Nephrotic Syndrome

What is nephrotic syndrome?

It is the name given to a condition when large amounts of protein leak out into the
urine. Normal urine should contain almost no protein. In nephrotic syndrome the
leak is large enough so that the levels of protein in the blood fall. This page has
quite detailed information. If you want a more simple summary, go to our page
with short information on nephrotic syndrome.

What trouble does it cause?

The most obvious symptom is usually swelling of the ankles and legs. Extra fluid
may also accumulate in the abdomen and around the face, especially overnight.
In children and young adults the ankles may be less affected and the abdomen
and face more affected. Most ankle swelling is caused by other diseases ;
nephrotic syndrome is a rare cause of ankle swelling. Urine tests and blood
samples are required to prove that nephrotic syndrome is the cause. The protein
leak can sometimes make the urine frothy. Some people feel tired.
Other problems can occur in nephrotic syndrome, probably as a result of some
particular proteins that are missing because of the leak.
Patients are unusually susceptible to some
infections.
In people who have nephrotic syndrome for a
long time, cholesterol is often very high. This
Cholesterol
may increase the risk of narrowing of the
arteries unless it is treated.
Blood is more likely to clot in the veins, which
may cause thrombosis in the leg veins and
Blood
occasionally elsewhere.
clotting
Some of these may require extra treatments to
prevent them
Infections

picture awaited!

Severe swelling of the ankles in

..... and after treatment
nephrotic syndrome

What tests are necessary?

Lots of blood tests are useful. The most important test however is a renal biopsy.
This test is designed to take a small piece of kidney to look at under the
microscope. It is done with local anaesthetic and involves putting a needle into
the kidney through the back; a scanner is used to find the kidney so the test is
done in the X-ray department. More information on kidney biopsies

Can I do without a biopsy?

There are a few exceptions. In children the nephrotic syndrome is nearly always
caused by a condition that responds easily to treatment, treatment is usually
started first, and the biopsy only done if the protein leak is not cured. In diabetes,
a biopsy may not be essential if there is strong evidence that it is likely to be
related to diabetes. In adults, however many causes are possible, making a renal
biopsy important. (See Table)

Disease
Minimal change
disease
FSGS
Membranous

Comments
Most common in children usually
responds quickly to steroids
Cause is unknown in most cases, some
response to special treatment
Cause is often unknown, but may occur
with other diseases drugs and infections.
Most improve with time but some

nephropathy
MCGN

Diabetes

SLE

deteriorate, these may respond to

treatment with immunosuppression
Rare cause of nephrotic syndrome, can
be associated with other medical
conditions
Occurs as a long term complication in
some patients. More likely if blood sugar
has been poorly controlled. Excellent
control of blood pressure and treatment
with ACE inhibitors reduces the risk of
renal failure
More common in young women mainly
affecting skin and joints, SLE affecting the
kidney is rare and usually requires special
treatment

What causes nephrotic syndrome?

In most cases, we don't know the cause. Some have recognised underlying
causes such as an allergic reactions to medicines, slow infections like Hepatitis
B, and diabetes. It is divided into a number of types according to the
appearances of the kidney under the microscope. These different types respond
to treatment differently, and may mean different things for your future health.

What treatment is available?

The effects of fluid retention are managed by diuretics that force the kidney to
put out more salt and water in the urine. This is helped by restricting the amount
of salt in the diet and by avoiding excessive fluid intake. If a lot of fluid has been
retained, it is important that diuretic therapy is carefully controlled by regular
blood tests and weighing. Some patients may require to be admitted to hospital.
Diet - dietary protein should not be increased above normal. Avoiding excessive
salt is very important.
Control of blood pressure(often high in people with kidney disease) is
important in all patients. A type of blood pressure drug known as an ACE inhibitor
has been proven to be particularly good at protecting kidney function and
reducing the amount of protein in the urine. You are very likely to be prescribed
one of these. More information on high blood pressure and kidney diseases

Special treatment to prevent the complications mentioned above (infection,

high cholesterol, thrombosis) is also important, especially if the nephrotic
syndrome is likely to last for a long time.
According to the type of kidney disease diagnosed by the biopsy, treatment to
control the cause of nephrotic syndrome may be recommended:
1. Nothing: some cases of the nephrotic syndrome will improve
with time and require no special treatment. Others are known to
respond very poorly to any known treatment.
2. Steroid tablets (eg prednisolone): one form of the disease
('minimal change disease') is very sensitive to steroid treatment and
short courses of these can be used, often with great success.
Short-term use of steroids minimises their potential side-effects.
3. Immunosuppression: some of the more difficult cases are
thought to be triggered by the body's own immune system, and
treatment to control this can be used. These therapies come either
as tablets or as drips which are given in hospital. These treatments
are not commonly used because they can be toxic but they can
also be very effective in some patients.
Further information on immunosuppressive drugs used in kidney diseases is
available here.

Are there any long term complications?

In some cases there are. Some people with severe disease do not respond to
treatment. After years of heavy protein leakage, the kidneys can fail, and some
people will progress onto kidney failure with the need for dialysis or a transplant
to keep them well. The renal biopsy and other tests help to predict the likelihood
of this.

