Kidney Biopsy

What is a kidney biopsy?

A biopsy is a diagnostic test that involves collecting small pieces of tissue, usually through a needle, for examination with a microscope. A kidney biopsy can help in forming a diagnosis and in choosing the best course of treatment. A kidney biopsy may be recommended for any of the following conditions:

• hematuria, which is blood in the urine
• proteinuria, which is excessive protein in the urine
• impaired kidney function, which causes excessive waste products in the blood

A pathologist will look at the kidney tissue samples to check for unusual deposits, scarring, or infecting organisms that would explain a person’s condition. The doctor may find a condition that can be treated and cured. If a person has progressive kidney failure, the biopsy may show how quickly the disease is advancing. A biopsy can also help explain why a transplanted kidney is not working properly.

Patients should talk with their doctors about what information might be learned from the biopsy and the risks involved so the patients can help make a decision about whether a biopsy is worthwhile.

[Top]

What are the preparations for a kidney biopsy?

Patients must sign a consent form saying they understand the risks involved in this procedure. The risks are slight, but patients should discuss these risks in detail with their doctors before signing the form.

Doctors should be aware of all the medicines a patient takes and any drug allergies that patient might have. The patient should avoid aspirin and other blood-thinning medicines for 1 to 2 weeks before the procedure. Some doctors advise their patients to avoid food and fluids before the test, while others tell patients to eat a light meal. Shortly before the biopsy, blood and urine samples are taken to make sure the patient doesn’t have a condition that would make doing a biopsy risky.

[Top]

What are the procedures for a kidney biopsy?

Kidney biopsies are usually done in a hospital. The patient is fully awake with light sedation. A local anesthetic is given before the needle is inserted.

Patients lie on their stomachs to position the kidneys near the surface of their backs. Patients who have a transplanted kidney lie on their backs. The doctor marks the entry site, cleans the area, and injects a local painkiller. For a biopsy using a needle inserted through the skin, the doctor uses a locating needle and x-ray or ultrasound equipment to find the kidney and then a collecting needle to gather the tissue. Patients are asked to hold their breath as the doctor uses a spring-loaded instrument to insert the biopsy needle and collect the tissue, usually for about 30 seconds or a little longer for each insertion. The spring-loaded instrument makes a sharp clicking noise that can be startling to patients. The doctor may need to insert the needle three or four times to collect the needed samples.

The kidneys filter wastes and extra fluid from the blood and direct them to the bladder as urine.

The entire procedure usually takes about an hour, including time to locate the kidney, clean the biopsy site, inject the local painkiller, and collect the tissue samples.

Patients who are prone to bleeding problems should not have a biopsy through the skin. These patients may still undergo a kidney biopsy through an open operation in which the surgeon makes an incision and can see the kidney to collect tissue samples.

[Top]

What happens after a kidney biopsy?

After the test, patients lie on their backs in the hospital for a few hours. Patients who have a transplanted kidney lie on their stomachs. During this time, the staff will monitor blood pressure and pulse and take blood samples to assess for blood loss. On rare occasions when bleeding does not stop on its own, a transfusion may be necessary to replace lost blood. Most patients leave the hospital the same day. Patients may notice some blood in their urine for 24 hours after the test.

A rare complication is infection from the biopsy.

Patients should tell their doctors or nurses if they have any of these problems:

• bloody urine more than 24 hours after the test
• inability to urinate
• fever
• worsening pain in the biopsy site
• faintness or dizziness

[Top]

How are kidney biopsy results reported?

After the biopsy, the doctor will inspect the tissue samples in the laboratory using one or more microscopes, perhaps using dyes to identify different substances that may be settled in the tissue. Electron microscopes may be used to see small details. Getting the complete biopsy results usually takes a few days. In urgent cases, a preliminary report may be given within a few hours.

Medical Tests for Prostate Problems

The prostate is a walnut-sized gland in men that produces fluid that is a component of semen. The gland has two or more lobes—or sections—enclosed by an outer layer of tissue. Located in front of the rectum and just below the bladder, where urine is stored, the prostate surrounds the urethra, which is the canal through which urine passes out of the body.

The most common prostate problem in men under 50 is inflammation or infection, which is called prostatitis. Prostate enlargement is another common problem. Because the prostate normally continues to grow as a man matures, prostate enlargement, also called benign prostatic hyperplasia or BPH, is the most common prostate problem for men over 50. Older men are at risk for prostate cancer as well, but it is much less common than BPH.

