By Cat Troiano

Anemia is the condition in which a patient’s red blood cell or hemoglobin count is too low or in which the red blood cells or hemoglobin that is produced is abnormal in size or shape. Since the role of red blood cells is to transport oxygen from the lungs to the rest of the body, anemia becomes damaging when organ tissues do not receive adequate oxygen. According to the American Society of Hematology, anemia affects more than three million individuals in the United States, and it is the most common blood disorder. Understanding the different types and presentations of anemia is beneficial in choosing the proper tests that will enable physicians to treat this debilitating and potentially life-threatening condition.

Types of Anemia

There are a number of different types and causes of anemia. In order to address a patient’s anemia with the most effective treatment, it is essential to diagnose the type of anemia. Anemia is classified into three groups:

Microcytic, in which the red blood cells are smaller than normal in size
Normocytic, in which the red blood cells are normal in size, but there is an insufficient number of them
Macrocytic, in which the red blood cells are enlarged in size

Within each classification are various types of anemia. Examples of microcytic anemia include:

• Iron deficiency, which results either from blood loss or from poor absorption of dietary iron
• Sickle cell anemia, which is a hereditary form of anemia that is characterized by abnormally-shaped red blood cells
• Thalassemia, which is a hereditary condition in which the hemoglobin level is too low

Examples of normocytic anemia include:

• Aplastic anemia, in which the bone marrow is unable to produce an adequate supply of all blood cells
• Hemolytic anemia, which results in the premature destruction of red blood cells before the end of their typical 120-day lifespan
• Anemia of chronic disease, such as that caused by chronic renal insufficiency in which the kidneys fail to produce enough erythropoietin, which is the hormone that aids in red blood cell production

Examples of macrocytic anemia include:

• Vitamin deficiency, such as a deficiency in vitamin B12 or in folate
• Alcoholism anemia
• Anemia caused by the use of chemotherapy agents, anti-seizure medications and antiviral drug therapies

Awareness of the different types of anemia and their causes is helpful in guiding physicians as they determine which patients should be screened for anemia.

Risk Factors and Signs of Anemia

Patients with certain risk factors should be monitored for anemia. Some of these risk factors include:

• Autoimmune diseases, such as rheumatoid arthritis
• Human immunodeficiency virus
• Gastrointestinal diseases, such as ulcerative colitis and Crohn’s disease
• Liver disease
• Kidney disease
• Hypothyroidism
• Cancer
• Pregnancy
• Heavy menstruation
• Bariatric surgical procedure
• Exposure to certain toxic chemicals, such as lead
• Travel to locations where malaria is prevalent
• Excessive aspirin or ibuprofen use
• Excessive alcohol consumption
• Being older than 65 years of age
• Family history of sickle cell anemia or other inherited forms of anemia

Some patients with mild cases of anemia may be asymptomatic, but most moderate and severe cases present with any of the following signs:

• Weakness
• Fatigue
• Dizziness
• Exercise intolerance
• Pallor
• Rapid or irregular heartbeat
• Headache
• Chest pain
• Shortness of breath
• Cold extremities

One of the first laboratory tests that reveals the presence of anemia is the routine complete blood count.

Complete Blood Count

The complete blood count (CBC) is typically ordered along with a metabolic profile as part of a routine physical or when a patient presents with signs of illness. The CBC, which is performed on a whole blood sample, measures the different components of blood, such as the various types of white blood cells, platelets and red blood cells (RBCs). The normal reference range for RBCs on a CBC is:

Men: 5 million to 6 million cells per mcL
Women: 4 million to 5 million cells per mcL

A test result that comes in lower than the reference range is indicative of anemia.

The CBC also measures hemoglobin, which is an iron-rich form of protein found in RBCs that takes up oxygen from the lungs for transport to other organs and tissues throughout the body. Each RBC has more than 200 million molecules of hemoglobin. The normal reference range for hemoglobin on a CBC is:

Men: 13.5 to 17.5 grams per deciliter
Women: 12 to 15.5 grams per deciliter

A test result that reveals the hemoglobin level to be lower than the reference range is indicative of anemia.

Hematocrit, or packed cell volume, is also measured on a CBC. The hematocrit level determines how much space the RBCs occupy within the blood. The normal reference range for hematocrit is:

Men: 41-50 percent
Women: 36-44 percent

A test result in which the hematocrit level is lower than the reference range is indicative of anemia.

Mean corpuscular volume, or MCV, is also assessed as part of the CBC, and it determines the average size of red blood cells. The normal reference range score for MCV is:

Men: 80-96
Women: 82 – 98

If a CBC result reveals that any of the aforementioned values are lower than the normal reference ranges, and if the metabolic panel reveals no evidence of chronic disease, additional tests may need to be ordered to determine the type of anemia.

