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Kidney Function Tests

Kidney function tests

Definition

Kidney function tests is a collective term for a variety of individual tests and procedures that can be done to evaluate how well the kidneys are functioning. A doctor who orders kidney function tests and uses the results to assess the functioning of the kidneys is called a nephrologist.


Purpose

The kidneys, the body's natural filtration system, perform many vital functions, including removing metabolic waste products from the bloodstream, regulating the body's water balance, and maintaining the pH (acidity/alkalinity) of the body's fluids. Approximately one and a half quarts of blood per minute are circulated through the kidneys, where waste chemicals are filtered out and eliminated from the body (along with excess water) in the form of urine. Kidney function tests help to determine if the kidneys are performing their tasks adequately.


Precautions

The doctor should take a complete history prior to conducting kidney function tests to evaluate the patient's food and drug intake. A wide variety of prescription and over-the-counter medications can affect blood and urine kidney function test results, as can some food and beverages.

Description

Many conditions can affect the ability of the kidneys to carry out their vital functions. Some conditions can lead to a rapid (acute) decline in kidney function; others lead to a gradual (chronic) decline in function. Both can result in a build-up of toxic waste substances in the blood. A number of clinical laboratory tests that measure the levels of substances normally regulated by the kidneys can help to determine the cause and extent of kidney dysfunction. Urine and blood samples are used for these tests.

The nephrologist uses these results in a number of ways. Once a diagnosis is made that kidney disease is present and what kind of kidney disease is causing the problem, the nephrologist may recommend a specific treatment. Although there is no specific drug therapy that will prevent the progression of kidney disease, the doctor will make recommendations for treatment to slow the disease as much as possible. For instance, the doctor might prescribe blood pressure medications, or treatments for patients with diabetes. If kidney disease is getting worse, the nephrologist may discuss hemodialysis (blood cleansing by removal of excess fluid, minerals, and wastes) or kidney transplantation (surgical procedure to implant a healthy kidney into a patient with kidney disease or kidney failure) with the patient.


Laboratory tests

There are a number of urine tests that can be used to assess kidney function. A simple, inexpensive screening testa routine urinalysisis often the first test conducted if kidney problems are suspected. A small, randomly collected urine sample is examined physically for things like color, odor, appearance, and concentration (specific gravity); chemically, for substances such a protein, glucose, and pH (acidity/alkalinity); and microscopically for the presence of cellular elements (red blood cells [RBCs], white blood cells [WBCs], and epithelial cells), bacteria, crystals, and casts (structures formed by the deposit of protein, cells, and other substances in the kidneys's tubules). If results indicate a possibility of disease or impaired kidney function, one or more of the following additional tests is usually performed to pinpoint the cause and the level of decline in kidney function.

  • Creatinine clearance test. This test evaluates how efficiently the kidneys clear a substance called creatinine from the blood. Creatinine, a waste product of muscle energy metabolism, is produced at a constant rate that is proportional to the individual's muscle mass. Because the body does not recycle it, all creatinine filtered by the kidneys in a given amount of time is excreted in the urine, making creatinine clearance a very specific measurement of kidney function. The test is performed on a timed urine specimena cumulative sample collected over a two to 24-hour period. Determination of the blood creatinine level is also required to calculate the urine clearance.
  • Urea clearance test. Urea is a waste product that is created by protein metabolism and excreted in the urine. The urea clearance test requires a blood sample to measure the amount of urea in the bloodstream and two urine specimens, collected one hour apart, to determine the amount of urea that is filtered, or cleared, by the kidneys into the urine.
  • Urine osmolality test. Urine osmolality is a measurement of the number of dissolved particles in urine. It is a more precise measurement than specific gravity for evaluating the ability of the kidneys to concentrate or dilute the urine. Kidneys that are functioning normally will excrete more water into the urine as fluid intake is increased, diluting the urine. If fluid intake is decreased, the kidneys excrete less water and the urine becomes more concentrated. The test may be done on a urine sample collected first thing in the morning, on multiple timed samples, or on a cumulative sample collected over a 24-hour period. The patient will typically be prescribed a high-protein diet for several days before the test and be asked to drink no fluids the night before the test.
  • Urine protein test. Healthy kidneys filter all proteins from the bloodstream and then reabsorb them, allowing no protein, or only slight amounts of protein, into the urine. The persistent presence of significant amounts of protein in the urine, then, is an important indicator of kidney disease. A positive screening test for protein (included in a routine urinalysis ) on a random urine sample is usually followed up with a test on a 24-hour urine sample that more precisely measures the quantity of protein.

There are also several blood tests that can aid in evaluating kidney function. These include:

  • Blood urea nitrogen test (BUN). Urea is a byproduct of protein metabolism. Formed in the liver, this waste product is then filtered from the blood and excreted in the urine by the kidneys. The BUN test measures the amount of nitrogen contained in the urea. High BUN levels can indicate kidney dysfunction, but because BUN is also affected by protein intake and liver function, the test is usually done together with a blood creatinine, a more specific indicator of kidney function.
  • Creatinine test. This test measures blood levels of creatinine, a by-product of muscle energy metabolism that, similar to urea, is filtered from the blood by the kidneys and excreted into the urine. Production of creatinine depends on an person's muscle mass, which usually fluctuates very little. With normal kidney function, then, the amount of creatinine in the blood remains relatively constant and normal. For this reason, and because creatinine is affected very little by liver function, an elevated blood creatinine level is a more sensitive indicator of impaired kidney function than the BUN.
  • Other blood tests. Measurement of the blood levels of other elements regulated in part by the kidneys can also be useful in evaluating kidney function. These include sodium, potassium, chloride, bicarbonate, calcium, magnesium, phosphorus, protein, uric acid, and glucose.

Results

Normal values for many tests are determined by the patient's age and gender. Reference values can also vary by laboratory, but are generally within the following ranges:


Urine tests

  • Creatinine clearance. For a 24-hour urine collection, normal results are 90 mL/min139 mL/min for adult males younger than 40, and 80125 mL/min for adult females younger than 40. For people over 40, values decrease by 6.5 mL/min for each decade of life.
  • Urine osmolality. With restricted fluid intake (concentration testing), osmolality should be greater than 800 mOsm/kg of water. With increased fluid intake (dilution testing), osmolality should be less than 100 mOSm/kg in at least one of the specimens collected. A 24-hour urine osmolality should average 300900 mOsm/kg. A random urine osmolality should average 500800 mOsm/kg.
  • Urine protein. A 24-hour urine collection should contain no more than 150 mg of protein.
  • Urine sodium. A 24-hour urine sodium should be within 75200 mmol/day.

Blood tests

  • Blood urea nitrogen (BUN) should average 820 mg/dL.
  • Creatinine should be 0.81.2 mg/dL for males, and 0.60.9 mg/dL for females.
  • Uric acid levels for males should be 3.57.2 mg/dL and for females 2.66.0 mg/dL.

Low clearance values for creatinine indicate a diminished ability of the kidneys to filter waste products from the blood and excrete them in the urine. As clearance levels decrease, blood levels of creatinine, urea, and uric acid increase. Because it can be affected by other factors, an elevated BUN, alone, is suggestive, but not diagnostic for kidney dysfunction. An abnormally elevated plasma creatinine is a more specific indicator of kidney disease than is BUN.

