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Basic Functions
The kidneys are essential for homeostasis (maintaining a constant internal environment) of the body's extracellular fluids. Their basic functions include:
1. Regulation of extracellular fluid volume. The kidneys work to ensure an adequate quantity of plasma to keep blood flowing to vital organs.
2. Regulation of osmolarity. The kidneys help keep extracellular fluid from becoming too dilute or concentrated with respect to the solutes carried in the fluid.
3. Regulation of ion concentrations. The kidneys are responsible for maintaining relatively constant levels of key ions including sodium, potassium and calcium.
4. Regulation of pH. The kidneys prevent blood plasma from becoming too acidic or basic by regulating ions.
5. Excretion of wastes and toxins. The kidneys filter out a variety of water-soluble waste products and environmental toxins into the urine for excretion.
6. Production of hormones. The kidneys produce erthryopoietin, which stimulates red blood cell synthesis, and renin, which helps control salt and water balance and
blood pressure. They are also involved in regulating plasma calcium and glucose levels.
ANATOMY
The two kidneys are located to the rear of the abdominal cavity on either side of the spine. They normally weigh about 5 onces each, but receive about 20% of the blood
flow coming from the heart. The urine produced by each kidney drains through a separate ureter into the urinary bladder, located in the pelvic region. The bladder is
emptied in turn by a single urethra, which exits the body.
Surrounding each tubule is a complex system of blood vessels that exchange water and solutes with the tubule. This system is special in that blood must pass
through two capillary beds.
1. An afferent arteriole takes blood to the renal corpuscle, where the blood passes through the first capillary bed, a ball-shape tuft known as the glomerulus.
2. An efferent arteriole takes blood away from the glomerulus.
3. From there the blood passes into a set of peritubular capillaries, which follow the remainder of the tubule and are the site of further exchange of water and
solutes between plasma and tubular fluid.
Several contributors have put together this well thought out answer.
The urinary system has three major functions:
(1) excretion: the removal of organic waste from body fluids.
(2) elimination: the discharge of these waste into the outside.
(3) homeostatic regulation of the volume and solutes of blood plasma.
There are two kidneys, the organs that produce urine which is a fluid containing water, ions, and small soluble compounds.
In addition to removing waste products generated by body cells the kidneys have several other essential homeostatic functions:
1. Regulating blood volume and blood pressure, by adjusting the volume of water lost in urine, releasing erythropoietin, and releasing renin.
2. Regulating plasma concentrations of sodium, potassium, chloride, and other ions.
3. Controlling calcium ion levels through the synthesis of calcitriol.
4. Helping to stabilize blood pH, by controlling the loss of hydrogen ions and bicarbonate ions.
5. Conserving valuable nutrients while excreting organic waste products, mainly nitrogenous wastes such as urea and uric acid.
6. Assisting the liver in detoxifying poisons.
Your kidneys receive 20-25 percent of your total cardiac output. Normally about 1200 ml of blood flows through the kidneys each minute.
Lastly:
The sympathetic innervation:
(1) adjusts rates of urine formation by changing blood flow and blood pressure in the kidney.
(2) stimulates the release of renin, which restricts losses of water and salt in the urine through reabsorption at the nephron.
The main purpose of the kidneys is to separate urea, mineral salts, toxins, and other waste products from the blood. In addition, the kidneys also
conserve water, salts, and electrolytes.
At least one kidney must function properly for life to be maintained.
Simply put, the kidneys filter the bloodstream in order to get all of the toxins out of your body, and also regulate certain body fluids.
Kidneys are vital organs that function to keep the blood clean and maintain chemical balance within. They process blood to extract waste products and
extra water. These by products become urine to be ultimately excreted from the body.
The kidney serves many important functions, including:
1.
2.
Regulating blood pressure via both urinary excretion of wastes and initiating the rein-angiotensen hormone regulatory
system
3.
4.
Stimulating red blood cell production via the release of the hormone erythropoietin.
The kidney is there to filter our blood entirely of molecules and small things we don't particularly need in our blood supply.
Urine is actually what our kidneys have filtered.
Interesting fact: We have two kidneys to get the filtering done well. Well enough to filter our blood entirely - several times every five minutes.
Definition
By Mayo Clinic Staf
Chronic kidney disease, also called chronic kidney failure, describes the gradual loss of kidney function. Your kidneys filter wastes and excess fluids from
your blood, which are then excreted in your urine. When chronic kidney disease reaches an advanced stage, dangerous levels of fluid, electrolytes and
wastes can build up in your body.
In the early stages of chronic kidney disease, you may have few signs or symptoms. Chronic kidney disease may not become apparent until your kidney
function is significantly impaired.
Treatment for chronic kidney disease focuses on slowing the progression of the kidney damage, usually by controlling the underlying cause. Chronic
kidney disease can progress to end-stage kidney failure, which is fatal without artificial filtering (dialysis) or a kidney transplant.
removing waste products from the body, keeping toxins from building up in the bloodstream
producing hormones that control other body functions, such as regulating blood pressure and producing red blood cells
regulating the levels of minerals or electrolytes (e.g., sodium, calcium, and potassium) and fluid in the body
It's entirely possible to live a full, healthy life with only one kidney - one fully functioning kidney can do the work of two - but it's essential to watch for
signs of any problems with the remaining kidney.
When kidneys get to the point where they can't function at all, kidney dialysis or a transplant is the only way to remove the body's waste products.
Causes of Chronic Renal Failure
The most common causes of chronic renal failure in North America arediabetes mellitus (type 1 or type 2 diabetes) and high blood
pressure. The most common cause of end-stage renal failure worldwide is IgA nephropathy (an inflammatory disease of the kidney).
One of the complications resulting from diabetes or high blood pressure is the damage to the small blood vessels in the body. The blood vessels in the
kidneys also become damaged, resulting in CKD.
Other common causes of chronic renal failure include:
hardening of the arteries, which can damage blood vessels in the kidney
urinary tract blockages and reflux, due to frequent infections, stones, or an anatomical abnormality that happened at birth
decreased urination
Other symptoms aren't as obvious, but are a direct result of the kidneys' inability to eliminate waste and excess fluid from the body:
fatigue
shortness of breath
loss of appetite
thirst
weight loss
As the kidney failure gets worse and the toxins continue to build up in the body, seizures and mental confusion can result.
Being diagnosed with chronic renal failure can be very frightening. The future of the condition, however, depends on the medical problem that
caused the kidney failure, how much kidney damage has occurred, and what, if any, complications are present.
Some of these complications may include:
anemia
dehydration
mineral abnormalities (e.g., hypercalcemia (high levels of calcium in the blood) or hyperphosphatemia (high levels of phosphorus in the
blood))
brittle bones
malnutrition
seizures
What is hemodialysis?
While healthy kidneys have several functions in the body, the most well-known job is to produce urine. When kidney function goes below 10%
to 15% kidneys are no longer able to filter the blood and make urine. This causes toxins to build up in the body along with excess fluid.
Fortunately, we live in a time when there are treatments and medicines that can replace the functions of the kidneys and keep the body alive.
One type of renal replacement therapy meaning a treatment that replaces kidney function is hemodialysis. Hemodialysis is a therapy that
filters waste, removes extra fluid and balances electrolytes (sodium, potassium, bicarbonate, chloride, calcium, magnesium and phosphate).
In hemodialysis, blood is removed from the body and filtered through a man-made membrane called a dialyzer, or artificial kidney, and then
the filtered blood is returned to the body. The average person has about 10 to 12 pints of blood; during dialysis only one pint (about two cups)
is outside of the body at a time. To perform hemodialysis there needs to be an accesscreated to get the blood from the body to the dialyzer
and back to the body. There are three access types for hemodialysis: arteriovenous (AV) fistula, AV graft and central venous catheter. The AV
fistula is the vascular access most recommended by the dialysis community; however, you and your doctor will decide which access is best for
you.
When a patient goes to hemodialysis, a nurse or technician will check vital signs and get the patients weight. The weight gain will tell how
much excess fluid the patient has to have removed during the treatment. The patient is then put on the machine. Patient with a vascular
access (AV fistula or AV graft) will get two needle sticks in their access; one needle takes blood out of the body, the other needle puts it back.
Patients with a central venous catheter will have the two tubes from their access connected to the blood tubes that lead to the dialyzer and
back to the body. Once the patient is put on the machine, the dialysis machine is programmed and then treatment begins.
Blood never actually goes through the dialysis machine. The dialysis machine is like a big computer and a pump. It keeps track of blood flow,
blood pressure, how much fluid is removed and other vital information. It mixes the dialysate, or dialysis solution, which is the fluid bath that
goes into the dialyzer. This fluid helps pull toxins from the blood, and then the bath goes down the drain. The dialysis machine has a blood
pump that keeps the blood flowing by creating a pumping action on the blood tubes that carry the blood from the body to the dialyzer and back
to the body. The dialysis machine also has many safety detection features. If you visit a dialysis center, you will likely hear some of the warning
sounds made by a dialysis machine.
The dialyzer is the key to hemodialysis. The dialyzer is called the artificial kidney because it filters the blood a job the kidneys used to do.
The dialyzer is a hollow plastic tube about a foot long and three inches in diameter that contains many tiny filters. (Dialyzers are made in
different sizes so doctors can prescribe the best one for their patients.) There are two sections in the dialyzer; the section for dialysate and the
section for the blood. The two sections are divided by a semipermeable membrane so that they dont mix together. A semipermeable
membrane has microscopic holes that allow only some substances to cross the membrane. Because it is semipermeable, the membrane
allows water and waste to pass through, but does not allow blood cells to pass through.
Dialysate, also called dialysis fluid, dialysis solution or bath, is a solution of pure water, electrolytes and salts, such as bicarbonate and
sodium. The purpose of dialysate is to pull toxins from the blood into the dialysate. The way this works is through a process called diffusion. In
the blood of the hemodialysis patient, there is a high concentration of waste, while the dialysate has a low concentration of waste. Due to the
difference in concentration, the waste will move through the semipermeable membrane to create an equal amount on both sides. The dialysis
solution is then flushed down the drain along with the waste. The electrolytes in the dialysis solution are also used to balance the electrolytes
in the patients blood. The extra fluid is removed through a process called filtration. The fluid is pushed off by higher pressure on the blood side
than on the dialysate side.
