Nephrotic Syndrome

Understanding kidneys and urine

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.