Sometimes, different prostate problems have similar symptoms. For example, one man with prostatitis and another with BPH may both have a frequent, urgent need to urinate. Other men with BPH may have different symptoms. For example, one man may have trouble beginning a stream of urine, while another may have to get up to go to the bathroom frequently at night. A man in the early stages of prostate cancer may have no symptoms at all. This confusing array of symptoms makes a thorough medical examination and testing very important. Diagnosing the problem may require a series of tests.

Male urinary tract, front and side views.

[Top]

Talking With Your Doctor or Nurse

Letting your doctor or nurse know you have a problem is the first step. Try to give as many details about the problem as you can, including when it began and how often it occurs. Tell the doctor or nurse whether you have had recurrent urinary tract infections or symptoms such as pain after ejaculation or during urination, sudden strong urges to urinate, or hesitancy and a weak urine stream. You should talk about the medicines you take, both prescription medicines and those you can buy over the counter, because they might be part of the problem. You should also talk about how much fluid you typically drink each day, whether you use caffeine or alcohol, and whether your urine has an unusual color or odor. In turn, the doctor or nurse will ask you about your general medical history, including any major illnesses or surgeries.

Other typical questions are as follows:

• Over the past month or so, how often have you had to urinate again in less than 2 hours?

• Over the past month, from the time you went to bed at night until the time you got up in the morning, how many times a night did you typically get up to urinate?

• Over the past month or so, how often have you had a sensation of not emptying your bladder completely after you finished urinating?

• Over the past month or so, how often have you had a weak urinary stream?

• Over the past month or so, how often have you had to push or strain to begin urinating?

Your answers to these questions may help your doctor or nurse identify the problem or determine what tests are needed. You may also receive a symptom score evaluation that can be used as a baseline to see how effective later treatments are at relieving those symptoms.

[Top]

Preparing for the Exam

The common tests your doctor or nurse will perform first require no special preparation. Digital rectal exams (DRE) and blood tests for prostate-specific antigen (PSA) are often included in routine physical examinations for men over 50. For African-American men and men with a family history of prostate cancer, it is recommended that tests be given starting at age 40. Some organizations even recommend that these tests be given to all men starting at age 40.

If you have urination problems or if the DRE or PSA test indicates that you might have a problem, you will probably be given additional tests that may require some preparation. Ask your doctor or nurse whether you should change your diet or fluid intake or stop taking any medications. If the tests involve inserting instruments into the urethra or rectum, you may be given antibiotics before and after the test to prevent infection.

[Top]

Procedures

DRE

This exam is usually done first. Many doctors perform a DRE as part of a routine physical exam for any man over 50, some even at 40, whether the man has urinary problems or not. You may be asked to bend over a table or to lie on your side holding your knees close to your chest. The doctor slides a gloved, lubricated finger into the rectum and feels the part of the prostate that lies next to it. You may find the DRE slightly uncomfortable, but it is very brief. This exam tells the doctor whether the gland has any bumps, irregularities, soft spots, or hard spots that require additional tests. If a prostate infection is suspected, the doctor might massage the prostate during the DRE to obtain fluid for examination with a microscope.

Digital rectal exam (DRE).

PSA Blood Test

To rule out cancer, your doctor may recommend a PSA blood test. The amount of PSA, a protein produced by prostate cells, is often higher in the blood of men who have prostate cancer. However, an elevated level of PSA does not necessarily mean you have cancer. The Food and Drug Administration has approved a PSA test for use in conjunction with a DRE to help detect prostate cancer in men age 50 or older and for monitoring men with prostate cancer after treatment. However, much remains unknown about how to interpret the PSA test, its ability to discriminate between cancer and benign prostate conditions, and the best course of action if the PSA is high.

Anemia in Kidney Disease and Dialysis

What is anemia?

A person whose blood is low in red blood cells has anemia. Red blood cells carry oxygen (O₂) to tissues and organs throughout the body and enable them to use the energy from food. Without oxygen, these tissues and organs—particularly the heart and brain—may not do their jobs as well as they should. For this reason, a person who has anemia may tire easily and look pale. Anemia may also contribute to heart problems.

