, etc) should be taken seriously and reported
promptly to a doctor.
• An increased risk of developing blood clots in the blood
vessels (thrombosis). For example, a deep vein
thrombosis (DVT) in a leg. This can cause pain,
swelling and other complications. The reason for this is
because there can be a change in the balance of proteins
in the blood that protect against blood clots forming.
• A high cholesterol level. If this persists long-term it is a
risk factor for developing heart disease.
• Increased risk of vitamin D deficiency which may lead
to bone problems. This is due to loss of vitamin D-
binding protein from the bloodstream.
• Anaemia. This is due to loss of proteins that help to
carry iron around in the bloodstream. You need iron to
make red blood cells and to prevent anaemia.
Depending on the duration and severity of the nephrotic
syndrome, you may be advised to take treatment to help prevent
or counter these possible complications.
Possible complications from the cause of the nephrotic
syndrome
You may also have various complications from the underlying
condition which has caused the nephrotic syndrome. For example:
• One of the most common complications of kidney
disorders is high blood pressure.
• Some kidney disorders lead to kidney failure.
• Some disorders (for example, diabetes, rheumatoid
arthritis, etc) that cause nephrotic syndrome can have
various other symptoms and complications.
Possible complications from treatment
Often, the treatment of nephrotic syndrome requires a course of
steroid medicines or other medicines to suppress the immune
system (see below). Some people develop side-effects and
complications from these treatments, especially if the treatment
requires high doses, or is for long periods.
Do I need any tests?
To confirm nephrotic syndrome
A simple 'dipstick' test of your urine can confirm that it contains a
lot of protein. The amount of protein lost can be measured by
more detailed urine and blood tests. A low blood level of albumin
combined with a lot of protein found in the urine usually confirms
that you have nephrotic syndrome.
To find the cause of the nephrotic syndrome
A range of blood tests may be done to try and identify the cause
of the nephrotic syndrome. A kidney biopsy may also be done. A
kidney biopsy is when a small sample of tissue is removed from a
kidney. The sample is looked at under a microscope, or tested in
other ways. This is often the most important test to clarify the
cause of the nephrotic syndrome in adults. However, a biopsy is
not usually done in children under the age of eight years. This is
because most cases in young children are due to minimal change
disease. A trial of treatment is usually advised first, and a biopsy
done only if treatment does not work. (There are some exceptions
to this general rule.)
To check on the function of the kidneys
Blood tests can check on the function of the kidneys. That is, how
well they are clearing waste products from the bloodstream.
What is the treatment for nephrotic syndrome?
Treatment of oedema
Diuretics ('water tablets') help to clear the body of oedema.
Diuretics work by acting on the cells in the kidney tubules to
make them pass out more water rather than 'reabsorbing' water
back into the bloodstream. So, you pass out more urine. The
excess fluid in the body's tissues then passes back into the
bloodstream to keep the blood volume up to normal. Your doctor
may also advise you to limit the amount of salt in your diet to try
and limit oedema.
Treatment of high blood pressure
Many people with kidney disorders have high blood pressure. If
you develop high blood pressure then treatment is usually advised
to bring your blood pressure down. A medicine called an ACE
inhibitor is commonly used for this.
Treatment of the underlying cause
As mentioned, there are many causes of nephrotic syndrome. The
treatment depends on the underlying cause. Some causes are more
serious than others, some causes can be treated more easily than
others.
For example, treatment for minimal change disease usually works
well to stop the leak of protein from the kidneys. The usual
treatment for minimal change disease is a course of steroid
medication which may last several months. In some cases, this is
a 'one off' treatment and the disease does not return. In some
cases of minimal change disease, the disease recurs from time to
time which needs repeated courses of steroid medication.
Steroids or other medicines called 'immunosuppressants' may be
used to reduce inflammation and abnormal immune responses in
various diseases that cause nephrotic syndrome. Your doctor will
advise on the treatment options for each situation.
What is the outlook (prognosis)?
The outlook depends on the cause. For example, the most
common cause of nephrotic syndrome in children (minimal
change disease) usually responds well to treatment, and generally
has a good outlook. The outlook is less good with some other
conditions. Your doctor will be able to give an outlook for your
particular condition.
Further help and information
Nephrotic Syndrome in Children Support Group
94 Bulford, Wellington, Somerset, TA21 8DH
Tel: 01823 652 886 Web: www.nephrotic.co.uk
Provides information for parents with affected children as well as
to GPs and other health professionals.