Blood needs to flow through the dialyzer for several hours to adequately clean the blood and rid the body of excess fluid. Traditional, in-center
hemodialysis is generally done three times a week for about four hours each session. Your doctor will prescribe how long your treatments will
be, usually between 3 to 5 hours, but most common is 4 hours. Talk to your doctor about how long you should be on hemodialysis. Some
people feel that dialysis lasts a long time; however, healthy kidneys work 24 hours a day, 7 days a week and dialysis must do the job in only 12
or so hours a week.
Alternative hemodialysis schedules include nocturnal and short daily. Normally, these treatments are performed by people who do home
hemodialysis. With nocturnal hemodialysis, the patient has dialysis for about eight hours overnight while sleeping. This is a longer, gentler
treatment so patients say they have fewer problems with cramping and the washed out feeling reported after traditional hemodialysis. More
dialysis centers are beginning to offer in-center nocturnal hemodialysis based on reports of patients feeling better about their quality of life and
having good lab results. Short daily hemodialysis is performed five or six times per week for about two to three hours each treatment. Talk to
your doctor if you are interested inhome hemodialysis or in-center nocturnal dialysis. You may want to ask your social worker if addition
treatments, such as the longer nocturnal hemodialysis and short daily hemodialysis will be covered through your insurance.
Hemodialysis is an effective treatment for those with end stage renal disease. However, hemodialysis alone will not provide a complete
treatment for those with kidney failure. Diet and fluid restrictions need to be followed, and medicines may need to be taken to replace other
functions of the kidneys, such as regulating blood pressure and stimulating production of red blood cells to prevent anemia.
For those who choose in-center hemodialysis, some of the benefits are that they will have their treatments performed in a dialysis center by
trained professionals. They can spend their time in dialysis sleeping, reading, writing, watching television, listening to music or doing other
quiet activities. There are four days a week when they will not have to go to dialysis. Some of the disadvantages are that they will have to
travel to and from hemodialysis three times each week and it takes advanced notice to travel and arrange for dialysis in a visiting dialysis
center. The diet restrictions include limiting foods that contain phosphorus, potassium and sodium anddrinking a limited amount of fluid. Some
people report a washed out feeling after hemodialysis and go home to take a nap. Those who perform nocturnal hemodialysis (in center or at
home) report that this washed out feeling is not as common. Also, because nocturnal dialysis is performed during nonproductive sleeping
hours, many people report they feel that their lives are more normal because they dont have to take time out of their days for dialysis.
People who choose to perform hemodialysis at home say they enjoy the feeling of control they have over their lives. Instead of going to the
dialysis center at a certain time, they can choose when to perform hemodialysis around their schedule.
There is another type of dialysis called peritoneal dialysis (PD). PD is done by filling the peritoneum in the abdomen with dialysate and using
the peritoneal membrane as a semipermeable membrane. There are diet and fluid restrictions with peritoneal dialysis; however, these are
usually not as limited as hemodialysis because this therapy is performed every day. PD treatments are performed at home, and so do not
require three visits to a treatment center each week. Peritoneal dialysis also has a nighttime treatment option that makes it easier for patients
to work, attend school or travel.
All dialysis treatments have their advantages and disadvantages. Based on your lifestyle and medical needs, you and your doctor can discuss
your options and decide which one is right for you.
Hemodialysis
Chronic kidney disease and acute kidney injury (also known as acute renal failure) cause the kidneys to lose their ability to filter and remove waste and
extra fluid from the body. Hemodialysis
is a process that uses a man-made membrane (dialyzer) to:
In-center hemodialysis. You go to a hospital or a dialysis center. Hemodialysis usually is done 3 days a week and takes 3 to 5 hours a day.
Home hemodialysis. After you are trained, you do your dialysis treatments at home. Hemodialysis is usually done 3 days a week (or every
other day). Discuss with your doctor how long each session needs to be. A session could be as long as 6 hours, which may help you feel better.
Daily home hemodialysis. After you are trained, you do your dialysis treatments at home. Hemodialysis is done 5 to 7 days a week. Each
session takes about 3 hours.
Nocturnal home hemodialysis. After you are trained, you do your dialysis treatments at home. Hemodialysis is done 3 to 7 nights a week. Each
session is done overnight (about 6 to 8 hours).
Before treatments can begin, your doctor will need to create a site where the blood can flow in and out of your body during the dialysis sessions. This is
called the dialysis access. The type of dialysis access you have will depend in part on how quickly you need to begin hemodialysis.
There are different types of access for hemodialysis:
Fistula. A fistula is created by connecting one of the arteries to one of the veins in your lower arm. A fistula allows repeated access for each
dialysis session. It may take several months for the fistula to form. A fistula may not clot as easily as other dialysis access methods. A fistula is the most
effective dialysis access and the most durable. Complications include infection at the site of access and clot formation (thrombosis).
Graft. A vascular access that uses a synthetic tube implanted under the skin in your arm (graft) may be used if you have very small veins. The
tube becomes an artificial vein that can be used repeatedly for needle placement and blood access during hemodialysis. A graft does not need to
develop as a fistula does, so a graft can sometimes be used as soon as 1 week after placement. Compared with fistulas, grafts tend to have more
problems with clotting or infection and need to be replaced sooner. A polytetrafluoroethylene (PTFE or Gore-Tex) graft is the most common type used for
hemodialysis.
Venous catheter. A tube, or catheter, may be used temporarily if you have not had time to get a permanent access. The catheter is usually
placed in a vein in the neck, chest, or groin. Because it can clog and become infected, this type of catheter is not routinely used for permanent access.
But if you need to start hemodialysis right away, a catheter may be used until your permanent access is ready.
Hemodialysis for acute kidney injury may be done daily until kidney function returns.
What To Expect After Treatment
About once a month, you will have blood tests to make sure you are getting the right amount of hemodialysis. These tests are done to help find out how
well hemodialysis is working. Your weight before and after each session will be recorded, as will the length of time it takes to complete the dialysis
session. If you have hemodialysis at home, you will need to keep records of your weight before and after each session and the length of each session.
Why It Is Done
Hemodialysis is often started after symptoms or complications ofkidney failure develop. Symptoms or complications may include:
Signs of uremic syndrome, such as nausea, vomiting, loss of appetite, and fatigue.
Signs of the kidneys' inability to rid the body of daily excess fluid intake, such as swelling.
Low blood pressure (hypotension). This is the most common complication of hemodialysis. It is seen more often in women and in people older
than 60.
Muscle cramps. If cramps occur, they usually happen in the last half of a dialysis session.
Hemodialysis fistulas are surgically created communications between the native artery and vein in an extremity. Direct communications are called native
arteriovenous fistulas (AVFs). Polytetrafluoroethylene (PTFE) and other materials (Dacron, polyurethane, bovine vessels, saphenous veins) are used or
have been used as a communication medium between the artery and the vein and are termed prosthetic hemodialysis access arteriovenous grafts
(AVGs). The access that is created is routinely used for hemodialysis 2-5 times per week.[1, 2]
Many patients who are not candidates for renal transplantation or those for whom a compatible donor cannot be secured are dependent on hemodialysis
for their lifetime. This situation results in the long-term need for and use of dialysis access. The preservation of patent, well-functioning dialysis fistulas is
one of the most difficult clinical problems in the long-term treatment of patients undergoing dialysis. As many as 25% of hospital admissions in the
dialysis population have been attributed to vascular access problems, including fistula malfunction and thrombosis.
History of the management of dialysis access
Historically, native fistula or graft malfunction and thrombosis were treated by using surgical thrombectomy and revision, resulting in the eventual
exhaustion of the veins and the need to create a new access. Initially applied in the 1980s, percutaneous techniques such as balloon angioplasty
(percutaneous transluminal angioplasty [PTA]), thrombolysis, and mechanical thrombectomy allowed the treatment of stenosis and fistula thrombosis
without surgery.
In the past 2 decades, interventional radiologists have increasingly been involved in angiographic evaluation and treatment of malfunctioning and
occluded hemodialysis access. The multidisciplinary management of dialysis access coordinated among interventional radiologists, vascular surgeons,
and nephrologists has proven extremely effective in prolonging the patency of the vascular access and decreasing the morbidity and mortality of patients
with chronic renal failure.[3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14]
Examples of a vessel with long-seg
Indications
Less than 15% of dialysis fistulas remain patent and can function without problems during the entire period of a patient's dependence on hemodialysis.
The mean problem-free patency period after creation of native fistulas is approximately 3 years, whereas prosthetic polytetrafluoroethylene (PTFE)
grafts last 1-2 years before indications of failure or thrombosis are noted. After multiple interventions to treat underlying stenosis and thrombosis, the
long-term secondary patency rates for native fistulas are reportedly 7 years for fistulas in the forearm and 3-5 years for fistulas in the upper arm;
prosthetic grafts remain patent for up to 2 years.
Causes of dialysis fistula failures
To the authors' knowledge, all observations and publications reported to date indicate that for prosthetic grafts, fistula failure and eventual occlusion
occur most commonly as a result of the progressive narrowing of the venous anastomosis; for native fistulas, failure occurs most commonly as a result
of the narrowing of the outflow vein. In some reports, venous anastomosis is identified in more than 90% of grafts. The primary underlying
pathophysiologic mechanism responsible for causing the failure is intimal hyperplasia at the anastomotic site. Additional causes include surgical and
iatrogenic trauma, such as repeated venipunctures. Stenoses along the venous outflow and in intragraft locations (for prosthetic PTFE grafts) are also
common and require appropriate treatment.
When to consult with an interventional radiologist
The following are indications for consultation with an interventional radiologist:
Ipsilateral arm edema and/or collateral venous pathways suggestive of a central venous stenosis
Contraindications
The presence of an infection is the only absolute contraindication to angiography and percutaneous treatment of a dysfunctional or thrombosed dialysis
access
rteriovenous (AV) fistula the gold standard hemodialysis access
Once kidney function goes below 10 to 15 percent of normal, dialysis treatments or a kidney transplant are necessary to sustain life.