Low clearance values for creatinine and urea indicate a diminished ability of the kidneys to filter these waste products from the blood and to excrete them in the urine. As clearance levels decrease, blood levels of creatinine and urea nitrogen increase. Since it can be affected by other factors, an elevated BUN alone is certainly suggestive for kidney dysfunction. However, it is not diagnostic. An abnormally elevated blood creatinine, a more specific and sensitive indicator of kidney disease than the BUN, is diagnostic of impaired kidney function.

The inability of the kidneys to concentrate the urine in response to restricted fluid intake, or to dilute the urine in response to increased fluid intake during osmolality testing, may indicate decreased kidney function. Because the kidneys normally excrete almost no protein in the urine, its persistent presence, in amounts that exceed the normal 24-hour urine value, usually indicates some type of kidney disease.


Patient education

Some kidney problems are the result of another disease process, such as diabetes or hypertension. Doctors should take the time to inform patients about how their disease or its treatment will affect kidney function, as well as the different measures patients can take to help prevent these changes.


Resources

books

Brenner, Barry M. and Floyd C. Rector Jr., eds. The Kidney, 6th Edition. Philadelphia, PA: W. B. Saunders Company, 1999.

Burtis, Carl A. and Edward R. Ashwood. Tietz Textbook of Clinical Chemistry. Philadelphia, PA: W.B. Saunders Company, 1999.

Henry, J. B. Clinical Diagnosis and Management by Laboratory Methods, 20th ed. Philadelphia, PA: W. B. Saunders Company, 2001.

Pagana, Kathleen Deska. Mosby's Manual of Diagnostic and Laboratory Tests. St. Louis, MO: Mosby, Inc., 1998.

Wallach, Jacques. Interpretation of Diagnostic Tests, 7th ed. Philadelphia: Lippincott Williams & Wilkens, 2000.


organizations

National Kidney Foundation (NKF). 30 East 33rd Street, New York, NY 10016. (800)622-9020. <http://www.kidney.org>.

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). National Institutes of Health, Building 31, Room 9A04, 31 Center Drive, MSC 2560, Bethesda, MD 208792-2560. (301) 496-3583. <http://www.niddk.nih.gov/health/kidney/kidney.htm>.

other

National Institutes of Health. [cited April 5, 2003]. <http://www.nlm.nih.gov/medlineplus/encyclopedia.html>.

National Institutes of Health. [cited June 29, 2003] <http://www.nlm.nih.gov/medlineplus/ency/article/003005.htm>.


Paula Ann Ford-Martin
Mark A. Best, M.D.

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Kidney Function Tests

Kidney Function Tests

Definition

Kidney function tests is a collective term for a variety of individual tests and procedures that can be done to evaluate how well the kidneys are functioning.

Purpose

The kidneys, the body's natural filtration system, perform many vital functions, including removing metabolic waste products from the bloodstream, regulating the body's water balance, and maintaining the pH (acidity/alkalinity) of the body's fluids. Approximately one and a half quarts of blood per minute are circulated through the kidneys, where waste chemicals are filtered out and eliminated from the body (along with excess water) in the form of urine. Kidney function tests help to determine if the kidneys are performing their tasks adequately.

Precautions

A complete history should be taken prior to kidney function tests to assess the patient's food and drug intake. A wide variety of prescription and over-the-counter medications can affect blood and urine kidney function test results, as can some food and beverages.

Description

Many conditions can affect the ability of the kidneys to carry-out their vital functions. Some lead to a rapid (acute) decline in kidney function; others lead to a gradual (chronic) decline in function. Both result in a build-up of toxic waste substances in the blood. A number of clinical laboratory tests that measure the levels of substances normally regulated by the kidneys can help determine the cause and extent of kidney dysfunction. These tests are done on urine samples, as well as on blood samples.

Urine tests

There are a variety of urine tests that assess kidney function. A simple, inexpensive screening test, called a routine urinalysis, is often the first test administered if kidney problems are suspected. A small, randomly collected urine sample is examined physically for things like color, odor, appearance, and concentration (specific gravity); chemically for substances such as protein, glucose, and pH (acidity/ alkalinity); and microscopically for the presence of cellular elements (red blood cells, white blood cells, and epithelial cells), bacteria, crystals, and casts (structures formed by the deposit of protein, cells, and other substances in the kidneys' tubules). If results indicate a possibility of disease or impaired kidney function, one or more of the following additional tests is usually performed to more specifically diagnose the cause and the level of decline in kidney function.

  • Creatinine clearance test. This test evaluates how efficiently the kidneys clear a substance called creatinine from the blood. Creatinine, a waste product of muscle energy metabolism, is produced at a constant rate that is proportional to the muscle mass of the individual. Because the body does not recycle it, all of the creatinine filtered by the kidneys in a given amount of time is excreted in the urine, making creatinine clearance a very specific measurement of kidney function. The test is performed on a timed urine specimena cumulative sample collected over a two to twenty-four hour period. Determination of the blood creatinine level is also required to calculate the urine clearance.
  • Urea clearance test. Urea is a waste product that is created by protein metabolism and excreted in the urine. The urea clearance test requires a blood sample to measure the amount of urea in the bloodstream and two urine specimens, collected one hour apart, to determine the amount of urea that is filtered, or cleared, by the kidneys into the urine.
  • Urine osmolality test. Urine osmolality is a measurement of the number of dissolved particles in urine. It is a more precise measurement than specific gravity for evaluating the ability of the kidneys to concentrate or dilute the urine. Kidneys that are functioning normally will excrete more water into the urine as fluid intake is increased, diluting the urine. If fluid intake is decreased, the kidneys excrete less water and the urine becomes more concentrated. The test may be done on a urine sample collected first thing in the morning, on multiple timed samples, or on a cumulative sample collected over a twenty-four hour period. The patient will typically be prescribed a high-protein diet for several days before the test and asked to drink no fluids the night before the test.
  • Urine protein test. Healthy kidneys filter all proteins from the bloodstream and then reabsorb them, allowing no protein, or only slight amounts of protein, into the urine. The persistent presence of significant amounts of protein in the urine, then, is an important indicator of kidney disease. A positive screening test for protein (included in a routine urinalysis) on a random urine sample is usually followed-up with a test on a 24-hour urine sample that more precisely measures the quantity of protein.

Blood tests

There are also several blood tests that can aid in evaluating kidney function. These include:

  • Blood urea nitrogen test (BUN). Urea is a by-product of protein metabolism. This waste product is formed in the liver, then filtered from the blood and excreted in the urine by the kidneys. The BUN test measures the amount of nitrogen contained in the urea. High BUN levels can indicate kidney dysfunction, but because blood urea nitrogen is also affected by protein intake and liver function, the test is usually done in conjunction with a blood creatinine, a more specific indicator of kidney function.
  • Creatinine test. This test measures blood levels of creatinine, a by-product of muscle energy metabolism that, like urea, is filtered from the blood by the kidneys and excreted into the urine. Production of creatinine depends on an individual's muscle mass, which usually fluctuates very little. With normal kidney function, then, the amount of creatinine in the blood remains relatively constant and normal. For this reason, and because creatinine is affected very little by liver function, an elevated blood creatinine is a more sensitive indication of impaired kidney function than the BUN.
  • Other blood tests. Measurement of the blood levels of other elements regulated in part by the kidneys can also be useful in evaluating kidney function. These include sodium, potassium, chloride, bicarbonate, calcium, magnesium, phosphorus, protein, uric acid, and glucose.

