Frequently Asked Questions | NIDDK
eGFR
1. What is a GFR estimating equation?
Glomerular filtration rate (GFR) is a marker of kidney function. It is
rarely measured outside of the research setting. An estimating equation
estimates GFR using laboratory measurements and demographic variables
that describe the patient. The two most commonly used estimating
equations are the Modification of Diet in Renal Disease (MDRD) Study
equation and the Chronic Kidney Disease Epidemiology Collaboration
(CKD-EPI) equation. Both equations incorporate four variables: serum
creatinine, age, race, and gender. Both equations give similar values
for patients with advanced kidney disease (eGFR less than 60 mL/min/1.73
m^{2}). However, for patients with less advanced disease, the
CKD-EPI equation gives better estimates of GFR and should be used when
the eGFR is greater than 60 mL/min/1.73 m^{2}.
2. Why use an estimated GFR instead of simple creatinine?
Serum creatinine may be increased or decreased due to changes in muscle
mass rather than changes in kidney function. In these situations, the
serum creatinine may over or underestimate kidney function. Estimating
equations utilizing serum creatinine include variables which are related
to muscle mass (age, gender, and race) and may provide a more accurate
indication of kidney function.
3. How is a GFR estimating equation developed?
Estimating equations are developed from study populations in which a
measured GFR has been obtained. Through regression analysis, equations
are developed which provide an estimate of GFR utilizing patient
characteristics (e.g. serum creatinine, age, gender, and race) which are
routinely available. Thus, estimating equations are developed in
populations and may be most useful in describing risk in populations of
patients. The estimated GFR will be less accurate for individual
patients who have characteristics, especially muscle mass, that are
different from the average in the population used to develop an
estimating equation.
4. Why is there more than one GFR estimating equation?
There are several GFR estimating equations currently used to assess
kidney function, and each equation has been developed
in different study populations. Estimating equations change over time;
as new equations are developed and validated in
larger populations, older ones become obsolete. For example, the MDRD
Study equation has been validated in CKD patients
with lower levels of GFR who were predominantly Caucasian, non-diabetic,
and did not have a kidney transplant.
The MDRD equation has not been validated in children less than 18 years
of age, pregnant women, the elderly above the age of 85, or in some
racial or ethnic subgroups such as Hispanics.
The CKD-EPI equation has been validated in a broader group of persons
consisting of predominately Caucasians and Blacks with and without
kidney diseases, diabetes, and solid organ transplants
who had a wide range of GFR and ages. As a result, CKD-EPI appears to
offer some improvement for eGFR between 60 and 120 mL/min/1.73 m^{2}.
5. How do we measure the performance of a GFR estimating equation?
Estimating equations reflect the best estimate for the population in
which they were developed. However, there can be significant imprecision
when using the equation when assessing an individual. The conventional
measure of precision has been the P30, which describes the percent of
GFR estimates that are within 30% of the measured GFR. Measures of P30
using the same equations vary in different studies depending on the age,
muscle mass, and amount of kidney disease prevalent in different
population groups that have been investigated.
6. Are certain equations better for estimating GFR in certain situations?
GFR estimating equations are derived from and validated in studies in
specific populations and include multiple variables, so it’s important
to recognize that a particular equation will be best suited for use with
individual patients with demographic and disease conditions most
similar to those of the population used to develop an equation. The MDRD
Study Equation was developed in CKD patients with lower levels of GFR
(mean GFR 40mL/min/1.73 m^{2}) who were predominantly Caucasian,
non-diabetic, and did not have a kidney transplant. The CKD-EPI
Equation has been validated in a group of predominately Caucasians and
Blacks with and without kidney disease, diabetes, and solid organ
transplants who had a wide range of GFR (2 to 198 mL/min.1.73 m^{2})
and ages (18-97 years). Neither the MDRD Study nor the CKD-EPI
equations have been validated in children, pregnant women, or in some
racial or ethnic subgroups. However, the CKD-EPI equation has been
evaluated in a broader range of conditions than has the MDRD equation.
7. Is there a role for the Cockcroft-Gault equation?
Creatinine measurement has now been standardized. Unfortunately, the
creatinine method used in the development of the Cockcroft-Gault
equation is no longer in use and samples from the study are not
available to evaluate how the results might compare to standardized
creatinine values. There is no version of the Cockcroft Gault equation
for use with standardized creatinine results. A large simulation study
compared eGFR by MDRD Study equation and estimated creatinine clearance
(eCrCl) by the Cockcroft-Gault equation calculated from standardized
creatinine values to each other and to measured GFR for the purpose of
drug dosing. The results suggested that, for the majority of patients
and for most drugs tested that did not have narrow thresholds for
toxicity, there was little difference in the drug dose that would be
administered using either equation to estimate kidney function. However,
for drugs with a narrow therapeutic index, the Cockcroft-Gault equation
was less reliable in assessing the risk of kidney damage.
8. Is there a role for collecting 24 hour urine to calculate a creatinine clearance?
For most people, creatinine clearance calculated from a 24 hour urine
collection does not provide a better indication of kidney function than
does an estimated value of GFR. However, for people for whom serum
creatinine may be increased or decreased due to changes in muscle mass
rather than changes in kidney function (e.g. amputation, cachexia, body
building), a calculated creatinine clearance may be helpful.