Anemia is common in people with kidney disease. Healthy kidneys produce a hormone called erythropoietin, or EPO, which stimulates the bone marrow to produce the proper number of red blood cells needed to carry oxygen to vital organs. Diseased kidneys, however, often don’t make enough EPO. As a result, the bone marrow makes fewer red blood cells. Other common causes of anemia include blood loss from hemodialysis and low levels of iron and folic acid. These nutrients from food help young red blood cells make hemoglobin, their main oxygen-carrying protein.

[d]
Healthy kidneys produce a hormone called erythropoietin, or EPO, which stimulates the bone marrow to make red blood cells needed to carry oxygen throughout the body. Diseased kidneys don’t make enough EPO, and bone marrow then makes fewer red blood cells.

[Top]

What are the laboratory tests for anemia?

A complete blood count (CBC), a laboratory test performed on a sample of blood, includes a determination of a person’s hematocrit, the percentage of the blood that consists of red blood cells. The CBC also measures the amount of hemoglobin in the blood. The range of normal hematocrit and hemoglobin in women who have a period is slightly lower than for healthy men and healthy women who have stopped having periods (postmenopausal). The hemoglobin is usually about one-third the value of the hematocrit.

[Top]

When does anemia begin?

Anemia may begin to develop in the early stages of kidney disease, when you still have 20 percent to 50 percent of your normal kidney function. This partial loss of kidney function is often called chronic renal insufficiency. Anemia tends to worsen as kidney disease progresses. End-stage kidney failure, the point at which dialysis or kidney transplantation becomes necessary, doesn't occur until you have only about 10 percent of your kidney function remaining. Nearly everyone with end-stage kidney failure has anemia.

[Top]

How is anemia diagnosed?

If a person has lost at least half of normal kidney function and has a low hematocrit, the most likely cause of anemia is decreased EPO production. The estimate of kidney function, also called the glomerular filtration rate, is based on a blood test that measures creatinine. Experts recommend that doctors begin a detailed evaluation of anemia in men and postmenopausal women on dialysis when the hematocrit falls below 37 percent. For women of childbearing age, evaluation should begin when the hematocrit falls below 33 percent. The evaluation will include tests for iron deficiency and blood loss in the stool to be certain there are no other reasons for the anemia.

[Top]

How is anemia treated?

EPO

If no other cause for anemia is found, it can be treated with a genetically engineered form of EPO. The EPO is usually injected under the skin two or three times a week. Patients on hemodialysis who can’t tolerate EPO shots may receive the hormone intravenously during treatment. The intravenous method, however, requires a larger, more expensive dose and may not be as effective.

The U.S. Food and Drug Administration (FDA) recommends that patients treated with EPO therapy should achieve a target hemoglobin between 10 and 12 grams per deciliter (g/dL). Recent studies have shown that raising the hemoglobin above 12 g/dL in people who have kidney disease increases the risk of heart attack, heart failure, and stroke. People who take EPO shots should have regular tests to monitor their hemoglobin. If it climbs above 12 g/dL, their doctor should prescribe a lower dose of EPO. The FDA recommends that patients whose hemoglobin does not rise to the target level with normal doses of EPO ask their doctor to check for other causes of anemia.

Anemia of Inflammation and Chronic Disease

What is anemia?

Anemia is a condition in which the blood has a lower-than-normal number of red blood cells (RBCs). RBCs contain hemoglobin, an iron-rich protein that gives blood its red color and allows RBCs to transport oxygen from the lungs to the tissues of the body. Because RBC numbers are low in anemia, blood hemoglobin levels are also low.

People with anemia may feel tired because their blood does not supply enough oxygen to the body’s organs and tissues. If anemia becomes severe and prolonged, the lack of oxygen in the blood can lead to shortness of breath or exercise intolerance—a condition in which a person becomes easily fatigued during or after physical activity—and eventually cause the heart and other organs to fail.

[Top]

What is anemia of inflammation and chronic disease (AI/ACD)?

AI/ACD is a type of anemia that commonly occurs with chronic, or long-term, illnesses or infections. Cancer and inflammatory disorders, in which abnormal activation of the immune system occurs, can also cause AI/ACD. Some people develop AI/ACD without having any signs of these health problems.

AI/ACD is easily confused with iron-deficiency anemia because in both forms of anemia, levels of iron circulating in the blood are low. Circulating iron is necessary for RBC production. Low blood iron levels occur in iron-deficiency anemia because levels of iron stored in the body’s tissues are depleted. In AI/ACD, however, iron stores are normal or high. Low blood levels occur in AI/ACD, despite normal iron stores, because inflammatory and chronic diseases interfere with the body’s ability to use stored iron and absorb iron from the diet. Certain treatments for chronic diseases may also impair RBC production and contribute to AI/ACD. AI/ACD is the second most common form of anemia, after iron-deficiency anemia, but it is rarely severe.

