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Nephrotic Syndrome

by Navin Jaipaul, MD, MHS

Nephrotic syndrome is a disorder of the glomeruli (clusters of microscopic blood vessels in the kidneys that have small pores through which blood is filtered) in which excessive amounts of protein are excreted in the urine. Excessive protein excretion typically leads to accumulation of fluid in the body (edema) and low levels of the protein albumin and high levels of fats in the blood.

  • Drugs and disorders that damage the kidneys may cause nephrotic syndrome.

  • People feel tired and have tissue swelling.

  • Diagnosis is based on blood and urine tests and sometimes imaging of the kidneys, a biopsy of the kidneys, or both.

  • People who have disorders that may cause nephrotic syndrome are given angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) to slow kidney damage.

  • Restriction of sodium intake plus diuretics and statins are also used to treat this disorder.

Nephrotic syndrome can develop gradually or suddenly. Nephrotic syndrome can occur at any age. In children, it is most common between the ages of 18 months and 4 years, and more boys than girls are affected. In older people, both sexes are equally affected.

Protein excretion into the urine (proteinuria) results in low levels of important proteins, such as albumin, in the blood. People also have increased levels of fats (lipids) in the blood, a tendency to increased blood clotting, and a greater susceptibility to infection. The decreased level of albumin in the blood causes fluid to leave the bloodstream and enter the tissues. Fluid in the tissues leads to edema. Fluid leaving the bloodstream causes the kidneys to compensate by retaining more sodium.


Nephrotic syndrome can be primary, originating in the kidneys, or secondary, caused by a vast array of other disorders. Those disorders may involve other parts of the body. The most common disorders are diabetes mellitus, systemic lupus erythematosus (lupus), and certain viral infections. Nephrotic syndrome can also result from kidney inflammation (glomerulonephritis—see see Glomerulonephritis (Nephritic Syndrome)). A number of drugs that are toxic to the kidneys can also cause nephrotic syndrome, especially nonsteroidal anti-inflammatory drugs (NSAIDs). The syndrome may be caused by certain allergies, including allergies to insect bites and to poison ivy or poison oak. Some types of nephrotic syndrome are hereditary.


Early symptoms include loss of appetite, a general feeling of illness (malaise), puffy eyelids and tissue swelling (edema) due to excess sodium and water retention, abdominal pain, and frothy urine. The abdomen may be swollen because of a large accumulation of fluid in the abdominal cavity (ascites). Shortness of breath may develop because fluid accumulates in the space surrounding the lungs (pleural effusion). Other symptoms may include swelling of the of the labia in women and, in men, the scrotum. Most often, the fluid that causes tissue swelling is affected by gravity and therefore moves around. During the night, fluid accumulates in the upper parts of the body, such as the eyelids. During the day, when the person is sitting or standing, fluid accumulates in the lower parts of the body, such as the ankles. Swelling may hide the muscle wasting that is progressing at the same time.

In children, blood pressure is generally low, and blood pressure may fall when the child stands up (orthostatic hypotension). Shock occasionally develops. Adults may have low, normal, or high blood pressure. Urine production may decrease, and kidney failure (loss of most kidney function) may develop if the leakage of fluid from blood vessels into tissues depletes the liquid component of blood and the blood supply to the kidneys is diminished. Occasionally, kidney failure with low urine output occurs suddenly.

Nutritional deficiencies may result because nutrients are excreted in the urine. In children, growth may be stunted. Calcium may be lost from bones, leading to osteoporosis (see Osteoporosis). The hair and nails may become brittle, and some hair may fall out. Horizontal white lines may develop in fingernail beds for unknown reasons.

The membrane that lines the abdominal cavity and abdominal organs (peritoneum) may become inflamed and infected. Opportunistic infections—infections caused by normally harmless bacteria—are common. The higher likelihood of infection is thought to occur because the antibodies that normally combat infections are excreted in the urine or not produced in normal amounts. The tendency for blood clotting (thrombosis) increases, particularly inside the main veins draining blood from the kidneys. Less commonly, the blood may not clot when clotting is needed, generally leading to excessive bleeding. High blood pressure accompanied by complications affecting the heart and brain is most likely to occur in people who have diabetes or systemic lupus erythematosus.


A doctor bases the diagnosis of nephrotic syndrome on the symptoms, physical examination findings, and laboratory findings. Sometimes nephrotic syndrome is at first mistaken for heart failure in older adults because swelling occurs in both disorders and heart failure is common among older people. A laboratory test of urine collected over a 24-hour period is useful for measuring the degree of protein loss, but collection of urine over such a long period is difficult for many people to accomplish. Alternatively, to estimate protein loss, a single urine specimen can be tested to measure the ratio of the level of protein to that of creatinine (a waste product). Blood tests and other urine tests detect additional characteristics of the syndrome. The level of albumin in the blood is low because this vital protein is excreted in the urine and its production is impaired. The urine often contains clumps of cells that may be combined with protein and fat (casts). The urine contains low levels of sodium and high levels of potassium.

Concentrations of lipid in the blood are high, sometimes exceeding 10 times that of a normal concentration. Levels of lipid in the urine are also high. Anemia may be present. Levels of blood clotting proteins may be increased or decreased.

The doctor investigates possible causes of nephrotic syndrome, including drugs. Analysis of the urine and blood may reveal an underlying disorder. For example, the blood is tested for evidence of previous infections that could cause nephrotic syndrome and for antibodies directed against the body's own tissues (called autoantibodies) that indicate an autoimmune disorder. An imaging test of the kidneys, such as ultrasonography or computed tomography (CT), may be done. If the person has lost weight or is older, a search for cancer is undertaken. A kidney biopsy is especially useful in determining the cause and extent of kidney damage.