Membranous Glomerulonephritis Support Group
Web: www.mgninfo.co.uk
A UK based group for sufferers of membranous
glomerulonephritis (membranous nephropathy).
National Kidney Federation
6 Stanley Street, Worksop, Nottinghamshire, S81 7HX
Helpline: 0845 601 0209 Web: www.kidney.org.uk
A national kidney charity run by patients, for patients.
References
• Travis L, eMedicine, Nephrotic Syndrome, 2005;
Paediatric overview
• Agraharkar M, Gala G, eMedicine, Nephrotic
Syndrome, 2007.
• Hodson E, Willis N, Craig J; Corticosteroid therapy for
nephrotic syndrome in children. Cochrane Database
Syst Rev. 2007 Oct 17;(4):CD001533. [abstract]
***********************
http://www.patient.co.uk/showdoc/40000676/
Nephrotic Syndrome
Description
Nephrotic syndrome is a pattern of presentation of renal disease,
rather than a single pathological entity or diagnosis. Nephrotic
syndrome is also known as nephrosis and is defined by the
presence of nephrotic-range proteinuria, oedema, hyperlipidemia,
and hypoalbuminaemia. It has serious complications and must be
on the differential diagnosis for any patient presenting with new
onset oedema.1
Pathophysiology
It comprises the following elements:
Features of the nephrotic syndrome:
• Glomerular dysfunction leading to excessive urinary
protein excretion (formerly defined as >3.5 g/day but
there appears to be individual variation around this cut-
off figure)
• Hypoalbuminaemia as a result of urinary protein loss
(albumin levels usually in range <25–30 g/l)
• Peripheral oedema due to hypoalbuminaemia
• Hypercholesterolaemia/dyslipidaemia
• Normal detoxifying renal function, at least initially
The primary abnormality in nephrotic syndrome is thought to be
loss of a layer of negatively-charged heparin sulphate within the
glomerular basement membrane, that allows the increased
passage of large amounts of low-molecular weight anionic
proteins during ultrafiltration. However, recent research has
shown that the loss of albumin in the urine may not be due to
excessive filtration across the glomerular basement membrane as
was previously supposed, rather a failure to reabsorb albumin
after its ultrafiltration. It appears that renal disease may cause an
impairment of the ability of cells in the proximal renal tubules to
endocytose albumin that has been filtered across the glomeruli,
and deliver it back into the blood supply around the renal
tubules.2
Oedema is thought to occur due to the loss of plasma oncotic
pressure secondary to hypoalbuminaemia, causing accumulation
of fluid in the extracellular space; a decrease in intravascular
volume is thought to cause renal hypoperfusion further enhancing
salt and water retention. However, this model cannot fully explain
all the pathophysiological and clinical features of the nephrotic
syndrome and other, as yet unelucidated, intra- and extra-renal
mechanisms may be responsible for the combination of
biochemical and clinical features seen in nephrotic syndrome.
Hypercholesterolaemia is thought to be caused by:
• Stimulation of the liver to increase synthesis of all
plasma proteins (including the lipoproteins), due to their
low level in the blood.
• Reduction of lipoprotein catabolism due to reduced
levels of lipoprotein lipase in blood.
Other consequences of nephrotic syndrome:3
• Decreased resistance to infections due to urinary
immunoglobulin loss.
• Increased risk of arterial and venous thrombosis due to
 loss of anti-thrombin III and plasminogen in the urine,
combined with an increase in hepatic synthesis of
clotting factors.
• Increased risk of osteitis fibrosa cystica and osteomalacia
due to loss of vitamin D-binding protein and its
complexes in the urine, through a combination of
calcium malabsorption and secondary
hyperparathyroidism.
Epidemiology
Nephrotic syndrome is a relatively rare but important
manifestation of kidney disease.
In the US, its annual incidence among children is reported to be
2–7 cases per 100,000.3 Incidence varies among adults depending
on the incidence of underlying causes for the condition,
particularly diabetes mellitus. Nephrotic syndrome has an
incidence of around three new cases per 100 000 each year in
adults.1
Commoner causes of the nephrotic syndrome
It can be caused by a wide range of primary (idiopathic) and
secondary glomerular diseases.