Where can I get further information?

We have not found much good general information about nephrotic syndrome on
the internet. The following causes of nephrotic syndrome have separate pages
within EdRenINFO: click on the names to read them.

Minimal change disease

FSGS (Focal Segmental GlomeruloSclerosis)
Membranous nephropathy
Diabetes

SLE

For other EdREN topics (including information on chronic renal failure, dialysis,
and transplantation) click here.
Medical staff and other healthcare workers may find the following pages useful:

Measuring proteinuria, from the EdREN handbook

Guideline on management of asymptomatic proteinuria from the GP section

Diagnosis
In addition to a physical examination and the assessment of family health history,
the following three tests are used to make a diagnosis:

Blood analysis
Urinalysis
Kidney biopsy

Blood analysis often shows high cholesterol levels and low albumin. BUN and
creatinine may or may not be elevated. If bun and creatinine are elevated the patient
has renal failure and the prognosis is worse.
Evaluation of the urine by a simple urine dipstick in the office can give preliminary
information on the amount of protein in the urine. However, this test is a qualitative
test. In order to determine the actual amount of protein in the urine, a 24-hour
quantitative test must be done, which indicates levels of protein and creatinine in the
urine. Often, a comparison of protein to creatinine based on a single sample is used
to determine 24-hour protein loss. This is helpful for quicker results or when the
patient cannot collect urine over 24 hours.
A closed kidney biopsy may be used to determine the underlying cause and extent of
disease with the exception of the following cases.

1. Children with NS most often have minimal change disease and respond well
2.

3.

to a short course of steroids. A biopsy should only be considered if they do

not show a favorable response to the steroids within 6-8 weeks.
Adult patients with a history of diabetes who have tested negative to other
disorders such as myeloma, infections, and collagen vascular diseases. It is
presumed the cause of the proteinuria is diabetic nephropathy and a kidney
biopsy is not necessary. If the duration of diabetes has been short or the
severity of the NS is profound, a kidney biopsy is considered.
Elderly patients, patients who are not expected to live long, or those for
whom immunosuppressive drug therapy is not advisable are typically not
candidates for a biopsy.

Treatment
Nonspecific treatment of nephrotic syndrome is aimed at complications like
hypertension. Specific treatment addresses underlying causes, which are determined
by kidney biopsy.
Nonspecific Treatment
Controlling hypertension is essential in reducing proteinuria. This is accomplished
with angiotensin converting enzyme (ACE-1) inhibitors. ACE-1 inhibitors are the
preferred blood pressure lowering medication because they provided added
protection to the kidneys. These drugs interfere with the production of angiotensin II
(AII), a chemical (vasoactive) produced in the body. AII causes vascular constriction,
which increases blood pressure, including pressure in the glomeruli. This causes
scarring of the kidney and exacerbates proteinuria, which accelerates the loss of
renal function. ACE-1 inhibitors encourage circulation, lower blood pressure in the
body, and decrease pressure in the glomeruli. This decreases protein spillage and
helps to delay progressive scarring of the glomeruli.
Patients with hypertension benefit from ACE-1 inhibitors, as aggressive blood
pressure control is key to protecting the kidneys and the cardiovascular system. The
goal is to lower the systolic blood pressure below 130 and the diastolic below 80.
ACE-1 inhibitors cause a dry cough in approximately 8% of patients who take them.
ACE-1 inhibitors are given in the highest dose tolerable to ensure kidney protection.
If a patient develops a cough, a new class of drugs may be used, known as
angiotensin receptor blockers (ARB). ARBs work by blocking angiotensin receptors,
which blocks the effects of angiotensin after it is produced. They offer the same
kidney protection as ACE-1 inhibitors without causing cough. If tolerable, ARBs may
be combined with an ACE-1 inhibitor for added benefit.
Treating hypercholesterolemia (high cholesterol) typically involves medication and
proper diet.
It is generally considered healthy to eat one gram of protein daily for every kilogram
of body weight; physicians usually help their patients define a diet that is appropriate
for kidney health.

Specific Treatment
Specific treatment is given for the following underlying causes of nephrotic
syndrome:

Diabetes
Glomerular disease
Minimal change disease
Renal failure

Treating minimal change disease in children usually involves the use of diuretics
to reduce edema and a corticosteroid called prednisone (Liquid Pred), which usually
resolves proteinuria in a couple of weeks. Corticosteroids heal the ongoing damage
at the level of the glomerular basement membrane (i.e., they patch the holes that
are allowing the proteins to leak through).
About 30% of children treated with prednisone have no recurrence of disease,
roughly 20% relapse after several months, and the remaining 50% relapse a short
time after discontinuing the medication.
Prognosis
The outcome of NS varies and is largely dependent on the underlying cause. Some
patients may have a spontaneous recovery not requiring any specific therapy, while
others worsen despite aggressive, specific therapy.
Complications that can arise during treatment include atherosclerosis "hardening of
the arteries" and adverse reaction to medications such as steroids. Some severe side
effects that can occur with the use of steroids include osteoporosis, cataract
development, increased risk of infection, and diabetes.