Nephrotic syndrome and the immune system

Studies show that different types of nephrotic syndrome are linked to the immune system, which normally protects the body against disease and infection. Many germs – including bacteria and viruses – can make us sick if they get into the body. The immune system can kill these germs. However, if the immune system is not working properly, it can start to cause problems. In nephrotic syndrome, the immune system can interfere with the tiny filters in the kidneys, the glomeruli.

The immune system protects the body against germs such as bacteria and viruses that can cause illness. These germs can enter the body in lots of ways, such as by the nose and throat or the urinary system. If we get a cold or flu, this means that a virus germ has got into the body and started to infect some of our body’s cells.

Germs have special ‘markers’ that are different from the markers on our own body’s cells. This means that the immune system can recognise that they are germs and kill them. We often feel sick for a few days or a few weeks while this is happening.

Parts of the immune system

The immune system has many different ways to protect the body against disease. Some of the parts include those listed below.

  • White blood cells are living cells in the blood. Often, the number of white blood cells found in a blood test can give information about someone’s immune system. The two main types of white blood cells in the immune system are neutrophils and lymphocytes.
  • Antibodies or immunoglobulins recognise the germs that have come into the body, and can bind (stick) to them. There are five types: immunoglobulin A (IgA), immunoglobulin D (IgD), immunoglobulin E (IgE), immunoglobulin G (IgG) and immunoglobulin M (IgM).
  • The complement system is made up of other proteins that float in the blood. These proteins work with (complement) other parts of the immune system to help kill germs or cells infected by germs. Normally, the body controls when complement is activated, so it does not attack the body itself.

When the immune system does not work properly

Sometimes the immune system does not work as expected and can cause problems. For example, sometimes the immune system cannot recognise the body’s own cells and may attack them as if they were invaders like germs.

Will it affect other family members?

It is very rare for nephrotic syndrome to run in families. If one of your children has nephrotic syndrome, it is not likely that another of your children or another family member will get it. However, a few types may run in families.

Why nephrotic syndrome happens

The name nephrotic syndrome can be broken down:

  • nephrotic – to do with the kidney
  • syndrome – a set of symptoms and signs.

How the kidney works

Inside each kidney, there are about one million nephrons. Each nephron is made up of a glomerulus (when we talk about more than one glomerulus, we say glomeruli), and a renal tubule.

  • Each glomerulus acts like a sieve, helping to remove extra water and waste from the body, and holding on to blood cells and protein, which the body needs.
  • Blood flows into the kidneys and to each glomerulus.
  • Most of the water and some other substances in the blood pass through the glomeruli.
  • This liquid flows into the renal tubule. Most of this liquid moves back into the bloodstream.
  • The rest of it becomes urine.
  • The urine leaves the kidney by the ureters and goes into the bladder, where it is stored until we are ready to go to the toilet.

Protein leak

It is important that we have the right amounts of protein in our body to stay healthy. Protein is an important part of our diet and is in most foods. When we eat protein, it is digested (broken down) in the stomach and intestines and taken into the blood.

Normally, most protein stays in the blood and does not get removed by the kidneys into the urine. This is mostly because they are too big to pass through the glomeruli.

In nephrotic syndrome, there is a change in the glomeruli. They become more leaky, and so some proteins pass through, leaving the body in urine. The main protein that leaks out is albumin which is quite a small protein and more likely to leak through the glomeruli. Albumin helps keep fluid in the blood and oedema (swelling) occurs asa result of albumin leaking into the urine.

Nephrotic syndrome: types and causes

There are different types of nephrotic syndrome, which depend on whether they can be treated by steroids. It is often not possible to find out which type your child has until after they have taken a course of steroids. Some causes of nephrotic syndrome can only be diagnosed (identified) in a kidney biopsy in which a tiny piece of one kidney is removed from the body with a needle and examined under special microscopes.