Primary renal diseases
• Minimal-change nephrotic syndrome (~85% of
childhood cases)
• Focal segmental glomerulosclerosis (~9% of childhood
cases)
• Mesangial proliferative glomerulonephritis (~2% of
childhood cases)
• Membranous nephropathy (~3% of childhood cases)
• Membranoproliferative glomerulonephritis
Secondary renal diseases
• Postinfectious causes, e.g. Group-A beta-haemolytic
streptococci, TB, malaria, syphilis, viruses such as VZV,
HBV, HIV, infectious mononucleosis
• Collagen vascular diseases, e.g. SLE, rheumatoid
arthritis, polyarteritis nodosa, Henoch-Schönlein
purpura, vasculitides
• Metabolic diseases, e.g. diabetes mellitus, amyloidosis
• Inherited disease, e.g. Alport's syndrome, hereditary
nephritis, sickle cell disease
• Malignant disease, e.g. multiple myeloma, leukaemia,
lymphoma, carcinoma of breast/lung/colon/stomach
• Medications, e.g. NSAIDs, captopril, lithium, gold,
diamorphine, interferon-alpha, penicillamine,
probenecid and many others
• Toxins, e.g. bee sting, snake bites, phytotoxins
• Pregnancy, e.g. pre-eclampsia
• Transplant rejection
Presentation
Symptoms
• In children facial swelling is a common presenting
feature, with periorbital oedema often being the first
evidence that something is wrong; oedema may progress
to involve the whole body.
• Adults tend to present with peripheral oedema affecting
the ankles and legs, which may progress to involve the
whole body.
• Some patients may notice frothiness of their urine.
• Hypercoagulability may manifest as venous or arterial
thrombosis, e.g. DVT, MI.
• Recurrent infections and/or general fatigue, lethargy,
poor appetite, weakness or episodic abdominal pain may
cause presentation to a doctor.
Signs
Clinical signs of nephrotic syndrome:1
• Oedema
o Periorbital oedema
o Lower limb oedema
o Oedema of the genitals
o Ascites
• Low albumin
o Tiredness
o Leukonychia
• Breathlessness
o Pleural effusion
o Fluid overload (high jugular venous pressure)
o Acute renal failure
• Breathlessness with chest pain
o Thromboemboli
• Dyslipidaemia
o Eruptive xanthomata
o Xanthelasmata
• Other
o Frothy urine
• Oedema of dependent parts or generalised oedema are
the main clinical findings.
• Facial oedema may be found in children.
• Occasionally, severely hypoalbuminaemic cases may
have pleural effusions or ascites.
• Urinalysis will reveal gross proteinuria.
• Hypertension and haematuria are not usually found but
may affect a minority of cases.
Investigations
The aim of investigations is to find the underlying cause, direct
future management, establish a baseline of severity and monitor
response to treatment. The initial sequence is:1
• Confirm proteinuria present: urine dipstick positive
• Check for concomitant invisible (microscopic)
haematuria: urine dipstick positive
• Exclude urine infection:urine microscopy/culture and
sensitivity
• Measure amount of proteinuria:
o Early morning urinary protein:creatinine ratio
or albumin:creatinine ratio (mg/mmol)
o Typically >300-350 mg/mmol in nephrotic
syndrome
• Basic blood testing:
o Full blood count and coagulation screen
o Renal function including plasma creatinine and
estimated glomerular filtration rate
o Liver function tests to exclude concomitant
liver pathology
o Bone profile—corrected (for albumin) plasma
calcium
• Check for other systemic diseases and causes of
nephrotic syndrome:
o C reactive protein and erythrocyte
sedimentation rate
o Glucose
o Immunoglobulins, serum and urine
electrophoresis
o Autoimmune screen if an underlying
autoimmune disease is suspected—antinuclear
antibody (ANA), anti-double stranded DNA
 antibody (dsDNA), and complement values
(C3 and C4)
o Hepatitis B and C and HIV (after obtaining
informed consent)
• Chest x ray and abdominal or renal ultrasound scan
(especially if renal function is abnormal):
o To check for pleural effusion or ascites
o To check for the presence of two kidneys, their
size and shape, and the absence of obstruction
o To exclude malignancy and exclude other
causes of oedema
• Be vigilant for complications such as thromboembolism:
o Doppler ultrasound of leg veins in suspected
deep vein thrombosis
o Abdominal ultrasound, renal vein Doppler
scan, venography of the inferior vena cava,
computed tomography and magnetic resonance
imaging of the abdomen if renal vein
thrombosis is suspected
o V/Q nuclear medicine lung scan, computed
tomography pulmonary angiography for
pulmonary embolism
• Investigate the underlying renal and systemic cause of
nephrotic syndrome:
o Renal biopsy under ultrasound (to assess size
and structural condition of kidneys)
o Obstructed or small kidneys may
contraindicate renal biopsy
o Make histological preparations for light
microscopy, immunofluoresence or
immunoperoxidase, electron microscopy
Most cases will require renal biopsy to determine the exact
underlying cause of the condition; children under 8 years old
usually have minimal-change nephrotic syndrome and so may be
spared this investigation, especially if they are steroid-responsive.