While AI/ACD can affect people at any age, older adults are especially susceptible because they have the highest rates of chronic disease. AI/ACD is also common among hospitalized patients, particularly those with chronic illnesses.

More than 130 million Americans live with chronic conditions.¹ Addressing the causes of anemia in people with chronic conditions can help improve their health and quality of life.

¹Chronic disease overview. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/nccdphp/overview.htm. Updated March 20, 2008. Accessed April 1, 2008.

[Top]

What causes AI/ACD?

A number of chronic diseases can cause anemia for different reasons.

Infectious and inflammatory diseases. As part of the immune response that occurs with infection and noninfectious inflammatory diseases, cells of the immune system release proteins called cytokines. These proteins help heal and defend the body against infection. But they can also affect normal body functions. In AI/ACD, immune cytokines interfere with the body’s ability to absorb and use iron. Cytokines may also interfere with the production and normal activity of erythropoietin (EPO), a hormone made by the kidneys that stimulates bone marrow to produce RBCs.

Infectious diseases that cause AI/ACD include tuberculosis, HIV, endocarditis—infection in the heart—and osteomyelitis, a bone infection. Sometimes acute infections—those that develop quickly and may not last long—can also cause AI/ACD.

Inflammatory diseases that can lead to AI/ACD include rheumatoid arthritis, lupus, diabetes, heart failure, degenerative joint disease, and inflammatory bowel disease (IBD). IBD, including Crohn’s disease, can also cause iron deficiency due to poor absorption of iron by the diseased intestine and bleeding from the gastrointestinal tract.

Kidney disease. People with kidney disease can develop anemia for several different reasons. For one, diseased kidneys often fail to make enough EPO. In addition, kidney disease results in abnormal absorption and use of iron, which is typical of AI/ACD. Because anemia worsens as kidney disease advances, nearly everyone with end-stage kidney disease has anemia.

People with kidney failure can also develop iron deficiency due to blood loss during hemodialysis, a procedure that removes blood from an artery, purifies it, and returns it to a vein, thereby doing the job that the kidneys no longer can. Low levels of iron and of folic acid—another nutrient required for normal RBC production—may also contribute to anemia in people with kidney disease.

Cancer. AI/ACD can occur with certain types of cancer, including Hodgkin’s disease, non-Hodgkin’s lymphoma, and breast cancer. Like chronic inflammatory disorders and infections, these types of cancer cause inflammatory cytokines to be released in the body. The anemia of AI/ACD can also be made worse by cancer chemotherapy and radiation treatments that damage the bone marrow—where RBCs are produced—and by the cancer’s invasion of bone marrow.

Your Urinary System and How It Works

The organs, tubes, muscles, and nerves that work together to create, store, and carry urine are the urinary system. The urinary system includes two kidneys, two ureters, the bladder, two sphincter muscles, and the urethra.

How does the urinary system work?

Front view of urinary tract.

Your body takes nutrients from food and uses them to maintain all bodily functions including energy and self-repair. After your body has taken what it needs from the food, waste products are left behind in the blood and in the bowel. The urinary system works with the lungs, skin, and intestines—all of which also excrete wastes—to keep the chemicals and water in your body balanced. Adults eliminate about a quart and a half of urine each day. The amount depends on many factors, especially the amounts of fluid and food a person consumes and how much fluid is lost through sweat and breathing. Certain types of medications can also affect the amount of urine eliminated.

The urinary system removes a type of waste called urea from your blood. Urea is produced when foods containing protein, such as meat, poultry, and certain vegetables, are broken down in the body. Urea is carried in the bloodstream to the kidneys.

The kidneys are bean-shaped organs about the size of your fists. They are near the middle of the back, just below the rib cage. The kidneys remove urea from the blood through tiny filtering units called nephrons. Each nephron consists of a ball formed of small blood capillaries, called a glomerulus, and a small tube called a renal tubule. Urea, together with water and other waste substances, forms the urine as it passes through the nephrons and down the renal tubules of the kidney.