B-12 Test

Vitamin B12 is needed to play a role in the production of healthy RBCs and in maintaining healthy nerve cells. This micronutrient is found only in animal-based food sources, including meat, fish, poultry, eggs and dairy products. If a patient is not taking in a sufficient amount of vitamin B12, then vitamin B12 deficiency anemia results. Alternately, if a patient’s stomach is not producing an adequate level of intrinsic factor, which is a protein that binds with vitamin B12 in the intestines to facilitate absorption, a specific type of vitamin B12 deficiency anemia known as pernicious anemia results. A patient’s vitamin B12 level can be assessed with serum from a blood sample. The normal reference range for a vitamin B12 test is:

180 to 914 ng/L

If the test result is lower than the reference range, then vitamin B12 deficiency anemia is diagnosed. Certain medications, including aspirin, contraceptive hormone drugs and anticonvulsants can cause a low vitamin B12 level. If the patient does not take any of these medications, an intrinsic factor blocking antibody test may then be performed to determine if the patient has pernicious anemia. Elevated vitamin B12 results can occur in patients with advanced liver disease, diabetes, heart failure and acquired immunodeficiency syndrome.

Folate

Folate deficiency anemia results when there is an abnormally low level of folic acid in the blood. Folic acid is another B vitamin that also plays a role in RBC production. Folic acid is consumed from leafy green vegetables, yeast and fresh fruits, and it is also found in fortified food products, such as cereals and orange juice. Since a growing fetus requires plenty of folic acid for brain and spinal cord development, pregnant women are especially at risk for folate deficiency anemia. Testing the serum from a blood sample can determine if a patient has a folate deficiency. The normal reference range for a serum folate test is:

Greater than or equal to 4.0 mcg/L

A test result that is lower than 4.0 is suggestive of folate deficiency.

Ferritin Serum

Ferritin is a type of protein that contains iron, which plays a role in healthy RBC production. The concentration of ferritin that is found in the serum of a blood sample reflects the level of iron stores in the body. The normal reference range for a ferritin serum test is:

Men: 24 to 336 mcg/L
Women: 11 to 307 mcg/L

When a test result is lower than the reference range, then iron deficiency anemia is suspected. An abnormally high result can occur in patients with certain chronic illnesses and neoplastic disease.

Reticulocyte Count

RBCs are produced in the bone marrow. Reticulocytes are immature RBCs. A reticulocyte count, which is performed on a whole blood sample, reveals the bone marrow’s level of production capability. The normal reference ranges for adults are:

Percentage of reticulocytes: 0.60 to 2.71 percent
Absolute reticulocytes: 30.4 to 110.9 X 10(9)/L

Results that are lower than the reference range can be due to heavy or chronic blood loss or hemolytic anemia. Results that exceed the reference range can be due to vitamin deficiency anemia, iron deficiency anemia, chronic kidney disease, cancer, aplastic anemia and alcoholism.

Some forms of anemia cannot be prevented and can be fatal. Others can be prevented or treated with dietary supplementation, and still others may be treated with medical procedures.
When a patient presents with potential signs of anemia and has abnormally low RBC, hemoglobin and hematocrit values on a CBC, conducting a thorough evaluation of his or her medical history and ordering the appropriate additional tests is essential in determining the type and cause of the anemia and in formulating the most effective treatment plan.

By Cat Troiano

Dementia is a collective term that applies to any condition that is characterized by a severe decline in mental capability. Alzheimer’s disease is one type of dementia, and it is the most common form, accounting for between 60 and 80 percent of all dementia cases. According to the Alzheimer’s Association, 5.7 million Americans are currently afflicted with this progressive and irreversible disease, and the Centers for Disease Control and Prevention projects that this figure will nearly triple, reaching 14 million by the year 2050.

Elusive Diagnosis

To date, there is no laboratory test available that definitively diagnoses Alzheimer’s disease in living patients. The only current option for definitive diagnosis is microscopic examinations of brain tissue samples from a deceased individual. These examinations reveal the presence of the characteristic amyloid plaques and/or neurofibrillary tangles. These formations are accumulations of specific protein deposits in the brain tissue. Their development is actually part of the normal aging process, but the abundance of plaques and tangles is significantly higher in patients with Alzheimer’s disease, and their emergence tends to follow a distinctive pattern. So how can a diagnosis of Alzheimer’s disease be made when a patient presents with signs of cognitive decline?

