Glomerulonephritis
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Many diseases affect kidney function by attacking the glomeruli,
the tiny units within the kidney where blood is cleaned. Glomerular
diseases include many conditions with a variety of genetic and
environmental causes, but they fall into two major categories:
- Glomerulonephritis (gloh-MAIR-yoo-loh-neh-FRY-tis) describes
the inflammation of the membrane tissue in the kidney that serves
as a filter, separating wastes and extra fluid from the
blood.
- Glomerulosclerosis (gloh-MAIR-yoo-loh-skleh-ROH-sis) describes
the scarring or hardening of the tiny blood vessels within the
kidney.
Although glomerulonephritis and glomerulosclerosis have different
causes, they can both lead to end-stage renal disease (ESRD).
The two kidneys
are bean-shaped organs located near the middle of the back, just
below the rib cage to the left and right of the spine. Each about
the size of a fist, these organs act as sophisticated filters for
the body. They process about 400 quarts of blood a day to sift out
about 2 quarts of waste products and extra water that eventually
leave the body as urine.
Blood enters the kidneys through arteries that branch inside the
kidneys into tiny clusters of looping blood vessels. Each cluster is
called a glomerulus, which comes from the Greek word meaning
filter. The plural form of the word is glomeruli. There are
approximately 1 million glomeruli, or filters, in each kidney. The
glomerulus is attached to the opening of a small fluid-collecting
tube called a tubule. Blood is filtered in the glomerulus,
and extra water and wastes pass into the tubule and become urine.
Eventually, the urine drains from the kidneys into the bladder
through larger tubes called ureters.
Each glomerulus-and-tubule unit is called a nephron. Each
kidney is composed of about 1 million nephrons. In healthy nephrons,
the glomerular membrane that separates the blood vessel from the
tubule allows waste products and extra water to pass into the tubule
while keeping blood cells and protein in the bloodstream.
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Glomerular diseases damage the glomeruli, letting protein and
sometimes red blood cells leak into the urine. Sometimes a
glomerular disease also interferes with the clearance of waste
products by the kidney, so they begin to build up in the blood.
Furthermore, loss of blood proteins like albumin in the urine can
result in a fall in their level in the bloodstream. In normal blood,
albumin acts like a sponge, drawing extra fluid from the body into
the bloodstream, where it remains until the kidneys remove it. But
when albumin leaks into the urine, the blood loses its capacity to
absorb extra fluid from the body. Fluid can accumulate outside the
circulatory system in the face, hands, feet, or ankles and cause
swelling.
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The signs and symptoms of glomerular disease include
- proteinuria: large amounts of protein in the
urine
- hematuria: blood in the urine
- reduced glomerular filtration rate: inefficient
filtering of wastes from the blood
- hypoproteinemia: low blood protein
- edema: swelling in parts of the body
One or more of these symptoms can be the first sign of kidney
disease. But how would you know, for example, whether you have
proteinuria? Before seeing a doctor, you may not. But some of these
symptoms have signs, or visible manifestations:
- Proteinuria may cause foamy urine.
- Blood may cause the urine to be pink or cola-colored.
- Edema may be obvious in hands and ankles, especially at the
end of the day, or around the eyes when awakening in the morning,
for example.
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Patients with glomerular disease have significant amounts of
protein in the urine, which may be referred to as "nephrotic range"
if levels are very high. Red blood cells in the urine are a frequent
finding as well, particularly in some forms of glomerular disease.
Urinalysis provides information about kidney damage by indicating
levels of protein and red blood cells in the urine. Blood tests
measure the levels of waste products such as creatinine and urea
nitrogen to determine whether the filtering capacity of the kidneys
is impaired. If these lab tests indicate kidney damage, the doctor
may recommend ultrasound or an x ray to see whether the shape or
size of the kidneys is abnormal. These tests are called renal
imaging. But since glomerular disease causes problems at the
cellular level, the doctor will probably also recommend a kidney
biopsy--a procedure in which a needle is used to extract small
pieces of tissue for examination under different types of
microscopes, each of which shows a different aspect of the tissue. A
biopsy may be helpful in confirming glomerular disease and
identifying the cause.
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A number of different diseases can result in glomerular disease.
It may be the direct result of an infection or a drug toxic to the
kidneys, or it may result from a disease that affects the entire
body, like diabetes or lupus. Many different kinds of diseases can
cause swelling or scarring of the nephron or glomerulus. Sometimes
glomerular disease is idiopathic, meaning that it occurs without an
apparent associated disease.
