Glomerulonephritis


Glomerulonephritis (nephritic syndrome) 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 (edema), high blood pressure, and the presence of red blood cells in the urine.

* Glomerulonephritis can be caused by various disorders, such as infections, an inherited genetic disorder, or autoimmune disorders।
* People may have tissue swelling, headaches, visual disturbances, and seizures.
* Diagnosis is based on tests of blood and urine and sometimes imaging tests, a biopsy of the kidneys, or both.
* People need to restrict salt and protein intake and take diuretics or antibiotics until kidney function improves.

Glomerulonephritis can develop over a short time period (acute glomerulonephritis) or develop and progress slowly (chronic glomerulonephritis). In 1% of children and 10% of adults who have acute glomerulonephritis, it evolves into rapidly progressive glomerulonephritis, in which most of the glomeruli are destroyed, resulting in kidney failure.

Causes

Glomerulonephritis can be primary, affecting only the kidneys, or secondary, caused by a vast array of disorders that affect other parts of the body.

Acute Glomerulonephritis: Acute glomerulonephritis most often occurs as a complication of throat or skin infection by streptococcus, a type of bacteria. Acute glomerulonephritis that occurs after a streptococcal infection (post-streptococcal glomerulonephritis) typically develops in children between the ages of 2 and 10 following recovery from the infection. Infections with other types of bacteria, such as staphylococcus and pneumococcus, viral infections, such as chickenpox, and parasitic infections, such as malaria, can also result in acute glomerulonephritis. Acute glomerulonephritis that results from any of these infections is called postinfectious glomerulonephritis. Noninfectious causes of acute glomerulonephritis include membranoproliferative glomerulonephritis, immunoglobulin A (IgA) nephropathy, thin basement membrane disease, Henoch-Schönlein purpura, systemic lupus erythematosus (lupus), cryoglobulinemia, Goodpasture's syndrome, and Wegener's granulomatosis. Acute glomerulonephritis that develops into rapidly progressive glomerulonephritis most often results from conditions that involve an abnormal immune reaction.

Chronic Glomerulonephritis: Often, chronic glomerulonephritis seems to result from one of the same conditions that cause acute glomerulonephritis, such as IgA nephropathy or membranoproliferative glomerulonephritis. Sometimes, acute glomerulonephritis does not resolve and instead becomes chronic. Occasionally, chronic glomerulonephritis is caused by hereditary nephritis, an inherited genetic disorder. In many people, the cause of chronic glomerulonephritis cannot be identified.








Secondary Causes of Glomerulonephritis

* Infections
o Bacterial infections (streptococcus, staphylococcus, pneumococcus)
o Fungal infections
o Parasitic infections (malaria)
o Viral infections (hepatitis B and C, HIV)
* Vasculitis
o Churg-Strauss syndrome
o Cryoglobulinemia
o Microscopic polyangiitis
o Wegener's granulomatosis
* Immune disorders
o Goodpasture's syndrome
o Serum sickness
o Systemic lupus erythematosus
* Hereditary disorders
o Hereditary nephritis
o Nail-patella syndrome
* Drugs
o Gold
o Pamidronate
o Penicillamine
o Propylthioracil

Symptoms

About half of the people with acute glomerulonephritis have no symptoms. If symptoms do occur, the first to appear are tissue swelling (edema) due to fluid retention, low urine volume, and production of urine that is dark because it contains blood. Edema may first appear as puffiness of the face and eyelids but later is prominent in the legs. Blood pressure increases as kidney function becomes impaired. In turn, high blood pressure and swelling of the brain may produce headaches, visual disturbances, and more serious disturbances of brain function (for example, seizures or coma). In older people, nonspecific symptoms, such as nausea and a general feeling of illness (malaise), are more common.