Symptoms, Risk Factors and Rule outs

When a patient alerts his or her physician to symptoms of dementia, diagnosis is made through a thorough evaluation of medical history, family health history and neurological tests that assess the patient’s cognitive function. Signs of dementia include:

• Memory loss
• Difficulty performing mental tasks
• Confusing or forgetting dates, times, places or people
• Decline in visual perception
• Impaired reasoning and decision-making skills
• Deficits in basic communication and language skills
• Misplacing items and being unable to retrace steps to find them
• Changes in mood

Anyone can experience these signs once in a while, but when they occur with an increasing frequency that may threaten to interfere with one’s independence and ability to safely and successfully navigate through life’s daily activities, it is time to consider the patient’s potential risk factors for dementia and Alzheimer’s disease. Some risk factors include:

• Being of African-American or Hispanic descent
• Family history of Alzheimer’s disease
• Type 2 diabetes
• Hypertension
• High cholesterol
• Obesity
• Down syndrome

More women than men suffer from Alzheimer’s disease, and advanced age is certainly a factor to consider as well. However, while most cases of Alzheimer’s disease manifest after 65 years of age, individuals who begin showing signs of the illness at a younger age account for 5 to 10 percent of Alzheimer’s disease patients. Alzheimer’s disease is not a normal result of the aging process.

Not all cases of dementia are specifically Alzheimer’s disease. The initial laboratory tests ordered, which include a complete blood count, thyroid and metabolic profiles, are performed to rule out other conditions that can cause dementia. Diabetes, abnormal thyroid function, certain vitamin deficiencies, infections, electrolyte imbalances and excessive alcohol use can all contribute to non-Alzheimer’s forms of dementia. If any of these conditions are diagnosed, steps can be taken to treat or manage the condition and to prevent further cognitive decline. If none of these conditions are diagnosed, and if diagnostic imaging tests reveal no evidence of stroke, brain trauma or brain tumors, then there are a couple of genetic screening tests that can be ordered which may help physicians to make a more confident diagnosis of probable Alzheimer’s disease.

APOE Genotyping

Apolipoprotein E (APOE) is a genetic component of lipoprotein that is found in the blood. There are three forms, called alleles, of APOE, which are designated as e2, e3 and e4. The APOE gene, particularly the e4 allele, poses an increased risk for late-onset Alzheimer’s disease. APOE genotyping, which is performed on a sample of whole blood, identifies the presence and combination of APOE alleles present. Rather than provide a definitive diagnosis of Alzheimer’s disease, this test helps to indicate a patient’s genetic risk factor for developing the illness, thereby enabling a physician to make a likely diagnosis of the patient’s dementia symptoms. Approximately 65 percent of patients who are diagnosed with Alzheimer’s disease have one or more APOE e4 alleles. However, possessing the APOE e4 allele is not a requisite for developing Alzheimer’s disease. Many individuals can test positive for this gene without ever having the disease.

PSEN1

Alzheimer’s disease that develops in patients who are younger than 65 years of age is known as early-onset familial Alzheimer’s disease, or Alzheimer’s disease type 3. Such cases tend to be hereditary, resulting from a genetic mutation. One genetic mutation that has been associated with between 30 and 70 percent of Alzheimer’s disease type 3 cases is a PSEN1 mutation. The PSEN1 gene is responsible for the production of a specific protein, presenilin 1, that aids in brain and spinal cord development. A mutation of this gene ultimately leads to the formation of amyloid plaques on the brain. PSEN1 is a dominant gene, and a developing fetus has a 50 percent chance of inheriting a PSEN1 mutation from the parent who has it.

The PSEN1 test, which is also performed on a sample of whole blood, may be ordered for patients who are less than 65 years of age and presenting with signs of dementia. The test may also be ordered for asymptomatic individuals who have family histories of Alzheimer’s disease type 3. Asymptomatic individuals that test positive for the mutation have a significant probability of developing Alzheimer’s disease type 3 at roughly the same ages as did their prior affected family members, but the presentation and progression of symptoms vary with each patient. Currently, there are more than 150 known PSEN1 genetic mutations, and the test does not identify all of them.

Prompt Testing for Extended Quality of Life

Researchers are tirelessly working to find a cure for Alzheimer’s disease. Until one is discovered, current treatment protocols can be implemented with the following goals:

• Slow the progression of dementia symptoms
• Maintain functional mental capacity for as long as possible
• Manage behavioral symptoms
• Enable the patient to plan and make decisions regarding his or her future care, living arrangements and management of legal and financial matters

These goals are most effectively achieved when Alzheimer’s disease is diagnosed in the early stage. Alzheimer’s disease progresses through three stages, which are mild, or early stage, moderate, or middle stage, and severe, or late stage. By addressing symptoms of dementia as early as possible, tests like the APOE genotyping and PSEN1 can increase the chance of making a probable diagnosis during the early stage. Patients who are diagnosed early may also benefit from opportunities to participate in clinical trials of emerging new treatments. While the tests are not perfect, the early diagnosis that they can provide for many patients is a valuable step toward extending quality of life.