There are two types of dialysis: hemodialysis and peritoneal dialysis. Both dialysis treatments are able to replace the kidneys
function of cleaning the blood of toxins and removing extra fluids for people withkidney failure.
Hemodialysis cleans blood by removing it from the body and passing it through a dialyzer, or artificial kidney. The dialyzer is a filter
with two parts: one for blood and another for dialysis fluid, called dialysate. The filter between these two parts has very small pores,
allowing some tiny particles to pass through. The particles that are filtered include the toxins that need to be removed from the body
such as urea, creatinine and potassium, while larger blood cells and protein the body needs cannot pass through. The filtered blood is
then returned to the body.
The process of removing blood from the body, filtering it and returning it takes time. Hemodialysis treatment usually takes three to
five hours and is repeated three times a week.
The type of access a person has is important for getting the best dialysis possible. There are three types of access: catheter,
arteriovenous (AV) graft and arteriovenous (AV) fistula.
Catheter for hemodialysis
For dialysis, a catheter is inserted into a large vein in either the neck or chest. A catheter is usually a short-term option; however, in
some cases a catheter is used as a permanent access. With most dialysis catheters, a cuff is placed under the skin to help hold the
catheter in place. The blood flow rate from the catheter to the dialyzer may not be as fast as for an AV graft or AV fistula; therefore,
the blood may not be cleaned as thoroughly as with an arteriovenous access.
Catheters have a greater tendency to become infected than the other access types because the device is both inside and outside of
the body. A catheter must always be kept clean and dry; swimming or bathing are usually restricted. Getting dressed may disturb the
catheter at the exit site, so care needs to be taken.
Arteriovenous (AV) graft for hemodialysis
An arteriovenous (AV) graft is created by connecting a vein to an artery using a soft plastic tube. After the graft has healed,
hemodialysis is performed by placing two needles; one in the arterial side and one in the venous side of the graft. The graft allows for
increased blood flow. Grafts tend to need attention and upkeep. Taking good care of your access may limit problems.
Arteriovenous (AV) fistula for hemodialysis
A fistula used for hemodialysis is a direct connection of an artery to a vein. Once the fistula is created it is a natural part of the body.
This is the preferred type of access because once the fistula properly matures and gets bigger and stronger; it provides an access
with good blood flow that can last for decades. After the fistula is surgically created, it can take weeks to months before the
fistula matures and is ready to be used for hemodialysis. People with kidney disease can do exercises including squeezing a rubber
ball to strengthen the fistula before use.
Fistula the gold standard access
The National Kidney Foundation (NKF), Centers for Medicare and Medicaid Services (CMS), DaVita Patient Citizens (DPC) and other
organizations and experts generally agree that fistulas are the best type of vascular access. Low rates of complications, clotting and
infection all contribute to the fistulas reputation as the gold standard of vascular access.
Dialysis experts also generally agree that the safest and longest lasting of the access types is the AV fistula. Because a fistula is made
by connecting a vein to an artery, the vein becomes bigger allowing for increased blood flow. The fistula is created from natural parts
of the body and can be repeatedly stuck to perform hemodialysis treatments.
A fistula is the gold standard because:
It allows for greater blood flow, increasing the effectiveness of hemodialysis as well as reducing treatment time
It stays functional for longer than other access types; in some cases a well-formed fistula can last for decades
Avoid tight clothing or jewelry that could put pressure on your access area
Do not carry bags, purses or any type of heavy item over your access area
Dont let anyone put a blood pressure cuff on your access arm have your blood pressure taken from your non-access arm
Request that blood being drawn is taken from your non-access arm
Dont sleep with your access arm under your head or pillow
Discuss the use of serum urea-nitrogen, serum creatine, and glomerular filtration rate in the workup, diagnosis, and
monitoring of renal disease and function
Describe physiological conditions in which the serum urea-nitrogen: creatinine ratio is increased
Describe physiological conditions in which the serum urea-nitrogen: creatinine ratio is decreased
Discuss the laboratory findings that differentiate prerenal from renal failure
KEY TERMS
Albuminuria - the presence of albumin in urine
Anuria - lack of urine output (< 50 mL per day)
Azotemia - an excess of urea, creatinine and other nitrogenous end products of amino acid metabolism in blood
Bowmans capsule - a structure consisting of glomeruli and extended opening of proximal tubule
Casts - protein aggregates, outlined in the shape of renal tubules and excreted into the urine; the matrix is the Tamm-Horsfall
protein
Creatinine - a spontaneous breakdown product of muscle creatine, used to monitor renal function
Creatinine clearance - an estimate of the glomerular filtration rate obtained by measurement of the amount of creatinine in the
plasma and its rate of excretion into the urine
End-stage renal disease (ESRD) - a condition in which renal function is inadequate to support life
Glomerular filtration rate (GFR) - the rate in milliliters per minute that substances such as creatinine and urea are filtered
through the kidneys glomeruli (mL/min); a reflection of the number of functioning nephrons; estimated by the creatinine clearance
(see above)
Glomerulonephritis - nephritis accompanied by inflammation of the capillary loops in the glomeruli of the kidney; occurs in acute,
subacute, and chronic forms and may be secondary to hemolytic streptococcal infection; evidence suggesting possible immune or
autoimmune mechanisms
Glomerulus - a tuft of blood vessels found in the nephron of the kidney that are involved in the filtration of the blood
Hematuria - blood in the urine
Hemodialysis - the exogenous removal of certain elements from the blood by virtue of the difference in the rates of their diffusion
through a semipermeable membrane (for example, by means of a hemodialysis filter)
Isosthenuria - urine with a fixed specific gravity in range of 1.008 to 1.012
Microalbuminuria - low-grade, dipstick-negative increase in urine albumin excretion, useful in monitoring renal status of individuals
prone to renal impairment from diseases such as diabetes
Nephritis - inflammation of the kidney with focal or diffuse proliferation or destructive processes that may involve the glomerulus,
tubule, or interstitial renal tissue
Nephron - the anatomical and functional unit of the kidney, consisting of the renal corpuscle, proximal convoluted tubule,
descending and ascending limbs of Henles loop, distal convoluted tubule, and collecting tubule
Nephrotic syndrome - general name for a group of diseases involving increased glomerular permeability, characterized by massive
proteinuria and lipiduria with varying degrees of edema, hypoalbuminemia, and hyperlipidemia
Oliguria - decreased urine output (< 400 mL per day)
Peritoneal dialysis - hemodialysis through the peritoneum, the dialyzing solution being introduced into and removed from the
peritoneal cavity as either a continuous or an intermittent procedure
Pyelonephritis - inflammation of the kidney and its pelvis
Pyuria - the presence of pus (an inflammation fluid with leukocytes and dead cells) in the urine
Renal threshold - the plasma concentration of a substance above which it will be excreted into the urine
Tamm-Horsfall protein - a mucoprotein produced by the ascending limb of the loop of Henle that is a normal constituent of urine
and is the major protein constituent of urinary casts
Urea - major nitrogen containing product of protein metabolism, used to monitor renal function
Uremia - an excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acid metabolism;
more correctly referred to as azotemia
BACKGROUND / SIGNIFICANCE
Most renal disease causes no symptoms until 50-75% of kidney function is destroyed. Lab tests often provide the initial recognition
of renal impairment and can be used to direct further therapy. In therapeutics, knowledge of renal function is essential for
recommending proper doses of prescription drugs. Many drugs are renally cleared and decreased renal clearance can lead to toxicity.
Dose adjustments are based on assessments of renal function.
EXCRETORY FUNCTION OF KIDNEY
The excretory function of the kidney serves to rid the body of undesirable end products of metabolism. One of these groups, the nonprotein nitrogenous (NPN) compounds, is listed in Table 1.
Table 1
Contributors
Urea
Nucleotides
Uric acid
Purine
Creatinine
Polypeptides
Creatine
Glutathione
Amino acids
Ammonia
The two most popular screening tests for renal function are serum urea nitrogen and serum creatinine. Better measures of
glomerular function are clearance tests. This is especially true in the aged, where serum creatinine measurements are less reliable
due to decreasing muscle mass.
In uremia (kidney failure) the increase is mainly in urea, creatinine and uric acid. Uric acid and the other NPN-compounds are
measured rarely in this context. Serum urea nitrogen (SUN) is normally ~45% of total NPN, but may be 80% of NPN in some disease
states. In hepatic failure the ratio of non-urea/urea nitrogen increases, because of the inability of the liver to synthesize urea and to
deaminate amino acids.
Urea Nitrogen
Historically, urea was reported as blood urea nitrogen (BUN) and this terminology has been incorrectly carried over to the present.
Urea nitrogen is now measured using serum and is reported as serum urea nitrogen (SUN). Urea is synthesized mostly in the liver
as a by-product of the deamination of amino acids arising from protein catabolism.
Urea is filtered by the glomeruli; however, about 40-70% (amount depends on urine flow) is reabsorbed by passive diffusion into
blood across the renal tubular epithelium. Thus, in conditions in which the glomerular filtration rate is decreased, SUN will be
increased. For this reason, urea clearance tests are less informative than creatinine clearance tests and have been discontinued.
Reference Range for serum urea nitrogen: 8-18 mg/dL
The serum urea nitrogen level is greatly influenced by diet.
Table 2
0.5
~5
~12
~22
SUN is not a sensitive indicator of renal dysfunction because renal function must be reduced by more than 50% to result in a rise of
SUN.
Creatinine
Derived from spontaneous conversion of muscle creatine (about 1-2% of total muscle mass per day)
Daily excretion is fairly constant and independent of urinary volume. Thus, this measurement can be used to assess the
relative completeness of a 24-hour urine collection.
o
Women: less
Athletes: more
Patients with hepatic disease, muscular dystrophy, paraplegia and poliomyelitis may excrete less creatinine due to decreased
production. It should be noted that many laboratories use alkaline picrate (Jaffe) method for measuring creatinine.
