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By Jay Wish, MD
Introduction
Patients with kidney disease need to
understand the meaning of the many tests that are performed to measure kidney
function, to assess the complications of kidney disease and to determine the
response to treatment. This article addresses some of the tests that are most
commonly performed on patients with chronic kidney disease (CKD), explaining the
rationale for the tests and the implications if the tests falls outside a normal
or target range. It is important for each patient with kidney disease to discuss
the results of his or her own tests with their
nephrologist.
Tests of Kidney Function
The blood
urea nitrogen (BUN) is a normal product of the breakdown of proteins, both in
the diet and in the body. Normal kidneys excrete urea efficiently, so the BUN
level rarely exceeds 20 in patients without kidney disease. The BUN level will
rise above the normal range when the ability of the kidneys to excrete urea is
impaired or in situations where protein breakdown is increased (such as a
high-protein diet or damage to cells). A decrease in BUN during dialysis is the
most commonly used test to measure dialysis adequacy.
Serum creatinine is
the most commonly used test of kidney function and is more accurate than the BUN
since its level is not affected by dietary protein intake. Serum refers to the
liquid part of the blood, and the tests described below using the term “serum”
just mean that they are blood tests. Creatinine is a normal product of muscle
breakdown, and is produced at approximately the same rate every day in each
person. Creatinine is normally excreted by the kidneys. A normal serum
creatinine level for an adult is around 1 (0.6-1.2). Using only serum creatinine
as a test of kidney function has been shown in many patients to underestimate
the degree of kidney disease. Other formulas which use serum creatinine along
with patient characteristics such as age, weight, gender and race are much more
accurate in determining kidney function.
Creatinine clearance is a
measure of kidney function that can be determined from a 24-hour urine
collection and a simultaneous blood sample, or it can be calculated from a
formula based on serum creatinine and the patient’s age, weight and gender. The
creatinine clearance test has recently fallen out of favor because it tends to
overestimate kidney function as compared to glomerular filtration rate (GFR)
also, because the collection of a 24-hour urine sample tends to be cumbersome
and often inaccurate since it may fail to capture the entire urine output of the
patient over a 24-hour period. Glomerular filtration rate (GFR) has become the
“gold standard” test for the measurement of kidney function. It is the basis for
the classification of the stages of CKD endorsed by the National Kidney
Foundation (NKF). Another advantage of GFR is that it is expressed in terms of a
value for a standard sized individual, making it possible to predict what the
consequences of abnormal kidney function will be on populations of individuals
irrespective of the size of a particular person. The most accurate way to
determine GFR is by a kidney scan, but this is expensive and cumbersome, and is
generally reserved for research protocols. It is possible to get a reasonably
accurate measurement of GFR with a formula that uses the patient’s serum
creatinine, age, gender and race. The GFR is also used by the Center for
Medicare Services (CMS) to determine the threshold at which dialysis is
initiated and by the United Network for Organ Sharing (UNOS) to determine when a
patient becomes eligible for a kidney transplant.
The NKF’s staging
classification of CKD is shown in Table 1 with a description of the action that
is recommended at each stage. If you have CKD and are not yet on dialysis, you
should ask your doctor what your GFR is, then you can determine what stage you
fall into and what the recommendations for further evaluation and treatment of
your kidney disease and its complications are at that stage. If you are on
peritoneal dialysis, the dose of peritoneal dialysis administered to you takes
into account any residual kidney function you might have, and this is based on a
GFR as well.