Preparation

Patients will be given specific instructions for collection of urine samples, depending on the test to be performed. Some timed urine tests require an extended collection period of up to 24 hours, during which time the patient collects all urine voided and transfers it to a specimen container. Refrigeration and/or preservatives are typically required to maintain the integrity of such urine specimens. Certain dietary and/or medication restrictions may be imposed for some of the blood and urine tests. The patient may also be instructed to avoid exercise for a period of time before a test.

Aftercare

If medication was discontinued prior to a urine kidney function test, it may be resumed once the test is completed.

Risks

Risks for these tests are minimal, but may include slight bleeding from a blood-drawing site, hematoma (accumulation of blood under a puncture site), or fainting or feeling light-headed after venipuncture. In addition, suspension of medication or dietary changes imposed in preparation for some blood or urine tests may trigger side-effects in some individuals.

Normal results

Normal values for many tests are determined by the patient's age and sex. Reference values can also vary by laboratory, but are generally within the ranges that follow.

Urine tests

  • Creatinine clearance. For a 24-hour urine collection, normal results are 90-139 ml/min for adult males less than 40 years old, and 80-125 ml/min for adult females less than 40 years old. For people over 40, values decrease by 6.5 ml/min for each decade of life.
  • Urea clearance. With maximum clearance, normal is 64-99 ml/min.
  • Urine osmolality. With restricted fluid intake (concentration testing), osmolality should be greater than 800 mOsm/kg of water. With increased fluid intake (dilution testing), osmolality should be less than 100 mOSm/kg in at least one of the specimens collected.
  • Urine protein. A 24-hour urine collection should contain no more than 150 mg of protein.

Blood tests

  • Blood urea nitrogen (BUN). 8-20 mg/dl.
  • Creatinine. 0.8-1.2 mg/dl for males, and 0.6-0.9 mg/dl for females.

Abnormal results

Low clearance values for creatinine and urea indicate diminished ability of the kidneys to filter these waste products from the blood and excrete them in the urine. As clearance levels decrease, blood levels of creatinine and urea nitrogen increase. Since it can be affected by other factors, an elevated BUN, by itself, is suggestive, but not diagnostic, for kidney dysfunction. An abnormally elevated blood creatinine, a more specific and sensitive indicator of kidney disease than the BUN, is diagnostic of impaired kidney function.

KEY TERMS

Blood urea nitrogen (BUN) The nitrogen portion of urea in the bloodstream. Urea is a waste product of protein metabolism in the body.

Creatinine The metabolized by-product of creatine, an organic acid that assists the body in producing muscle contractions. Creatinine is found in the bloodstream and in muscle tissue. It is removed from the blood by the kidneys and excreted in the urine.

Osmolality A measurement of urine concentration that depends on the number of particles dissolved in it. Values are expressed as milliosmols per kilogram (mOsm/kg) of water.

Urea A by-product of protein metabolism that is formed in the liver. Because urea contains ammonia, which is toxic to the body, it must be quickly filtered from the blood by the kidneys and excreted in the urine.

Inability of the kidneys to concentrate the urine in response to restricted fluid intake, or to dilute the urine in response to increased fluid intake during osmolality testing may indicate decreased kidney function. Because the kidneys normally excrete almost no protein in the urine, its persistent presence, in amounts that exceed the normal 24-hour urine value, usually indicates some type of kidney disease as well.

Resources

ORGANIZATIONS

National Kidney Foundation. 30 East 33rd St., New York, NY 10016. (800) 622-9010. http://www.kidney.org.

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Kidney Function Tests

Kidney Function Tests

Definition

Kidney function tests are a cadre of tests that are used to screen for and manage renal disease. Tests commonly used for this purpose are plasma creatinine, blood urea nitrogen (BUN), electrolytes, and routine urinalysis. Additional laboratory tests are performed to evaluate abnormal renal function and help differentiate between causes. The most commonly used follow-up tests are creatinine clearance, plasma and urine osmolality, and urine sodium.

Purpose

Renal function tests are used to screen for renal disease, to differentiate the cause of renal disease, and to determine the extent of renal dysfunction. These tests attempt to define the clinical state of renal dysfunction and not the process of injury. The latter is determined primarily by a combination of clinical data and biopsy to determine the histological pattern of injury.

Precautions

A complete history should be taken prior to kidney function tests to assess the patient's symptoms and food and drug intake. A wide variety of prescription and over-the-counter medications can affect blood and urine kidney function test results, as can some food and beverages. Renal function tests are performed on both blood and urine. Blood samples are collected by venipuncture from a vein in the crease of the arm. The nurse or phlebotomist performing the procedure should observe universal precautions for the prevention of transmission of bloodborne pathogens. The creatinine clearance test requires a timed urine sample. Explicit written instruction must accompany the explanation of how to collect this sample. It is imperative that the patient empty his or her bladder at the start of the test and not include this urine in the collection. It is equally important that all urine produced during the time of the test be saved and refrigerated, and that the bladder be emptied completely and this urine added to the collection at the end of the test.

Description

The kidneys are a pair of organs located in the back of the abdominal cavity on either side of the vertebral column. Their purpose is to filter the blood and remove wastes and excess water. They also selectively reabsorb compounds that have been filtered, thus conserving essential nutrients, electrolytes, amino acids and other biomolecules. Approximately one-quarter of the cardiac output, 1200 mL of blood per minute are received by the kidneys. Each kidney is made up of functional microscopic units called nephrons. Each nephron contains a capillary tuft, the glomerulus and a tubule. Blood flows into the kidneys, and engorges the capillary tufts. Water and small solutes pass through the vessel walls forming a filtrate of the plasma which enters the underlying space, Bowman's capsule. The walls of the capsule form a tubule that traverses the kidney. Blood leaves the glomerular capillaries through an efferent arteriole which forms a capillary network, the vasa recta, that follows the path of the tubules. The cells of the renal tubule modify the filtrate along its length ultimately forming urine that passes out of the body. The tubule is responsible for two processes, reabsorption and secretion. Reabsorption is the process of moving solutes from the tubular lumen into the interstitium that bathes the tubules, so that they can be absorbed by the vasa recta. Some substances such as glucose and sodium are one-hundred percent reabsorbed until the plasma level exceeds a certain concentration called the renal threshold. Secretion is the process of transporting solutes from the interstitium into the tubular lumen, so that they can be excreted in the urine. Secretion allows substances such as hydrogen ions to be eliminated at a rate that exceeds glomerular filtration. These processes are controlled by the selective permeability of different segments of the tubule to water, salt and urea, and the response of the distal collecting tubules to hormones such as aldosterone, antidiuretic hormone, and parathyroid hormone.

When kidney function becomes compromised by disease, the processes of glomerular filtration and tubular reabsorption and secretion become affected to different extents. This can result in retention of waste products that are incompletely filtered, loss of essential solutes that are not reabsorbed, and failure of the tubules to respond to hormonal control of electrolyte and water balance. Blood and urine biochemistry tests reflect the extent of this dysfunction and are used to characterize the clinical state of the patient. Fortunately, the kidneys have a large reserve capacity, and a significant amount of damage must be incurred before kidney function tests become significantly abnormal.