0.6-1.3 mg/dL
0.5-1.1 mg/dL
Note: Creatinine production is based on weight and gender that is generally related to muscle mass. Thus, be circumspect when
treating individuals with a high normal creatinine when a low creatinine is appropriate due to small muscle mass. This would include
children, elderly, women, paralyzed patients, and amputees.
Glomerular Filtration Rate
A useful assessment of renal function is the measurement of the glomerular filtration rate (GFR), especially in older people. The
inulin clearance rate closely approximates the true GFR since inulin is freely filtered by the glomerulus with minimal tubular
absorption or secretion. However, this test is difficult to perform routinely. Measuring the clearance of endogenous creatinine
(clearance of creatinine produced by metabolic processes) is much more practical and convenient but less accurate. Creatinine, for
the most part, is freely filtered; thus, clearance of endogenous creatinine is a reflection of GFR. Normally, only small amounts (<
6%) are reabsorbed by the tubules and an equal amount may be secreted by the tubules. The endogenous creatinine clearance rate
is computed by the following formula:
(1)
Ccreat = UcreatPcreat V 1.73m2A
Since creatinine clearance is related to patient size, a more accurate formula includes an estimation of body surface area in square
meters obtained from a nomogram using the height and weight of the patient. A = body surface area in m 2, and 1.73 m2 is the
average body surface area. In essence this formula normalizes the clearance to that of a normal-sized person. Patients being
tested for the GFR must be well hydrated to provide a urine flow of > 2 mL/ min.
Reference Range: male = 117 20 mL/min; female = 95 20 mL/min
The relationship between serum creatinine and creatinine clearance is logarithmic (see Figure 1). Thus, initially, for small numeric
changes in serum creatinine, there are significant numeric changes for creatinine clearance. In later stages of uremia, small numeric
changes in the clearance are associated with significant changes in serum creatinine. Note the decrease in the number of nephrons
with decrease of clearance and increase in serum creatinine.
Figure 1: Correlation of Plasma Creatinine and Creatinine Clearance. Relationship between serum creatinine, creatinine
clearance and number of remaining nephrons.
The endogenous creatinine clearance rate is primarily an estimate of GFR; however, a small amount of tubular secretion augments
glomerular filtration. Therefore, total urinary creatinine is slightly higher than the amount actually filtered by the glomeruli. The
amount of urinary creatinine derived from tubular secretion rises proportionally in renal failure with an increase in serum creatinine.
With advancing renal failure and increase in serum creatinine, the tubular secretion proportionally increases up to 40-60%. From an
interpretation standpoint this is important. With normal or early renal failure creatinine clearance approximates true GFR. With
advanced renal failure creatinine clearance overestimates true GFR, which is because of the increased amount of creatinine in urine
due to tubular secretion, which in turn is caused by the high concentration of creatinine in circulation.
Alternatively, more accurate isotopic methods for measuring GFR can be utilized, e.g. the clearance of injected 51Cr-labelled EDTA
from the blood. This compound is completely filtered by the glomeruli and is not secreted or reabsorbed by the tubules. However,
this method requires a special laboratory equipped to handle and measure radioactive isotopes.
An alternative to measuring GFR is to use the Cockroft and Gault equation[1] to estimate creatinine clearance based on a single
measurement of serum creatinine. Where Screat is serum creatinine (mg/dL) and weight is in kilograms.
(2)
Ccreat(males) = (140age)(Weight)(Screat)(72)
(3)
Ccreat(females) = (140age)(Weight)(Screat)(72) (0.85)
TUBULAR FUNCTION
The most often used function tests are renal concentrating power and the ability to produce an acid urine (in suspected renal tubular
acidosis).
Urine Osmolality and Renal Concentrating Ability
Osmolality refers to the concentration of osmotically active particles (osmolutes) in solution, expressed in mOsm/kg of water. Urine
osmolality varies widely in health, between about 60 and 1250 mOsm/kg. The failing kidney loses its capacity to concentrate urine. A
patient with polyuria due to chronic renal failure (CRF) is unable to produce either a dilute or a concentrated urine. Instead, urine
osmolality in these patients is generally within 50 mOsm/kg of the plasma osmolality (i.e., between about 240 and 350 mOsm/kg).
Urine osmolality is a measure of concentrating power of the kidney. Urine specific gravity is usually directly proportional to
osmolality. Both give misleadingly high results if there is significant glycosuria or proteinuria. The error can be mathematically
corrected. Measurement of osmolality with an osmometer is more accurate, but also more difficult than specific gravity
measurements.
Random testing of either specific gravity or osmolality is not very informative, due to the effect of fluid intake. Repeated
measurements, or measurements under controlled fluid intake are more reliable. Specific gravity values of more than 1.025 or
osmolality values more than 875 mOsm/kg indicate adequate renal concentrating ability. Recurring values of 1.010 (1.008-1.012)
indicate isosthenuria (fixed specific gravity). This finding suggests loss of tubular concentrating and diluting ability and is frequently a
prelude to anuria.
SUN/CREATININE RATIOS IN VARIOUS CONDITIONS
Normal ratio: ~12-20 (or 10-18 with less specific methods)
In practice, the greatest increase in the ratio may be seen in prerenal azotemia, where ratios of 30/1 or 35/1 may be observed.
However, other conditions may also change the ratio, depending on the rate of urea synthesis, kidney blood flow, or glomerular
filtration rate. When evaluating SUN/creatinine ratios realize that SUN production is dependent on available protein (increased
protein intake increases the ratio) and liver function (decreased liver function lowers the ratio). In addition, the ratio is affected by
the specificity of the creatinine method. (Less specific methods give higher creatinine values.)
The ratio is increased in conditions in which there is increased urea synthesis, as observed in the presence of blood in the GI tract,
in muscle wasting disease, and in severe tissue trauma, all of which provide proteins that are catabolized into their constituent amino
acids, which are then deaminated and converted into urea. Other conditions such as intraperitoneal extravasation of urine and
urinary enteric fistulas lead to greater urea reabsorption. Increased tubular reabsorption of urea occurs with decreased tubular flow
as a result of dehydration, decreased cardiac output, or shock (= prerenal azotemia), or due to renal disease, such as early acute
glomerulonephritis, malignant nephrosclerosis, or postrenal obstruction.
Decreased ratios are seen in the presence of decreased urea synthesis (chronic glomerulonephritis with protein deficiency, severe
hepatic insufficiency, and starvation) and decreased urea reabsorption (overhydration and rapid hydration). The decrease in ratio due
to hemodialysis is caused by the more efficient dialysis of urea vs. creatinine. In acute tubular necrosis, urea and creatinine are
equally and passively returned to the tubular blood. Therefore, the ratio is decreased.
RENAL FAILURE
Acute renal failure occurs rapidly and is potentially reversible if the initial illness or insult is survived (60% survival rate). Chronic
renal failure usually develops over years in an insidious manner leading to endstage renal disease requiring lifelong dialysis or renal
transplant.
Azotemia (increase of urea or other non-protein nitrogenous - compounds) is divided into 3 categories:
1.
Prerenal azotemia is caused by a decrease in renal blood flow, e.g. due to decreased cardiac output
2.
3.
Postrenal azotemia is due to obstruction of urine flow, e.g. by prostatic hypertrophy or tumor
Elevated SUN
Elevated creatinine
GFR decreased
Metabolic acidosis due to retention of phosphate, sulfate, amino acids, and other metabolic acids
Urinalysis
Selectivity ratio
The ratio of the clearances of a high and a low molecular weight protein (IgG and albumin, respectively) gives an indication of the
nature of glomerular damage in glomerular proteinuria (selective vs. non-selective).
(4)
Selectivity ratio =IgG clearancealbumin clearance
The selectivity index is identical to the ratio, except that it is expressed in percent, (i.e., it is multiplied times 100).
Elevated SUN may not be as much as in acute glomerulonephritis, due to loss of protein in the urine
Hyponatremia
Hypocalcemia (Secondary to loss of albumin into the urine and phosphate retention)
GFR decreased
Urinalysis
Proteinuria (Massive)
GFR decreased
Table 3: Triad
Proteinuria, > 3.5 g/day
Hypoalbuminemia
GFR normal
Hyperlipidemia
In addition, edema is generally present
The loss of protein leads to a decrease in oncotic pressure, resulting in edema. The decreased oncotic pressure stimulates a
compensatory increase in hepatic lipoprotein synthesis, and, thus, hyperlipidemia is often seen in this condition. Increase in
lipoproteins is also caused by loss of factors regulating lipoprotein synthesis. In the nephrotic syndrome there is a loss of a variety of
proteins, such as transferrin, cortisol-binding globulin, thyroxine-binding globulin, and some coagulation factors. However, some
coagulation factors are increased, e.g. Factor V and VIII, leading to thrombosis.
Major diagnostic findings
Urinalysis
Large amounts of protein, usually 3.5-10 g/d; values up to 50 g/24 h are possible
Casts: many hyaline and finely granular casts due to low urine flow
Oval fat bodies (Epithelial cells and macrophages loaded with fat)
Serum
Thyroxine-binding globulin may be decreased; accordingly, total T 4 (thyroxine) may be decreased; thyroid function, however, is
normal (normal free thyroxine). Total globulin concentration may be normal, but 2-globulins are increased (alpha-2 macroglobulin
and low-density lipoprotein), and -globulins may be low (see serum protein section). Hence, serum protein electrophoresis typically
demonstrates diminished albumin and elevated alpha-2 globulin fraction.
Laboratory Findings in Acute Pyelonephritis
Acute infective tubulo-interstitial nephritis; acute pyogenic infection of the kidney - one of the most common diseases of the kidney
Serum chemistry values
Normal: Urea N, serum creatinine, SUN, serum SUN/creatinine ratio (~12), creatinine clearance, GFR, and uric acid
Urinalysis
Hematology
Peripheral leukocytosis
Table 4
Prerenal failure
Renal failure
>500
<350
>10:1
<3:1
>1.5:1
<1.1:1
>20:1
variable
URINALYSIS
The routine urinalysis is carried out in three phases: macroscopic, chemical, and microscopic analysis.
