Nephrotic syndrome is a condition where the glomeruli (tiny filtering units in the kidneys) do not work properly and leak a lot of protein.
The protein is lost in the urine so, in turn, 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 or puffiness. The medical term for this swelling is oedema.
How does the urinary system work?
The urinary system consists of the kidneys, ureters, the bladder and urethra. The kidneys filter the blood to remove waste products and produce urine. The urine flows from the kidneys down through the ureters to the bladder, where it is stored until we go to the toilet. It passes through another tube called the urethra to the outside when urinating (peeing).
The kidneys contain around a million tiny filtering units called glomeruli. As blood flows through the tubes in the glomerulus at pressure, waste products pass through the walls of the tubes to form urine.
Blood cells and other things such as protein cannot pass through the walls because they are too big. The urine then passes through small tubes (tubules) where fluids, salts and minerals are removed for recycling around the body before flowing to the ureters.
What are the symptoms of childhood nephrotic syndrome?
The primary problem in childhood nephrotic syndrome is in the kidney, specifically the glomeruli, causing leakage of proteins.
This can be the result of a genetic or inherited condition where the glomeruli have not developed normally or due to an over-active immune system that is targeting both kidneys.
In the long term, if the protein leak persists this can lead to a decline in kidney function with eventual kidney failure.
Initially the symptoms are caused by the loss of proteins. Proteins have a lot of very important functions in our blood. As mentioned above, they help regulate the amount of water in our blood vessels, so with proteins lost in the urine, children with nephrotic syndrome can swell up.
Proteins have many more functions. Specialised proteins called antibodies are an important part of our immune system. If antibodies are lost, children are much more likely to get infections.
Proteins also act as carriers for many substances in the blood such as hormones and lipids. Therefore, the regulation of these substances can be disturbed in nephrotic syndrome.
Proteins are also important building blocks for our bodies in general so children with nephrotic syndrome often have difficulties in growth and development.
Finally important proteins that prevent the blood from clotting are also lost in the urine. This makes children with nephrotic syndrome more prone to blood clots.
How is childhood nephrotic syndrome diagnosed?
The initial test for nephrotic syndrome is to check the child’s early morning urine (first urine sample of the day) with a dipstick. This will change colour if protein is present in his or her urine.
Blood tests will usually be needed too, both to confirm the dipstick result and to measure how well the kidneys are working to remove waste products. In some cases, a kidney biopsy may be suggested.
This is a procedure to remove a very small piece of kidney tissue to examine under a microscope. The biopsy is processed in three different ways. First of all, we look at it under a microscope. This may give us some information within a day or two. We then do special stains on the sample, which takes a bit longer, and electron microscopy, which takes longer again.
All the information gained from the urine tests, blood tests and biopsy will help identify what is causing the child’s nephrotic syndrome so that the best treatment can be suggested.
What causes childhood nephrotic syndrome?
The term ‘nephrotic syndrome’ means a collection of symptoms affecting the kidney that are often seen together.
Nephrotic syndrome can develop as a result of a variety of other kidney conditions. Some of these conditions are inherited while others develop following an infection, allergy or other disease process such as a type of vasculitis (inflammation of the blood vessels). In many circumstances it is difficult to define what actually started the process.
Nephrotic syndrome causes changes that affect both kidneys. In broad terms, these changes can be divided into three groups:
Minimal change disease (MCD). In this condition, the glomeruli are affected but these changes are so small that they cannot be seen under a regular microscope, only an electron scanning microscope.
Focal segmental glomerulosclerosis (FSGS). FSGS is not one but many different diseases. When someone has focal segmental glomerulosclerosis (FSGS), some of the glomeruli are damaged and become scarred.
Membranoproliferative glomerulonephritis (MPGN). Glomerulonephritis is the term used when the glomeruli become inflamed. Membranoproliferative glomerulonephritis (MPGN, sometimes called mesangiocapillary glomerulonephritis) is one of several forms of glomerulonephritis and one that is rather uncommon.
How common is childhood nephrotic syndrome?
Nephrotic syndrome tends to affect primary school age children. Between two and four children in every 100,000 develop nephrotic syndrome.
It is more common in children of Asian descent, although we do not yet fully understand why. MCD is the most common cause of nephrotic syndrome affecting around 78 per cent of children.
FSGS affects around eight per cent and MPGN around six per cent.
What treatments are available?
Nephrotic syndrome is mainly treated using medicines. The first line of treatment for children with MCD is a course of steroids. These work by damping down the immune system, reducing the damage to the glomeruli, which in turn, reduces the amount of protein leakage. Steroid medicines cannot be stopped suddenly without causing side effects so towards the end of the course (or if it is clear that they are not controlling the symptoms) the dosage is gradually reduced.
In around 80 per cent of children, this first course of treatment stops the symptoms of protein leakage. However, about 75 per cent of these children have a relapse (the symptoms come back) later.
Children who have FSGS or MPGN are also started on a course of steroids, although in many cases, this is not successful, so additional medicines need to be used.
If a child does not respond to steroids, another medicine called levamisole will be used alongside the steroids. Other medicines that will be suggested if the symptoms do not respond to steroids and levamisole include cyclophosphamide, ciclosporin, tacrolimus and mycophenolate mofetil (MMF).
These medicines are immunosuppressant medicines, that is, they damp down the immune system. They are stronger than steroid medicines and need careful handling. If your child is likely to be taking these medicines, we will explain about how to give them before you go home.
Another medicine that may be considered is called rituximab. This is a relatively new medicine which works on the immune system. It removes some of the white blood cells in the body, called B cells, that are thought to play an important role in your child’s illness. Decisions about whether to try rituximab are made after discussion with you, on an individual basis.
What is the outlook for children with nephrotic syndrome?
Relapses tend to occur less frequently as your child grows older and he or she is likely to stop having relapses by adulthood.
As a general rule, if there is no protein in your child’s urine for five years, he or she is unlikely to have a relapse.
There is little risk of kidney failure with MCD that responds to steroid treatment.
Other kidney conditions, such as FSGS and MPGN have a variable outlook, with a small proportion of children developing permanent kidney damage.