The categories presented below can overlap: that is, a disease
might belong to two or more of the categories. For example, diabetic
nephropathy is a form of glomerular disease that can be placed in
two categories: systemic diseases, since diabetes itself is a
systemic disease, and sclerotic diseases, because the specific
damage done to the kidneys is associated with scarring.
Autoimmune Diseases
When the body's immune system functions properly, it creates
protein-like substances called antibodies and immunoglobulins to
protect the body against invading organisms. In an autoimmune
disease, the immune system creates autoantibodies, which are
antibodies or immunoglobulins that attack the body itself.
Autoimmune diseases may be systemic and affect many parts of the
body, or they may affect only specific organs or regions.
Systemic lupus erythematosus (SLE) affects many parts of
the body: primarily the skin and joints, but also the kidneys.
Because women are more likely to develop SLE than men, some
researchers believe that a sex-linked genetic factor may play a part
in making a person susceptible, although viral infection has also
been implicated as a triggering factor. Lupus nephritis is the name
given to the kidney disease caused by SLE, and it occurs when
autoantibodies form or are deposited in the glomeruli, causing
inflammation. Ultimately, the inflammation may create scars that
keep the kidneys from functioning properly.
Goodpasture's syndrome involves an autoantibody that
specifically targets the kidneys and the lungs. Often, the first
indication that patients have the autoantibody is when they cough up
blood. But lung damage in Goodpasture's syndrome is usually
superficial compared with progressive and permanent damage to the
kidneys. Goodpasture's syndrome is a rare condition that affects
mostly young men but also occurs in women, children, and older
adults. Treatments include immunosuppressive drugs and a
blood-cleaning therapy called plasmapheresis that removes the
autoantibodies.
IgA nephropathy is a form of glomerular disease that
results when immunoglobulin A (IgA) forms deposits in the glomeruli,
where it creates inflammation. Researchers funded by the National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) are
trying to discover why these deposits in the glomeruli are formed
and whether dietary supplements of fish oil can inhibit IgA-induced
inflammation and scarring in the kidney. A study is being conducted
to compare the effectiveness of therapy involving daily fish oil
supplements with that of a therapy involving prednisone, a drug that
blocks the body's immune system. The study includes a placebo group.
All three groups of patients in the study are receiving medication
to control blood pressure. IgA nephropathy was not recognized as a
cause of glomerular disease until the late 1960s, when sophisticated
biopsy techniques were developed that could identify IgA deposits in
kidney tissue.
The most common symptom of IgA nephropathy is blood in the urine,
but it is often a silent disease that may go undetected for many
years. The silent nature of the disease makes it difficult to
determine how many people are in the early stages of IgA
nephropathy, when specific medical tests are the only way to detect
it. This disease is estimated to be the most common cause of primary
glomerulonephritis--that is, glomerular disease not caused by a
systemic disease like lupus or diabetes mellitus. It appears to
affect men more than women. Although IgA nephropathy is found in all
age groups, young people rarely display signs of kidney failure
because the disease usually takes several years to progress to the
stage where it causes detectable complications.
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The primary indicator of Alport syndrome is a family history of
chronic glomerular disease, although it may also involve hearing or
vision impairment. This syndrome affects both men and women, but men
are more likely to experience chronic renal failure and sensory
loss. Men with Alport syndrome usually first show evidence of renal
insufficiency while in their twenties and reach ESRD by age 40.
Women rarely have significant renal impairment, and hearing loss may
be so slight that it can be detected only through testing with
special equipment. Usually men can pass the disease only to their
daughters. Women can transmit the disease to either their sons or
their daughters.
Infection-related Glomerular Disease
Glomerular disease sometimes develops rapidly after an infection
in other parts of the body. Acute post-streptococcal
glomerulonephritis (PSGN) can occur after an episode of strep
throat or, in rare cases, impetigo (a skin infection). The
Streptococcus bacteria do not attack the kidney directly, but
an infection may stimulate the immune system to overproduce
antibodies, which are circulated in the blood and finally deposited
in the glomeruli, causing damage. PSGN can bring on sudden symptoms
of swelling (edema), reduced urine output (oliguria), and blood in
the urine (hematuria). Tests will show large amounts of protein in
the urine and elevated levels of creatinine and urea nitrogen in the
blood, thus indicating reduced kidney function. High blood pressure
frequently accompanies reduced kidney function in this disease.