Table 1: NKF Staging of
CKD
| Stage |
Description |
Glomerular Filtration Rate (GFR) |
Action |
| 0 |
At increased risk |
>90% |
Screening, risk reduction |
| 1 |
Chronic kidney damage with normal or increased GFR |
>90% |
Diagnosis and treatment of comorbidities, slowing progression
and CVD risk |
| 2 |
Mild decrease in GFR |
60-89% |
Estimating progression |
| 3 |
Moderate decrease in GFR |
30-59% |
Evaluation and treatment of complications |
| 4 |
Severe decrease in GFR |
15-29% |
Preparation for renal replacement therapy |
| 5 |
Kidney failure |
<15% - or dialysis |
RRT if uremia present |
Anemia in Renal Disease
Virtually all patients
with CKD will develop anemia due to decreased production of erythropoietin (EPO)
by the kidneys. EPO is a hormone produced by normal kidneys that stimulates the
bone marrow to make an adequate number of red blood cells assuring oxygen
delivery to all tissues. With increasing damage to the kidneys, the production
of EPO decreases, so the bone marrow produces fewer red blood cells and anemia
develops. Red blood cells carry oxygen to the tissues by binding the oxygen to
hemoglobin which contains iron. The initial evaluation of anemia should include
tests of iron, as well as certain vitamins that are required for hemoglobin
production. Tests should also check for small amounts of blood leaking out in
the stool.
The most commonly used test to diagnose anemia is the
hemoglobin level in the blood. A decreased level of hemoglobin in the blood
impairs the ability to deliver oxygen to the tissues, and leads to symptoms
including weakness, fatigue and shortness of breath. More importantly, a low
hemoglobin level puts an additional strain on the heart, since the heart has to
pump more blood in order to keep up with the oxygen demands of the tissues in
the body. This may lead to cardiac complications including heart failure and
heart attacks. The lower limit of a normal hemoglobin level is 12 in
menstruating females and 13.5 in males and postmenopausal
females.
Hematocrit is the percentage volume of blood occupied by the red
cells after the blood is centrifuged, and is approximately three times the
hemoglobin level. It’s not as accurate a test as is measuring the hemoglobin
directly. The lower limit of normal hematocrit for menstruating females is 36
and for males and postmenopausal females is 41. The two major tests to diagnose
iron deficiency are transferrin saturation (TSAT) and serum ferritin. TSAT is a
measure of the iron that is carried in the blood that can be delivered to the
bone marrow to be incorporated into new red blood cells. When patients are
treated with EPO-like drugs, it accelerates red blood cell production to a
higher than normal level, so a higher than normal TSAT is required to keep up
with the demand for iron by the bone marrow. The target TSAT for patients with
CKD who are being treated with EPO-like drugs is 20–50 percent. Serum ferritin
is another test of iron and correlates with the amount of iron that your body
holds in storage. This is not iron that is in the blood or is available to the
bone marrow for production of new red blood cells. It is important for patients
receiving EPO-like drugs to maintain adequate iron stores so that the body does
not run out of iron as new red blood cells are produced. Unfortunately, the
serum ferritin may also be elevated in the setting of inflammation, independent
of iron stores, so sometimes an elevated serum ferritin can be difficult to
interpret by your physician. If you are an anemic patient with CKD whose TSAT is
less than 20 percent or whose serum ferritin is less than 100, you should be
treated with an oral or intravenous iron supplement to get your TSAT and serum
ferritin back into the target range. The presence of iron deficiency will make
it more difficult for your anemia to be corrected even if you are given an
EPO-like agent.
Vitamin deficiencies may also contribute to anemia in
patients with CKD, especially if you are not eating a balanced diet. The two
most important vitamins for red blood cell production are vitamin B12 and folic
acid. The levels of these vitamins in the blood should be measured as part of a
complete evaluation of anemia, and these vitamins should be replaced if they are
deficient. Reticulocytes are the youngest red blood cells in your circulation,
one or two days old, and can be identified because they take on a special stain
in the blood analyzer machine. Measurement of these newest red blood cells can
be helpful in determining whether anemia is due to an underproduction of red
blood cells or due to the loss or destruction of existing red blood cells.
Patients with anemia in the setting of CKD, because they are deficient in EPO,
have an underproduction of red blood cells and, therefore, a low reticulocyte
count. If your reticulocyte count is elevated, then consideration should be
given as to whether your anemia might be due, in part, to the loss or
destruction of red blood cells in addition to EPO deficiency.
