Each glomerulus-and-tubule unit is called a
Eric P. Cohen, MD
Walter F. Piering, MD
Lakshmi Raman, MD
Kevin Regner, MD
Glomerulonephritis is the term used to describe a group of diseases that damage the part of the kidney that filters blood. When the kidney is damaged, it cannot get rid of wastes and extra fluid in the body. If the illness continues, the kidneys may stop working completely. Some other terms you may hear used are nephritis and nephrotic syndrome.
What are the kidneys and what do they do?
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 200 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.
How do glomerular diseases interfere with kidney function?
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.
What are the symptoms of glomerular disease?
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.
How is glomerular disease diagnosed?
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 with 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.
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. Sometimes glomerular disease is idiopathic, meaning that it occurs without an apparent associated disease.
Types of glomerular disease:
Lupus is a short name for a disease called "lupus erythematosus." The word lupus means wolf in Latin. The skin rash that some patients get can form a butterfly pattern over the bridge of the nose, resembling the bite of a wolf. Lupus is called an "autoimmune" disease because the immune system, which usually protects the body from disease, turns against the body, causing harm to organs and tissues. There are two types of lupus. Systemic lupus erythematosus can harm your skin, joints, kidneys and brain and may be fatal. The other type, called "discoid" lupus erythematosus, affects only your skin. No one knows what causes the disease. Your family history and things in your environment such as infections, viruses, toxic chemicals or pollutants (car fumes, factory smoke) may play a role in causing the disease. Men and women of all ages and races get lupus. However, it is about 10 times more common in women than in men. About 500,000 Americans have lupus. Different people get different symptoms. These may include skin rashes, joint pain, hair loss, sun sensitivity, tiredness, weight loss, fever, swelling of lymph glands, chest pain and nerve involvement. About 90 percent of lupus patients will have some kidney damage, but only two to three percent actually develop kidney disease severe enough to require treatment. The kidney disease may be "silent" and not cause any symptoms. However, you may have dark urine, flank pain, high blood pressure, weight gain from extra fluid and swelling around your eyes and in your hands and feet. Lupus is treated with drugs that block your body's immune system. Some of these are prednisone, azathioprine, cyclophosphamide or cyclosporine.
Goodpasture's Syndrome is an uncommon disease that affects both the kidneys and the lungs. If you have the disease, usually you will:
• bleed from the lungs
• cough up blood
• have inflamed kidneys (glomerulonephritis).
Usually, symptoms will occur because your body is making antibodies that hurt the lining of your lungs and kidneys. It is not known why your antibodies begin to attack your own body. Usually they only do helpful things such as fight infections. This problem is most common in people between the ages of 15 and 35 or after age 55. It is not contagious and it is more common in men and Caucasians. Goodpasture's Syndrome may cause life-threatening bleeding in the lungs, but does not usually cause long-term damage in that area. The harm done to your kidneys, however, can result in kidney failure. Early diagnosis and treatment are the best ways to prevent kidney damage. Your doctor will give you medicine that will fight the harmful antibodies. The doctor may suggest that you undergo a special blood filtering process (plasmapheresis) to remove harmful antibodies. Usually, your body will make the antibodies for a short time, anywhere from a few weeks to two years. Once this stops, you should not have any more problems with your lungs. However, your kidneys may have been harmed a little or a lot.
IgA nephropathy is a form of glomerular disease that results when immunoglobulin A (IgA) forms deposits in the glomeruli, where it creates inflammation. 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. 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. No treatment is recommended for early or mild cases of IgA nephropathy when the patient has normal blood pressure and less than 1 gram of protein in a 24-hour urine output. When proteinuria exceeds 1 gram/day, treatment is aimed at protecting kidney function by reducing proteinuria and controlling blood pressure. Blood pressure medicines—angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin receptor blockers (ARBs)—that block a hormone called angiotensin are most effective at achieving those two goals simultaneously.
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 kidney disease and sensory loss. Men with Alport syndrome usually first show evidence of renal insufficiency while in their twenties and reach total kidney failure 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. Treatment focuses on controlling blood pressure to maintain kidney function.
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. Endocarditis sometimes produces chronic kidney disease (CKD).
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 total kidney failure. 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.
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. 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. No universal remedy has been found, and most patients with FSGS progress to total kidney failure over 5 to 20 years. Treatments involving steroids or other immunosuppressive drugs appear to help some patients by decreasing proteinuria and improving kidney function. 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.
Membranous nephropathy, also called membranous glomerulopathy, is the second most common cause of the nephrotic syndrome (proteinuria, edema, high cholesterol) in U.S. 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. About 20 to 40 percent of patients with membranous nephropathy progress, usually over decades, to total kidney failure, but most patients experience either complete remission or continued symptoms without progressive kidney failure. 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. MCD may occur at any age, but it is most common in childhood.
Points to Remember
• 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.