Image courtesy of the Alzheimer’s Association

By Cat Troiano

According to the Lyme Action Network, Lyme disease is the most common vector-borne disease and the second most common infectious disease in the United States. Lyme disease is a tick-borne disease that can have debilitating effects on the joints, nervous system and heart if the infection is not diagnosed and treated. The good news is that early treatment with an extended period of antibiotic therapy cures most Lyme disease cases, making diagnosis a critical first step toward recovery.

Lyme Disease Prevalence
Lyme disease was first identified in Lyme, Connecticut in 1982, where it was determined to be transmitted by the blacklegged tick, which is also known as the deer tick. Since that time, the geographic range of Lyme disease has expanded. Although the illness has been reported in all 50 states, 95 percent of all cases are concentrated within the northeast and Midwestern states. A significant number of cases have also been diagnosed along the Pacific coast in northern California, Oregon and Washington. In the Pacific region, Lyme disease is transmitted by the western blacklegged tick. The Centers for Disease Control and Prevention (CDC) estimates that roughly 300,000 cases of Lyme disease are diagnosed in the United States each year.

Initial Presentation of Lyme Disease
In order to transmit Lyme disease, an infected tick must remain attached to a host for a period of at least 36 to 48 hours. If a patient is unsure as to how long the tick was attached before it was extricated, he or she must be vigilant for the onset of symptoms. Within 3 to 30 days, the characteristic erythema migrans rash may appear. This rash is circular, red and can resemble a bulls-eye target site. Some patients are unaware of ever having been bitten by a tick, and the appearance of this rash is their first clue. The presentation of the erythema migrans rash, along with a few additional early-stage symptoms, is a strong indicator of Lyme disease infection. These other initial symptoms may include:

• Fever
• Chills
• Headache
• Joint pain
• Muscle aches
• Swollen lymph nodes
• Fatigue

A complicating factor in the diagnosis of Lyme disease is that the rash does not present in all cases. In the absence of the rash, particularly in individuals who are unaware of being bitten by a tick, the generalized symptoms listed above can be indicative of a number of other illnesses that present with the same complaints. Any patient who presents with the rash or who has a known history of exposure to the blacklegged tick and is experiencing these symptoms, with or without the rash, should undergo laboratory testing for Lyme disease.

Diagnosis Through Two Tests
There are two recommended laboratory tests that screen for Lyme disease, and they can both be performed on serum from the same blood sample. The two tests are:

• Enzyme immunoassay, such as the enzyme-linked immunosorbent assay (ELISA) test
• Immunoblot, also known as a Western blot test

Testing guidelines set forth by the CDC recommend a two-tiered system for performing these tests. If the Lyme ELISA test result is negative, then no further testing for Lyme disease is recommended. If the Lyme ELISA test result is either positive or equivocal, then a Western blot test should be performed to confirm a diagnosis of Lyme disease. The diagnosis is conclusive when both the Lyme ELISA and the Western blot tests yield positive results.

Borrelia burgdorferi is the bacterium that causes Lyme disease. Whenever the human body is invaded by a foreign organism, the immune system releases proteins to fight infection. These proteins are called antibodies, and the invading organisms that they target are called antigens.
Both tests measure the levels of borrelia immunoglobulin M (IgM) antibodies and borrelia immunoglobulin G (IgG) antibodies present in the blood. Borrelia IgM levels are detectable two to three weeks after the initial onset of Lyme disease, peaking in concentration at six weeks before diminishing. Borrelia IgG levels take several weeks to show up, exhibiting high levels between four to six months after the onset of infection, and these high levels can remain for years.

Lyme ELISA Test
The Lyme ELISA test is always performed first in the two-tiered Lyme disease testing sequence, and the results determine the next step.

The reference ranges for the Lyme ELISA test results are as follows:

• A negative result is equal to or less than 0.90.
• An equivocal result is between 0.91 and 1.09.
• A positive result is equal to or greater than 1.10.

If the result is negative, either the patient’s symptoms are caused by another condition or the Lyme infection is at such an early stage that the patient’s level of antibodies is still too low to detect. Other conditions that present with similar symptoms should be considered in efforts to diagnose the cause of the patient’s symptoms. If no other condition is diagnosed and the patient remains symptomatic two to three weeks later, repeating the Lyme ELISA test is advised.