From the kidneys, urine travels down two thin tubes called ureters to the bladder. The ureters are about 8 to 10 inches long. Muscles in the ureter walls constantly tighten and relax to force urine downward away from the kidneys. If urine is allowed to stand still, or back up, a kidney infection can develop. Small amounts of urine are emptied into the bladder from the ureters about every 10 to 15 seconds.

The bladder is a hollow muscular organ shaped like a balloon. It sits in your pelvis and is held in place by ligaments attached to other organs and the pelvic bones. The bladder stores urine until you are ready to go to the bathroom to empty it. It swells into a round shape when it is full and gets smaller when empty. If the urinary system is healthy, the bladder can hold up to 16 ounces (2 cups) of urine comfortably for 2 to 5 hours.

Circular muscles called sphincters help keep urine from leaking. The sphincter muscles close tightly like a rubber band around the opening of the bladder into the urethra, the tube that allows urine to pass outside the body.

Nerves in the bladder tell you when it is time to urinate, or empty your bladder. As the bladder first fills with urine, you may notice a feeling that you need to urinate. The sensation to urinate becomes stronger as the bladder continues to fill and reaches its limit. At that point, nerves from the bladder send a message to the brain that the bladder is full, and your urge to empty your bladder intensifies.

When you urinate, the brain signals the bladder muscles to tighten, squeezing urine out of the bladder. At the same time, the brain signals the sphincter muscles to relax. As these muscles relax, urine exits the bladder through the urethra. When all the signals occur in the correct order, normal urination occurs.

[Top]

What causes problems in the urinary system?

Problems in the urinary system can be caused by aging, illness, or injury. As you get older, changes in the kidneys’ structure cause them to lose some of their ability to remove wastes from the blood. Also, the muscles in your ureters, bladder, and urethra tend to lose some of their strength. You may have more urinary infections because the bladder muscles do not tighten enough to empty your bladder completely. A decrease in strength of muscles of the sphincters and the pelvis can also cause incontinence, the unwanted leakage of urine. Illness or injury can also prevent the kidneys from filtering the blood completely or block the passage of urine.

[Top]

How are problems in the urinary system detected?

Urinalysis is a test that studies the content of urine for abnormal substances such as protein or signs of infection. This test involves urinating into a special container and leaving the sample to be studied.

Urodynamic tests evaluate the storage of urine in the bladder and the flow of urine from the bladder through the urethra. Your doctor may want to do a urodynamic test if you are having symptoms that suggest problems with the muscles or nerves of your lower urinary system and pelvis—ureters, bladder, urethra, and sphincter muscles.

Urodynamic tests measure the contraction of the bladder muscle as it fills and empties. The test is done by inserting a small tube called a catheter through your urethra into your bladder to fill it either with water or a gas. Another small tube is inserted into your rectum or vagina to measure the pressure put on your bladder when you strain or cough. Other bladder tests use x-ray dye instead of water so that x-ray pictures can be taken when the bladder fills and empties to detect any abnormalities in the shape and function of the bladder. These tests take about an hour.

The Kidneys and How They Work

What do the kidneys do?

The kidneys are bean-shaped organs, each about the size of a fist. They are located near the middle of the back, just below the rib cage, one on each side of the spine. The kidneys are sophisticated reprocessing machines. Every day, a person’s kidneys process about 200 quarts of blood to sift out about 2 quarts of waste products and extra water. The wastes and extra water become urine, which flows to the bladder through tubes called ureters. The bladder stores urine until releasing it through urination.

The kidneys remove wastes and water from the blood to form urine. Urine flows from the kidneys to the bladder through the ureters.

Wastes in the blood come from the normal breakdown of active tissues, such as muscles, and from food. The body uses food for energy and self-repairs. After the body has taken what it needs from food, wastes are sent to the blood. If the kidneys did not remove them, these wastes would build up in the blood and damage the body.

The actual removal of wastes occurs in tiny units inside the kidneys called nephrons. Each kidney has about a million nephrons. In the nephron, a glomerulus—which is a tiny blood vessel, or capillary—intertwines with a tiny urine-collecting tube called a tubule. The glomerulus acts as a filtering unit, or sieve, and keeps normal proteins and cells in the bloodstream, allowing extra fluid and wastes to pass through. A complicated chemical exchange takes place, as waste materials and water leave the blood and enter the urinary system.

In the nephron (left), tiny blood vessels intertwine with urine-collecting tubes. Each kidney contains about 1 million nephrons.