When rapidly progressive glomerulonephritis develops, weakness, fatigue, and fever are the most frequent early symptoms. Loss of appetite, nausea, vomiting, abdominal pain, and joint pain are also common. About 50% of people have a flu-like illness in the month before kidney failure develops. These people have edema and usually produce very little urine. High blood pressure is uncommon and rarely severe when it does occur.

Because chronic glomerulonephritis usually causes only very mild or subtle symptoms, it goes undetected for a long time in most people. Edema may occur. High blood pressure is common. The disease may progress to kidney failure, which can cause itchiness, fatigue, decreased appetite, nausea, vomiting, and difficulty breathing.

Diagnosis

Doctors investigate the possibility of acute glomerulonephritis in people whose laboratory test results indicate kidney dysfunction or blood in the urine and in people who develop symptoms of the disorder, particularly those who have had strep throat or other infections. Laboratory tests show variable amounts of protein and blood cells in the urine and often kidney dysfunction, as shown by a high concentration of urea and creatinine (waste products) in the blood.

In people with rapidly progressive glomerulonephritis, casts (clumps of red blood cells or white blood cells) are almost always visible in a urine sample that is examined under a microscope. Blood tests detect anemia and often an abnormally high number of white blood cells. When doctors suspect glomerulonephritis, a biopsy of the kidney is usually done to confirm the diagnosis, help determine the cause, and determine the amount of scarring and potential for reversibility. Kidney biopsy is done by inserting a needle in one of the kidneys under ultrasound or computed tomography (CT) guidance to obtain a small amount of kidney tissue. Although kidney biopsy is an invasive procedure and occasionally can become complicated, it is usually safe.

Additional tests are sometimes helpful for identifying the cause. For example, a throat culture may provide evidence of streptococcal infection. Blood levels of antibodies against streptococci may be higher than normal or progressively increase over several weeks. Acute glomerulonephritis that follows an infection other than strep throat is usually easier to diagnose, because its symptoms often begin while the infection is still obvious. Cultures and blood tests that help identify the organisms that cause these other types of infections are sometimes needed to confirm the diagnosis.

Chronic glomerulonephritis develops gradually, and therefore, a doctor may not be able to tell exactly when it began. It may be discovered when a urine test, done as part of a medical examination, reveals the presence of protein and blood cells in a person who is feeling well, has normal kidney function, and has no symptoms. Doctors usually do an imaging test of the kidneys, such as an ultrasound, CT scan, or magnetic resonance imaging (MRI) scan. A kidney biopsy is the most reliable way to distinguish chronic glomerulonephritis from other kidney diseases. A biopsy, however, is rarely done in advanced stages. In these cases, the kidneys are shrunken and scarred, and the chance of obtaining specific information about the cause is small. Doctors suspect that the kidneys are shrunken and scarred if kidney function has been poor for a long time and the kidneys appear abnormally small on an imaging test.

Prognosis

Acute poststreptococcal glomerulonephritis resolves completely in most cases, especially in children. About 0.1% of children and 25% of adults develop chronic kidney failure.

The prognosis for people with rapidly progressive glomerulonephritis depends on the severity of glomerular scarring and whether the underlying disease, such as infection, can be cured. In about 75% of the people who are treated early (within weeks to a few months), kidney function is preserved and dialysis is not needed. However, because the early symptoms can be subtle and vague, many people who have rapidly progressive glomerulonephritis are not aware of the underlying disease and do not seek medical care until kidney failure develops. If treatment occurs late, the person is more likely to develop chronic kidney failure. The prognosis also depends on the cause, the person's age, and any other diseases the person might have. When the cause is unknown or the person is older, the prognosis is worse.

In some children and adults who do not recover completely from acute glomerulonephritis, other types of kidney disorders develop, such as asymptomatic proteinuria and hematuria syndrome or nephrotic syndrome। Other people with acute glomerulonephritis, especially older adults, often develop chronic glomerulonephritis.