If the result is positive or equivocal and the patient has been experiencing symptoms of Lyme disease for 30 days or fewer, then a combination Western blot test that evaluates the levels of both IgM and IgG antibodies should be performed. If the Lyme ELISA test is positive or equivocal and the patient has been symptomatic for longer than 30 days, then a Western blot test that evaluates only IgG levels should be performed.

Western Blot
The results of a Western blot test appear as bands that are labeled by numbers, each of which represents a specific molecular component of the borrelia burgdorferi bacterium. The test evaluates the levels of antibodies against each of these components. The CDC reference guidelines for interpreting a positive Western blot test result for confirmation of a Lyme disease diagnosis are:

• When IgM levels are assessed, two out of the following three bands must be positive:

OspC (21-25)
39
41

• When IgG levels are assessed, five out of the following ten bands must be positive:

18
OspC (21-25)
28
30
39
41
45
58
66
93

If both the Lyme ELISA and Western blot tests have positive results, then the patient is diagnosed with Lyme disease, but how are test results that seem to contradict one another interpreted?

What Can Different Test Results Mean?
When a Lyme ELISA test result is positive for IgM antibodies and negative for IgG antibodies, but the Western blot test result is negative, the patient is either in the early stage of infection or the IgM result is a false-positive. Remember that IgG antibodies do not show up during the first couple of weeks of infection.

Conversely, when the Lyme ELISA test is negative for IgM antibodies and positive for IgG antibodies, but the Western blot test result is negative, the patient either has recovered from Lyme disease previously or the IgG result is a false-positive. IgM antibodies leave the bloodstream after six weeks, and IgG antibodies, which show up later, remain in the bloodstream for years. Once a patient contracts Lyme disease, some IgG antibodies will always be detected thereafter in his or her blood.

If the Lyme ELISA test result is negative for IgM antibodies and positive for IgG antibodies and the Western blot test result is positive, the patient is either in the latter stage of infection or had a previous infection.

Other diseases can trigger false-positive results on a Lyme ELISA test. One reason for this is because borrelia is a member of the spirochete class of bacteria. In addition to Lyme disease, leptospirosis and syphilis are two other examples of spirochete diseases. A patient who does not have Lyme disease and instead has another spirochete disease can end up with a false-positive result on a Lyme ELISA test.

Other medical conditions that are not spirochete diseases and can produce false-positive results on the Lyme ELISA test include:

• HIV
• Autoimmune disorders, such as lupus
• Mononucleosis
• Epstein Barr
• Some bacterial infections, such as helicobacter pylori

There are also other tick-borne diseases that can be the cause of a false-positive Lyme ELISA test result.
Other Tick-Borne Diseases
Ticks transmit more than just Lyme disease. In fact, one feeding of a single tick can transmit multiple diseases into its host. This can result in what is known as coinfection.

In addition to Lyme disease, ticks are responsible for the transmission of the following diseases:

• Alpha-gal/meat allergy
• Anaplasmosis*
• Babesiosis*
• Bartonellosis
• Borrelia mayonii**
• Borrelia miyamotoi*
• Bourbon virus
• Colorado tick fever
• Ehrlichiosis
• Heartland virus
• Pacific Coast tick fever
• Powassan virus*
• Rickettsia parkeri rickettsiosis
• Rocky Mountain spotted fever
• STARI
• Tick-borne relapsing fever
• Tularemia
• 364D rickettsiosis

* diseases transmitted by the blacklegged tick
** a new species of borrelia that, like borrelia burgdorferi, has been determined to cause Lyme disease

Laboratory tests are available for diagnosing many of these diseases.

The most proactive thing that physicians can do to ensure prompt diagnosis and treatment of Lyme disease and other tick-borne disease infections is to monitor the prevalence and geographic range of these illnesses and of the ticks that transmit them. Assessing a patient’s symptoms, acquiring a history of the patient’s travel and outdoor activities, confirming a patient’s exposure to a tick and ordering the appropriate laboratory tests are the keys to enabling your patient to achieve a full recovery instead of suffering the lasting adverse effects that compromise quality of life

Deer Tick

 

By Cat Troiano

More than 1.5 million Americans are estimated to be diagnosed with new cancer cases this year, according to the American Cancer Society projections. Cancer remains one of the leading causes of mortality in the United States, with more than 600,000 deaths predicted for 2018. These numbers are disconcerting to everyone, but encouraging statistics reveal that the overall cancer mortality rate for some types of cancer dropped by 25 percent from 1990 to 2014. This is due in part to research advancements that have led to more effective treatment protocols as well as improved cancer screening methods. Some types of cancer can even be detected in a sample of blood, thanks to their tell-tale tumor markers.

What Are Tumor Markers?