PSGN is most common in children between the ages of 3 and 7,
although it can strike at any age, and it most often affects boys.
It lasts only a brief time and usually allows the kidneys to
recover. In a few cases, however, kidney damage may be permanent,
requiring dialysis or transplantation to replace renal function.
Bacterial endocarditis, infection of the tissues inside
the heart, is also associated with subsequent glomerular disease.
Researchers are not sure whether the renal lesions that form after a
heart infection are caused entirely by the immune response or
whether some other disease mechanism contributes to kidney damage.
Treating the heart infection is the most effective way of minimizing
kidney damage. Chronic renal failure can result from endocarditis,
but is not inevitable.
HIV, the virus that leads to AIDS, can also cause
glomerular disease. Between 5 and 10 percent of people with HIV
experience kidney failure, even before developing full-blown AIDS.
HIV-associated nephropathy usually begins with heavy proteinuria and
progresses rapidly (within a year of detection) to ESRD. Researchers
are looking for therapies that can slow down or reverse this rapid
deterioration of renal function, but some possible solutions
involving immunosuppression are risky because of the patients'
already compromised immune system.
Sclerotic Diseases
Glomerulosclerosis is scarring (sclerosis) of the
glomeruli. In several sclerotic conditions, a systemic disease like
lupus or diabetes is responsible. Glomerulosclerosis is caused by
the activation of glomerular cells to produce scar material. This
may be stimulated by molecules called growth factors, which may be
made by glomerular cells themselves or may be brought to the
glomerulus by the circulating blood that enters the glomerular
filter.
Diabetic nephropathy is the leading cause of glomerular
disease and of ESRD in the United States. Kidney disease is one of
several problems caused by elevated levels of blood glucose, the
central feature of diabetes. In addition to scarring the kidney,
elevated glucose levels appear to increase the speed of blood flow
into the kidney, putting a strain on the filtering glomeruli and
raising blood pressure.
Diabetic nephropathy usually takes many years to develop. People
with diabetes can slow down damage to their kidneys by controlling
their blood glucose through healthy eating with moderate protein
intake, physical activity, and medications. People with diabetes
should also be careful to keep their blood pressure at a level below
130/85 mm Hg, if possible. Blood pressure medications called
angiotensin-converting enzyme (ACE) inhibitors and angiotensin
receptor blockers (ARBs) are particularly effective at minimizing
kidney damage and are now frequently prescribed to control blood
pressure in patients with diabetes and in patients with many forms
of kidney disease.
Focal segmental glomerulosclerosis (FSGS)
describes scarring in scattered regions of the kidney, typically
limited to one part of the glomerulus and to a minority of glomeruli
in the affected region. FSGS may result from a systemic disorder or
it may develop as an idiopathic kidney disease, without a known
cause. Proteinuria is the most common symptom of FSGS, but, since
proteinuria is associated with several other kidney conditions, the
doctor cannot diagnose FSGS on the basis of proteinuria alone.
Biopsy may confirm the presence of glomerular scarring if the tissue
is taken from the affected section of the kidney. But finding the
affected section is a matter of chance, especially early in the
disease process, when lesions may be scattered.
Confirming a diagnosis of FSGS may require repeat kidney
biopsies. Arriving at a diagnosis of idiopathic FSGS requires the
identification of focal scarring and the elimination of possible
systemic causes such as diabetes or an immune response to infection.
Since idiopathic FSGS is, by definition, of unknown cause, it is
difficult to treat. No universal remedy has been found, and most
patients with FSGS progress to ESRD over 5 to 20 years. Some
patients with an aggressive form of FSGS reach ESRD in 2 to 3 years.
Treatments involving steroids or other immunosuppressive drugs
appear to help some patients by decreasing proteinuria and improving
kidney function. But these treatments are beneficial to only a
minority of those in whom they are tried, and some patients
experience even poorer kidney function as a result. ACE inhibitors
and ARBs may also be used in FSGS to decrease proteinuria. Treatment
should focus on controlling blood pressure and blood cholesterol
levels, factors that may contribute to kidney scarring.
Other Glomerular Diseases
Membranous nephropathy, also called membranous
glomerulopathy, is the second most common cause of the nephrotic
syndrome (proteinuria, edema, high cholesterol) in U.S. adults after
diabetic nephropathy. Diagnosis of membranous nephropathy requires a
kidney biopsy, which reveals unusual deposits of immunoglobulin G
and complement C3, substances created by the body's immune system.
