Nephrotic Syndrome Causes, Symptoms, Diagnosis, Treatment, Prevention

Nephrotic Syndrome Causes, Symptoms, Diagnosis, Treatment, Prevention

What is nephrotic syndrome?

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:

  • A low level of protein in the blood as a result of protein loss in the urine. Although there is a drop in many of the proteins normally found in the bloodstream, the main protein that leaks from the blood into the urine is called albumin. A low blood level of albumin is a main feature of nephrotic syndrome.
  • Fluid retention (oedema). This is a consequence of the low level of albumin in the bloodstream, and other complex factors not fully understood.
  • A high blood level of cholesterol and other fats (lipids). This is due to the change in the balance of various protein levels in the blood due to the protein leakage.
  • Normal kidney function, at least initially. This means that the 'waste clearing' function of the kidneys is not affected - at least not at first. However, some of the conditions that cause nephrotic syndrome can progress to cause kidney failure.

Other typical symptoms and signs of nephrotic syndrome are discussed later.

What are the causes of nephrotic syndrome?

Various diseases can affect the glomeruli and can result in nephrotic syndrome. The following gives a brief description of the main ones:

Minimal change disease

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 5 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.

Membranous nephropathy

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 medicines can cause this disease.

Focal segmental glomerulosclerosis (FSGS)

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.

Other disorders of the glomeruli

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.

Other general conditions

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 medicines, and as a consequence of various poisons or toxins.

What are the symptoms of nephrotic syndrome?

Fluid retention (oedema) is a main symptom

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 tummy (abdominal) cavity (where it is called 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:

  • Your urine may appear frothy.
  • Tiredness, lethargy and a poor appetite.
  • Diarrhoea and/or being sick (vomiting) - especially in children.
  • If the nephrotic syndrome persists for a long time then you may develop wasting of your muscles, and your nails may become white (called leukonychia).
  • Depending on the cause of the nephrotic syndrome, you may also have other symptoms. For example, if you have nephrotic syndrome as a complication of rheumatoid arthritis you may have a range of other symptoms caused by the arthritis. Some conditions of the kidney can cause high blood pressure and/or kidney failure.

Diagnosis of Nephrotic Syndrome

In addition to a physical examination and the assessment of family health history, the following three tests are used to make a nephrotic syndrome diagnosis:
  • Blood analysis
  • Urinalysis
  • Kidney biopsy
Blood analysis often shows high cholesterol levels and low albumin. BUN and creatinine may or may not be elevated. If bun and creatinine are elevated the patient has renal failure and the prognosis is worse.
Evaluation of the urine by a simple urine dipstick in the office can give preliminary information on the amount of protein in the urine. However, this test is a qualitative test. In order to determine the actual amount of protein in the urine, a 24-hour quantitative test must be done, which indicates levels of protein and creatinine in the urine. Often, a comparison of protein to creatinine based on a single sample is used to determine 24-hour protein loss. This is helpful for quicker results or when the patient cannot collect urine over 24 hours.
A closed kidney biopsy may be used to determine the underlying cause and extent of disease with the exception of the following cases.
  • Children with NS most often have minimal change disease and respond well to a short course of steroids. A biopsy should only be considered if they do not show a favorable response to the steroids within 6-8 weeks.
  • Adult patients with a history of diabetes who have tested negative to other disorders such as myeloma, infections, and collagen vascular diseases. It is presumed the cause of the proteinuria is diabetic nephropathy and a kidney biopsy is not necessary. If the duration of diabetes has been short or the severity of the NS is profound, a kidney biopsy is considered.
  • Elderly patients, patients who are not expected to live long, or those for whom immunosuppressive drug therapy is not advisable are typically not candidates for a biopsy.

What is the treatment for nephrotic syndrome?

Treatment of oedema

'Water tablets' (loop diuretics) 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.

Treatment of high blood pressure

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 angiotensin-converting enzyme (ACE) inhibitor or an angiotensin-II receptor antagonist (AIIRA) - sometimes called an angiotensin receptor blocker (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).

Treatment of the underlying cause

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 for 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 comes back (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.

What happens if there is no treatment for my nephrotic syndrome?

If your nephrotic syndrome is caused by a disease that has no specific treatment, help may still be available. Reducing salt in your diet will help to control the edema. Your doctor may also prescribe diuretics (water pills) to help with the swelling. The doctor may also prescribe the use of certain medicines that can reduce the protein in your urine. Although the syndrome is caused by the loss of protein into your urine, eating a high-protein diet does not help and may actually make matters worse. If the level of fats in your blood is too high, your doctor may recommend treatment for the increased levels of fat in your blood.

How to Prevent Nephrotic Syndrome

Keeping your blood pressure at less than 125/75 mm Hg with medicine, diet, and exercise.

Keeping strict control over your blood glucose level if you have diabetes.

Maintaining healthy levels of fats (lipids), such as cholesterol and triglycerides.

Not smoking or using other tobacco products.

Eat a low-salt diet to help control the swelling (edema) you experience.

Changes to your diet may help you cope with nephrotic syndrome. Your doctor may refer you to a dietitian to discuss how what you eat can help you cope with the complications of nephrotic syndrome.