Macroscopic Examination (Gross Examination)
Color
Turbidity
Chemical Examination
Protein
Glucose
Ketone bodies
Urobilinogen
Microscopic Examination
Larger elements are: casts, mucous threads, parasites, ova, foreign bodies, etc. (low power)
Casts, if present, are also examined under the high power field to determine their types
The numbers of red cells, white cells, epithelial cells, bacteria, yeast, trichomonas, and crystals are also counted and an
average count for each is recorded
Urine Casts
Casts are found in the urine sediment. They are formed in two ways, by precipitation and gelling of proteins in tubular fluid, and by
clumping of cells in tubules. Casts are molded in the lumen of the distal renal tubules or collecting ducts. The matrix of all casts is a
specific mucoprotein common to all casts, namely Tamm-Horsfall protein. The classification of casts is based on appearance, physical
properties, and type of cellular components. Cells within the matrix can degenerate into coarse and finely granular casts and to waxy
casts.
Types of urine casts
Hyaline casts.
The casts consist only of Tamm-Horsfall protein. They are excreted by the normal kidney in small amounts. Excretion of numerous
casts is seen in all renal diseases associated with benign essential hypertension, and nephrotic syndrome.
White blood cell (leukocyte) casts.
These casts are formed when WBC's are incorporated into the protein matrix. They enter the urine stream by ameboid movement
through and between tubular epithelial cells and sometimes they cross the glomerular capillary lumen. These casts are associated
with diseases with leukocytic exudation and interstitial inflammation. Example: pyelonephritis.
Red cell (erythrocyte) casts.
Presence of these casts indicates severe injury to the glomerular basement membrane. The reddish orange color is secondary to
hemoglobin pigmentation. Erythrocytes (RBCs) are biconcave disks packed in fibrin meshwork within the cast matrix. These casts
are associated with acute glomerulonephritis (most common), lupus nephritis, Goodpastures syndrome, and subacute bacterial
endocarditis (SBE).
Renal epithelial casts.
These casts are due to constant desquamation and renewal of the renal epithelium. Their presence points to a pathological process
occurring in the kidney and affecting the tubular portion of the nephron (tubular damage). Epithelial casts are associated with
exposure to nephrotoxic agents and exposure to some viruses.
Granular casts.
These casts are formed from breakdown products of cellular casts and immunoglobulins. There is a progression from coarsely
granular to finely granular casts.
Waxy casts.
These are the result of progressive degenerative changes occurring in cellular casts and they are associated with severe chronic renal
disease and amyloidosis.
Fatty casts.
These casts are probably due to leakage of lipoproteins through the glomerular filter and are associated with nephrotic syndrome,
diabetes mellitus, and damaged renal tubular epithelial cells.
Mixed cell casts.
Appearance
Urine pH
Calcium oxalates
"Envelopes"
acid
Sodium urates
"Whetstones"
acid
"Coffin lids"
alkaline
Ammonium biurates
"Thorn apples"
alkaline
Amorphous phosphates
Amorphous debris
alkaline
Tyrosine
Needles in rosettes
acid
Leucine
Spheres
acid
Sulfonamides
Sheaves
acid
Cystine
Hexagons
acid
Drug crystals (e.g., ampicillin needles, primidone hexagons) are formed from drugs that are present in relatively high concentrations
and that are relatively insoluble in water at the urina
How this test is conducted: A blood sample is taken and sent for analysis.
When this test is performed: Throughout the early stages of chronic kidney disease and the later stages, including end stage renal disease
(ESRD).
Creatinine is a waste product that is passed through the kidneys. It is a by-product formed by muscle contractions. It also comes from protein foods we
eat, mostly from muscle meats. Women produce less creatinine than men because women have less muscle tissue. When your kidneys are not getting
rid of creatinine, it remains in the bloodstream. Increased levels of creatinine may signal that your kidneys arent eliminating this waste, leaving it in the
body.
GFR Glomerular Filtration Rate
How the test is conducted: This test is a calculation based on your creatinine level, age, race, gender and other factors.
When this test is performed: Throughout the early stages of CKD and the later stages, including ESRD.
The glomerular filtration rate (GFR) is a test that measures your kidney function. The result tells your doctor what stage of chronic kidney disease you
are experiencing. Your doctor will calculate your GFR by using your creatinine level, age, race, gender and other factors. The GFR is an important test
because in order to treat your condition effectively, your doctor must know what stage of kidney disease you are experiencing.
People in stage 1 kidney disease can have a GFR of 90+. However, there may be protein or albumin in their urine. Although people with high GFRs have
plenty of kidney function, damage still occurs over time. As the kidneys become more damaged, the GFR will decrease. Changes to your GFR will tell
your doctor how fast or slow your condition is progressing.
Stage
GFR Level
Description
Stage 1
90 mL/min or more
Stage 2
60 to 89 mL/min
Stage 3
30 to 59 mL/min
Stage 4
15 to 29 mL/min
Stage 5
Kidney failure
Microalbumin
Purpose: To detect a protein called albumin in the urine, which may indicate kidney damage.
How this test is conducted: A urine sample is taken from the person being tested.
When this test is performed: In the early diagnostic stage of chronic kidney disease. Yearly for people with diabetes or high blood pressure.
The microalbumin test detects very small amounts of albumin in the urine. Albumin is protein. One of the early signs of damaged kidneys is the presence
of albumin in the urine.
Damage to the tiny blood vessels in the kidneys allow albumin to leak into the urine. Diabetes and high blood pressure are two conditions that can
damage these vessels. If not managed properly, the damage can accelerate over time. Increased microalbumin levels can mean you are in an early
stage of kidney disease.
BUN Blood Urea Nitrogen
Purpose: To detect elevated waste levels in the bloodstream, which is an early sign of reduced kidney function.
How this test is conducted: A blood sample is taken and sent for analysis.
When this test is performed: In the diagnostic stage, the early stages of chronic kidney disease and the later stages, including end stage
renal disease (ESRD), to measure effectiveness of treatment.
The blood urea nitrogen (BUN) test is an important diagnostic tool. Chronic kidney disease happens over time, but many people do not know they have
it. This is because symptoms in the early stages of the disease may go unnoticed. An early diagnosis is important so that treatment can begin. Waste in
the blood can be the first signal that your kidneys arent working as well as they should. The BUN test measures the amount of urea in your bloodstream.
Urea is a waste product left over from the protein you eat, which is normally eliminated through the kidneys. High levels of urea mean your kidneys are
not getting rid of waste and it remains in the body. This could make you feel tired and ill.
CCr Creatinine Clearance
How this test is conducted: A blood sample is taken and the person tested in addition to a urine sample. Both samples are sent for analysis.
When this test is performed: When a person is starting dialysis or to assist with a nutritional assessment.
The creatinine clearance test (CCr) measures the amount of creatinine in your urine and blood. A urine sample and blood sample are needed for this
test. Your urine sample will tell your doctor how much creatinine your kidneys are eliminating. A blood sample will be taken before or after you take your
urine sample and analyzed for the amount of serum creatinine. Both measurements will be used to calculate how well your kidneys get rid of waste.
Hb Hemoglobin
Purpose: To determine the amount of hemoglobin in red blood cells and screen for anemia.
How the test is conducted: A blood sample is taken and sent for analysis. This test is often part of a comprehensive test called a complete
blood count (CBC) or complete blood test.
When the test is performed: Throughout the early stages of chronic kidney disease and the later stages, including ESRD.
The hemoglobin test is part of a complete blood count (CBC), which is a comprehensive exam that looks at the different cells found in the blood. Each
type of cellwhite blood cells, red blood cells and plateletsundergo a panel of tests. These tests will determine the number, size and physical
characteristics of the cells. If you have renal disease, your kidney doctor will look at your hemoglobin and hematocrit levels, both taken from analyzing
your red blood cells.
Hemoglobin is a protein found in your red blood cells. It helps transport oxygen throughout the body. Low levels can signal anemia. Patients in the later
stages of renal disease are at risk for anemia because damaged kidneys lose the ability to make a hormone called erythropoietin. This hormone is
required for red blood cell production. In addition, their diets are often restricted in the amount of protein they can have. Protein is an important source of
iron, which is also required to make red blood cells. If your hemoglobin levels are low, your doctor will prescribe iron supplements and/or Epogen
(EPO), the man-made form of erythropoietin.
Hct Hematocrit
Purpose: To determine the percentage of red blood cells in the blood and screen for anemia.
Normal range: For adult females the range is usually 36% to 47%, for adult males the range is 40% to 53%. For dialysis patients the
recommended target hematocrit range is 33% to 36%.
How this test is conducted: A blood sample is taken and sent for analysis. This test is often part of a comprehensive test called a complete
When this test is performed: Throughout the early stages of chronic kidney disease and the later stages, including ESRD.
Hematocrit measures the percentage of blood that is made up of red blood cells. A low hematocrit level may indicate your body is not making enough
red blood cells. Red blood cells carry oxygen throughout the body. This oxygen provides energy to the cells of the body. If your body has low amounts of
red blood cells, your bodys cells arent getting enough oxygen to do their jobs. This can lead to feeling tired and having no energy.
URR Urea Reduction Ratio
Purpose: To measure how much urea was removed during a hemodialysis session.
How this test is performed: A blood sample is taken at the start of a dialysis session and another sample is taken afterwards.
When this test is performed: Once every 12 to 14 dialysis sessions, this is approximately once a month.
Your urea reduction ratio (URR) is a test that will tell your health care team how well dialysis is cleaning your blood. Dialysis removes waste products like
urea and excess fluid. If too much waste or fluid remains in your blood, you will feel ill. By comparing the urea levels in your blood samples before and
after a single hemodialysis treatment, a member of your health care team can calculate your URR. If it falls below 65% or the goal your physician has
set, your health care team may adjust the rate of flow on the dialysis machine or recommend increasing the amount of time you spend dialyzing.
Kt/V
How this test is conducted: For hemodialysis, a blood sample is taken at the start and end of a dialysis session. Information about your
treatment is collected, and a computer calculates the Kt/V result. For peritoneal dialysis (PD), a blood sample is taken along with a sample of the PD
fluid and the volume removed over 24 hours.
When this test is performed: Once a month for hemodialysis patients and once every four months for PD patients or after a prescription
change.