There are several renal states that can be categorized by renal function test results, but the two major ones are acute and chronic renal failure. Renal failure is a term used to describe a loss of renal function characterized by uremia, the retention of nitrogenous wastes in the blood. The acute form is rapid in onset and often reversible. It can occur as three different states, termed prerenal, renal (intrarenal), and postrenal failure. Prerenal failure results from decreased blood flow to the kidneys, and its most common cause is congestive heart failure. Renal failure results from injury to the glomerulus and the tubules. The most common causes are glomerulonephritis which is mediated by autoantibodies that damage the glomerulus and obstruct the tubules; pyelonephritis which is caused by a bacterial infection of the interstitium; and tubular damage caused by drugs, heavy metals, and viral infections. Postrenal failure is caused by obstruction below the kidneys. This can result from urinary tract stones, tumors, or anatomic obstruction as in benign prostatic hypertrophy. The chronic form is characterized by slow onset without accompanying symptoms in its early stage. Chronic renal failure often follows episodes of acute renal failure, and it is not reversible. Chronic renal failure is most commonly a sequalae to acute glomerulonephritis or pyelonephritis which together account for more than half the cases. Other causes of chronic renal failure are chronic diseases such as diabetes mellitus, renal vascular disease (e.g., atherosclerosis of the renal vessels), hypertension, polycystic kidney disease, drug damage, and kidney stones. Kidneys from patients with chronic renal failure will appear smaller than average and a biopsy of the kidney will demonstrate scarring of the tubules.

Laboratory tests

Regardless of the cause, most persons with acute renal failure are characterized by three common laboratory findings: reduced creatinine clearance, azotemia (excessive nitrogen compounds in the blood), and hyperkalemia (excessive potassium in the blood). Creatinine is a waste product of muscle metabolism. It is produced at a constant rate and filtered freely by the glomeruli without reabsorption. Therefore, creatinine levels in the blood are increased when there is reduced glomerular filtration. Although specific for glomerular disease, plasma creatinine is not a sensitive test, and about 60% of the renal capacity is usually lost before levels become abnormal. A more sensitive indicator of glomerular dysfunction is the creatinine clearance test. This test measures the ratio of urine to plasma creatinine. As plasma levels rise, urine levels fall causing the ratio to decrease before plasma creatinine becomes definitively abnormal.

CREATININE CLEARANCE TEST. The creatinine clearance is defined as the volume of plasma that contains the same amount of creatinine as is excreted in the urine in one minute. Because the tubules do not reabsorb creatinine, all of the creatinine filtered by the glomeruli in a given amount of time is excreted in the urine. This test is an estimate of the glomerular filtration rate. The test is performed by measuring creatinine in a timed urine specimen-a cumulative sample collected over a four, 12, or 24-hour hour period. Determination of the plasma creatinine is also required to calculate the urine clearance. The clearance formula is U/P × V × 1.73/A. "U" is the urine creatinine in gm/dL; "P" is the plasma creatinine in mg/dL; and "V" is the volume of urine produced per minute. This is usually calculated by dividing the volume of urine produced per day by 1440 minutes per day. "A" is the person's body surface area expressed in square meters, and 1.73 is the average body surface area in square meters. During the test, the patient must be well hydrated because under conditions of slow filtrate flow the tubules will secrete some creatinine causing an overestimate of clearance. Creatinine can be measured by a colormetric method called the Jaffe reaction or by a coupled enzymatic reaction. The Jaffe reaction is performed by mixing a plasma or diluted urine sample with a solution of sodium hydroxide and saturated picric acid. At an alkaline pH, the creatinine combines with picric acid to form creatinine picrate and the rate of absorbance change is measured over a precisely defined timed interval to eliminate interference from proteins and other reducing agents

Azotemia is the accumulation of nitrogenous (azo) waste products in the blood as a consequence of renal failure. The azo compounds routinely measured are creatinine, urea, and uric acid. While an increase of plasma urea or uric acid is not specific for renal disease, both compounds are retained whenever there is a reduction in the glomerular filtration rate. Of the two compounds, urea is the more sensitive, and urea levels can be used with creatinine to help differentiate prerenal and renal failure.

BLOOD UREA NITROGEN (BUN) TEST. Historically, urea concentration has been expressed as the concentration of nitrogen derived from urea, called the BUN. This test is performed by an enzymatic-ultraviolet photometric method using the enzyme urease. The enzyme catalyzes the hydrolysis of urea by water forming ammonia and carbon dioxide. A coupling enzyme, glutamate dehydrogenase, catalyzes the formation of glutamate from alpha-ketoglutamate and ammonia. In this reaction NADPH is converted to NADP+ which causes a decrease in the absorbance of 340 nm light. The rate of absorbance decrease is proportional to the urea nitrogen concentration of the sample. Urea is freely filtered by the glomerulus but is reabsorbed by the tubules to a variable extent depending upon the movement of filtrate through the tubule. When filtrate flow is slow, 40% or more of the filtered urea can be reabsorbed. For this reason, BUN levels increase much more than creatinine in prerenal failure. In prerenal failure, the kidney is not damaged, but glomerular filtration is reduced because of insufficient blood flow to the glomeruli. This results in increased retention of all three azo compounds. However, poor renal blood flow is a stimulus for ADH secretion that promotes water and urea reabsorption. Since the tubules are undamaged, they reabsorb a maximal amount of urea. This causes the ratio of plasma BUN to creatinine to increase dramatically. The reabsorption of BUN is impaired in renal failure caused by renal damage because the tubules are impaired. Ratios in prerenal failure are approximately 20:1, twice that seen in renal failure caused by damaged kidneys.

Electolyte disturbances are common to all forms of renal failure. Potassium is filtered by the glomerulus and partly reabsorbed in the proximal tubule. A significant amount of potassium is secreted by the collecting tubule in response to aldosterone. Therefore, when the kidneys receive insufficient blood flow potassium is incompletely filtered. When the tubules are damaged, potassium levels rise further because the exchange of potassium for sodium is impaired.

Plasma potassium levels must be maintained within a very narrow range to avoid cardiac arrhythmia. Elevated plasma potassium is the single most important (life-threatening) consequence of renal failure. Plasma potassium is the criterion used to determine the need for dialysis and the frequency and duration of treatment. Urine sodium is very useful in helping to differentiate prerenal from renal failure. In prerenal failure, the daily excretion of sodium is lower than normal because the kidneys attempt to reabsorb sodium in order to restore blood flow. However, in renal failure, daily urine sodium loss is increased owing to tubular failure. Urinary sodium is about twofold higher in intrarenal failure than in prerenal failure.