At first, the tubules receive a combination of waste materials and chemicals the body can still use. The kidneys measure out chemicals like sodium, phosphorus, and potassium and release them back to the blood to return to the body. In this way, the kidneys regulate the body’s level of these substances. The right balance is necessary for life.

In addition to removing wastes, the kidneys release three important hormones:

• erythropoietin, or EPO, which stimulates the bone marrow to make red blood cells
• renin, which regulates blood pressure
• calcitriol, the active form of vitamin D, which helps maintain calcium for bones and for normal chemical balance in the body

Analgesic Nephropathy (Painkillers and the Kidneys)

An analgesic is any medicine intended to relieve pain. Over-the-counter analgesics—that is, painkillers available without a prescription—include aspirin, acetaminophen, ibuprofen, naproxen sodium, and others. These drugs present no danger for most people when taken in the recommended dosage. But some conditions make taking even these common painkillers dangerous for the kidneys. Also, taking one of these drugs regularly over a long period of time may increase the risk for kidney problems. Most drugs that can cause kidney damage are excreted only through the kidneys. That is, they are not broken down by the liver, as alcohol is, or passed out of the body through the digestive tract.

Analgesic use has been associated with two different forms of kidney damage: acute renal failure and a type of chronic kidney disease called analgesic nephropathy.

Acute Kidney Failure

Some patient case reports have attributed incidents of sudden-onset acute kidney failure to the use of over-the-counter painkillers, including aspirin, ibuprofen, and naproxen sodium. Some of these patients experienced acute illnesses involving fluid loss or decreased fluid intake. Other patients in these reports had risk factors such as systemic lupus erythematosus, advanced age, chronic kidney disease, or recent heavy alcohol consumption. These cases involved a single dose in some instances and generally short-term analgesic use of not more than 10 days.

Acute kidney failure requires emergency dialysis to clean the blood. Kidney damage is frequently reversible, with normal kidney function returning after the emergency is over and the analgesic use is stopped.

Analgesic Nephropathy

A second form of kidney damage, called analgesic nephropathy, can result from taking painkillers every day for several years. Analgesic nephropathy is a chronic kidney disease that over years gradually leads to irreversible kidney failure and the permanent need for dialysis or a kidney transplant to restore kidney function. Researchers estimate that four out of 100,000 people will develop analgesic nephropathy. It is most common in women over 30.

The painkiller phenacetin has been taken off the market because of its association with analgesic nephropathy. Recent studies have suggested that longstanding daily use of analgesics such as acetaminophen or ibuprofen may also increase the risk of chronic kidney damage, but this evidence is not as clear.

In view of these findings, people with conditions that put them at risk for acute kidney failure should check with their health care provider before taking any analgesic medicine. People who take over-the-counter painkillers regularly should check with their primary care physician to make sure the drugs are not hurting their kidneys. The physician may be able to recommend a safer alternative and can order regular tests to monitor their kidney function.

Treatment

If you have been taking analgesics regularly to control chronic pain, you may be advised to find new ways to treat your pain, such as behavior modification or relaxation techniques. Depending on how much your kidney function has declined, you may be advised to change your diet, limit the fluids you drink, or take medications to avoid anemia and bone problems caused by kidney disease. Your doctor will monitor your kidney function with regular urine and blood tests.

Amyloidosis and Kidney Disease

Proteins are important building blocks for all body parts, including muscles, bones, hair, and nails. Proteins circulate throughout the body in the blood and are normally harmless. Occasionally, cells produce abnormal proteins that can settle in body tissue, forming deposits and causing disease. When these deposits of abnormal proteins were first discovered, they were called amyloid, and the disease process amyloidosis.

In recent years, researchers have discovered that different kinds of proteins can form amyloid deposits and have identified several types of amyloidosis. Two of these types are closely related to kidney disease. In primary amyloidosis, abnormal protein production occurs as a first step and can lead to kidney disease. Dialysis-related amyloidosis (DRA), on the other hand, is a result of kidney disease.

[Top]

Primary Amyloidosis

Primary amyloidosis occurs when the body's antibody-producing cells do not function properly and produce abnormal protein fibers made of antibody fragments. Some people with primary amyloidosis have a condition called multiple myeloma. The antibody fragments come together to form amyloid deposits in different organs, including the kidneys, where they cause serious damage. Injured kidneys can't function effectively and may be unable to remove urea and other wastes from the blood. Elevated levels of these protein fibers can also damage the heart, lungs, brain, and digestive system.

