Kidney Disease

Kidney disease occurs when the kidneys are damaged and cannot function properly. Numerous conditions and diseases can result in damage to the kidneys, thus affecting their ability to filter waste from the blood while reabsorbing important substances. Generally, kidney disease may present or develop in a few different ways:

• Acute kidney injury (AKI) is the rapid loss of kidney function. It may be recognized when a person suddenly produces urine much less frequently and/or has a dramatic increase in the level of waste products in the blood that the kidneys normally filter out. AKI is often the result of trauma, illness, or a medication that damages the kidneys. It is most common in people who are already hospitalized, such as those who are critically ill and in the intensive care unit. If the damage caused by AKI persists, it can eventually progress to chronic kidney disease.
• Chronic kidney disease (CKD) occurs over time and is usually defined as lasting over 3 months. The most common causes are diabetes and high blood pressure (hypertension). According to the National Kidney Foundation, 26 million American adults have CKD and many more are at risk. However, in some cases, it is preventable or, if detected early enough, treatable to prevent or delay progression to kidney failure.
• Nephrotic syndrome is characterized by the loss of too much protein in the urine. It is caused by damage to the glomeruli and can be a primary disorder of the kidney or secondary to an illness or other condition, such as cancer or lupus. Along with a high amount of protein in the urine, signs and symptoms of nephrotic syndrome include a low amount of albumin in the blood, higher than normal lipid levels in the blood, and swelling (edema) in the legs, feet, and ankles. The condition may be acute or chronic, and the outcome can vary.
• Kidney failure, also called end-stage renal disease or ESRD, is the total or near total loss of kidney function and is permanent. Treatment with hemodialysis or kidney transplant is the only option at this stage of kidney disease to sustain life.

Various factors can cause different patterns of injury to the kidneys and can affect kidney function. Some factors affect the blood-filtering units, the nephrons, or parts of the nephrons, such as the glomeruli or the tubules. Some factors affect the passage of urine from the kidney while others cause damage to the kidney(s) as a whole.

The most common causes of and main risk factors for kidney disease are:

• Diabetes: a sustained high level of blood glucose from uncontrolled diabetes can over time damage the nephrons in the kidneys. This can be avoided by maintaining good glucose control.
• High blood pressure (hypertension): can damage blood vessels within the kidneys, preventing them from filtering wastes from the blood as they should. Hypertension can therefore cause CKD, but having CKD can cause high blood pressure as well.
• Family history of kidney disease: for example, polycystic kidney disease (PKD) is an inherited disorder in which cysts grow in the kidneys, reducing kidney function over time and eventually leading to kidney failure.

Some other examples of factors affecting the kidneys or patterns of kidney disease include:

• Glomerulonephritis (also called chronic nephritis or nephritic syndrome): a group of diseases that cause inflammation and damage to the blood filtering units of the kidneys (glomeruli) and the third most common type of kidney disease. As blood filtering becomes impaired, urine output decreases, water and waste products accumulate in the blood, and blood appears in the urine. Because the blood cells break down, urine often becomes brown instead of red. Certain body tissues swell with the excess water (a condition called edema). Outcomes can vary: the condition may go away in a few weeks, permanently reduce kidney function, or progress to end-stage renal disease.
• Obstruction: the urinary tract can become blocked, or obstructed, from such things as a kidney stone or tumor. The blockage can lead to infection and injury of the kidney.
• Autoimmune disease: sometimes an autoimmune disorder such as systemic lupus erythematosus or Goodpasture syndrome can lead to glomerular disease and affect the kidneys. In autoimmune diseases, the body's immune system mistakenly attacks and damages its own tissue and organs, including the kidneys.
• Infections: certain bacteria and viruses can infect the kidneys and cause damage. Repeated urinary tract infections (UTIs) that spread to the kidneys is an example.
• Immune response: infections in other parts of the body can stimulate an immune response that has an adverse effect on the kidneys. Examples include strep infection of the throat or skin, the skin infection impetigo, an infection inside the heart (endocarditis), or a viral infection such as HIV, hepatitis B, or hepatitis C.
• Congenital defects: defects present at birth, such as those that impede the normal flow of urine.
• Injury: trauma to the kidneys can cause AKI that can lead to chronic kidney disease.
• Toxins: some contrast dyes used for imaging procedures and certain medications can have toxic effects on the kidneys.
• Drugs: use and/or overuse of non-steroidal anti-inflammatory drugs (NSAIDS), such as over-the-counter ibuprofen, and various prescription drugs can damage the kidneys. Use of analgesics (pain killers) has been associated with two different forms of kidney damage: acute renal failure and a type of chronic kidney disease called analgesic nephropathy. Certain antibiotics can be directly toxic to the kidneys if their levels are too high. Other drugs may trigger an immune response by the body that subsequently causes kidney damage.
• Pre-renal azotemia: any situation in which there is severe blood loss or reduced blood flow may prevent the kidneys from working properly, such as a blood clot, severe burn, severe dehydration, or septic shock.
• Interstitial nephritis: a kidney disorder in which the spaces between the kidney tubules become inflamed and swollen. It may be acute or chronic. Causes include side effects of certain medications, certain autoimmune disorders, and having a low blood potassium level or a high blood level of calcium or uric acid. It is associated with decreased urine output, blood in the urine, and edema. Usually, this is a short-term condition.
• Acute tubular necrosis (ATN): a kidney disorder involving damage to the tubules in the kidneys. It is one of the most common causes of kidney failure in hospitalized patients. It is caused by a lack of oxygen to the kidney tissues or from damage to the kidneys by toxic substances such as contrast dyes used for x-ray studies and certain medications. In most cases, ATN is reversible.

Chronic kidney disease (CKD) can progress silently over many years, with no signs or symptoms or with ones that are too general for a person to suspect as related to kidney function. For that reason, routine blood and urine tests are especially important. They detect blood or protein in the urine and abnormal levels of certain waste products in the blood, such as creatinine and urea (blood urea nitrogen or BUN), which are early signs of kidney dysfunction. The following problems may, however, be warning signs of kidney disease and should not be ignored. Prompt medical attention is required when any of these are present:

• Swelling or puffiness, particularly around the eyes or in the face, wrists, abdomen, thighs or ankles
• Urine that is foamy, bloody, or coffee-colored
• A decrease in the amount of urine
• Problems urinating, such as a burning feeling or abnormal discharge during urination, or a change in the frequency of urination, especially at night
• Mid-back pain (flank), below the ribs, near where the kidneys are located
• High blood pressure (hypertension)

As kidney disease worsens, symptoms may include:

• Urinating more or less often
• Feeling itchy
• Tiredness, loss of concentration
• Loss of appetite, nausea and/or vomiting
• Swelling and/or numbness in hands and feet
• Darkened skin
• Muscle cramps

Acute kidney injury (AKI) is a sudden loss of kidney function and can be fatal. It requires prompt treatment. Symptoms may include:

• Urinating less frequently
• Fluid retention, causing swelling in the legs, ankles or feet
• Drowsiness, fatigue
• Shortness of breath
• Nausea
• Confusion
• Seizures or coma
• Chest pain

The routine blood and urine tests listed below may provide the first indication of a kidney problem or may be ordered if chronic kidney disease (CKD) is suspected due to a person's signs and symptoms. These tests reflect how well the kidneys are removing excess fluids and wastes and some are included in the basic and comprehensive metabolic panels (BMP and CMP).

A blood pressure measurement is also important since high blood pressure (hypertension) can lead to CKD. When a structural problem is suspected, a variety of imaging tests can be used to evaluate the kidneys. A sample of kidney tissue, a biopsy, is sometimes helpful in diagnosing the specific cause of a problem.

