Nephrotic Syndrome

Nephrotic syndrome is a kidney disorder where your body loses too much protein through urine, causing swelling and other health complications that require careful medical management.

Table of contents

• What is Nephrotic Syndrome?
• Signs and Symptoms
• Causes and Related Conditions
• Complications
• Diagnosis
• Treatment Options
• Diet and Lifestyle Management
• Outlook and Living with Nephrotic Syndrome

What is Nephrotic Syndrome?

• Kidneys
• Glomeruli (kidney filters)

Nephrotic syndrome is a condition in which your kidneys release an excessive amount of protein into your urine^[1]. Your kidneys contain up to one million filtering units called nephrons. Inside each nephron, there is a tiny set of blood vessels called a glomerulus (the plural is glomeruli). These glomeruli work like filters to remove waste and excess water from your blood while keeping important proteins and blood cells in your bloodstream^[2].

When the glomeruli become damaged, they allow blood proteins to leak into your urine. The most important protein that leaks out is called albumin. In healthy kidneys, the glomeruli allow only tiny amounts of protein to pass through. However, if you have nephrotic syndrome, your damaged glomeruli allow three or more grams of protein to leak into your urine over 24 hours—that’s about 20 times the normal amount^[2].

Nephrotic syndrome is relatively rare. It affects about 3 in every 100,000 adults each year. In children, it occurs in about 1 in every 50,000 children annually, most commonly between the ages of 2 and 5. Boys are about twice as likely to develop nephrotic syndrome as girls^[2].

Signs and Symptoms

The main symptoms of nephrotic syndrome result from the loss of protein from your blood and the buildup of fluid in your body. Common symptoms include^[1][2]:

• Severe swelling (edema), particularly around your eyes and in your ankles and feet. Swelling may also occur in your hands or face. In children, swelling of the face is often the first sign, typically noticed in the morning
• Foamy urine, which results from excess protein in your urine
• Weight gain due to fluid retention
• Fatigue and feeling unwell
• Loss of appetite
• Abdominal pain

Another symptom of nephrotic syndrome is the loss of essential minerals and vitamins, including calcium and vitamin D. In children, this loss can affect their growth. Adults may develop osteoporosis, which weakens bones, hair, and nails^[2].

Causes and Related Conditions

Nephrotic syndrome can be classified as either primary (caused by kidney diseases) or secondary (caused by other medical conditions)^[3].

The most common primary causes of nephrotic syndrome in adults include intrinsic kidney diseases such as membranous nephropathy, minimal change disease, and focal segmental glomerulosclerosis^[3]. In children, minimal change disease (also called lipoid nephrosis) is the most common form. This condition is called “minimal change” because the kidney filters appear normal or nearly normal under a regular microscope, though changes can be seen with a powerful electron microscope^[6].

Secondary causes of nephrotic syndrome include systemic diseases and other medical conditions such as^[3][4]:

• Diabetes mellitus
• Systemic lupus erythematosus
• Amyloidosis
• Certain infections
• Certain medications
• Some types of cancer

In some cases, nephrotic syndrome can occur due to genetic mutations in proteins found in the kidney’s filtering cells, leading to congenital or hereditary forms of the condition^[3].

Nephrotic syndrome is most common in people with diabetes-related kidney disease, people who have allergies, and people who have a biological family history of kidney disease with nephrotic syndrome^[2].

Complications

Nephrotic syndrome is a serious condition. Without treatment, it can lead to several important complications^[2]:

Blood clots are a major risk. Some proteins that help prevent blood clots are lost in the urine. When you lose these proteins, blood clots can form more easily. The blood also becomes more concentrated during the illness, which further increases clotting risk^[2][5].

Infections are another common complication. Immunoglobulins are proteins that help your immune system fight diseases and infections. When you lose immunoglobulins through your urine, you become more vulnerable to infections. These can include pneumonia, cellulitis, and peritonitis^[2].

Other potential complications include^[2]:

• Acute kidney injury—when your kidney suddenly stops functioning properly
• Anemia—not having enough healthy blood cells to carry oxygen
• Coronary artery disease
• High blood pressure
• High fat and cholesterol levels in your blood (hyperlipidemia)

Diagnosis

Nephrotic syndrome can usually be diagnosed after dipping a dipstick into a urine sample. If there are large amounts of protein in your urine, there will be a color change on the stick. A blood test showing a low level of the protein albumin will confirm the diagnosis^[6].

Tests and procedures used to diagnose nephrotic syndrome include^[8]:

Urine tests: A urinalysis can reveal abnormalities in your urine, such as large amounts of protein. You might be asked to collect urine samples over 24 hours. Instead of 24-hour urine collection, doctors often use a spot urine protein-to-creatinine ratio, which is more convenient^[11].