  • About 9 in 10 children with nephrotic syndrome will have a type that can be treated with steroids – this is called steroid-sensitive nephrotic syndrome (SSNS) or minimal change nephrotic syndrome (MCNS).
  • In some children the nephrotic syndrome keeps coming back, even after successful treatment with steroids – this is called frequently relapsing nephrotic syndrome.
  • A few children (about 1 in 10) have a type that cannot be treated by steroids alone – this is called steroid resistant nephrotic syndrome (SRNS) because it is “resistant” (does not respond) to steroid treatment. Focal segmental glomerulosclerosis (FSGS) and IgM nephropathy are causes of steroid-resistant nephrotic syndrome.
  • A small number of children have nephrotic syndrome because of another condition or infection that affects the kidneys.
  • Occasionally, babies are born with congenital nephrotic syndrome. These babies may have serious damage to their kidneys and will usually need intensive treatment.

Steroid-sensitive nephrotic syndrome / Minimal change nephrotic syndrome

About 9 in 10 children with nephrotic syndrome will have a type that can be treated with steroids – this is called steroid-sensitive nephrotic syndrome (SSNS) because it is “sensitive” to steroids.

Your doctor may also use the term minimal change nephrotic syndrome (MCNS) or minimal change disease (MCD). It is called this because there is minimal (very little) change to the way the kidney looks compared to a kidney that is working normally.

MCNS can only be diagnosed in a child who has a kidney biopsy. However, doctors assume the nephrotic syndrome is MCNS if the child responds to steroids and has no other risk factors.

Other names are:

  • idiopathic nephrotic syndrome (idiopathic means that the condition has no known cause)
  • childhood nephrotic syndrome (because it usually affects children).

Steroid-resistant nephrotic syndrome

A few children have a type of nephrotic syndrome that cannot be treated by steroids alone. This is called steroid-resistant nephrotic syndrome (SRNS) because it is resistant to (does not respond to) steroid treatment. Children may be more likely to have SRNS if they:

  • are very young, usually under 1 year old
  • are older teenagers
  • have a rash or pain in their joints
  • have high blood pressure (hypertension)
  • have blood in their urine that can be seen (macroscopic haematuria)
  • have reduced kidney function (their kidneys are not working properly)
  • have abnormal results in tests related to their immune system.

If your child has SRNS, it may be due to a rarer type of nephrotic syndrome that is caused by different conditions such as focal segmental glomerulosclerosis and IgM nephropathy:

Other causes of nephrotic syndrome

Other cases of nephrotic syndrome are very rare in children:

  • Glomerulonephritis: A group of conditions that cause inflammation (swelling) in the glomeruli, the tiny filters in the kidneys. Children have both protein and blood cells in their urine. There are different types of glomerulonephritis.
  • Systemic lupus erythematosus (SLE or lupus):  The immune system does not work properly and can start to damage blood vessels in many parts of the body, sometimes including the kidney.
  • Henoch-Schönlein purpura (HSP): Blood vessels in the body, including in the kidney, become inflamed (swollen), causing symptoms such as a skin rash, pain in the tummy, and pain in the arms and legs.
  • Alport syndrome: A very rare condition that runs in families, which may also be called hereditary nephritis. Children have an abnormality of the walls of the blood vessels that make up their glomeruli. They may have problems with hearing or seeing. The complications are usually more serious in boys than in girls.
  • Diabetes: Children who have diabetes are not able to control the level of sugar in their blood. If there is too much sugar in their blood, it may damage their glomeruli.
  • Infections: Some infections, including hepatitis B and malaria, can, rarely, cause nephrotic syndrome.
  • Drugs and poisons: Rarely, poisons such as the metals lead and mercury can cause nephrotic syndrome. A small number of children are affected by the medicine penicillamine, which is sometimes used to treat disease in children.

More information

  • Nephrotic syndrome: frequently relapsing

    If your child's nephrotic syndrome keeps coming back, this is said to be frequently relapsing and may need further treatment.

  • FSGS and IgM nephropathy

    These conditions cause nephrotic syndrome in children, where the kidneys leak too much protein into the urine and lead to swelling in the body.

  • Steroids and immunosuppressants

    Understand more about the steroids and immunosuppressants your child may be prescribed.