9. Why don’t you endorse one equation?
eGFR provides a better indication of kidney function than serum
creatinine alone and NIDDK promotes routine reporting of eGFR with serum
creatinine. However, estimating equations provide only an estimate of
kidney function, not the actual GFR. Development of estimating equations
is a dynamic field with improved versions of existing and new
equations, and equations incorporating new markers (e.g. cystatin C)
appearing on a constant basis. All estimating equations are imperfect
and none offer an overwhelming advantage for all clinical situations.
The goal of NIDDK’s educational effort around eGFR is to explain the
routine and appropriate use of eGFR to clinicians rather than to
disseminate and implement each incremental advance in estimating GFR.
10. What are considered average estimated GFR (eGFR) values for adults?
The table below shows population estimates for mean (average) estimated glomerular filtration rate (eGFR) by age. These means, derived from the NHANES III survey of over 10,000 individuals, demonstrate that eGFR varies across age groups and that kidney function tends to decline with age. There is no difference between races or sexes when eGFRs are expressed per meter squared body surface area.
Reference Table for Population Mean eGFRs From NHANES III^{4}
Age (Years) | Mean eGFR* |
---|---|
Age (Years)20-29 | Mean eGFR* 116 mL/min/1.73 m^{2} |
Age (Years)30-39 | Mean eGFR* 107 mL/min/1.73 m^{2} |
Age (Years)40-49 | Mean eGFR* 99 mL/min/1.73 m^{2} |
Age (Years)50-59 | Mean eGFR* 93 mL/min/1.73 m^{2} |
Age (Years)60-69 | Mean eGFR* 85 mL/min/1.73 m^{2} |
Age (Years)70+ | Mean eGFR* 75 mL/min/1.73 m^{2} |
*In general, the NIDDK recommends laboratories report eGFR values greater than or equal to 60 as “≥ 60 mL/min/1.73 m2,” not as an exact number. Reasons for this recommendation are given in the Reporting GFR section of the website ^{[2]}.
11. Can eGFRs be used in hospitalized patients?
Estimated GFR derived from the MDRD Study or CKD-EPI equation can be
used in patients who are in the hospital. However, it is important to
pay attention to potential inaccuracies due to the non-steady state of
serum creatinine, co-morbidities that cause malnutrition, and the use of
medications that interfere with the measurement of serum creatinine.^{5}
UACR
1. Why is it important to measure urine albumin?
Urine albumin is one indicator of kidney damage. Albumin is the
predominant protein normally found in the blood. Normally only very
small amounts of albumin appear in the urine (less than 30 mg per day).
When the kidneys are damaged, increased amounts of albumin leak into the
urine. This condition is called albuminuria. For many people,
albuminuria is the earliest sign of CKD. In addition, urine albumin
excretion is an early predictor of cardiovascular disease morbidity and
mortality and progression of kidney disease.
2. Once a patient is found to have albuminuria, why repeat the measurement?
Like all physiologic variables, albumin excretion varies and may be
caused by physiologic stress factors other than persistent kidney
damage. The presence of increased urine albumin should be confirmed with
a second determination within three months. Additional measurements
over time can inform management and prognosis.
3. Which test should be used to measure urine albumin?
To test for urine albumin, a urine albumin-to-creatinine ratio (UACR) on
a spot urine sample will provide an excellent indication of 24 hour
albumin excretion in most clinical situations. It is generally not
necessary to collect a 24 hour urine specimen. It is recommended to
perform a follow up confirming UACR test on a first morning sample of
urine.
4. What is the UACR?
UACR is a ratio between two measured substances—albumin and
creatinine—in the urine. UACR is usually expressed as mg albumin/g
creatinine and estimates 24-hour urine albumin excretion. Unlike a
dipstick test for albumin, UACR is unaffected by variation in urine
concentration. Albuminuria is diagnosed when UACR is greater than 30
mg/g.
5. How do I interpret the UACR results?
Albuminuria is present when UACR is greater than 30 mg/g and is a marker
for CKD. Change in albuminuria may reflect response to therapy and risk
for progression. A decrease in urine albumin may be associated with
improved renal and cardiovascular outcomes.
6. Why not use a dipstick to sample urine in the measurement of albumin?
Urine dipstick tests afford low sensitivity and may fail to detect early
stage kidney disease, when the level of albuminuria is below the
sensitivity of the test strip used.
7. What is the role of the urine protein/creatinine ratio?
The protein-to-creatinine ratio is similar to the
albumin-creatinine-ratio; it is obtained on a spot urine specimen and
indicates 24 hour total protein excretion. Total urine protein includes
urine albumin. However, because of the wide range of proteins included,
it is not feasible to standardize total protein measurement and it is
likely that use of this test will decrease over time.
8. When will the urine albumin test be standardized?
To begin addressing urine albumin measurement and reporting issues,
NIDDK and the International Federation of Clinical Chemistry and
Laboratory Medicine convened a group of international experts in March
2007. They identified the issues associated with the urine albumin
measurement and developed a plan to improve harmonization and
standardization of this test. Several NIDDK-funded studies are underway
addressing a number of issues including urine albumin and creatinine
reference materials, and urine albumin reference measurement procedures.
As a result of these efforts, we expect the urine albumin test to be
standardized in the near future.
References
www.cdc.com
www.who.com