In addition to red blood cells, white blood cells and platelets, blood contains other substances, including proteins, antigens, enzymes and other biochemical matter. Some cancer patients can have abnormally high levels of specific substances in their blood. As their illness advances, the levels increase, but if their cancer treatment is effective in combatting their illness, then the levels decrease. These demonstrated fluctuations have led to the identification of such biochemicals as tumor markers, which may increase as a result either from the body’s immune response to the illness or from the tumor’s cells as they produce more of the tumor marker. Some tumor markers can also be found in urine, bone marrow and tissue samples. The majority of tumor markers are proteins, but progress in genetic research has paved the way for the development of tests that evaluate changes in the genetic material of cancer patients.

What Are Tumor Marker Tests Used For?

Once patients have been diagnosed with certain types of cancer, tumor marker tests can provide helpful information for physicians in their quests to provide successful treatment. Some ways in which tumor marker test results are used include:

• Monitor treatment progress – when tumor marker tests are periodically performed throughout the cancer treatment duration, the results can reveal if the treatment protocol is working. A decrease in the tumor marker level indicates success. Conversely, an increase in the tumor marker level indicates that the disease is advancing.
• Detect cancer recurrence – when tumor marker tests are periodically performed once a patient has entered remission, the results can reveal if the cancer recurs.
•  Stage cancer by detecting metastasis – based on how high the elevated tumor marker level is, physicians can get an idea of how advanced the patient’s cancer is and whether or not the disease has metastasized, or spread, to other areas of the body.
• Guide treatment option choice – some tumor markers can help oncologists to determine which treatment protocols will be the most successful for their patients.
• Predict prognosis – when compared with similar tumor marker test results of other patients, the prognosis for a new patient’s cancer treatment outcome can be predicted based on that of those other previous patients.

All of the aforementioned can be beneficial in guiding and tracking cancer treatment, but what about cancer screening and diagnosis?

Can Tumor Marker Tests Diagnose Cancer?

According to the National Cancer Institute, there are more than 100 different types of cancer. There are not tumor marker tests for all of them because researchers have not yet identified specific tumor markers for each and every type of cancer. Another problem is that while some tumor markers are specific to one particular cancer, others can become elevated by any one of several types of cancer. Furthermore, some tumor markers can become elevated for reasons other than cancer. Finally, not every individual who has cancer will have an elevation in the specific tumor marker’s level, especially if the cancer is in its early stage. Despite these limitations, there are a few tumor marker tests that can contribute to the screening and diagnostic process. The following tests are performed as a step toward diagnosis, and they are further used to monitor cancer treatment and to screen for recurrence.

Prostate specific antigen (PSA)

• This test screens for prostate cancer.
• The normal reference range for PSA is less than 4 ng/ml.
• PSA is an example of a tumor marker that is specific to prostate cancer and not to other types of cancer. The PSA test is recommended as a routine screening for all male patients who are 50 years of age or older and have a remaining life expectancy of ten years or longer.
• Some benign conditions, such as prostate enlargement or prostate inflammation, can cause an elevation in the PSA level.

Calcitonin

• This test detects the presence of medullary thyroid cancer.
• The normal reference range for calcitonin is less than 8.5 pg/mL in men and less than 5.0 pg/mL in women.
• Chronic proton-pump inhibitor treatment as well as chronic renal failure can cause an increase in the calcitonin level.

Alpha-fetoprotein (AFP)

• This test can detect the presence of liver cancer. Elevations can also be indicative of other cancers, including germ cell ovarian cancer and testicular cancer.
• The normal reference range for AFP is 0 to 15 IU/ml.
• An elevation in AFP can result from some noncancerous conditions as well, including inflammatory bowel disease, cirrhosis and hepatitis.

Cancer antigen 125 (CA 125)

•  This test detects the presence of epithelial ovarian cancer, which is the most commonly diagnosed type of ovarian cancer.
• The normal reference range for CA 125 is 0 to 35 U/ml.
• An elevation in CA 125 can also occur in patients with breast cancer and colorectal cancer. Some noncancerous conditions that can cause an elevation in CA 125 include inflammatory bowel disease, pancreatitis, peritonitis, endometriosis and ovarian cysts.

Human chorionic gonadotropin (hCG)

• This test is used to detect the presence of testicular cancer as well as germ cell ovarian cancer and choriocarcinoma.
• The normal reference range for hCG is less than 2.5 U/ml in men and less than 5.0 U/ml in non-pregnant women.
• hCG levels can rise in women who are pregnant as well as in patients with inflammatory bowel disease and duodenal ulcers.

Chromogranin A (CgA)

• This test can detect the presence of neuroendocrine and carcinoid tumors.
• The normal reference range for CgA is less than 39 ng/l.
• Chronic use of proton pump inhibitor drugs can also increase the level of CgA.