Many
patients with CKD have abnormalities in blood clotting which may lead to a
low-grade loss of red blood cells in the gastrointestinal tract through the
stools. Therefore, a complete evaluation of anemia should include a test for
hidden blood in the stool that can be done by your physician in his/her office.
If blood is present in the stool, then it is important for this to be followed
up by additional tests to determine whether or not this represents a condition
that needs to be treated more extensively.
Tests of Bone
Disease
Bone disease often occurs in patients with CKD. This is
due to the inability of the kidneys to completely excrete phosphorus from the
blood and due to the inability of the kidneys to convert vitamin D to its active
form. Both of these problems lead to a decrease in serum calcium levels, which
stimulates the parathyroid gland in the neck to make a hormone, called
parathyroid hormone (PTH). This hormone raises the serum calcium level back
towards normal by breaking down bone and releasing calcium from the bone.
Treatment and prevention of bone disease in patients with CKD is directed at
treating the elevated serum phosphorus with phosphate binders and dietary
phosphate restriction, and providing the active form of vitamin D with a
medication. This can be administered either orally or intravenously on dialysis.
Therefore, it is important to periodically monitor the effectiveness of this
therapy by measuring serum calcium, serum phosphorus and serum PTH levels. The
target range for serum calcium in patients with CKD is 8.4-9.5. A low serum
calcium level should be avoided because it stimulates the parathyroid gland to
make more PTH and to accelerate bone disease. On the other hand, high serum
calcium levels may lead to the deposition of calcium in soft tissues and
vessels, increasing the risk of heart attacks, strokes and other forms of
cardiovascular disease. The target range for serum phosphorus in patients with
CKD is 3.5-5.5. Almost all patients with CKD will require dietary phosphorus
restriction and/or phosphate binders to maintain serum phosphorus levels within
the target range. Although elevated serum phosphorus levels generally do not
produce symptoms other than itching, it is extremely important for you to
monitor your serum phosphorus levels. Working with your physician and dietitian
to modify your diet and phosphate therapy as needed to keep the serum phosphorus
level within the target range will help.
Parathyroid hormone (PTH) levels
correlate with the development of bone disease in patients with CKD, and should
be measured periodically. Elevated PTH levels can be treated in two ways: the
administration of an activated form of vitamin D either orally or intravenously
and with a newer drug called cinacalcet which directly suppresses the release of
PTH from the parathyroid gland. The most commonly used test is called intact PTH
(iPTH) which has a target range of 150-300 in patients on dialysis, 70-110 in
patients with stage 4 CKD, and 35-70 in patients with stage 3 CKD. PTH levels
higher than the target are bad because they are associated with the increased
breakdown of bone which leads to loss of bone strength and increased incidence
of fractures. If your PTH level is out of the target range for your stage of
CKD, you should discuss this with your nephrologist.
Other Lab
Tests
The monitoring of serum potassium levels in patients with
more advanced stages of CKD and those on dialysis is important because very high
serum potassium levels can lead to cardiac arrest. The level of CKD at which
serum potassium levels rise above the normal range varies from individual to
individual. Although the upper limit of potassium for the normal population is
5.0, patients with CKD and longstanding high potassium levels can generally
tolerate potassium levels as high as the 5.5-6.0 range. Many physicians will
become concerned with potassiums in this range and initiate treatment with an
agent that removes potassium from the body through the gastrointestinal tract,
such as Kayexalate. If your serum potassium level is elevated and you are a CKD
patient not yet on dialysis, then your physician should evaluate the drugs you
are receiving to determine if any might be contributing to the high potassium
levels, and you may benefit from an increased dose of diuretic to augment the
excretion of potassium through your urine. You should also examine your diet
with a dietitian to determine whether or not you are consuming foods that are
high in potassium and change your food choices accordingly.