Kt/V is a mathematical formula, where:
K = clearance (the amount of urea your dialyzer has removed (liters/minute)) multiplied by
t = time (the duration of treatment (minutes)) divided by
V = volume (the amount of body fluid (liters)).
Kt/V is another test that tells you how well dialysis is cleaning your blood. Kt/V is considered more accurate than URR because it takes into account your
size, treatment time, blood flow rate, how much urea your body makes during dialysis and the extra urea and fluid removed in your dialysis session.
Hitting the target range for your Kt/V is important. Good, effective dialysis can help you feel better and stay healthier. If youre not hitting the target range,
your health care team will recommend adjustments to your dialysis treatment.
A1c Glycosylated Hemoglobin Test, also known as Hemoglobin A1c
Purpose: To determine average blood glucose levels over a two to three month period. This test is for people with diabetes.
Target range: American Diabetes Association goal is less than 7.0 gm/dl for good blood glucose management for diabetics.
How this test is conducted: A blood sample is taken and sent for analysis.
When this test is performed: This test is done when you are first diagnosed with diabetes and then 2 to 4 times a year thereafter.
The A1c is a test performed on people with diabetes. The A1c gives your doctor a snapshot of your average blood glucose levels for the past two or
three months.
Diabetes is the leading cause of chronic kidney disease. High glucose in the bloodstream can damage the tiny blood vessels in the kidneys. Keeping
your blood glucose down is important in preventing further damage to your kidneys. The A1c can tell you and your doctor how well you are managing
your diabetes and whether the treatment plan you are following is working.
Blood electrolyte levels
Purpose: To measure the levels of electrolytes (sodium, potassium, calcium, phosphorus) in the body that help move nutrients and waste in
and out of cells.
Normal range: Sodium: 135 to 145 mEq/L. Potassium: 3.5 to 5.0 mEq/L. Calcium: 8.5 to 10.5 mg/dL. Phosphorus: 3.0 to 4.5 mg/dL. The
goals for people on dialysis vary from some of these levelspotassium goal 3.5 to 5.5, calcium 8.4 to 9.5, phosphorus 3.5 to 5.5.
How the test is conducted: A blood sample is taken and sent for analysis.
When this test is performed: During stages 3, 4 and 5 of kidney disease, when the renal diet is prescribed or if the person is on dialysis.
Sodium, potassium, calcium and phosphorus are minerals that are important for the body to function correctly. If the levels of these minerals become out
of balance, they can cause health complications. A blood electrolyte test can tell your doctor and your dietitian if these levels are too high or too low. The
kidneys help keep these minerals in balance by getting rid of any excess. But if you have chronic kidney disease, or are on dialysis, your kidneys may
have a difficult time managing the electrolyte levels properly. This can lead to complications such as excess fluid retention, erratic heartbeats and bone
disease.
People in the later stages of kidney disease, or who are on dialysis, are often placed on a special diet. This renal diet will help keep your electrolyte
levels in balance by restricting food that is high in sodium, potassium, calcium and phosphorus. The blood electrolyte test can also help you and your
dietitian make any necessary adjustments to your diet.
Summary
Knowing your lab results can help you understand what is going on in your body. Your dietitian, doctor and the rest of your healthcare team will monitor
your test results and recommend dietary adjustments or make changes to your treatment. If you dont know what your numbers are, or have questions
about these tests, be sure to ask a member of your kidney care team for more information. Also get your lab results on the DaVita Health Portal when
you are a DaVita patient.
Kidney Disease
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Overview | Diseases | Symptoms | Tests | Treatment | Related Pages
Tests
The routine blood and urine tests listed below may provide the first indication of a kidney problem or may be ordered if chronic kidney disease (CKD) is
suspected due to a person's signs and symptoms. These tests reflect how well the kidneys are removing excess fluids and wastes and some are
included in the basic and comprehensive metabolic panels (BMP and CMP).
A blood pressure measurement is also important since high blood pressure (hypertension) can lead to CKD. When a structural problem is suspected, a
variety of imaging tests can be used to evaluate the kidneys. A sample of kidney tissue, a biopsy, is sometimes helpful in diagnosing the specific cause
of a problem.
Tests commonly used for screening and diagnosis
The National Kidney Foundation (NKF) and the National Kidney Disease Education Program (NKEDP) recommend that people who are at high risk be
screened for kidney disease to detect it in its earliest stages. Risk factors include diabetes, high blood pressure, heart disease, or a family history of
these or kidney disease. The NKF recommends that everyone with diabetes between the ages of 12 and 70 be screened for kidney disease at least
once a year. At this time, there is no consensus on screening people who have no risk factors or symptoms. The NKF and NKDEP recommend two
tests, in addition to blood pressure measurement, to screen for kidney disease:
Urine proteina few different tests may be used to screen for protein in the urine:
Urine albuminthis test may be done on a 24-hour urine sample, or both urine albumin and creatinine can be measured in a
random urine sample and the albumin/creatinine ratio (ACR) can be calculated. The American Diabetes Association recommends ACR as
the preferred test for screening for albumin in the urine (microalbuminuria).
Urinalysisthis is a routine test that can detect protein in the urine as well as red blood cells and white blood cells. These are not
normally found in the urine and, if present, may indicate kidney disease.
Urine total protein or urine protein to creatinine ratio (UP/CR)detects not just albumin, but all types of proteins that may be present
in the urine.
While urinalysis and urine total protein are not as sensitive as urine albumin for detecting kidney damage, these tests give fewer false signals of
kidney damage.
Estimated glomerular filtration rate (eGFR)a blood creatinine test or possibly a cystatin C test is performed in order to calculate the eGFR.
The glomerular filtration rate refers to the amount of blood that is filtered by the glomeruli per minute. As a person's kidney function declines due to
damage or disease, the filtration rate decreases and waste products begin to accumulate in the blood.
Some additional tests that may be ordered to evaluate for kidney disease include:
Urea (urea nitrogen or BUN)the level of this waste product in the blood increases as kidney filtration declines. Increased BUN levels suggest
impaired kidney function, although they can also be elevated due to a condition that results in decreased blood flow to the kidneys, such
as congestive hear failure, heart attack, or shock.
Creatinine clearancethis test measures creatinine levels in both a sample of blood and a sample of urine from a 24-hour urine collection.
The results are used to calculate the amount of creatinine that has been cleared from the blood and passed into the urine. This calculation allows
for a general evaluation of the amount of blood that is being filtered by the kidneys in a 24-hour time period.
Blood levels of BUN and creatinine are measured from time to time to see if the kidney disease is getting worse.
The amount of calcium and phosphorus in the blood, blood gases (ABGs), and the balance of serum and urine electrolytescan also be
measured as these are often affected by kidney disease.
Hemoglobin in the blood, measured as part of a complete blood count (CBC), may also be evaluated as the kidneys make a hormone,
erythropoietin, that controls red blood cell production and this may be affected by kidney damage.
Parathyroid hormone (PTH), which controls calcium levels, is often increased in kidney disease and may be checked to help determine if
enough calcium and vitamin D are being taken to prevent bone damage.
Cystatin C is another test that may sometimes be used as an alternative to creatinine to screen for and monitor kidney dysfunction in those
with known or suspected kidney diseases.
Both blood and urine beta 2 microglobulin (B2M) tests may be ordered along with other kidney function tests to evaluate kidney damage and
disease and to distinguish between disorders that affect the glomeruli and the renal tubules. Normally, only small amounts of B2M are present in
the urine, but when the renal tubules become damaged or diseased, B2M concentrations increase due to the decreased ability to reabsorb this
protein. When the glomeruli in the kidneys are damaged, they are unable to filter out B2M, so the level in the blood rises. B2M tests may
sometimes be ordered to monitor people who have had a kidney transplant, to detect early signs of rejection, and ordered to monitor people who
are exposed to high levels of cadmium and mercury, such as with occupational exposure.
Urinalysis with a urine culture may be done when someone has symptoms suggesting infection to confirm the presence of abacterial infection.
Hepatitis B or C testingto detect a hepatitis viral infection associated with some types of kidney disease
Antinuclear antibody (ANA)to help identify an autoimmune condition such as lupus that may be affecting the kidneys.
Kidney stone risk panelthis test evaluates a person's risk of developing a kidney stone, to help guide and monitor treatment and prevention
Kidney stone analysisthis test determines the composition of a kidney stone passed or removed from the urinary tract and may be done to
help determine the cause of its formation, to guide treatment, and prevent recurrence
Complement tests, most commonly C3 and C4may be tested and monitored with glomerulonephritis
Urine protein electrophoresismay be done to determine the source of a high level of protein in the urine
Myoglobinin people who have had extensive damage to their skeletal muscles (rhabdomyolysis), a urine myoglobin test may be ordered to
determine the risk of kidney damage. With severe muscle injury, blood and urine levels of myoglobin can rise very quickly.
Imaging techniques
If a structural problem or blockage is suspected, imaging of the kidneys can be helpful. Imaging techniques such as an ultrasound, CT scan (computed
tomography), isotope scan, or intravenous pyelogram (IVP) may be used. For more on these see RadiologyInfo's web pages on Kidney and Bladder
Stones or Kidney (Renal) Failure.
Kidney biopsy
A biopsy is sometimes used to help determine the nature and extent of structural damage to a kidney. Analyzing a small piece of kidney tissue, obtained
using a biopsy needle and diagnostic imaging equipment, can sometimes be useful when disease of the glomeruli (or sometimes the tubules) is
suspected.
Hematology Studies
Test: Total Hemoglobin (Hgb or Hb)
A test used to determine the amount of hemoglobin in the blood. Hgb is the pigment part of the erythrocyte, and the
oxygen-carrying part of the blood.
Normal Values:
males: 12-17 grams/100ml
females: 11-15 grams/100ml
Clinical Implications:
A Low hemoglobin level indicates anemia. Estimates of Hgb in each RBC are moderately important when determining
the total blood Hgb. However, hemoglobin findings are even more dependent upon the total number of RBC's. In other
words, for the diagnosis of anemia, the number of RBC's is as important as the hemoglobin level.