Neuron specific enolase (NSE)

•  Although it is not used to diagnose lung cancer, this test helps to determine if a lung cancer case is small cell lung cancer, as opposed to non-small cell lung cancer. This test can also detect the presence of neuroblastoma.
• The normal reference range for NSE is less than 9 ug/L.
• NSA can also become elevated in patients with COPD and chronic bronchitis. Other causes of a high NSE level include stroke, seizure activity, end stage renal failure, liver failure and hemolytic anemia.

Even these few tests that do play a role in cancer screening should be used as just one piece of the diagnostic puzzle to be put together with other pieces, such as patient medical history, patient symptoms, diagnostic imaging tests and tissue biopsies, to achieve a definitive diagnosis.

Research is constantly underway to develop more tests with greater sensitivity to hone in on specific tumor markers. A new test that is currently under development has shown promise in its ability to detect any of eight different common cancers from one blood sample. In the meantime, there are already many more tumor marker tests available that are valuable tools in cancer treatment planning, implementation and monitoring. These benefits alone can make the difference needed to extend the life expectancies of patients who are diagnosed with cancer.

By Cat Troiano

According to the National Kidney Foundation, one-third of the American population is at risk of developing kidney disease, and the degenerative condition is the ninth leading cause of death in the United States. Over time, kidney disease leads to end-stage renal failure. Performing renal function screenings is crucial for early diagnosis and monitoring so that the disease can be slowed in its progression.

Kidney Form and Function

The two bean-shaped kidneys are located beneath the ribcage toward the back of the abdominal cavity, with one kidney situated on each side of the vertebral column. The kidneys are responsible for several life-preserving functions. Each day, 180 liters of blood pass through millions of filters, called nephrons, within the kidneys to remove metabolic wastes. Glomeruli are additional filters within the nephrons. Glomeruli pass the filtered toxins and excess water along to be eliminated from the body through urination, and they direct the filtered blood to continue circulating through the body. When renal function is compromised, the kidneys are unable to carry out the filtration process as efficiently, and toxins build up in the bloodstream.

The kidneys also play roles in other critical functions:

• Kidneys produce renin, an enzyme that aids in blood pressure regulation.
• Kidneys produce erythropoietin, a hormone that aids in red blood cell production.
• Kidneys maintain the body’s water, acid and electrolyte balances.
• Kidneys produce an activated form of vitamin D that aids in maintaining bone strength.

Kidney disease hinders all of these functions, and that causes a number of complications.

 

Causes of Kidney Disease

Chronic kidney disease occurs when damage to the kidneys and the deterioration of their function is gradually sustained. Chronic kidney disease is diagnosed when kidney function is decreased for more than three months. Acute kidney failure is a sudden onset of kidney damage that poses an immediate threat of kidney failure.

Some examples of chronic kidney disease include:

• Polycystic kidney disease, which is a genetic condition in which fluid-filled cysts form and overtake the kidneys
• Diabetic kidney disease, which is caused by uncontrolled type 1 or type 2 diabetes as high blood glucose levels inflict damage to the kidneys
• Hypertensive nephrosclerosis, which is caused by uncontrolled hypertension as the high blood pressure inflicts damage to the kidneys’ blood vessels
• Analgesic nephropathy, which results from extensive use of nonsteroidal anti-inflammatory drugs, such as ibuprofen, naproxen and celecoxib

Diabetics and patients with hypertension are at high risk for developing chronic kidney disease. Other conditions can cause chronic kidney disease as well, including autoimmune disorders, HIV/AIDS, hepatitis B and hepatitis C.

Some conditions that can result in acute kidney failure include:

• Prostate enlargement, which can cause a urinary obstruction and allow a backflow of urine to the kidneys
• Kidney stones
• Pyelonephritis, which is the development of scar tissue in the kidneys caused by repeated bouts of urinary tract infections
• Glomerulonephritis, which is inflammation of the glomeruli

Regularly monitoring blood pressure and checking blood glucose levels on all patients are important first steps toward the preservation of renal health. Ordering renal function laboratory tests enables physicians to assess and monitor how efficiently their patients’ kidneys are working. Renal function tests are performed on blood serum and urine samples.

 

Blood Serum Kidney Values

A comprehensive metabolic panel reveals two specific values that are key indicators of renal performance.

Blood urea nitrogen (BUN)
• BUN is the waste that is produced when the liver breaks down dietary protein.
• The normal reference range for BUN is between 7 and 20.
• A high BUN result is indicative of a decrease in blood flow through the kidneys. As kidney disease advances, the BUN value escalates.

