Nephrotic syndrome is a condition where the 'filters' in the kidney become 'leaky' and large amounts of protein leak from your blood into your urine. The main symptom is oedema (fluid retention) which is mainly due to the low protein level in the blood. Various diseases can cause nephrotic syndrome, some more serious than others. Treatment and outcome (prognosis) vary, depending on the cause. The common cause in children (minimal change disease) usually responds very well to treatment.
The kidneys clear waste materials from the body and maintain a normal balance of fluids and chemicals in the body.
The two kidneys lie to the sides of the upper abdomen, behind the intestines, and on either side of the spine. The kidneys are higher up in the body than people imagine - from behind they are actually partially protected by the lowest ribs. The kidneys move slightly with change in your body position and with movement of the diaphragm with breathing.
Each kidney is about the size of a large orange, but bean-shaped.
'Renal' is a descriptive medical word, meaning 'related to the kidney'. For example, a renal physician is a doctor who looks after people with kidney (renal) diseases (so-called 'renal medicine').
. A large renal artery takes blood to each kidney. The artery divides into many tiny blood vessels (capillaries) throughout the kidney. In the outer part of the kidneys tiny blood vessels cluster together to form structures called glomeruli.
Each glomerulus (the singular form of glomeruli) is like a filter. The structure of the glomerulus allows waste products and some water and salt to pass from the blood into a tiny channel called a tubule, while keeping blood cells and protein in the bloodstream. Each glomerulus and tubule is called a nephron. There are about one million nephrons in each kidney.
As the waste products, water and salts pass along the tubule there is a complex adjustment of the content. For example, some water and salts may be absorbed back into the bloodstream, depending on the current level of water and salt in your blood. Tiny blood vessels next to each tubule enable this 'fine tuning' of the transfer of water and salts between the tubules and the blood.
The liquid that remains at the end of each tubule is called urine. This drains into larger channels (collecting ducts) which drain into the renal pelvis (the inner part of the kidney). From the renal pelvis the urine passes down a tube called a ureter which goes from each kidney to the bladder. Urine is stored in the bladder until it is passed out through another tube, called the urethra, when we go to the toilet. The 'cleaned' (filtered) blood from each kidney collects into a large renal vein which takes the blood back towards the heart. The kidneys, ureters, bladder and urethra are, together, called the urinary tract.
Doctors can assess how well (or poorly) your kidneys are working by testing your blood and your urine.
'U&Es' is the abbreviation medical professionals use for urea and electrolytes. These are a group of blood tests to measure the levels of salts in the blood (such as sodium and potassium), as well as the urea and creatinine levels, which show the kidney function as they are waste products. The eGFR is a term you might hear your doctors use. It stands for estimated glomerular filtration rate and is another measure of kidney function. The levels of protein and albumin (a type of protein) can also be measured with blood tests.
Urine can be tested for blood and protein with a 'dipstick' in clinic, or an exact measurement can be calculated by the laboratory. Other chemicals in urine can be measured and the urine is often examined under the microscope to see if it contains any abnormal cells or sediment. Sometimes doctors refer to CKD which stands for chronic kidney disease, which itself is a general term and can be caused by many different diseases or processes.
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 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:
Other typical symptoms and signs of nephrotic syndrome are discussed later.
Various diseases can affect the glomeruli and can result in nephrotic syndrome. The following gives a brief description of the main ones:
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.
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.
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.
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.
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, systemic lupus erythematosus (SLE), rheumatoid arthritis, polyarteritis nodosa, Henoch-Schönlein purpura, various infections, some cancers and amyloidosis. It can also occur as a side-effect of certain drugs, and as a consequence of various poisons or toxins.
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, 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). Ascites can cause abdominal pain and discomfort due to distension. Pleural effusions may cause chest pain and breathlessness.
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 that may develop include:
Complications can be caused by nephrotic syndrome itself due to the loss of normal proteins from the blood. These include:
Depending on the duration and severity of the nephrotic syndrome, you may be advised to take treatment to help prevent or reduce the risk of these possible complications.
You may also have various complications from the underlying condition which has caused the nephrotic syndrome. For example:
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.
A simple 'dipstick' test of your urine can confirm that it contains a lot of protein. Protein in the urine is not always due to nephrotic syndrome but is often a cause of underlying kidney disease. (An exception would be protein in the urine caused by a urinary tract infection.) The amount of protein lost can be measured by more detailed urine and blood tests. Often you have to collect all the urine that you pass in a 24-hour period, so the total amount of protein lost in a day can be measured. A low blood level of albumin combined with a lot of protein found in the urine usually confirms that you have nephrotic syndrome.
A range of blood tests may be done to try to 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.)
Blood tests can check on the function of the kidneys. The U&Es and eGFR (mentioned earlier in 'Understanding the kidneys and urine') show how well the kidneys are clearing waste products from the bloodstream.
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 to limit oedema. One way of trying to measure whether you are retaining fluid (or to see if the diuretics are helping), is to weigh yourself regularly.
Many people with kidney disorders have high blood pressure (hypertension). This is because the kidney makes chemicals involved in the control of 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 or an A2 antagonist/ARB is commonly used for this. These medicines seem to have a protective effect on the kidneys and can reduce the amount of protein leaking. These medicines might not be suitable for everyone but your doctor can advise you whether you need to take them. In very rare circumstances they can make your kidney function worse (if you have an undiagnosed problem called renal artery stenosis).
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.
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.
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Helpline: 0845 601 0209 Web: www.kidney.org.uk
A national kidney charity run by patients, for patients.
UK organisation raising money for research in nephrotic syndrome. Some useful links.