Tests commonly used for screening and diagnosis
The National Kidney Foundation (NKF) and the National Kidney Disease Education Program (NKEDP) recommend that people who are at high risk be screened for kidney disease to detect it in its earliest stages. Risk factors include diabetes, high blood pressure, heart disease, or a family history of these or kidney disease. The NKF recommends that everyone with diabetes between the ages of 12 and 70 be screened for kidney disease at least once a year. At this time, there is no consensus on screening people who have no risk factors or symptoms. The NKF and NKDEP recommend two tests, in addition to blood pressure measurement, to screen for kidney disease:

• Urine protein—a few different tests may be used to screen for protein in the urine:
  • Urine total protein or urine protein to creatinine ratio (UP/CR)—detects not just albumin, but all types of proteins that may be present in the urine.
  • Urinalysis—this is a routine test that can detect protein in the urine as well as red blood cells and white blood cells. These are not normally found in the urine and, if present, may indicate kidney disease.
  • Urine albumin—this test may be done on a 24-hour urine sample, or both urine albumin and creatinine can be measured in a random urine sample and the albumin/creatinine ratio (ACR) can be calculated. The American Diabetes Association recommends ACR as the preferred test for screening for albumin in the urine (microalbuminuria).

While urinalysis and urine total protein are not as sensitive as urine albumin for detecting kidney damage, these tests give fewer false signals of kidney damage.

• Estimated glomerular filtration rate (eGFR)—a blood creatinine test or possibly a cystatin C test is performed in order to calculate the eGFR. The glomerular filtration rate refers to the amount of blood that is filtered by the glomeruli per minute. As a person's kidney function declines due to damage or disease, the filtration rate decreases and waste products begin to accumulate in the blood.

Some additional tests that may be ordered to evaluate for kidney disease include:

• Urea (urea nitrogen or BUN)—the level of this waste product in the blood increases as kidney filtration declines. Increased BUN levels suggest impaired kidney function, although they can also be elevated due to a condition that results in decreased blood flow to the kidneys, such as congestive heart failure, heart attack, or shock.
• Creatinine clearance—this test measures creatinine levels in both a sample of blood and a sample of urine from a 24-hour urine collection. The results are used to calculate the amount of creatinine that has been cleared from the blood and passed into the urine. This calculation allows for a general evaluation of the amount of blood that is being filtered by the kidneys in a 24-hour time period.
   

Tests to monitor kidney function
If a person has been diagnosed with a kidney disease, several laboratory tests may be ordered to help monitor kidney function. Some of these include:

• Blood levels of BUN and creatinine are measured from time to time to see if the kidney disease is getting worse.
• The amount of calcium and phosphorus in the blood, blood gases (ABGs), and the balance of serum and urine electrolytes can also be measured as these are often affected by kidney disease.
• Hemoglobin in the blood, measured as part of a complete blood count (CBC), may also be evaluated as the kidneys make a hormone, erythropoietin, that controls red blood cell production and this may be affected by kidney damage.
• Erythropoietin may be measured directly, although this is not a routine test.
• Parathyroid hormone (PTH), which controls calcium levels, is often increased in kidney disease and may be checked to help determine if enough calcium and vitamin D are being taken to prevent bone damage.
• Cystatin C is another test that may sometimes be used as an alternative to creatinine to screen for and monitor kidney dysfunction in those with known or suspected kidney diseases.
• Both blood and urine beta 2 microglobulin (B2M) tests may be ordered along with other kidney function tests to evaluate kidney damage and disease and to distinguish between disorders that affect the glomeruli and the renal tubules. Normally, only small amounts of B2M are present in the urine, but when the renal tubules become damaged or diseased, B2M concentrations increase due to the decreased ability to reabsorb this protein. When the glomeruli in the kidneys are damaged, they are unable to filter out B2M, so the level in the blood rises. B2M tests may sometimes be ordered to monitor people who have had a kidney transplant, to detect early signs of rejection, and ordered to monitor people who are exposed to high levels of cadmium and mercury, such as with occupational exposure.
   