One common sign of kidney amyloidosis is the presence of abnormally high levels of protein in the urine, a condition known as proteinuria. Healthy kidneys prevent protein from entering the urine, so the presence of protein may be a sign that the kidneys aren't working properly. A physician who finds large amounts of protein in the urine may also perform a biopsy—take a small sample of tissue for examination with a microscope—to confirm amyloidosis.

Current treatments are aimed at slowing the progression of amyloid build-up. Combination drug therapy with melphalan, a cancer drug, and prednisone, an anti-inflammatory steroid drug, may improve organ function and survival rates by interrupting the growth of the abnormal cells that produce amyloid protein. These are the same drugs used in chemotherapy to treat certain cancers, such as multiple myeloma, and they may have serious side effects, such as nausea and vomiting, hair loss, and fatigue.

Some clinics have reported promising results treating amyloidosis by transplanting the patient’s own blood stem cells to replace diseased or damaged bone marrow. The therapy also requires high doses of melphalan, so side effects can be serious. Patients with heart problems may not be considered for this treatment.

[Top]

Dialysis-Related Amyloidosis

Normal kidneys filter and remove excess small proteins from the blood, thus keeping blood levels normal. When the kidneys don't work properly, as in patients receiving dialysis, one type of small protein calle beta-2-microglobulin builds up in the blood. When this occurs, beta-2-microglobulin molecules may join together, like the links of a chain, forming a few very large molecules from many smaller ones. These large molecules can form deposits and eventually damage the surrounding tissues and cause great discomfort. This condition is called dialysis-related amyloidosis (DRA).

DRA is relatively common in patients, especially older adults, who have been on hemodialysis for more than 5 years. Hemodialysis membranes that have been used for many years don't effectively remove the large, complex beta-2-microglobulin proteins from the bloodstream. Newer hemodialysis membranes, as well as peritoneal dialysis, remove beta-2-microglobulin more effectively, but not enough to keep blood levels normal. As a result, blood levels remain elevated, and deposits form in bone, joints, and tendons (the tissue that connects the muscle to the bone). DRA may result in pain, stiffness, and fluid in the joints. Patients with DRA may also develop hollow cavities, or cysts, in some of their bones; these may lead to unexpected bone fractures. Amyloid deposits may cause tears in ligaments and tendons. Most patients with these problems can be helped by surgical intervention.

Half of the people with DRA also develop a condition called carpal tunnel syndrome, which results from the unusual buildup of protein in the wrists. Patients with this condition may experience numbness or tingling, sometimes associated with muscle weakness, in their fingers and hands. This is a treatable condition.

Amyloid may build up in the wrist and cause bone
cysts or carpal tunnel syndrome.

Unfortunately, no cure for DRA has been found, although a successful kidney transplant may stop the disease from progressing. However, DRA has caught the attention of dialysis engineers, who are attempting to develop new dialysis membranes that can remove larger amounts of beta-2-microglobulin from the blood.

[Top]

Hope through Research

In recent years, researchers have learned a great deal about kidney disease. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) sponsors several programs aimed at understanding kidney failure and finding treatments to stop its progression.

The NIDDK's Division of Kidney, Urologic, and Hematologic Diseases supports basic research into normal kidney function and the diseases that impair normal function at the cellular and molecular levels, including amyloidosis. Recently, NIDDK-sponsored researchers have identified several genes that may contribute to a hereditary form of primary amyloidosis. In 2001, a team of researchers at the Indiana University School of Medicine located a mutation in the apolipoprotein A-II gene of a patient with kidney damage caused by amyloidosis. The researchers noted that the patient had reabsorbed most of the amyloid. They theorize that learning how this reabsorption occurs may point the way to possible therapies for all forms of amyloidosis. The NIDDK is also supporting multiple efforts to develop a blood detoxification system that will eliminate beta-2-microglobulin.

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.

In the nephron (left), tiny blood vessels intertwine with fluid-collecting tubes. Each kidney contains about 1 million nephrons.

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.

[Top]

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.

[Top]

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.

[Top]

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.

[Top]

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.

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. Conventional treatment for lupus nephritis includes a combination of two drugs, cyclophosphamide, a cytotoxic agent that suppresses the immune system, and prednisolone, a corticosteroid used to reduce inflammation. A newer immunosuppressant, mychophenolate mofetil (MMF), has been used instead of cyclophosphamide. Preliminary studies indicate that MMF may be as effective as cyclophosphamide and has milder side effects.