Adults with an obvious cause (e.g. diabetes with evidence of
other complications) may be spared a biopsy at the discretion of a
renal specialist. Other investigations to diagnose less usual causes
such as abdominal fat/gingival biopsy to detect amyloidosis may
be needed in place of or in addition to a renal biopsy.
Diagnosis
Diagnostic criteria for nephrotic syndrome:1
• Proteinuria greater than 3-3.5 g/24 hour or spot urine
protein:creatinine ratio of >300-350 mg/mmol
• Serum albumin <25 g/l
• Clinical evidence of peripheral oedema
• Severe hyperlipidaemia (total cholesterol often >10
mmol/l) is often present
Initial management
Initial management should focus on investigating the cause,
identifying complications, and managing the symptoms of the
disease.1 All patients should be referred to a nephrologist for
further investigation, which often includes a renal biopsy.1
Indications for acute admission include:
• Severe generalised oedema, particularly if pleural
effusion/oedema causing respiratory compromise
• Tense scrotal/labial oedema
• Complications of the nephrotic state (e.g. sepsis,
pneumonia, MI, DVT, growth failure)
• Inability to comply with therapy/inability to cope with
condition in family/independently
• Any features of a possible nephritic syndrome such as
haematuria, hypertension and impaired renal function
parameters
• Most cases do not require acute hospitalisation.
• Reduce salt intake in diet (avoid processed foods and
adding salt to food).
• Give diet with adequate calorific intake and sufficient
protein content (1–2 g/kg daily).4
• Hyperlipidaemia – does not initially require therapy but
may do so if prolonged.4
• Fluid restriction is not usually necessary (if severe
enough to need this then may need admission).4
• Referral to a renal service for urgent outpatient
assessment is advisable, to confirm the mode of
presentation and direct any future investigations/therapy.
• Oedema is treated through diuretic therapy with
furosemide (~1 mg/kg/day) ± spironolactone (~2
mg/kg/day).
• Check weight regularly to assess response to diuretics
and ensure fluid retention is not worsening, or that
patient is over-diuresed.
• Patients with very low albumin levels may not respond
to diuretics and may require admission to receive
intravenous albumin therapy.
• Some children with severe oedema may be prescribed
antibiotic prophylaxis against infection and this should
usually be on the advice of a renal specialist.
• Most children will have minimal-change nephrotic
syndrome and usually respond to a trial of steroid
therapy under the direction of a renal specialist.
• Other forms of nephrotic syndrome are less treatment
responsive; ACE inhibitors are frequently used in adults
to some effect.
• In children who do not respond to steroids, and in some
adults, treatment may be with other immunomodulatory
drugs such as cyclophosphamide, ciclosporin,
tacrolimus and levamisole.4
Prognosis
• This is highly variable depending on the underlying
cause.
• Congenital nephrotic syndrome usually carries a very
poor prognosis.
• Outlook for the vast majority of children with minimal-
change nephrotic syndrome is excellent; response to
steroids is the norm, although there may be relapses and
a need to use alternative immunomodulatory drugs.
Since the introduction of corticosteroids, the overall
mortality of primary nephrotic syndrome has decreased
dramatically from over 50% to approximately 2-5%.
• Adult prognosis is variable and largely related to the
underlying cause, its severity, progression and response
to any treatment used to modify it.
Document references
1. Hull RP, Goldsmith DJ; Nephrotic syndrome in adults.
BMJ. 2008 May 24;336(7654):1185-9.
2. Russo LM, Sandoval RM, McKee M, et al; The normal
kidney filters nephrotic levels of albumin retrieved by
proximal tubule cells: Retrieval is disrupted in nephrotic
states. Kidney Int. 2007 Jan 17;. [abstract]
3. Agraharkar M, Gala G, Gangakhedkar AK; Nephrotic
Syndrome. eMedicine, February 2007.
4. Lane J; Nephrotic Syndrome. eMedicine, Dec 2008;
Paediatric overview.