Urinalysis

There are a variety of urine tests that assess kidney function. A simple, inexpensive screening test, routine urinalysis, is often the first test administered when kidney problems are suspected. A first-morning or randomly voided urine sample is examined visually for color and clarity, and a series of up to ten dry reagent strip biochemical tests are performed. Protein, blood, leukocytes, and specific gravity are four tests that are often abnormal in persons with renal failure. Glomerular damage causes albumin and red blood cells to pass through the basement membrane and enter the filtrate in Bowman's space. Leukocytes migrate to the site of injury and enter the filtrate through glomerular lesions and by passing between the tubular cells. Tubular failure disables the concentrating and diluting capacity of the kidneys and the urine produced is consistently of the same specific gravity as the plasma (1.010). Glucose and pH are also useful because a high percentage of diabetics develop renovascular disease, and renal failure results in acidosis (hydrogen ion retention) with concomitant failure to acidify the urine. While these findings can occur in severe lower urinary tract disease, the renal origin of the cells can often be confirmed by microscopic analysis of urinary sediment. In renal injury, stasis, protein, and obstruction of the tubules by cells cause the precipitation of mucoproteins in the tubules. When these are washed out by urine flow, they can be seen using the microscope, and are called casts. The finding of cellular casts in the urinary sediment, identifies the kidney as the source of the cells. Experienced technologists can often distinguish glomerular bleeding from bleeding below the kidney because the former causes characteristic abnormalities in red blood cell structure (dysmorphic cells). Furthermore, the presence of cells and casts signifies renal damage and rules out prerenal failure as the cause of abnormal biochemistry results.

Glomerulonephritis is the most common cause of intrarenal failure. Urinary sediment in this condition displays large numbers of both red and white blood cells, and usually a predominance of red blood cell casts. Pyleonephritis, the second most common renal disease is characterized by a predomonance of white blood cells and white blood cell casts. Bacteria are usually abundant in the sediment signaling the causative infection.

Postrenal failure may also result in abnormal sediment. The presence of large numbers of crystals in association with biochemical evidence of worsening renal function and hematuria may alert the clinician to the presence of a urinary tract stone. The presence of large numbers of abnormal (cancerous) transitional epithelial cells may be shed into the urine by a bladder tumor and seen in the urine microscopic exam. In such cases, an imaging test, the intravenous pyelogram, is often performed in order to identify the size, location, and possible cause of the obstruction.

OSMOLALITY. Urine osmolality is a measure of the number of dissolved particles in urine. It is a more precise measurement than specific gravity for evaluating the ability of the kidneys to concentrate or dilute the urine. Kidneys that are functioning normally will excrete water in relation to the amount consumed. Those with failing kidneys may not be able to concentrate urine. Solutes will equilibrate by passive diffusion in the tubule and the osmolality will be the same as plasma, approximately 290 mOsm/Kg water. The test may be done on a urine sample collected first thing in the morning as water deprivation overnight should concentrate the urine; multiple timed samples, or on a cumulative sample collected over a 24-hour period. In addition, the ratio of urine to plasma osmolality is another useful way to differentiate prerenal and intrarenal failure. In prerenal failure the kidneys attempt to restore blood volume by reabsorbing sodium. This raises the plasma osmolality causing release of antidiuretic hormone (ADH) from the posterior pituitary. Under the influence of ADH, the tubules reabsorb more water concentrating the urine. As mentioned, the plasma and urine osmolality are the same in intrarenal disease. The urine to plasma osmolality ratio in prerenal failure is usually twofold higher than in renal disease, in which the ratio is one.

The acute and chronic forms of renal failure display some distinguishing characteristics. In chronic renal failure, the tubules become scarred causing water loss. This results in polyruria (increased urine volume) as opposed to oliguria (low urine volume) seen in acute renal failure. Scarring also results in salt wasting causing the serum potassium to be lower than seen in acute renal failure. The urinary sediment shows heavy proteinuria, hematuria (red blood cells) and abundant casts. The casts are usually broad and waxy, which are unique characteristics of end-stage renal failure.

OTHER BLOOD TESTS. Measurement of the blood levels of other analytes regulated or affected in part by the kidneys can be useful in evaluating kidney function and in managing conditions such as osteomalacia and renal acidosis that are secondary to renal disease. These include bicarbonate, calcium, magnesium, phosphorus, plasma renin activity, and parathyroid hormone.

Preparation

Patients will be given specific instructions for collection of urine samples, depending on the test to be performed. During routine urinalysis, the patient will be given a sealed cup to urinate into. Nurses stress that the patient obtain a "clean catch" by initiating urination and placing the sample cup in the urine stream after a few seconds. This prevents the collection of the initial urine which may contain bacteria that are present in the lower urethra or on the skin. Some timed urine tests require an extended collection period of up to 24 hours, during which time the patient collects all urine voided and transfers it to a specimen container. Refrigeration and/or preservatives are typically required to maintain the integrity of such urine specimens. Certain dietary and/or medication restrictions may be imposed for some of the blood and urine tests. The patient may also be instructed to avoid exercise for a period of time before a test to prevent changes in creatinine.

Aftercare

If medication was discontinued prior to a kidney function test, it may be resumed once the test is completed.

Complications

Complications for these tests are minimal, but may include slight bleeding from a venipuncture site, hematoma (accumulation of blood under a puncture site), or fainting or feeling light-headed after venipuncture. In addition, suspension of medication or dietary changes imposed in preparation for some blood or urine tests may trigger side effects in some individuals.

Results

Normal values for many tests are determined by the patient's age and sex. Reference values can also vary by laboratory, but are generally within the ranges that follow.

Urine tests

  • Creatinine clearance. For a 24-hour urine collection, normal results are 90-139 mL/min for adult males less than 40 years old, and 80-125 mL/min for adult females less than 40 years old. For people over 40, values decrease by 6.5 mL/min for each decade of life.
  • Urine osmolality. With restricted fluid intake (concentration testing), osmolality should be greater than 800 mOsm/kg of water. With increased fluid intake (dilution testing), osmolality should be less than 100 mOsm/kg in at least one of the specimens collected. A 24-hour urine osmolality should average 300-900 mOsm/kg. A random urine osmolality should average 500-800 mOsm/kg.
  • Urine protein. A 24-hour urine collection should contain no more than 150 mg of protein.
  • Urine sodium. A 24-hour urine sodium should be within 75-200 mmol/day.

Blood tests

  • Blood urea nitrogen (BUN) should average 8-20 mg/dL.
  • Creatinine should be 0.8-1.2 mg/dL for males, and 0.6-0.9 mg/dL for females.
  • Uric acid levels for males should be 3.5-7.2 mg/dL and for females 2.6-6.0 mg/dL.

KEY TERMS

Blood urea nitrogen (BUN)— The nitrogen portion of urea in the bloodstream. Urea is a waste product of protein metabolism in the body.

Creatinine— The metabolized by-product of creatine, an organic compound that assists the body in producing muscle contractions. Creatinine is found in the bloodstream and in muscle tissue. It is removed from the blood by the kidneys and excreted in the urine.

Creatinine clearance rate— The clearance of creatinine from the plasma compared to its appearance in the urine. Since there is no reabsorption of creatinine, this measurement can estimate glomerular filtration rate.

Diuretic— A drug that increases the excretion of salt and water, increasing the output of urine.

Glomerular filtration rate The rate in millimeters per minute at which plasma is filtered through the glomerular membrane.

Hematuria— The presence of blood in the urine.

Nephrologist— A doctor specializing in kidney disease.

Nephron— The functional unit of the kidney.

Oliguria— The formation of very small amounts of urine.

Osmolality— A measurement of urine concentration that depends on the number of particles dissolved in it. Values are expressed as milliosmols per kilogram (mOsm/kg) of water.

Polyuria— The formation of very large amounts of urine.

Proteinuria— The presence of protein in the urine often caused by damage to the glomerular membrane.

Renal— Pertaining to the kidney

Specific gravity— The ratio of the weight of a body fluid when compared to water.

