What Causes Glomerular Disease?
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.
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.
Hereditary nephritis--Alport
syndrome
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 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. A
class of blood pressure medications called angiotensin-converting enzyme
(ACE) inhibitors is particularly effective at minimizing kidney damage and
is now frequently prescribed to control blood pressure in patients with
diabetes.
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 proceed to 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 only to a minority of
those in whom they are tried, and some patients experience even poorer
kidney function as a result of therapy. ACE inhibitors 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.
Idiopathic nephrotic syndrome--minimal change
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 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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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.