Blood tests: A blood test can show low levels of the protein albumin and often decreased levels of blood protein overall. Loss of albumin is often associated with an increase in blood cholesterol and blood triglycerides. The creatinine and urea nitrogen levels in your blood also might be measured to assess your overall kidney function^[8].

Kidney biopsy: Your doctor might recommend removing a small sample of kidney tissue for testing. During a kidney biopsy, a needle is inserted through your skin and into your kidney. Kidney tissue is collected and sent to a lab for testing. In some cases, when the initial treatment does not work, a kidney biopsy may be needed to determine the specific type of kidney disease causing nephrotic syndrome^[6][8].

The patient history and selected diagnostic studies help rule out important secondary causes, including diabetes mellitus, systemic lupus erythematosus, and medication side effects^[11].

Treatment Options

Treatment for nephrotic syndrome involves treating any medical condition that might be causing your nephrotic syndrome. Your doctor might also recommend medications and changes in your diet to help control your symptoms or treat complications^[8].

Medications that may be prescribed include^[8]:

Blood pressure medications: Drugs called angiotensin-converting enzyme (ACE) inhibitors reduce blood pressure and the amount of protein released in urine. Medications in this category include lisinopril, benazepril, captopril, and enalapril. Another group of drugs that works similarly is called angiotensin II receptor blockers (ARBs) and includes losartan and valsartan. These medications are appropriate for most patients with nephrotic syndrome^[8][11].

Water pills (diuretics): These help control swelling by increasing the amount of urine your body produces. They work by helping remove excess fluid that has built up in your body^[8].

In children with idiopathic nephrotic syndrome, corticosteroids (such as prednisolone) are the mainstay of treatment. Children diagnosed with nephrotic syndrome for the first time are normally prescribed at least a 4-week course of prednisolone, followed by a smaller dose every other day for 4 more weeks. When prednisolone is prescribed for short periods, there are usually no serious or long-lasting side effects, although some children may experience increased appetite, weight gain, red cheeks, and mood changes^[14].

For adults and children who do not respond well to corticosteroids or who experience frequent relapses, other immunosuppressive medications may be used. These can include cyclophosphamide, mycophenolate mofetil, or calcineurin inhibitors such as tacrolimus. Corticosteroids and other immunosuppressant drugs may have some benefit in patients with nephrotic syndrome, but the potential risks are significant^[11][13].

Most children with nephrotic syndrome respond well to treatment with steroids, and the protein often disappears from their urine within a few weeks. This period is known as remission. However, most children have relapses (when symptoms return) until their late teens. Relapses typically become less frequent as they get older and often stop by their late teens^[14].

Diet and Lifestyle Management

Dietary changes are an important part of managing nephrotic syndrome. General measures include^[8][11]:

• Reducing salt (sodium) intake to help control swelling
• Limiting fluid intake to help manage fluid retention
• Following a careful diet plan as recommended by your healthcare team

Changing your diet is crucial to avoiding kidney damage. Although protein is lost through the urine, a high-protein diet is not recommended for nephrotic syndrome. What you eat could worsen symptoms and cause other complications, such as high blood pressure and increased strain on the kidneys^[18].

Although hyperlipidemia (high fat and cholesterol levels) is a common complication of nephrotic syndrome, there is limited evidence that lipid-lowering therapy should be started solely to treat the manifestations of nephrotic syndrome. However, these medications may be prescribed as part of overall treatment^[11].

Outlook and Living with Nephrotic Syndrome

Although nephrotic syndrome can be a serious condition, most people respond well to treatment and can live essentially a normal life, particularly if the condition goes into remission. Depending on the cause, patients may respond to treatment within a few days but may take several weeks or even months^[22].

Most people with nephrotic syndrome would be well enough to study, go to work, and drive during treatment. Nephrotic syndrome does not normally affect sexual activity, and women can become pregnant and deliver healthy babies. However, nephrotic syndrome can increase the risk of problems in pregnancy, and patients should not attempt to become pregnant while taking certain medications. Any plan to try for a family should be discussed with a kidney specialist (nephrologist)^[22].

In general, most diseases causing nephrotic syndrome are not hereditary, so they cannot be passed on to children^[22].

All patients with nephrotic syndrome would usually be seen regularly in a hospital nephrology outpatient clinic where they would be monitored by blood and urine tests. Sometimes diseases causing nephrotic syndrome go into remission and appear to be cured. In other cases, the disease doesn’t respond completely or relapses at a later point^[22].

Patients whose disease is in remission may be given some dipsticks to test their urine at home if they think it is getting frothy or if their ankles are swollen. This is a good way to detect a relapse. If there are signs of a relapse, patients should contact their doctor or nephrologist without waiting until the next scheduled appointment^[22].

Living with nephrotic syndrome requires developing an in-depth understanding of the condition in order to participate in treatment decisions, develop self-management skills, and integrate illness into daily life^[17].