Kidney Disease in African Americans

• African Americans are nearly four times more likely than Caucasians to develop kidney failure,¹ which requires dialysis or a kidney transplant.

• An NKDEP survey of African Americans found that only eight percent named kidney disease as a consequence of high blood pressure, and only 17 percent named kidney disease as a consequence of diabetes. Of those surveyed who had high blood pressure and diabetes, only 10 percent and 29 percent, respectively, identified kidney disease as a negative consequence of not treating their conditions.²

• African Americans make up about 12 percent of the population but account for 32 percent of people with kidney failure.¹

• Among new patients whose kidney failure was caused by high blood pressure, more than half (51.2 percent) are African-American.¹

• Among new patients whose kidney failure was caused by diabetes, almost one third (31.3 percent) are African-American.¹

• African-American men ages 20 to 29 are 10 times more likely to develop kidney failure due to high blood pressure than Caucasian men in the same age group. African-American men ages 30 to 39 are about 14 times more likely to develop kidney failure due to high blood pressure than Caucasian men in the same age group.¹

Kidney Disease in the United States

• Approximately 20 million Americans have kidney disease.³

• Early kidney disease has no symptoms. If left undetected, it can progress to kidney failure with little or no warning.

• By the end of 2003, more than 128,000 people were living with a kidney transplant, and almost 325,000 were on dialysis – a number that has nearly tripled since 1988.¹

• Public and private spending to treat patients with kidney failure in the United States in 2003 was $27.3 billion,¹ up from around $22 billion in 2001.

• The most common causes of kidney failure are diabetes and high blood pressure, together accounting for about 70 percent of new cases.¹

• By 2030, more than 2 million people will be receiving treatment for kidney failure.⁴

• Kidney disease can be effectively treated if detected early. ACE (angiotensin-converting enzyme) inhibitors^5,6,7,8 or ARBs^9,10 (angiotensin receptor blockers) can prevent or slow progression of kidney disease to kidney failure.

---

1. U.S. Renal Data System (2005). National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD.
2. National Kidney Disease Education Program. NKDEP Survey of African-American Adults' Knowledge, Attitudes and Behaviors Related to Kidney Disease. National Institutes of Health, U.S. Department of Health and Human Services; 2003. (Unpublished study)
3. U.S. Renal Data System (2004). National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD.
4. Gilbertson D, Solid C, Xue JL, Collins AJ. Projecting the U.S. ESRD population to 2030. Presented at 2003 ASN Annual Meeting. Available at: www.usrds.org/2003/pres/html/ 5U_ASN_projections_files/frame.htm. Posted November 2003. Accessed April 3, 2006.
5. Giatras I, Lau J, Levey AS, Angiotensin-Converting-Enzyme Inhibition and Progressive Renal Disease Study Group. Effect of angiotensin-converting enzyme inhibitors on the progression of nondiabetic renal disease: a meta-analysis of randomized trials. Annals of Internal Medicine. 1997;127(5):337-345.
6. Jafar TH, Schmid CH, Landa M, Giatras I, Toto R, Remuzzi G, Maschio G, Brenner BM, Kamper A, Zucchelli P, Becker G, Himmelmann A, Bannister K, Landais P, Shahinfar S, de Jong PE, de Zeeuw D, Lau J, Levey AS. Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease: a meta-analysis of patient-level data. Annals of Internal Medicine. 2001;135(2):73-87.
7. Kshirsagar AV, Joy MS, Hogan SL, Falk RJ, Colindres RE. Effect of ACE inhibitors in diabetic and nondiabetic chronic renal disease: a systematic overview of randomized placebo-controlled trials. American Journal of Kidney Diseases. 2000;35(4):695-707.
8. Wright JT Jr, Bakris G, Greene T, Agodoa LY, Appel LJ, Charleston J, Cheek D, Douglas- Baltimore JG, Gassman J, Glassock R, Hebert L, Jamerson K, Lewis J, Phillips RA, Toto RD, Middleton JP, Rostand SG, African American Study of Kidney Disease and Hypertension Study Group. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. JAMA. 2002;288(19):2421-2431.
9. Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, Ritz E, Atkins RC, Rohde R, Raz I. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. New England Journal of Medicine. 2001;345(12):851-860.
10. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S, RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. New England Journal of Medicine. 2001;345(12):861-869.