Primary Glomerular Disorders That Can Cause Glomerulonephritis
Disorder
Description
Prognosis
Fibrillary glomerulonephritis

A rare disease in which abnormal proteins are deposited around the glomerulus; it may also cause nephrotic syndrome

The prognosis is poor; end-stage kidney failure occurs in half of people within 4 years. It is not clear how much treatment (with corticosteroids and immunosuppressants) helps
Primary rapidly progressive glomerulonephritis

A group of disorders that cause microscopic damage to the glomeruli and progress rapidly; sometimes they are caused by an infection or other treatable disorder

The prognosis is poor; at least 80% of people develop end-stage kidney failure within 6 months without treatment. The prognosis is better for people younger than 60 years or if an underlying disorder causing the glomerulonephritis responds to treatment

Immunoglobulin A (IgA) nephropathy

The most common form of glomerulonephritis in the world; caused by immune complexes (combinations of antigens and antibodies) deposited in the kidney

Usually the disorder progresses slowly; end-stage kidney failure develops in about 20% to 40% of people after 5 to 25 years; progresses more slowly in children

Thin basement membrane disease (benign familial hematuria)

A hereditary disorder caused by thinning of a part of the glomerulus called the basement membrane

The prognosis is excellent; most people do not develop end-stage kidney failure

Membranoproliferative glomerulonephritis

An uncommon type of glomerulonephritis primarily occurring between the ages of 8 and 30; sometimes the cause is unknown, or the disorder may be caused by immune complexes (combinations of antigens and antibodies) attaching to the kidney

If caused by immune complex disease, a partial remission may occur; the outcome is not as good in people in whom the cause remains unknown. About half of untreated people will progress to end-stage kidney failure within 10 to 15 years, while in most others the kidney function stabilizes or improves

Treatment
No specific treatment is available in most cases of acute glomerulonephritis. Following a diet that is low in protein and sodium may be necessary until kidney function recovers. Diuretics may be prescribed to help the kidneys excrete excess sodium and water. High blood pressure needs to be treated.

When a bacterial infection is suspected as the cause of acute glomerulonephritis, antibiotics are usually ineffective because the nephritis begins 1 to 6 weeks (average, 2 weeks) after the infection, which has, by then, usually resolved. However, if a bacterial infection is still present when acute glomerulonephritis is discovered, antibiotic therapy is started. Antimalarial drugs may be beneficial if the cause of the syndrome is malaria.

For rapidly progressive glomerulonephritis, drugs to suppress the immune system are started promptly. High doses of corticosteroids are usually given intravenously for about a week, followed by a variable period of time when they are taken by mouth. Cyclophosphamide

, an immunosuppressant, may also be given. In addition, plasmapheresis is sometimes used to remove antibodies from the blood. The sooner treatment occurs, the less likely are kidney failure and the need for dialysis. Kidney transplantation is sometimes considered for people who develop chronic kidney failure, but rapidly progressive glomerulonephritis may recur in the transplanted kidney.

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) either alone or in combination often slow progression of chronic glomerulonephritis. Taking drugs to reduce high blood pressure and reducing sodium intake are considered beneficial. Restricting the amount of protein in the diet is modestly helpful in reducing the rate of kidney deterioration. End-stage kidney failure can be treated with dialysis or a kidney transplant.

ASYMPTOMATIC PROTEINURIA AND HEMATURIA SYNDROME
Asymptomatic proteinuria and hematuria is the result of diseases of glomeruli (clusters of microscopic blood vessels in the kidneys that have small pores through which blood is filtered) characterized by steady or intermittent loss of small amounts of protein and blood in the urine.