Fully 75 percent of cases are idiopathic, which means that the cause
of the disease is unknown. The remaining 25 percent of cases are the
result of other diseases like systemic lupus erythematosus,
hepatitis B or C infection, or some forms of cancer. Drug therapies
involving penicillamine, gold, or captopril have also been
associated with membranous nephropathy. About 20 to 40 percent of
patients with membranous nephropathy progress, usually over decades,
to ESRD, but most patients experience either complete remission or
continued symptoms without progressive kidney failure. Doctors
disagree about how aggressively to treat this condition, since about
20 percent of patients recover without treatment. ACE inhibitors and
ARBs are generally used to reduce proteinuria. Additional medication
to control high blood pressure and edema is frequently required.
Some patients benefit from steroids, but this treatment does not
work for everyone. Additional immunosuppressive medications are
helpful for some patients with progressive disease.
Minimal change disease (MCD) is the diagnosis given when a
patient has the nephrotic syndrome and the kidney biopsy reveals
little or no change to the structure of glomeruli or surrounding
tissues when examined by a light microscope. Tiny drops of a fatty
substance called a lipid may be present, but no scarring has taken
place within the kidney. MCD may occur at any age, but it is most
common in childhood. A small percentage of patients with idiopathic
nephrotic syndrome do not respond to steroid therapy. For these
patients, the doctor may recommend a low-sodium diet and prescribe a
diuretic to control edema. The doctor may recommend the use of
nonsteroidal anti-inflammatory drugs to reduce proteinuria. ACE
inhibitors and ARBs have also been used to reduce proteinuria in
patients with steroid-resistant MCD. These patients may respond to
larger doses of steroids, more prolonged use of steroids, or
steroids in combination with immunosuppressant drugs, such as
chlorambucil, cyclophosphamide, or cyclosporine.
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Renal failure is any acute or chronic loss of kidney function and
is the term used when some kidney function remains. ESRD is total,
or nearly total, and permanent kidney failure. Depending on the form
of glomerular disease, renal function may be lost in a matter of
days or weeks or may deteriorate slowly and gradually over the
course of decades.
Acute Renal Failure
A few forms of glomerular disease cause very rapid deterioration
of kidney function. For example, PSGN can cause severe symptoms
(hematuria, proteinuria, edema) within 2 to 3 weeks after a sore
throat or skin infection develops. The patient may temporarily
require dialysis to replace renal function. This rapid loss of
kidney function is called acute renal failure (ARF). Although ARF
can be life-threatening while it lasts, kidney function usually
returns after the cause of the kidney failure has been treated. In
many patients, ARF is not associated with any permanent damage.
However, some patients may recover from ARF and subsequently develop
chronic renal failure (CRF).
Chronic Renal Failure
Most forms of glomerular disease develop gradually, often causing
no symptoms for many years. CRF is the slow, gradual loss of kidney
function. Some forms of CRF can be controlled or slowed down. For
example, diabetic nephropathy can be delayed by tightly controlling
blood glucose levels and using ACE inhibitors and ARBs to reduce
proteinuria and control blood pressure. But CRF cannot be cured.
Partial loss of renal function means that some portion of the
patient's nephrons have been scarred, and scarred nephrons cannot be
repaired. In most cases, CRF leads to ESRD.
End-Stage Renal Disease
To stay alive, a patient with ESRD must go on
dialysis--hemodialysis or peritoneal dialysis--or receive a new
kidney through transplantation. Patients with CRF who are
approaching ESRD should learn as much about their treatment options
as possible so they can make an informed decision when the time
comes. With the help of dialysis or transplantation, many people
continue to lead full, productive lives after reaching ESRD.
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- The kidneys filter waste and extra fluid from the
blood.
- The filtering process takes place in the nephron, where
microscopic blood vessel filters, called glomeruli, are attached
to fluid-collecting tubules.
- A number of different disease processes can damage the
glomeruli and thereby cause kidney failure. Glomerulonephritis and
glomerulosclerosis are broad terms that include many forms of
damage to the glomeruli.
- Some forms of kidney failure can be slowed down, but scarred
glomeruli can never be repaired.
- Treatment for the early stages of kidney failure depends on
the disease causing the damage.