Urea— A by-product of protein metabolism that is formed in the liver. Because urea contains ammonia, which is toxic to the body, it must be quickly filtered from the blood by the kidneys and excreted in the urine.

Uric acid— A product of purine breakdown that is excreted by the kidney. High levels of uric acid, caused by various diseases, can cause the formation of kidney stones.

Urine— A fluid containing water and dissolved substances excreted by the kidney.

Low clearance values for creatinine indicate diminished ability of the kidneys to filter waste products from the blood and excrete them in the urine. As clearance levels decrease, blood levels of creatinine, urea, and uric acid increase. Since it can be affected by other factors, an elevated BUN, by itself, is suggestive, but not diagnostic, for kidney dysfunction. An abnormally elevated plasma creatinine is a more specific indicator of kidney disease than is BUN.

Inability of the kidneys to concentrate the urine in response to restricted fluid intake, or to dilute the urine in response to increased fluid intake during osmolality testing indicates decreased tubular function. Because the kidneys normally excrete almost no protein in the urine, its persistent presence, in amounts that exceed the normal 24-hour urine value, usually indicates glomerular or tubular injury. These can be distinguished by urine protein electrophoresis. This procedure separates proteins in an electric field based upon their charge. Albuminuria is characteristic of glomerular disease, while urinary excretion of alpha-1 and beta-2 microglobulins is characteristic of tubular damage. Proteinuria of tubular origin is caused by drugs, heavy metals, or viral infection of the kidneys. Urine protein electrophoresis also detects monoclonal immunoglobulin light chains (multiple myeloma and related conditions) and immunoglobulin fragments (systemic autoimmune diseases), which are nonrenal causes of proteinuria.

Health care team roles

Kidney function tests are ordered and interpreted by a physician. Blood samples are collected by a nurse or phlebotomist. Nurses should educate the patient on why the tests are being done and how to collect timed urine samples. In addition, patients with kidney disease may be advised to change their diets. A dietitian may be consulted.

Patient education

Some kidney problems are the result of another disease process such as diabetes or high blood pressure. Clinicians should take the time to inform patients about how their disease or its treatment will alter kidney function and the different measures they can take to help prevent these changes.

Resources

BOOKS

Brenner, Barry M., and Floyd C. Rector Jr., eds. The Kidney, 6th Edition. Philadelphia, PA: W.B. Saunders Company, 1999.

Burtis, Carl A., and Edward R. Ashwood. Tietz Textbook of Clinical Chemistry. Philadelphia, PA: W.B. Saunders Company, 1999.

Kaplan, Lawrence A., and Amadeo J. Pesce. Clinical Chemistry Theory, Analysis and Correlation. St. Louis: Mosby Publishers, 1996.

ORGANIZATIONS

National Kidney Foundation (NKF). 30 East 33rd Street, Ste.1100 New York, NY 10016. (800)622-9020. 〈http://www.kidney.org〉.

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Kidney Function Tests

Kidney function tests

Definition

Kidney function tests are a variety of tests designed to test how well the kidneys are functioning.

Purpose

Kidney function tests are an important diagnostic tool for cases in which kidney disease is suspected. Some tests provide information only about how well the kidneys are functioning, while others offer some insight into the possible causes of the problem. Kidney function tests can be used to monitor individuals who are believed to be at high risk for developing kidney disease, such as individuals with diabetes. For these individuals one or more kidney function tests may be part of regular heath screenings. Early diagnosis and intervention can help drastically slow the advance of kidney disease. Kidney function tests can also be used to help monitor the progression of the disease and the success or failure of treatment in individuals already experiencing kidney disease.

Precautions

There are a variety of medications, as well as some food and drinks, that can interfere with the results of certain kidney function tests. In some cases strenuous exercise before the test may also cause inaccurate results. Individuals should inform their doctor of all medications, vitamins , and supplements, including herbs, that they are taking to help ensure the accuracy of the test results.

Description

Each healthy individual has two kidneys located towards the back of the body, slightly below the rib cage. They are shaped like beans, and each one is about the size of an adult's fist. The kidneys filter out waste products and extra water from the blood so that it can be excreted as urine. Healthy kidneys filter about 200 quarts of blood every day, and remove about 2 quarts of waste each day. When the kidneys are damaged they can no longer filter properly, and stop filtering out some things that should be filtered out, while accidentally filtering out some things, like protein, that should not be filtered out. When the kidneys stop filtering properly waste products can building up in the blood to toxic levels, eventually causing death . Significant health problems occur when the kidneys function at about one quarter of capacity, and kidney function below one-tenth of normal can be fatal without intervention in the form of dialysis or kidney transplant.

There are a variety of kidney function tests. Each measures levels of different substances filtered by the kidneys, and can provide different information about the level of kidney functioning and what may be the cause of any problems. The tests fall into two broad categories: blood tests and urine tests.

Blood Tests

  • Blood Urea Nitrogen (BUN)-BUN is the urea nitrogen in the blood. Urea is produced when protein ingested as food is broken down by the body. As kidney function decreases the kidney's ability to filter out the urea nitrogen decreases, leading to increased levels in the blood.
  • Serum Creatinine-This test measures the levels of creatinine, a product of the break down of creatine. Creatine is found in muscle tissue, and can accumulate in the blood through the normal breakdown associated with wear-and tear on the muscles, or through consuming animal protein. When the kidneys are not working well they cannot filter creatinine as effectively, leading to elevated levels in the blood.

Urine Tests

  • Creatinine Clearance-This test is usually done using urine collected over a full 24 hours. It compares the urine creatinine levels with blood creatinine levels, so a blood draw is also required. Creatinine clearance provides information about the rate at which the kidneys are filtering blood.
  • Urine Protein-This test is often done during a normal urinalysis as a first line test for kidney problems. Normally, the kidneys do not filter protein out into the urine. If, however, the kidneys are damaged, protein molecules can begin to slip through and are passed out of the body in the urine. Testing the urine for the presence of protein is a quick, inexpensive test, and is often done even for patients with no symptoms of kidney disease.

Preparation

A variety of medications, food, and beverages may interfere with the results of certain kidney function tests. Therefore the individual may be asked to stop taking certain medications for one or more days before the samples are collected. Depending on the type of test the individual may be asked to refrain from drinking any fluids after a certain time, or may be asked to drink extra fluids. The individual may be advised to avoid certain types of food, drinks, or exercise before the samples are collected.

Aftercare

No aftercare is generally required for kidney function tests.

Complications

No complications are generally expected from kidney function tests. Anytime blood is drawn there is a small risk of excessive bleeding, bruising , swelling, or infection at the puncture site.

Results

The results of kidney function tests can help the doctor determine the level of kidney functioning, the degree of disease, if present, and in some cases give information about the cause of the kidney problems. In general information about the results of kidney function tests is combined with a physical examination, health history , and other diagnostic tests to make a diagnosis

Blood Tests

  • Blood Urea Nitrogen (BUN)-Normal levels of BUN are generally between 7 and 20 mg/dL, although normal levels can depend on the laboratory doing the testing. Higher levels of BUN indicate lower levels of kidney function.
  • Serum Creatinine-Normal results are generally from 0.6 to 1.4 mg/dL. Women often have lower levels than men because women generally have a lower level of body musculature than men. Higher than normal levels indicate kidney disease, and the higher the level of creatinine the more progressed the disease.