Blood hemoglobin level has become a "routine" lab test for most patients admitted to hospitals today. Hgb is obviously
important for the diagnosis of anemia and hemorrhage. It is equally important for diagnosing many lesser known
diseases.
The test can be performed upon capillary blood, such as drawn from the finger stick. The test is often performed along
with other tests, thereby requiring a larger specimen of blood, as from venipuncture. Hemoglobin in the body is
dependent upon amounts of iron. A lack of available iron causes one type of anemia, due to the reduced production of
hemoglobin. Remember that in the strictest sense, anemia is not in itself a diagnosis, but rather a symptom that there
is something else wrong in the body. For example, malnutrition (low iron levels), would be the diagnosis of the patient,
not just the anemia. The secondary diagnosis would be anemia, but malnutrition must be treated in order to "cure" the
anemia.
*Note--Fetal Hemoglobin:
Fetal Hb (Hb F), is a normal Hb product in the red blood cells of a fetus and in smaller amounts in infants. It
constitutes 50% to 90% of Hb in a newborn; the remaining Hb consists of Hb A1 and Hb A2 the Hb in adults.
Under normal conditions, the body ceases to manufacture fetal Hb sometime during the first year of life, and from that
point on manufactures adult Hb. If this changeover does not occur and fetal Hb continues to constitute more than 5%
of the Hb after age six months, an abnormality should be suspected, particularly thalassemia.
VARIATIONS OF HEMOGLOBIN TYPE AND DISTRIBUTION (in adults)
Percentage of total
Hemoglobin
hemoglobin
Clinical Implications
Hb A
95% to 100%
Normal
Hb A2
4% to 5.8%
b-thalassemia minor
1.5% to 3%
b-thalassemia major
Under 1.5%
b-d-thalassemia minor
Under 2%
Normal
2% to 5%
b-thalassemia minor
10% to 90%
b-thalassemia major
5% to 15%
b-d-thalassemia minor
5% to 35%
100%
Homozygous HPFH
15%
Homozygous Hb S
Homozygous Hb S
70% to 98%
Homozygous Hb C
90% to 98%
Hb C disease
Heterozygous Hb C
24% to 44%
Hb C trait
Hb F
A report of the individual characteristics of the RBC. The following are those characteristics which are used to indicate
anemia. If abnormal findings are present, the anemias can be defined as macrocytic, microcytic, hypochromic, others.
When this is discovered, the exact cause of the anemia can be determined more easily.
The following are all part of indices:
1.
MCV
2.
MCH
3.
MCHC
b.
should be performed to confirm the diagnosis if sickle cell disease is strongly suspected.
**See Hemoglobin electrophoresis test earlier in this chapter.
Test: Iron and Total Iron-binding Capacity
Iron is essential to the formation and function of hemoglobin, as well as many other heme and nonheme compounds.
After iron is absorbed by the intestine, it is distributed to various body compartments for synthesis, storage, and
transport. Serum iron concentration is normally highest in the morning and declines progressively during the day.
Thus, the sample should be drawn in the morning.
An iron assay is used to measure the amount of iron bound to transferrin in blood plasma. Total iron-binding capacity
(TIBC) measures the amount of iron that would appear in plasma if all the transferrin were saturated with iron.
Serum iron and TIBC are of greater diagnostic usefulness when performed with the serum ferritin assay, but together,
these tests may not accurately reflect the state of other iron compartments, such as myoglobin iron and the labile iron
pool. Bone marrow or liver biopsy, and iron absorption or excretion studies may yield more information.
Normal Values:
Serum Iron:
males: 50 to 150 u/g/dl
females: 35 to 145 ug/dl
TIBC, Total Iron-binding capacity:
males and females: 250 to 400 ug/dl
Saturation:
males and females: 14% to 50%
Test: Ferritin
Ferritin is a major iron-storing protein found in reticuloendothelial cells. It normally appears in small quantities in
serum. In healthy adults, serum ferritin levels are directly related to the amount of available iron stored in the body and
can be measured accurately by radioimmunoassay.
Normal Values:
Men: 20 to 300 NG/ml
Women: 20 to 120 NG/ml
6 mo to 15 yr
7 to 140 NG/ml
2 to 5 months
50 to 200 NG/ml
1 month old
Neonates
25 to 200 NG/ml
Normal serum Ferritin values will vary with age. Remember to check with your lab, as normal values may be different
in different labs. The blood is collected via venipuncture in a standard 10-ml red-top tube. A random blood specimen is
used. No special instructions need to be given to the patient except for explaining the procedure. Recent blood
transfusions may elevate serum ferritin levels.
Increased Serum Ferritin Levels: may indicate acute or chronic hepatic disease, iron overload, leukemia, acute or
chronic infection or inflammation, Hodgkin's Disease, or chronic hemolytic anemias.
Slight increase, or normal Ferritin Level: may indicate chronic renal disease
Decreased serum Ferritin Levels: may indicate chronic iron deficiency
Test: ESR--Erythrocyte Sedimentation Rate
The ESR measures the time required for erythrocytes from a whole blood sample to settle to the bottom of a vertical
tube. Factors influencing the ESR include red cell volume, surface area, density, aggregation, and surface charge.
The sample must be examined within 2 hours of collection and it must be handled gently, no clotting of sample must
take place.
Normal values: 0-20 mm/hr (gradually increase with age)
The ESR is a sensitive, but nonspecific test that is frequently the earliest indicator of disease. It often rises
significantly in widespread inflammatory disorders due to infection or autoimmune mechanisms. Such elevations may
be prolonged in localized inflammation and malignancies.
Increased ESR: may indicate pregnancy, acute or chronic inflammation, tuberculosis, rheumatic fever,
paraproteinemias, rheumatoid arthritis, some malignancies, or anemia.
Decreased ESR: may indicate polycythemia, sickle cell anemia, hyperviscosity, or low plasma protein.
Test: Osmotic Fragility
Osmotic fragility measures red blood cell (RBC) resistance to hemolysis when exposed to a series of increasingly
dilute saline solutions. The sooner hemolysis occurs, the greater the osmotic fragility of the cells.
Purpose of test - The purpose of this test is to help diagnose hereditary spherocytosis and to supplement a stained
cell examination to detect morphologic RBC abnormalities.
Normal results: Osmotic fragility values (percentage of RBC's hemolyzed) are determined by the tonicity of the saline.
neutrophils (granulocyte)
lymphocytes (non-granulocyte)
monocytes (non-granulocyte)
eosinophils (granulocyte)
basophils (granulocyte)
Clinical Implications:
As we all know, WBC's are our body's first line of defense against invading bacteria and most other harmful
organisms. This test (WBC), measures the total number of all types of WBC's. Further examination of the different
types and numbers of cells present, could tell much about the state of the body's defense system. WBC count will
normally vary as much as 2,000 on any given day.
Test: Differential Cell Count also known as "diff" or "differential"
Laboratory test that counts actual numbers of different types of WBC's.
Clinical Implications:
The following chart gives the normal values for each type of WBC. Interpretation of the results of the differential must
always be done with the total number of WBC's in mind.
The WBC differential evaluates the distribution and morphology of white blood cells. Therefore, it provides more
specific information about a patient's immune system than the WBC count alone. In the differential test, the lab
classifies 100 or more white cells in a stained film of peripheral blood according to two major types of leukocytes.
They are: (1) Granulocytes (neutrophils, eosinophils, basophils); (2) non-Granulocytes (lymphocytes, monocytes). The
percentage of each type is then determined.
The differential count is the relative number of each type of white cell in the blood. By multiplying the percentage value
of each type, by the total WBC count, the lab obtains the absolute number of each type of white cell. Although little is
known about the function of eosinophils in the blood, abnormally high levels of them are associated with various types
of allergic disorders and reactions to parasites. In such cases, the eosinophil count is sometimes ordered as a followup to the white cell differential. This test is also appropriate if the differential WBC count shows a depressed
eosinophil level.
range.
The patient's neutrophil count, however, is low (30%), and when this is multiplied by the white cell count (6,000 x 30%
= 1,800 neutrophils/ul), the result is a low absolute number. This low result indicates decreased neutrophil production,
which may mean depressed bone marrow.
CELL
ADULT
ABSOLUTE
TYPE
VALUE
VALUE
BOYS
GIRLS
Neutrophils
47.6% to 76.8%
1,950 to 8,400/ul
38.5% to 71.5%
41.9% to 76.5%
Lymphocytes
16.2% to 43%
660 to 4,600/ul
19.4% to 51.4%
16.3% to 46.7%
Monocytes
0.6% to 9.6%
24 to 960/ul
1.1% to 11.6%
0.9% to 9.9%
Eosinophils
0.3% to 7%
12 to 760/ul
1% to 8.1%
0.8% to 8.3%
Basophils
0.3% to 2%
12 to 200/ul
0.25% to 1.3%
0.3% to1.4%
NEUTROPHILS:
Increased by:
Decreased by:
EOSINOPHILS:
Increased by:
Miscellaneous; collagen vascular disease, ulcerative colitis, pernicious anemia, scarlet fever, excessive
exercise, others
Decreased by:
Stress response; due to trauma, shock, burns, surgery, mental distress, Cushing's Syndrome
BASOPHILS:
Increased by:
Miscellaneous disorders; Chronic myelocytic leukemia, polycythemia vera, some chronic hemolytic
anemias, Hodgkin's disease, myxedema, ulcerative colitis, chronic hypersensitivity states,
Decreased by:
LYMPHOCYTES:
Increased by:
Decreased by:
Severe debilitating illness; congestive heart failure, renal failure, advanced tuberculosis
MONOCYTES:
Increased by:
2.
3.
Coagulation Studies
Nursing implications related to clotting studies are numerous. An increase in clotting of blood or a decrease in clotting
ability will be considered the two main problems of coagulation of the blood.
Following is a summary of the overall phases of blood clotting. Circulating blood generally has two main inactive
proteins relating to clotting. These are prothrombin and fibrinogen. It must also be remembered that platelets stimulate
the clotting process.
