# Frequently Asked Questions

Recommended eGFR equations will be changing. Once guidance is adopted, we will update this content accordingly.

## 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 m2). 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 m2.

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 m2.

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 m2) 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 m2) 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 III4

Age (Years) Mean eGFR*
20-29 116 mL/min/1.73 m2
30-39 107 mL/min/1.73 m2
40-49 99 mL/min/1.73 m2
50-59 93 mL/min/1.73 m2
60-69 85 mL/min/1.73 m2
70+ 75 mL/min/1.73 m2

*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.

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.