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Nephrotic Syndrome

By

Frank O'Brien

, MD, Washington University in St. Louis

Last full review/revision Jul 2021| Content last modified Jul 2021
Click here for the Professional Version
Topic Resources

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 (edema).

  • 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.

Excessive 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.

Causes

Nephrotic syndrome can be

  • Primary, originating in the kidneys

  • Secondary, caused by a vast array of other disorders

A variety of primary kidney disorders can damage the glomeruli and cause nephrotic syndrome. Minimal change disease is the most common cause of nephrotic syndrome in children.

The secondary causes may involve other parts of the body. The most common disorders causing nephrotic syndrome are diabetes mellitus Diabetes Mellitus (DM) Diabetes mellitus is a disorder in which the body does not produce enough or respond normally to insulin, causing blood sugar (glucose) levels to be abnormally high. Urination and thirst are... read more , systemic lupus erythematosus Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a chronic autoimmune inflammatory connective tissue disorder that can involve joints, kidneys, skin, mucous membranes, and blood vessel walls. Problems in the... read more Systemic Lupus Erythematosus (SLE) (lupus), and certain viral infections. Nephrotic syndrome can also result from kidney inflammation (glomerulonephritis Glomerulonephritis Glomerulonephritis is a disorder of glomeruli (clusters of microscopic blood vessels in the kidneys with small pores through which blood is filtered). It is characterized by body tissue swelling... read more ). A number of drugs that are toxic to the kidneys can also cause nephrotic syndrome, especially nonsteroidal anti-inflammatory drugs Nonsteroidal Anti-Inflammatory Drugs In some cases, treating the underlying disorder eliminates or minimizes the pain. For example, setting a broken bone in a cast or giving antibiotics for an infected joint helps reduce pain.... read more (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.

Secondary Causes of Nephrotic Syndrome

* Asterisks indicate the most common causes.

Symptoms

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

  • Frothy urine

The abdomen may be swollen because of a large accumulation of fluid in the abdominal cavity (ascites Ascites Ascites is the accumulation of protein-containing (ascitic) fluid within the abdomen. Many disorders can cause ascites, but the most common is high blood pressure in the veins that bring blood... read more ). Shortness of breath may develop because fluid accumulates in the space surrounding the lungs (pleural effusion Pleural Effusion Pleural effusion is the abnormal accumulation of fluid in the pleural space (the area between the two layers of the thin membrane that covers the lungs). Fluid can accumulate in the pleural... read more Pleural Effusion ). Other symptoms may include swelling 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.

Urine production may decrease, and kidney failure Overview of Kidney Failure Kidney failure is the inability of the kidneys to adequately filter metabolic waste products from the blood. Kidney failure has many possible causes. Some lead to a rapid decline in kidney function... read more (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, and people may have a vitamin D deficiency, Vitamin D Deficiency Vitamin D deficiency is most commonly caused by a lack of exposure to sunlight. Some disorders can also cause the deficiency. The most common cause is lack of exposure to sunlight, usually when... read more leading to osteoporosis. Osteoporosis Osteoporosis is a condition in which a decrease in the density of bones weakens the bones, making breaks (fractures) likely. Aging, estrogen deficiency, low vitamin D or calcium intake, and... read more 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. Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a chronic autoimmune inflammatory connective tissue disorder that can involve joints, kidneys, skin, mucous membranes, and blood vessel walls. Problems in the... read more Systemic Lupus Erythematosus (SLE)

Diagnosis

  • Urine and blood tests

A doctor bases the diagnosis of nephrotic syndrome on 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.

Determining the cause of nephrotic syndrome

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 Imaging Tests of the Urinary Tract There are a variety of tests that can be used in the evaluation of a suspected kidney or urinary tract disorder. (See also Overview of the Urinary Tract.) X-rays are usually not helpful in evaluating... read more , 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.

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Prognosis

The prognosis varies depending on the

  • Cause of the nephrotic syndrome

  • Person's age

  • Type of kidney damage

  • 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, provided the condition is treated early and effectively. 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 human immunodeficiency virus (HIV) infection Human Immunodeficiency Virus (HIV) Infection Human immunodeficiency virus (HIV) infection is a viral infection that progressively destroys certain white blood cells and can cause acquired immunodeficiency syndrome (AIDS). HIV is transmitted... read more Human Immunodeficiency Virus (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 Dialysis Dialysis is an artificial process for removing waste products and excess fluids from the body, a process that is needed when the kidneys are not functioning properly. There are a number of reasons... read more Dialysis treatments or a kidney transplant. Kidney Transplantation Kidney transplantation is the removal of a healthy kidney from a living or recently deceased person and then its transfer into a person with end-stage kidney failure. (See also Overview of Transplantation... read more Kidney Transplantation

Prevention

Use of an angiotensin-converting enzyme (ACE) inhibitor, such as enalapril, benazepril, 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 Systemic Lupus Erythematosus (SLE) Systemic lupus erythematosus is a chronic autoimmune inflammatory connective tissue disorder that can involve joints, kidneys, skin, mucous membranes, and blood vessel walls. Problems in the... read more Systemic Lupus Erythematosus (SLE) or diabetes mellitus Diabetes Mellitus (DM) Diabetes mellitus is a disorder in which the body does not produce enough or respond normally to insulin, causing blood sugar (glucose) levels to be abnormally high. Urination and thirst are... read more 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.

Treatment

  • Drugs, often including an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB)

  • Treating the cause

  • Treating complications

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.

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.

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.

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 sidebar Corticosteroids: Uses and Side Effects Corticosteroids: Uses and Side Effects Rheumatoid arthritis is an inflammatory arthritis in which joints, usually including those of the hands and feet, are inflamed, resulting in swelling, pain, and often destruction of joints.... read more Corticosteroids: Uses and Side Effects ).

More Information

The following is an English-language resource that may be useful. Please note that THE MANUAL is not responsible for the content of this resource.

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Tubulointerstitial Nephritis
The kidneys contain tubules, which are structures in the kidneys that are involved in filtering fluids. Tubulointerstitial nephritis is inflammation that affects the tubules and the tissue surrounding them, called “interstitial tissue.” Onset of tubulointerstitial nephritis may be acute (sudden) or chronic (gradual) and often results in kidney failure. Which of the following is the most common cause of acute tubulointerstitial nephritis?
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