Blood Clotting Process
PHASE I
Initiation Phase
platelets plus initiation factor
PHASE II
Thromboplastin Phase
* platelet factors plus Calcium
* plus factors 8, 9, 10, 11, 12
.....yields thromboplastin
PHASE III
Thrombin Phase
*prothrombin plus calcium
*plus thromboplastin
*plus accelerator factors 5, 7, 10
..........yields Thrombin
PHASE IV
Fibrin Phase
*fibrinogen plus factor 8
*plus Thrombin
.........yields Fibrin CLOT
Platelets are the smallest formed elements in the blood. They are vital to the formation of the hemostatic
plug in vascular injury. They promote coagulation by supplying phospholipids to the intrinsic thromboplastin
pathway.
o
2.
When the platelet count is abnormal, diagnosis usually requires further studies, such as CBC, bone marrow
biopsy, direct antiglobulin test (direct Coomb's test), and serum protein electrophoresis.
3.
Use a 7-ml lavender-top tube for collection. A random specimen is used. Mix the blood GENTLY with the
anticoagulant in the tube. Rough handling will interfere with the results.
4.
Hemolysis due to rough handling or to excessive probing at the venipuncture site may alter test results.
5.
Many medications will decrease platelet count; they include acetazolamide, acetohexamide, antimony,
antineoplastic drugs, brompheniramine maleate, carbamazepine, chloramphenicol, furosemide, gold salts,
isoniazid, mephentoin, methyldopa, sulfonamides, thiazide, and many others.
Platelets normally increase in persons living at high altitudes for extended periods of time. They also increase with
persistent cold temperatures, and during strenuous exercise and excitement. The count decreases just prior to
menstruation.
Test: Prothrombin Time PT or Pro Time
This test is a measure of phase III of the clotting process. The PT may give false readings due to some other clotting
defects. However, it is usually indicative of a phase III problem.
Normal values: (child or adult): 11-15 seconds or 70%-100% (depends on method used)
Clinical Implications:
Prothrombin is also known as factor II of the coagulation factors. It is produced by the liver and requires vitamin K for
its synthesis. In liver disease, PT is usually prolonged. The test requires 7 to 10 ml of blood with an anticoagulant in
the blood tube. It can be collected in a black-top tube (sodium oxalate in the tube), or blue-top tube (sodium citrate in
the tube). The most common is the blue-top tube, the specimen must be tested within 4 hours of collection and is
usually packed in ice and delivered to the lab quickly. This is a very common lab test and is usually performed as a
routine hospital admission screening test. A high-fat diet may cause decreased PT, and alcohol can cause an
increased PT result.
Test: Partial Thromboplastin Time PTT
A test similar to the PT, the PTT is also used to detect clotting abnormalities. APTT, Activated PTT, similar to PTT but
is more sensitive than PTT test; it will help to identify the defective factor, if one is defective.
Normal Values:
PTT: 60-70 seconds
APTT: 30-45 seconds
*these results may vary due to test methods in different hospitals.
Clinical Implications:
The PTT is very similar to the PT. It is used to detect Phase II defects in the clotting process. It will usually detect
deficiencies in all clotting factors except factors VII and XIII. It is usually performed for monitoring Heparin therapy.
Heparin doses are usually adjusted according to the PTT test results. The PTT is usually more sensitive than the PT
test.
Test: Bleeding Time
A raw measurement of the time needed for an artificially produced skin puncture to stop bleeding.
Normal Values:
Ivy method: 1-6 minutes
Duke method: 1-3 minutes
Clinical Implications:
Hodgkin's disease is suspected if there is decreased bleeding time. Prolonged rate may indicate: thrombocytopenic
purpura, platelet abnormality, vascular abnormality, leukemia, severe liver disease, DIC disease, aplastic anemia,
factor deficiencies (V, VII, XI), Christmas disease, hemophilia. The following drugs can affect bleeding time: aspirin,
dextran, mithramycin, coumadin, streptokinase-streptodornase (fibrinolytic agent). Aspirin, alcohol, and also
anticoagulants may increase bleeding time.
This test is usually inconclusive. It can however, be helpful for diagnosing capillary abnormalities and other disorders.
For detecting other clotting problems, this test will usually show a normal result. This test is usually just a general
screening test.
It would be very difficult to name a physiologic process that does not depend, in one way or another, on calcium. It is critical to
maintain blood calcium concentrations within a tight normal range. Deviations above or below the normal range frequently
lead to serious disease.
Hypocalcemia refers to low blood calcium concentration. Clinical signs of this disorder reflect increased
neuromuscular excitability and include muscle spasms, tetany and cardiac dysfunction.
Hypercalcemia indicates a concentration of blood calcium higher than normal. The normal concentration of calcium and
phosphate in blood and extracellular fluid is near the saturation point; elevations can lead to diffuse precipitation of calcium
phosphate in tissues, leading to widespread organ dysfunction and damage.
Preventing hypercalcemia and hypocalcemia is largely the result of robust endocrine control systems.
Body Distribution of Calcium and Phosphate
There are three major pools of calcium in the body:
Intracellular calcium: A large majority of calcium within cells is sequestered in mitochondria and endoplasmic
reticulum. Intracellular free calcium concentrations fluctuate greatly, from roughly 100 nM to greater than 1 uM, due
to release from cellular stores or influx from extracellular fluid. These fluctuations are integral to calcium's role in
intracellular signaling, enzyme activation and muscle contractions.
Calcium in blood and extracellular fluid: Roughly half of the calcium in blood is bound to proteins. The
concentration of ionized calcium in this compartment is normally almost invariant at approximately 1 mM, or 10,000
times the basal concentration of free calcium within cells. Also, the concentration of phosphorus in blood is
essentially identical to that of calcium.
Bone calcium: A vast majority of body calcium is in bone. Within bone, 99% of the calcium is tied up in the mineral
phase, but the remaining 1% is in a pool that can rapidly exchange with extracellular calcium.
As with calcium, the majority of body phosphate (approximately 85%) is present in the mineral phase of bone. The remainder
of body phosphate is present in a variety of inorganic and organic compounds distributed within both intracellular and
extracellular compartments. Normal blood concentrations of phosphate are very similar to calcium.
Facilitates mobilization of calcium and phosphate from bone. To prevent detrimental increases in phosphate,
parathyroid hormone also has a potent effect on the kidney to eliminate phosphate (phosphaturic effect).
Maximizes tubular reabsorption of calcium within the kidney. This activity results in minimal losses of calcium in
urine.
Vitamin D acts also to increase blood concentrations of calcium. It is generated through the activity of parathyroid
hormone within the kidney. Far and away the most important effect of vitamin D is to facilitate absorption of calcium from the
small intestine. In concert with parathyroid hormone, vitamin D also enhances fluxes of calcium out of bone.
Calcitonin is a hormone that functions to reduce blood calcium levels. It is secreted in response to hypercalcemia and has at
least two effects:
Suppression of renal tubular reabsorption of calcium. In other words, calcitonin enhances excretion of calcium into
urine.
Inhibition of bone resorption, which would minimize fluxes of calcium from bone into blood.
Although calcitonin has significant calcium-lowing effects in some species, it appears to have a minimal influence on blood
calcium levels in humans.
A useful way of looking at how hormones affect tissues to preserve calcium homeostasis is to examine the effects of
calcium deprivation and calcium loading. The following table summarizes body responses to conditions that would
otherwise lead to serious imbalances in calcium and phosphate levels in blood.
Calcium Deprivation
Parathyroid hormone
Calcium Loading
Secretion stimulated
Secretion inhibited
Vitamin D
Calcitonin
Renal excretion of
calcium
Renal excretion of
phosphate
General Response
Summary
alcium and phosphorus are essential minerals found in the bone, blood and soft tissue of the body and have a role in numerous body
functions. Phosphorus levels can affect calcium levels in the body, and vice versa. Parathyroid hormone, vitamin D and the kidneys all
help to regulate calcium and phosphorus levels in the blood.
The Role of PTH and Vitamin D
The body must maintain certain levels of calcium and phosphorus in the blood. Parathyroid hormone, or PTH, and vitamin D work to
keep these levels in balance. Calcium and phosphorus are absorbed into the blood through the small intestine after eating foods that
contain these nutrients. The bones will also release the nutrients to help maintain necessary blood levels. The parathyroid gland can
sense an imbalance of calcium or phosphorus. If the calcium level is low, the parathyroid gland will release PTH, which tells the
kidneys to produce more active vitamin D. This helps the body to absorb more dietary calcium and phosphorus through the intestine,
tells the bone to release calcium and phosphorus into the blood and tells the kidneys to excrete more phosphorus in the urine.
Calcium, Phosphorus and the Kidneys
Healthy kidneys will eliminate excess phosphorus and calcium in the blood. If kidney function is impaired, the body will not be able to
get rid of extra phosphorus. High phosphorus levels stimulate the release of parathyroid hormone, which can cause complications
when the normal mechanism for bone mineral management does not work correctly. A high phosphorus level may also result in a low
calcium level. Calcium binds with phosphate and is deposited in the tissue. A buildup of these deposits causes calcification in the
tissue, which can disrupt normal organ function. People with chronic kidney disease should work closely with their dietitian and doctor
to control phosphorus, calcium and parathyroid levels.
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Bone Health
About 85 percent of the body's phosphorus and 99 percent of calcium are found in the bones. People with impaired kidney function
are at greater risk for bone disease because they are more likely to have high phosphorus and PTH levels, which can lead to
progressive bone loss. According to the Linus Pauling Institute, there is increasing concern for the effect of a high intake of
phosphorus even in healthy individuals due to its possible impact on bone health. Excessive consumption of foods with phosphorus
additives and a low calcium intake seem to be especially harmful.
Calcium and Phosphorus in Food
Calcium and phosphorus levels are controlled in part through dietary intake. The Food and Nutrition Board set the recommended
dietary allowance of phosphorus at 700 milligrams daily. Sources of phosphorus include dairy products, meat, nuts, beans and foods
that contain phosphorus additives such as convenience foods and colas. The RDA for calcium is 1,000 milligrams for most adults,
though adolescents and older adults need more calcium. Sources of calcium include dairy products, soy, vegetables such as bok
choy, broccoli and kale and beans such as pinto and red.