- Early signs of kidney failure include blood or protein in the
urine and swelling in the hands, feet, abdomen, or face. Kidney
failure may be silent for many years.
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Signs and Symptoms of Glomerulonephritis
edema (eh-DEE-muh): Swelling caused by the accumulation of
fluid in cells and tissues. In kidney failure, fluid may collect in
the feet, hands, abdomen, or face.
hematuria (HEE-muh-TOOR-ee-uh): Blood in the urine. Blood
may turn the urine pink or cola-colored.
hypoproteinemia (HY-po-PRO-teen-EE-mee-uh): Reduced levels
of protein in the blood.
proteinuria (PRO-teen-YOOR-ee-uh): Large amounts of
protein in the urine.
uremia (yoo-REE-mee-uh): Accumulation of urea and other
wastes in the blood. These wastes, which become toxic in large
amounts, are normally eliminated through urination.
Diseases and Conditions
autoimmune (AW-toh-im-YOON) disease: A disease in which
the body's own disease-fighting cells attack the body itself.
hypertension (HY-per-TEN-shun): High blood pressure, a
condition that can cause kidney damage or be caused by kidney
disease.
idiopathic (id-ee-o-PATH-ik) disease: A disease that
occurs without a known cause.
nephrotoxic (NEF-ro-TOKS-ik): Damaging to the kidneys.
sclerotic (skleh-ROT-ik) disease: A disease in which
tissues become hardened or scarred.
systemic (sis-TEM-ik) disease: A disease that affects
multiple parts of the body, often as a result of substances
circulating in the blood.
Treatments and Procedures
biopsy (BY-op-see): A procedure in which a needle is used
to obtain small pieces of tissue from an organ for examination under
different types of microscopes, each of which shows a different
aspect of the tissue.
dialysis (dy-AL-ih-sis): A medical treatment that removes
wastes and extra fluid from the blood after the kidneys have stopped
working.
immunosuppressant (ih-MYOON-oh-suh-PRESS-unt): A medicine
given to block the body's immune system.
plasmapheresis (PLAZ-muh-fer-EE-sis): A medical treatment
in which the blood is treated outside the body to remove harmful
antibodies, and then returned to the patient.
Kidney Parts and Organic Substances
antibody (AN-tee-BOD-ee): A molecule that protects the
body against disease by attacking foreign tissues or organisms.
Antibodies are also called immunoglobulins.
antigen (AN-tih-jen): A substance that triggers a response
from the body's immune system.
autoantibody (AW-toh-AN-tee-bod-ee): An antibody that
attacks the body itself.
creatinine (kree-AT-ih-nin): A waste product in the blood
that results from the normal breakdown of muscle. Healthy kidneys
filter creatinine from the blood.
glomerulus (glo-MAIR-yoo-lus): The tiny cluster of looping
blood vessels in the nephron, where wastes are filtered from the
blood.
lipid (LIP-id): One of several fatty substances used in
cells. Excess lipids in the blood may result in harmful deposits in
blood vessels.
nephron (NEF-ron): One of a million tiny filtering units
in each kidney. Each nephron is made up of both a glomerulus and a
fluid-collecting tubule that processes extra water and wastes.
protein (PRO-teen): A substance found in food and used by
the body to grow, repair tissue, and fight disease.
urea (yoo-REE-uh): A waste material found in blood after
protein has been broken down. Healthy kidneys remove urea from the
blood. Damaged kidneys may allow urea to accumulate in the blood,
thus causing uremia.
The Nephrotic Syndrome
- The nephrotic syndrome is a condition marked by very high
levels of protein in the urine; low levels of protein in the
blood; swelling, especially around the eyes, feet, and hands; and
high cholesterol.
- The nephrotic syndrome is a set of symptoms, not a disease in
itself. It can occur with many diseases, so prevention relies on
controlling the diseases that cause it.
- Treatment of the nephrotic syndrome focuses on identifying and
treating the underlying cause, if possible, and reducing high
cholesterol, blood pressure, and protein in the urine through
diet, medication, or both.
- The nephrotic syndrome may go away once the underlying cause,
if known, is treated. However, often a kidney disease is the
underlying cause and cannot be cured. In these cases, the kidneys
may gradually lose their ability to filter wastes and excess water
from the blood. If kidney failure occurs, the patient will need to
be on dialysis or have a kidney transplant.
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American Association of Kidney Patients
American Kidney Fund
Life
Options/Rehabilitation Resource Center
National Kidney Foundation