Tests to help determine the cause and/or guide treatment
Other tests may be ordered to help determine the cause and/or guide treatment, depending on several factors including a person's signs and symptoms, physical examination, and medical history. Some examples of these tests include:

• Urinalysis with a urine culture may be done when someone has symptoms suggesting infection to confirm the presence of a bacterial infection.
• Hepatitis B or C testing—to detect a hepatitis viral infection associated with some types of kidney disease
• Antinuclear antibody (ANA)—to help identify an autoimmune condition such as lupus that may be affecting the kidneys.
• Kidney stone risk panel—this test evaluates a person's risk of developing a kidney stone, to help guide and monitor treatment and prevention
• Kidney stone analysis—this test determines the composition of a kidney stone passed or removed from the urinary tract and may be done to help determine the cause of its formation, to guide treatment, and prevent recurrence
• Complement tests, most commonly C3 and C4—may be tested and monitored with glomerulonephritis
• Urine protein electrophoresis—may be done to determine the source of a high level of protein in the urine
• Myoglobin—in people who have had extensive damage to their skeletal muscles (rhabdomyolysis), a urine myoglobin test may be ordered to determine the risk of kidney damage. With severe muscle injury, blood and urine levels of myoglobin can rise very quickly.

Imaging techniques
If a structural problem or blockage is suspected, imaging of the kidneys can be helpful. Imaging techniques such as an ultrasound, CT scan (computed tomography), isotope scan, or intravenous pyelogram (IVP) may be used. For more on these see RadiologyInfo's web pages on Kidney and Bladder Stones or Kidney (Renal) Failure.

Kidney biopsy
A biopsy is sometimes used to help determine the nature and extent of structural damage to a kidney. Analyzing a small piece of kidney tissue, obtained using a biopsy needle and diagnostic imaging equipment, can sometimes be useful when disease of the glomeruli (or sometimes the tubules) is suspected.

Tests for biomarkers of acute kidney injury
Several biomarkers are gaining attention as early indicators of acute kidney injury (AKI). Studies suggest that blood or urine tests for these biomarkers can detect acute kidney damage earlier than currently used kidney function tests, such as serum creatinine. Early detection of AKI is critical because injury occurs rapidly over a period of hours to days. AKI biomarkers are still being studied and may become more widely available in the future.

Although AKI is a serious condition and costs the U.S. healthcare system millions of dollars each year, the measurement of AKI biomarkers does not directly help in treating people with AKI because there are no FDA-approved therapies currently available. When AKI is diagnosed, imaging scans of the kidneys are frequently performed to rule out the presence of an obstruction in the urinary tract. General supportive treatment may be given, such as IV fluids or transfusion of blood components. Drugs used to improve blood pressure and heart function may be used if a person is in shock. If a person does not recover from AKI spontaneously, some type of dialysis is required.

Examples of promising AKI biomarkers include:

• Urinary insulin-like growth factor-binding protein 7 (IGFBP7) and urinary tissue inhibitor of metalloproteinases-2 (TIMP-2)—these two markers have been combined into a point-of-care test. It is the first test approved by the U.S. Food and Drug Administration to help assess critically ill patients for risk of developing AKI within the next 12 hours.
• Neutrophil gelatinase-associated lipocalin (NGAL)—this is a protein that is found in many tissues in the body, including kidney cells. Part of the reason NGAL is a good indicator of AKI is that its level rises rapidly in response to kidney injury, typically within 2-4 hours.

Appropriate treatment will vary, depending on the cause of the kidney disorder. In general, the earlier kidney disease is recognized, the more likely it is to be treatable, and sometimes – as may occur with acute kidney disease – the damage may be reversible. Goals of treatment are to treat underlying conditions, minimize kidney dysfunction, control symptoms, and prevent the progression of kidney disease to the extent possible.

In the case of diabetics, monitoring and controlling blood glucose levels are paramount. For people with hypertension, lowering blood pressure, sometimes through the use of medications, can help protect the kidneys from damage.

Other medications may be used to relieve some of the symptoms of kidney disease, such as anemia and edema, or to lower cholesterol in order to reduce the risk of heart disease. Dietary changes may also be recommended.

Some kidney conditions, such as infections and some acute kidney injuries, can be resolved without causing permanent kidney damage. In many cases, however, the damage cannot be reversed. If the damage is severe and end-stage renal disease has been reached, treatment involves dialysis – a machine used several times a week to take over kidney filtration – or kidney transplant surgery.