Urine Tests

  • Creatinine Clearance-The normal rate for men is 97 to 137 ml/minute. The normal range for women is 88 to 128 ml/minute. This rate has been found to decline with age, so normal functioning for seniors is generally less than that for younger adults. Normal rates must also be adjusted for body size, and can vary depending on the laboratory in which the tests are done. Lower than normal rates indicate decreased kidney function.
  • Urine Protein-Protein in the urine above very trace amounts is considered abnormal. In addition to kidney disease, stress, exercise, and some medications can also sometimes cause protein in the urine. Therefore a positive test for urine protein is often repeated or followed up to with other function tests to determine if kidney disease is actually present.

Caregiver concerns

A doctor determines the need for kidney function tests based on symptoms, risk factors, a physical examination, and the patient's health history. After the doctor orders the test the patient will have the test explained to him or her by the doctor or a nurse familiar with the test procedure. He or she will provide the patient with information about what specific preparations, if any, are required for the test. If urine collection is needed, the patient collects the urine him or herself, unless unable to do so. If the patient is confined to bed the sample may be collected by a nurse using a catheter. If a blood sample is required it is drawn by a phlebotomist, an individual specially trained in drawing blood.

The blood and urine samples are labeled with the patient's information, then stored by the nurse as necessary to maintain their integrity. They are then sent to a laboratory for analysis. At the laboratory a laboratory technician performs a variety of chemical tests and examines the samples under a microscope as needed. The results of the tests are then summarized and returned to the doctor who ordered the test. The doctor or doctor's representative then shares the results with the patients, and the doctor determines what, if any, further diagnostic tests or treatment is required.

QUESTIONS TO ASK YOUR DOCTOR

  • Are there any medicines I should stop taking before the test?
  • Should I continue to eat and drink normally before the test?
  • If the tests show abnormal results, what is the next step?

Resources

BOOKS

Cortes, Pedor, and Carl Erik Mogensen, eds. The Diabetic Kidney. Totowa, NJ: Humana Press, 2006.

Fischbach, Frances Talaska, and Marshall Barnet Dunnin III. A Manual of Laboratory and Diagnostic Tests.

Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2009.

Li, Wei, David Frierman, and Ben Luna. Diseases of the Kidney and Bladder: Diagnosis and Treatment with Chinese Medicine. Boulder: Blue Poppy Press, 2006.

Nunez, Juan F. Macias, J. Stewart Cameron, and Dimitrios G. Oreopolous, eds. The Aging Kidney in Health and Disease. New York: Springer, 2007.

PERIODICALS

Collier-Ramirez, Shelly, and Paris Roach. “Monitor Your Kidney Function.” Diabetes Forecast 60.7 (June 2007):12.

Marsik, C., et al. “Classification of Chronic Kidney Disease by Estimated Glomerular Filtration Rate.” European Journal of Clinical Investigation 38.4 (April 2008): 253-260.

ORGANIZATIONS

American Clinical Laboratory Association, 1250 H Street, Suite 880, Washington, DC, 20005, (202) 637-9466, (202) 637-2050, [email protected], www.clinical-labs.org.

National Kidney Foundation, 30 East 33rd Street, New York, NY, 10016, (212) 889-2210, (800) 622-9010, (212) 689-9261, www.kidney.org.

Robert Bockstiegel

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Kidney Function Tests

Kidney Function Tests

Definition
Purpose
Precautions
Description
Results

Definition

Kidney function tests include a variety of individual tests and procedures that can be done to evaluate how well the kidneys are functioning. A doctor who orders kidney function tests and uses the results to assess the functioning of the kidneys is called a nephrologist.

Purpose

The kidneys, the body’s natural filtration system, perform many vital functions, including removing metabolic waste products from the bloodstream, regulating the body’s water balance, and maintaining the pH (acidity/alkalinity) of the body’s fluids. Approximately one and a half quarts of blood per minute are circulated through the kidneys, where waste chemicals are filtered out and eliminated from the body (along with excess water) in the form of urine. Kidney function tests help to determine if the kidneys are performing their tasks adequately.

Precautions

The doctor should take a complete history prior to conducting kidney function tests to evaluate the patient’s food and drug intake. A wide variety of prescription and over-the-counter medications can affect blood and urine kidney function test results, as can some food and beverages.

Description

Many conditions can affect the ability of the kidneys to carry out their vital functions. Some conditions can lead to a rapid (acute) decline in kidney function; others lead to a gradual (chronic) decline in function. Both can result in a buildup of toxic waste substances in the blood. A number of clinical laboratory tests that measure the levels of substances normally regulated by the kidneys can help to determine the cause and extent of kidney dysfunction. Urine and blood samples are used for these tests.

The nephrologist uses these results in a number of ways. Once a diagnosis is made that kidney disease is present and what kind of kidney disease is causing the problem, the nephrologist may recommend a specific treatment. Although there is no specific drug therapy that will prevent the progression of kidney disease, the doctor will make recommendations for treatment to slow the disease as much as possible. For instance, the doctor might prescribe blood pressure medications, or treatments for patients with diabetes. If kidney disease

KEY TERMS

Blood urea nitrogen (BUN)— The nitrogen portion of urea in the bloodstream. Urea is a waste product of protein metabolism in the body.

Creatinine— The metabolized by-product of creatinine, an organic compound that assists the body in producing muscle contractions. Creatinine is found in the bloodstream and in muscle tissue. It is removed from the blood by the kidneys and excreted in the urine.

Creatinine clearance rate— The clearance of creatinine from the plasma compared to its appearance in the urine. Since there is no reabsorption of creatinine, this measurement can estimate glomerular filtration rate.

Diuretic— A drug that increases the excretion of salt and water, increasing the output of urine.

Kilogram— Metric unit of weight.

Osmolality— A measurement of urine concentration that depends on the number of particles dissolved in it. Values are expressed as milliosmols per kilogram (mOsm/kg) of water.

Nephrologist— A doctor specializing in kidney disease.

Specific gravity— The ratio of the weight of a body fluid when compared with water.

Urea— A by-product of protein metabolism that is formed in the liver. Because urea contains ammonia, which is toxic to the body, it must be quickly filtered from the blood by the kidneys and excreted in the urine.

Uric acid— A product of purine breakdown that is excreted by the kidney. High levels of uric acid, caused by various diseases, can cause the formation of kidney stones.

Urine— A fluid containing water and dissolved substances excreted by the kidney.

is getting worse, the nephrologist may discuss hemodialysis (blood cleansing by removal of excess fluid, minerals, and wastes) or kidney transplantation (surgical procedure to implant a healthy kidney into a patient with kidney disease or kidney failure) with the patient.

Laboratory tests

There are a number of urine tests that can be used to assess kidney function. A simple, inexpensive screening test—a routine urinalysis—is often the first test conducted if kidney problems are suspected. A small, randomly collected urine sample is examined physically for things like color, odor, appearance, and concentration(specific gravity); chemically, for substances such a protein, glucose, and pH (acidity/ alkalinity); and microscopically for the presence of cellular elements (redblood cells [RBCs], white blood cells [WBCs], and epithelial cells), bacteria, crystals, and casts (structures formed by the deposit of protein, cells, and other substances in the kidneys’s tubules). If results indicate a possibility of disease or impaired kidney function, one or more of the following additional tests is usually performed to pinpoint the cause and the level of decline in kidney function.