The prognosis varies depending on the cause of the nephrotic syndrome, the person's age, and the type and degree of kidney damage. Symptoms may disappear completely if the nephrotic syndrome is caused by a treatable disorder, such as an infection, cancer, or drugs. This situation occurs in about half the cases in children but less often in adults. If the underlying disorder responds to corticosteroids, sometimes progression of the disease is halted, and less often the condition partially or, rarely, completely reverses. When the syndrome is caused by HIV infection, it usually progresses relentlessly, often resulting in complete kidney failure in 3 or 4 months. Children born with the nephrotic syndrome rarely live beyond their first birthday, although a few have survived by means of dialysis treatments or a kidney transplant.

When the cause is systemic lupus erythematosus or diabetes mellitus, drug treatment often stabilizes or decreases the amount of protein in the urine. However, some people do not respond to drug treatment and develop chronic kidney disease that progresses to kidney failure within a few years.

In cases of nephrotic syndrome resulting from conditions such as an infection, allergy, or intravenous heroin use, the prognosis varies, depending on how early and effectively the underlying condition is treated.

Primary Glomerular Disorders That Can Cause Nephrotic Syndrome

Glomerular Disorder



Minimal change disease

This mild disease of the glomerulus is more common in children but also affects adults.

The prognosis is good. About 90% of children and nearly as many adults respond to treatment. In 30 to 50% of adults, disease relapses. After treatment for 1 or 2 years, more than 80% of people have permanent remission.

Focal segmental glomerulosclerosis

This disease damages glomeruli. It affects mainly adolescents but also young and middle-aged adults. It is more common in blacks.

The prognosis is poor because treatment is not very effective. In most adults and children, the disease progresses to end-stage kidney failure 5 to 20 years after diagnosis.

Membranous nephropathy

This serious type of glomerular disease affects mainly adults. It is more common in whites.

In about 25% of people, protein stops being excreted in the urine. About 25% develop end-stage kidney failure. The rest continue to have protein in the urine, as either the nephrotic syndrome or the asymptomatic proteinuria and hematuria syndrome.

Congenital and infantile nephrotic syndrome

These rare disorders are inherited. Congenital nephrotic syndrome (Finnish type) and diffuse mesangial sclerosis are the two main causes. They closely resemble focal segmental glomerulosclerosis. Symptoms are present at birth in the Finnish type and develop during childhood in diffuse mesangial sclerosis.

These disorders do not respond to corticosteroids. Because the level of albumin in the blood is extremely low, removal of both kidneys is often considered. Supportive therapy, including dialysis, is given until the child is eligible for a kidney transplant.

Membranoproliferative glomerulonephritis

This uncommon type of glomerulonephritis occurs primarily between the ages of 8 and 30. It is caused by deposits of immune complexes (combinations of antigens and antibodies) attaching to the kidneys, sometimes for unknown reasons.

If caused by a disorder that can be treated (for example, systemic lupus erythematosus or hepatitis B or C infection), a partial remission may occur. The outcome is not as good in people in whom the cause remains unknown. About half of untreated people progress to end-stage kidney failure within 10 years and 90% within 20 years.

Mesangial proliferative glomerulonephritis

This disorder accounts for about 3 to 5% of people with nephrotic syndrome of unknown cause. It affects all ages.

About 50% of people initially respond to corticosteroids. About 10 to 30% develop progressive kidney failure. Relapses may respond to cyclophosphamide.

Prevention and Treatment

Use of an angiotensin-converting enzyme (ACE) inhibitor, such as enalapril, quinapril, or lisinopril, or an angiotensin II receptor blocker (ARB), such as candesartan, losartan, or valsartan, is the mainstay of both prevention and treatment. When a person with a disease such as systemic lupus erythematosus or diabetes mellitus has mild or moderate proteinuria, an ACE inhibitor or ARB is used as soon as possible because the drug may prevent proteinuria from increasing and kidney function from worsening.

When a person who already has nephrotic syndrome is treated with an ACE inhibitor or ARB, symptoms may decrease, the amount of protein excreted in the urine usually decreases, and fat concentrations in the blood are likely to decline. However, these drugs can increase the potassium levels in the blood in people who have moderate to severe kidney failure, which can cause potentially dangerous heart rhythm abnormalities.

General therapy for nephrotic syndrome includes a diet that contains normal amounts of protein and potassium but that is low in saturated fat, cholesterol, and sodium. Statins, drugs that lower the amount of cholesterol in the blood, may also be needed if people have increased levels of fats (lipids) in the blood.

If fluid accumulates in the abdomen, the person may need to eat frequent, small meals because the fluid reduces the capacity of the stomach. High blood pressure is usually treated with diuretics. Diuretics can also reduce fluid retention and tissue swelling but may increase the risk of blood clots. Anticoagulants may help control clot formation if it occurs. Infections can be life threatening and must be treated promptly.

People should receive the pneumococcal vaccine. Rarely, so much protein is lost in the urine that the kidneys must be removed.

Whenever possible, specific treatment is aimed at the cause. Treating an infection that causes nephrotic syndrome may cure the syndrome. If a treatable disease, such as certain cancers, causes the syndrome, treating that disease can eliminate the syndrome. If a heroin user with nephrotic syndrome stops using heroin in the early stages of the disease, the syndrome may resolve. If other drugs are responsible for the syndrome, stopping the drugs may be curative. People who are sensitive or allergic to poison oak, poison ivy, or insect bites should avoid these irritants. If no reversible cause can be found, the person may be given corticosteroids and other drugs that suppress the immune system, such as cyclophosphamide. However, corticosteroids cause problems, particularly for children, in whom these drugs can stunt growth and suppress sexual development (see Corticosteroids: Uses and Side Effects).

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