Creatinine
• Creatinine is the metabolic waste from muscle activity.
• The general normal reference range for creatinine is 0.84 mg/dL to 1.21 mg/dL, with some variance when age and gender are considered.
• A high creatinine result is indicative of kidney disease. Like the BUN value, the creatinine value increases as kidney disease worsens.

If the BUN or creatinine levels are higher than the normal ranges, other comprehensive metabolic panel values can provide additional clues for assessing renal function, including:

Minerals

• Phosphorus
The normal reference range for phosphorus in adults is 2.5 to 4.5 mg/dL, with a slight variation based on a patient’s age.
A high phosphorus level, or hyperphosphatemia, can be the result of kidney disease.

• Calcium
The normal reference range for total calcium is 8.6 to 10.5 mg/dL, with slight variations based on a patient’s gender and age.
A low calcium level, or hypocalcemia, can be indicative of kidney disease.

Electrolytes

• Sodium
• Potassium
• Chloride

Since the kidneys help to maintain normal electrolyte balances, imbalances can reveal inadequate renal function.

 

Urine Kidney Values

A urinalysis also provides valuable insight into renal function. Some particular kidney values that are evaluated in a urinalysis include:

Urine specific gravity
The normal reference range for urine specific gravity is between 1.005 and 1.025.
If the urine specific gravity result is lower than the normal range, kidney disease is suspected.

Urinary pH
The normal reference range for urinary pH is 4.5 to 8.
If the urinary pH exceeds the normal range, this may indicate kidney disease.

Creatinine Clearance Test
If any of the aforementioned kidney function values do not fall within normal parameters, an additional urine test that evaluates kidney filtration may be ordered. The creatinine clearance test
is run on a sample of all urine that has been collected over a 24-hour period. When the level of creatinine in this sample is compared to that of the blood serum sample, a calculation can then determine how much blood per minute the kidneys are able to filter creatinine.

The normal creatinine clearance for women is approximately 95 milliliters per minute, and the normal creatinine clearance for men is approximately 120 milliliters per minute. A lower creatinine clearance result may be indicative of kidney disease.

 

Glomerular Filtration Rate and Disease Staging

The glomerular filtration rate (GFR) is calculated by a physician from the results of the patient’s serum creatinine value and other factors, including age, gender and weight. The normal reference range for GFR in healthy adults is greater than 90. The GFR indicates how much renal functioning capacity a patient has and enables physicians to determine the stage of a patient’s chronic kidney disease. The stages for GFR are designated as follows:

Stage 1 – there is evidence of kidney damage, but the GFR is a normal value of 90 or greater.
Stage 2 – there is evidence of kidney damage and the GFR has dropped to between 60 and 89.
Stage 3 – the GFR is between 30 and 59.
Stage 4 – the GFR is between 15 and 29.
Stage 5 – the GFR is less than 15.

Kidney disease is diagnosed when the GFR is at least 60. A GFR of 15 prompts immediate treatment for kidney failure. At this stage, the options of dialysis, a kidney transplant and palliative care must be considered.

If any renal function tests yield abnormal results, additional tests may be ordered. Such tests may include diagnostic imaging, such as an ultrasound or CT scan of the kidneys, or a renal biopsy.

Who Should Be Tested?

Comprehensive metabolic screenings should be ordered for all patients as part of their routine physicals. Abbreviated tests that screen specifically for renal function may be ordered more frequently for patients who carry higher risks for kidney disease. High risk factors include:

• Diabetes
• Hypertension
• Obesity
• Cardiovascular disease
• Family history of kidney failure

Hispanic Americans, African Americans, Pacific Islanders, Asians and American Indians all have an increased risk for kidney disease due to the higher prevalence of diabetes and hypertension in these groups.

Symptoms of chronic kidney disease do not emerge until the illness has advanced to its later stages. Renal function tests should be ordered for any patient who presents with the following complaints:

• Nausea or vomiting
• Decreased appetite
• Urinating more frequently than normal, including at night
• Swelling around the ankles
• Puffiness around the eyes
• Unintentional weight loss
• Fatigue
• Shortness of breath
• Foamy appearance to urine
• Muscle cramping
• Dry or itchy skin

In patients who have been diagnosed with chronic kidney disease, periodic orders for renal function screenings will serve to monitor the advancement of the disease so that adjustments in treatment protocols can be made.

Kidney damage and diminishing function cannot be reversed. The goal of treatment for chronic kidney disease is to slow down the rate of degeneration and maintain an adequate level of kidney function to stave off kidney failure as long as possible. Treatment includes a therapeutic diet, management of diabetes or hypertension, medications to reduce complications and dialysis. The best chance for a longer survival time is to make renal function testing part of preventative patient care.

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