The serum
sodium level is a reflection of whether or not there is too much or too little
water in the body. Patients with kidney disease have an inability to excrete as
much water as normal individuals, so a large water intake may lead to the
retention of water in the body which dilutes the serum sodium to a lower than
normal level. The normal serum sodium level is 135-145. If the serum sodium
level gets down to the low 120’s, the water that has been retained, causes
swelling. The symptoms that occur are due to swelling of the brain, which has no
place to expand because it is enclosed in the rigid skull cavity. These symptoms
include headache, nausea, vomiting and seizures. A restriction of fluid in the
diet may be necessary in some patients with CKD to avoid this
complication.
The serum bicarbonate level usually falls below the normal
range in patients with more advanced kidney disease because their kidneys are no
longer able to excrete acids at the rate the acids are produced by the body. The
bicarbonate on the blood combines with these retained acids and prevents the
acids from combining with other molecules that would produce more damage to the
body. As more acids are retained, the bicarbonate level falls further, and then
the acids start to combine with the phosphorus in bone. When that happens,
calcium is released from the bone, and this makes the bone weaker. So it is
important for patients to maintain a serum bicarbonate level over 20 to minimize
the amount of acid that goes into bone. This may require the administration of
an oral bicarbonate supplement or a medication which the body converts to
bicarbonate.
Table 2: Summary of Commonly Used Tests in Patients
with CKD
| Test |
Meaning |
Normal Range |
Target Range in CKD |
Blood urea nitrogen
(BUN) |
Level of protein breakdown product |
Less than 20 |
Varies by stage, the lower the better in most cases |
| Serum creatinine |
Level of muscle breakdown product in blood |
0.6-1.2 |
Varies by stage, the lower the better |
| Creatinine clearance |
Measure of kidney function |
Greater than 50-70, depending on age |
Varies by stage, the higher the better |
| Glomerular filtration rate (GFR) |
Measure of kidney function |
Greater than 60-90, depending on age |
Varies by stage, the higher the better |
| Hemoglobin |
Oxygen carrying capacity of blood |
Males 13.5-17
Females 12-15 |
11-12 if on EPO |
| Hematocrit |
Percent volume of packed red blood cells after blood is
centrifuged |
Males 41-52
Females 36-46 |
11-12 if on EPO |
| Transferrin saturation (TSAT) |
Iron in blood available for new red blood cell production by
marrow |
25-25 |
25-50 |
| Serum ferritin |
Iron in storage |
20-300 |
100-800 |
| Serum calcium |
Needed for bone health |
8.5-10.5 |
8.4-9.5 |
| Serum phosphorus |
High levels bad for bone and blood vessels |
2.4-4.5 |
3.5-5.5 |
| Parathyroid hormone (iPTH) |
Maintains serum calcium level and bone health |
10-60 |
35-70 in Stage 3
70-110 in Stage 4
150-300 In Stage
5 |
| Serum potassium |
High levels can cause abnormal heart rhythms |
3.5-5.0 |
Less than 5.5-6.0 |
| Serum sodium |
Amount of water in the body (low level means too much
water) |
135-145 |
135-145 |
| Serum bicarbonate |
Ability to prevent accumulation of excess acid |
22-30 |
20-30 |
Conclusion
There are other tests that may be
performed on patients with CKD that are beyond the scope of this article. These
include x-rays and other imaging studies of the kidneys to evaluate for
structural abnormalities of the urinary tract, abnormal blood flow to the
kidneys and kidney function, and evaluation of blood vessels including venous
mapping and angiography that may be performed as part of your preparation for
hemodialysis vascular access placement. Patients with CKD who are not yet on
dialysis should understand that many abnormalities may develop which do not
produce symptoms but must be treated before complications occur. Knowledge is
power to control your destiny. By understanding and responding to abnormalities
in your medical tests, you have a much better chance of achieving favorable
healthcare outcomes.
Jay B. Wish, M.D. is Professor of Medicine
at Case Western Reserve University and Medical Director, Hemodialysis Services
at the University Hospitals of Cleveland. Dr. Wish is also a member of the AAKP
Medical Advisory Board.
This article originally
appeared in the June/July 2006 issue of Kidney Beginnings: The Magazine, Vol. 5,
No. 2. |
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