Small amounts of protein excreted in the urine (proteinuria) or blood excreted in the urine (hematuria) are sometimes discovered in people without symptoms, when urine tests are done for some routine purpose. The presence of casts (clumps of red blood cells) or abnormally shaped red blood cells is a clue for doctors that the blood in the urine came from glomeruli. Casts and proteinuria may be present because the person is recovering from a recent undiagnosed episode of nephritis. If this situation seems likely, a doctor needs only to recheck the person over the next weeks or months to make sure that the abnormalities resolve. If casts and proteinuria persist, the cause is usually one of three disorders. One is immunoglobulin A (IgA) nephropathy, a type of nephritis caused by deposition of immune complexes (combinations of antibodies and antigens) in the kidney that can be very mild and nonprogressive or become a severe disease leading to kidney failure. Another is hereditary nephritis (Alport's syndrome), a progressive disorder that can be severe and lead to kidney failure. The third disorder is thin basement membrane disease (benign familial hematuria). Thin basement membrane disease is a hereditary disorder caused by thinning of a part of the glomerulus called the basement membrane. It follows a mild and nonprogressive course. The diagnosis can usually be made with a kidney biopsy. However, a kidney biopsy is rarely done because the likelihood of finding a treatable disease is very low.

Doctors usually recommend that people with asymptomatic proteinuria and hematuria have a physical examination and undergo urine testing once or twice a year. Additional tests are done if the amount of protein or blood increases much, or if symptoms occur that suggest the development of a specific disease. Most people with asymptomatic proteinuria and hematuria syndrome do not worsen, and the condition may persist indefinitely.

HEREDITARY NEPHRITIS (ALPORT'S SYNDROME)
Hereditary nephritis (Alport's syndrome) is a genetic disorder in which kidney function is poor, blood is present in the urine, and deafness and eye abnormalities sometimes occur.

Hereditary nephritis is usually caused by a defective gene on the X chromosome, but it sometimes results from an abnormal gene on a nonsex (autosomal) chromosome. Other factors influence how severe the disorder is in a person who has the gene. Females with the defective gene on one of their two X chromosomes usually do not have symptoms, although their kidneys may function somewhat less efficiently than normal. Most of these females have some blood in the urine. Males with the defective gene develop more severe problems because males do not have a second X chromosome to compensate for the defect. Males usually develop kidney failure between the ages of 20 and 30. Many people with the defective gene on only one autosomal chromosome have no symptoms other than blood in the urine, but the urine may also contain varying amounts of protein, white blood cells, and casts (small clumps of cells) that are visible under a microscope. Kidney function in people who have the defective gene on two autosomal chromosomes slowly worsens, and kidney failure usually occurs.

Hereditary nephritis can affect other organs. Hearing problems, usually an inability to hear sounds in the higher frequencies, are common. Cataracts can also occur, although less often than hearing loss. Abnormalities of the cornea, lens, or retina sometimes cause blindness. Other problems include a low number of platelets in the blood (thrombocytopenia) and abnormalities that affect several nerves (polyneuropathy).

People who develop kidney failure need to undergo dialysis or receive a kidney transplant. Genetic testing is usually offered to people who want to have children.

NAIL-PATELLA SYNDROME
The nail-patella syndrome (also called osteo-onychodysplasia, arthro-onychodysplasia, and onycho-osteodysplasia) is a rare hereditary disorder that results in abnormalities of the kidneys, bones, joints, and fingernails.

The gene that causes nail-patella syndrome is dominant. Commonly, people who have this syndrome have one or both kneecaps (patellas) missing, one of the arm bones (the radius) dislocated at the elbow, and the pelvic bone abnormally shaped. They have either no fingernails or poorly developed ones, with pitting and ridges. About 30% to 40% of people with this syndrome have blood or protein in their urine, which may prompt the doctor to order kidney function tests. Kidney failure eventually develops in about 30% of the people with affected kidneys by the time they are 50 or 60. The diagnosis is confirmed by bone x-rays and a biopsy of kidney tissue.

There is no effective treatment for this syndrome. Controlling blood pressure may slow the rate of deterioration of kidney function. Those who develop kidney failure need dialysis or a kidney transplant. Genetic testing is usually offered to people who want to have children.

Last full review/revision March 2007 by Seyed-Ali Sadjadi, MD