What is Nephrotic Syndrome?

Nephrotic syndrome is the name of a collection of symptoms that arises following damage to the kidneys. So, in order to answer that question we need to understand some things about the kidneys. This is because the nephrotic syndrome is usually a result of kidney disease. Healthy kidneys are made up of various structures, all with varying functions. Nephrons are one of these structures. 

Nephrons are tubes that are presentwithin the kidney. They consist of a network of tiny blood vessels (glomerulus) and various tubular structures. Nephrons are essential to kidney function as they are responsible for filtering the blood that flows through the kidney. Therefore, if there is a problem with the nephrons this will lead to kidney damage. 

Overview

Nephrotic syndrome is a condition in which protein leaks out of the kidneys and into the urine. It can affect anyone, however, it is more common in children aged 1-6 years of age. In healthy kidneys, the nephrons filter out a lot of substances from the urine. In those with kidney disease, this function is impaired. In those with nephrotic syndrome, this leads to high levels of protein in the urine. 

There are three main characteristics of nephrotic syndrome:

• High levels of protein in the urine 
• Decreased levels of protein in the blood
• Swelling in the body (oedema)

As we know, the nephrons play a key part in filtering the blood in the kidney. Therefore damage to them means an increase in the amount of waste byproducts in the blood. The nephrotic syndrome typically arises when the glomerulus is damaged. This is because in the healthy kidney, the glomerulus usually filters protein very effectively. 

In nephrotic syndrome the glomerulus is no longer able to do this, therefore there are high levels of protein in the urine and low levels of protein in the blood. Low levels of circulating protein in the blood cause water to seep out of the blood vessel, therefore leading to swelling in the body. This is because the water leaves the blood vessel and enters into cells, meaning that your body retains the water. 

Causes of nephrotic syndrome

Nephrotic syndrome has various causes. These causes can be either renal in nature (i.e. there is kidney disease) or extra-renal (i.e. the kidney damage is secondary to another disease process). Examples of renal causes of nephrotic syndrome include:

• Minimal change disease
  • Main type of childhood nephrotic syndrome is minimal change disease
  • Minimal change disease means that when a renal biopsy is taken the kidney tissue looks fairly normal
  • So, under a microscope there won’t be many changes to the cellular structures, therefore the disease is termed minimal change disease 
• Membranous nephropathy
  • Membranous nephropathy occurs when the glomerulus has a thickened membrane
  • In membranous nephropathy the thickened membrane is usually due to the immune system reacting poorly to something
  • Examples of this include: systemic lupus erythematosus, hepatitis B, cancer etc.
• Idiopathic nephrotic syndrome
• Focal segmental glomerulosclerosis
  • Focal segmental glomerulosclerosis is when there is scarring of the glomerulus
  • Focal segmental glomerulosclerosis can be a result of disease progression from another disease, a reaction to medication or as a result of genetic factors
• Glomerulonephritis (nephritic syndrome)
  • Usually autoimmune
• Congenital nephrotic syndrome
  • This is an inherited form of nephrotic syndrome
  • Tends to have a poorer prognosis
  • Children may go on to develop chronic kidney disease or kidney failure and require a kidney transplant

As with any disease, there are various risk factors that can increase the likelihood of someone developing nephrotic syndrome. These include the following:

• Diabetic kidney disease
  • Diabetes can lead to nephrotic damage (diabetic nephropathy) 
• High blood pressure (hypertension)
  • High blood pressure can cause damage to the tiny blood vessels in the glomerulus
• Sickle cell anaemia
• Certain types of cancer
  • E.g. multiple myeloma or lymphoma
• Amyloidosis
  • Build of an abnormal protein (amyloid) in the body 
  • This can be deposited in the kidneys, leading to kidney damage 

Signs and symptoms of Nephrotic syndrome

Think you might have a nephrotic syndrome symptom or two? Well, here are some examples of nephrotic syndrome signs and symptoms:

• Swelling in the body (oedema)
  • This is caused by low levels of circulating protein
  • Tends to start near the eyes, then the lower legs, then the rest of the body
  • Can also cause weight gain 
• Increased risk of infections
  • Certain proteins help to fight infection, if there are low levels of protein in the blood then there can be an increased risk of infection
• Changes to your urine
  • High levels of protein in the urine (aka proteinuria) can lead to frothy urine
  • You may experience decrease in urinary volume or a decrease in the frequency of urination 
• Increased risk of blood clot
  • Proteins are an essential part of preventing clot formation
  • A decrease in the levels of protein means that there is an increased likelihood of a clot forming 
  • Blood also gets more concentrated as the kidney is not filtering it effectively, meaning there is an increased chance of a blood clot
• Malnutrition
  • You may lose too much protein in your urine
  • Alongside this you can experience loss of blood cells leading to anaemia
  • Damage to the kidneys will also increase the risk of anaemia and vitamin D deficiency
• High blood pressure
  • Damage to the filtering system of the kidney can lead to an increase in the volume of fluid circulating in your system
  • This increase in volume can lead to high blood pressure
• Acute kidney injury
  • This is usually seen on blood tests
  • Happens when your kidneys struggle to filter out toxins and waste substances from the body, leading to a build of these substances in the blood 

Management and treatment for nephrotic syndrome

In an acute setting the primary goal is to give your kidneys a break and prevent worsening of the kidney damage. Things that your healthcare provider might do if you have nephrotic syndrome include:

• Prescribe steroid medication
• Prescribe diuretics
• Prescribe medication to lower blood pressure
• Prescribe medication to prevent high cholesterol
• Prescribe blood thinners
• Dietary changes
• Referral to paediatric nephrology (kidney specialist) 
• Arrange a kidney biopsy
• In some extreme cases a kidney transplant may be required

There are various organisations that can help with understanding and living with nephrotic syndrome (e.g. nephcure kidney international or the national kidney foundation). If neither of these are local to you, ask your healthcare provider for similar organisations in your area! Alongside this, there is ongoing research into nephrotic syndrome (e.g. the nephrotic syndrome study network). If you have any concerns regarding your management or treatment you can always speak to your healthcare provider. 

FAQs

How is nephrotic syndrome diagnosed?

Nephrotic syndrome is usually diagnosed with a combination of the following:

• Urine test
  • Check the level of protein in the urine
• Blood tests
  • This can assess kidney function and blood protein levels
  • Blood tests are also useful to look for other differential diagnoses
• Ultrasound scan of the kidneys
  • This will not help with the diagnosis of nephrotic syndrome, but it can help visualise the kidneys to rule out other  diseases that could be causing abnormal kidney function
• Kidney biopsy
  • This is when they take a sample of kidney tissue and look at it under a microscope
  • This can be particularly useful if the cause of the nephrotic syndrome is renal e.g. minimal change disease, membranous nephropathy, focal segmental glomerulosclerosis etc

How can I prevent nephrotic syndrome?

The best way to prevent nephrotic syndrome is to treat the underlying cause. If you can prevent kidney damage then you can prevent nephrotic syndrome from occurring! It is best to treat nephrotic syndrome as early as possible to prevent chronic kidney disease or kidney failure. 

Who are at risk of nephrotic syndrome?

Nephrotic syndrome commonly affects children aged 1 to 6 years old.

How common is nephrotic syndrome?

Nephrotic syndrome is not very common. Worldwide approximately 5 in 100,000 children develop nephrotic syndrome each year.¹

When should I see a doctor?

If you experience problems with your urine, or think that you may have nephrotic syndrome you should see your doctor as soon as possible. This is because there may be other causes for your symptoms and it is important to get investigations done in order to see what the underlying cause is. If in doubt, give your healthcare provider a shout!

Summary

Nephrotic syndrome is the term given to a triad caused by poor kidney function (protein in the urine leading to frothy urine, swelling in the body, and low levels of protein in the blood). It is diagnosed using clinical history, urine tests, blood tests, and occasionally a kidney biopsy. There are various causes, which can be either renal disease or extra-renal disease. The mainstay of treatment is treating the underlying cause and preventing worsening of the disease. Supportive treatment includes steroid therapy. 

If you have any concerns you should speak to your doctor as soon as possible in order to get treatment. There are plenty of resources out there (e.g. nephcure kidney international or the national kidney foundation) which can help if you, or your child, get a diagnosis of nephrotic syndrome.