  • Creatinine clearance test. This test evaluates how efficiently the kidneys clear a substance called creatinine from the blood. Creatinine, a waste product of muscle energy metabolism, is produced at a constant rate that is proportional to the individual’s muscle mass. Because the body does not recycle it, all creatinine filtered by the kidneys in a given amount of time is excreted in the urine, making creatinine clearance a very specific measurement of kidney function. The test is performed on a timed urine specimen—a cumulative sample collected over a two to 24-hour period. Determination of the blood creatinine level is also required to calculate the urine clearance.
  • Urea clearance test. Urea is a waste product that is created by protein metabolism and excreted in the urine. The urea clearance test requires a blood sample to measure the amount of urea in the bloodstream and two urine specimens, collected one hour apart, to determine the amount of urea that is filtered, or cleared, by the kidneys into the urine.
  • Urine osmolality test. Urine osmolality is a measurement of the number of dissolved particles in urine. It is a more precise measurement than specific gravity for evaluating the ability of the kidneys to concentrate or dilute the urine. Kidneys that are functioning normally will excrete more water into the urine as fluid intake is increased, diluting the urine. If fluid intake is decreased, the kidneys excrete less water and the urine becomes more concentrated. The test may be done on a urine sample collected first thing in the morning, on multiple timed samples, or on a cumulative sample collected over a 24-hour period. The patient will typically be prescribed a high-protein diet for several days before the test and be asked to drink no fluids the night before the test.
  • Urine protein test. Healthy kidneys filter all proteins from the bloodstream and then reabsorb them, allowing no protein, or only slight amounts of protein, into the urine. The persistent presence of significant amounts of protein in the urine, then, is an important indicator of kidney disease. A positive screening test for protein (included in a routine urinalysis) on a random urine sample is usually followed up with a test on a 24-hour urine sample that more precisely measures the quantity of protein.

There are also several blood tests that can aid in evaluating kidney function. These include:

  • Blood urea nitrogen test (BUN). Urea is a byproduct of protein metabolism. Formed in the liver, this waste product is then filtered from the blood and excreted in the urine by the kidneys. The BUN test measures the amount of nitrogen contained in the urea. High BUN levels can indicate kidney dysfunction, but because BUN is also affected by protein intake and liver function, the test is usually done together with a blood creatinine, a more specific indicator of kidney function.
  • Creatinine test. This test measures blood levels of creatinine, a byproduct of muscle energy metabolism that, similar to urea, is filtered from the blood by the kidneys and excreted into the urine. Production of creatinine depends on a person’s muscle mass, which usually fluctuates very little. With normal kidney function, then, the amount of creatinine in the blood remains relatively constant and normal. For this reason, and because creatinine is affected very little by liver function, an elevated blood creatinine level is a more sensitive indicator of impaired kidney function than the BUN.
  • Other blood tests. Measurement of the blood levels of other elements regulated in part by the kidneys can also be useful in evaluating kidney function. These include sodium, potassium, chloride, bicarbonate, calcium, magnesium, phosphorus, protein, uric acid, and glucose.

Results

Normal values for many tests are determined by the patient’s age and gender. Reference values can also vary by laboratory, but are generally within the following ranges:

Urine tests

  • Creatinine clearance. For a 24-hour urine collection, normal results are 90 mL/min-139 mL/min for adult males younger than 40, and 80-125 mL/min for adult females younger than 40. For people over 40, values decrease by 6.5 mL/min for each decade of life.
  • Urine osmolality. With restricted fluid intake (concentration testing), osmolality should be greater than 800 mOsm/kg of water. With increased fluid intake (dilution testing), osmolality should be less than 100 mOSm/kg in at least one of the specimens collected. A 24-hour urine osmolality should average 300–900 mOsm/kg. A random urine osmolality should average 500–800 mOsm/kg.
  • Urine protein. A 24-hour urine collection should contain no more than 150 mg of protein.
  • Urine sodium. A 24-hour urine sodium should be within 75-200 mmol/day.

Blood tests

Blood urea nitrogen (BUN) should average 8-20 mg/dL.

  • Creatinine should be 0.8-1.2 mg/dL for males, and0.6-0.9 mg/dL for females.
  • Uric acid levels for males should be 3.5-7.2 mg/dL and for females 2.6-6.0 mg/dL.

Low clearance values for creatinine indicate a diminished ability of the kidneys to filter waste products from the blood and excrete them in the urine. As clearance levels decrease, blood levels of creatinine, urea, and uric acid increase. Because it can be affected by other factors, an elevated BUN, alone, is suggestive, but not diagnostic for kidney dysfunction. An abnormally elevated plasma creatinine is a more specific indicator of kidney disease than is BUN.

Low clearance values for creatinine and urea indicate a diminished ability of the kidneys to filter these waste products from the blood and to excrete them in the urine. As clearance levels decrease, blood levels of creatinine and urea nitrogen increase. Since it can be affected by other factors, an elevated BUN alone is certainly suggestive for kidney dysfunction. However, it is not diagnostic. An abnormally elevated blood creatinine, a more specific and sensitive indicator of kidney disease than the BUN, is diagnostic of impaired kidney function.

The inability of the kidneys to concentrate the urine in response to restricted fluid intake, or to dilute the urine in response to increased fluid intake during osmolality testing, may indicate decreased kidney function. Because the kidneys normally excrete almost no protein in the urine, its persistent presence, in amounts that exceed the normal 24-hour urine value, usually indicates some type of kidney disease.

Patient education

Some kidney problems are the result of another disease process, such as diabetes or hypertension. Doctors should take the time to inform patients about how their disease or its treatment will affect kidney function, as well as the different measures patients can take to help prevent these changes.

Resources

BOOKS

Brenner, Barry M., and Floyd C. Rector Jr., eds. The Kidney, 6th Edition. Philadelphia, PA: W. B. Saunders Company, 1999.

Burtis, Carl A. and Edward R. Ashwood. Tietz Textbook of Clinical Chemistry. Philadelphia, PA: W.B. Saunders Company, 1999.

Henry, J. B. Clinical Diagnosis and Management by Laboratory Methods, 20th ed. Philadelphia, PA: W. B. Saunders Company, 2001.

Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and Laboratory Tests. St. Louis, MO: Mosby, Inc., 1998.

Wallach, Jacques. Interpretation of Diagnostic Tests, 7th ed. Philadelphia: Lippincott Williams & Wilkens, 2000.

ORGANIZATIONS

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). National Institutes of Health, Building 31, Room 9A04, 31 Center Drive, MSC 2560, Bethesda, MD 208792-2560. (301) 496-3583. http://www.niddk.nih.gov/health/kidney/kidney.htm.

National Kidney Foundation (NKF). 30 East 33rd Street, New York, NY 10016. (800)622-9020. http://www.kidney.org.

OTHER

National Institutes of Health. [cited April 5, 2003] http://www.nlm.nih.gov/medlineplus/encyclopedia.html.

National Institutes of Health. [cited June 29, 2003] http://www.nlm.nih.gov/medlineplus/ency/article/003005.htm.

Paula Ann Ford-Martin

Mark A. Best, M.D.

Kidney removal seeNephrectomy

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