Nephrotic syndrome is a condition where the kidney's filtering units, the glomeruli, 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. Nephrotic syndrome occurring in the first three months of life is called congenital (present at birth) nephrotic syndrome.
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 causes congenital nephrotic syndrome?
Congenital nephrotic syndrome can be associated with infections that occurred during pregnancy. However, in pregnancies that have been monitored regularly, this is very rare, as testing for these infections is part of routine pregnancy care. Sometimes, a cause cannot be established. However, in the vast majority of cases, this condition is inherited. That means there is a mistake in one of the genes that is responsible for making the components of the glomeruli, making them leaky.
How is it inherited?
Human beings have about 20,000 to 30,000 different genes, each of which has a function in making an individual person. The genes are arranged on 23 pairs of chromosomes (one of the pair from each parent). We can think of these chromosomes as books containing our genetic information. With each generation, the books are copied to pass on the genetic information. Over time, many “spelling mistakes” (mutations) have accumulated in these books, which can lead to instructions for a faulty gene.
Most of the time, this does not matter, as the correct information is still provided by the other copy of the book. But if both books contain mistakes for the same gene, the genetic instructions cannot work. In inherited congenital nephrotic syndrome, typically the parents each have one healthy copy and one faulty one, so they do not have the condition. However, by chance, they both passed on the faulty (mutated) copy to the child, so the disease occurs.
What are the symptoms of congenital nephrotic syndrome?
The primary problem in congenital nephrotic syndrome is in the kidney, specifically the glomeruli, causing leakage of proteins. In the long term, this defect usually leads to a decline in kidney function with eventual kidney failure.
Initially however, the problems 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 congenital 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 congenital 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.
How can congenital nephrotic syndrome be treated?
Unfortunately, there is no specific treatment. In cases associated with infections, treatment of the infection is enough to also make the nephrotic syndrome disappear. The cases without clear cause sometimes just get better with time. However, in inherited cases, no specific treatment exists to repair the glomeruli. Some medications can help reduce the protein losses, but not enough to prevent the symptoms. Depending on the severity of the disease and the decisions you make with the doctors, there are two main treatment possibilities:
This involves a long-term admission to hospital. The aim is to allow the child to grow and develop and this is done initially by protein supplementation. The main protein lost in the urine is called albumin and this can be given as an infusion.
Typically, this treatment involves a small operation to place a central venous catheter (thin plastic tube) into one of the large veins in the arm or neck. This will make giving the daily infusion of albumin much easier and more comfortable for your child.
Additionally, medications can be given to increase the excretion of salt and water (diuretics). Obviously, because of the leak in the kidney, a substantial amount of the infused albumin is also lost in the urine, but nevertheless these infusions can stabilise the albumin levels in the blood, minimise the swelling (oedema) and provide building blocks for the child’s growth and development.
Unfortunately, this treatment can have complications. Having a plastic catheter enter the body gives potential for infections, and the loss of antibodies in the urine makes the child even more vulnerable to infection. As the bacteria can directly enter the bloodstream, these infections can be life threatening, but can usually be treated with antibiotics. Often removal of the catheter is needed to get rid of the infection totally.
Another complication is the potential for a blood clot to develop at the site of the infected catheter that blocks the vein. With recurrent infections it can become impossible to find open veins in which to place a new catheter.
To prevent this happening, your doctors may recommend removing the child’s kidney(s) as the only way to stop the protein losses.
Since congenital nephrotic syndrome typically leads to kidney failure eventually, this radical approach merely pre-empts the inevitable. However, it makes the child dependent on dialysis at an age when this is much more complicated than in older children. In milder cases, it may be enough to remove only one kidney. While protein losses will continue in the remaining kidney, the total loss is reduced and this may allow for adequate growth and discharge home. Yet in most cases, both kidneys are removed, typically when the baby has reached a size where dialysis is feasible, usually around 5kg.
Dialysis is then carried out until the child receives a kidney transplant, which is usually possible when he or she reaches 10kg in weight.
The intensive treatment described above is very demanding on everybody involved. It typically involves the child staying in hospital for the first six to 12 months of life and many further hospital admissions after that. This puts an enormous strain on the family, especially if one parent stays with the child in hospital and the other with the other children at home.
Some parents feel that such long-term hospitalisation with multiple interventions, operations and potential complications is not the right treatment for their child and would rather take their child home. This obviously increases the risk that the child may not grow and develop normally and, in fact, may die.
The child can still be checked in clinic regularly and receive medications to minimise the consequences of the congenital nephrotic syndrome but there is a very real risk of irreversible loss of growth and development and even death. However, the child would be in the natural environment of family and home. Yet, even if the child survives the initial time, kidney failure would typically occur after a few years as part of the natural course of congenital nephrotic syndrome. However, if active treatment such as transplantation were decided at that point, this would occur at an age where it has fewer complications compared to in infancy.
In summary, congenital nephrotic syndrome is a severe disease. There is no right or wrong answer to the question of which treatment option should be followed. Rather, each family needs to decide with the medical team, what the right option is for them.
If you have any questions, please call Eagle Ward on 020 7829 8815.