Estimating Glomerular Filtration Rate

(GFR)
The normal serum creatinine reference interval does not necessarily reflect a normal GFR for a
patient. Because mild and moderate kidney injury is poorly inferred from serum creatinine alone,
NKDEP strongly encourages clinical laboratories to routinely estimate glomerular filtration rate
(GFR) and report the value when serum creatinine is measured for patients 18 and older, when
appropriate and feasible. An estimated GFR (eGFR) calculated from serum creatinine using an
isotope dilution mass spectrometry (IDMS) traceable equation is a simple and effective way in
which laboratories can help health care providers detect CKD among those with risk factors
diabetes, hypertension, cardiovascular disease, or family history of kidney disease. Assessment
of kidney function through eGFR is essential once albuminuria is discovered. Providers also may
use eGFR to monitor patients already diagnosed with CKD.

IDMS Traceable Equations

Laboratories should program their information systems to use an IDMS traceable creatininebased equation to automatically estimate and report GFR for patients ages 18 and older, when
appropriate and feasible.
To reduce interlaboratory variation in creatinine assay calibration and enable more accurate
eGFR results, all major manufacturers have calibrated their serum creatinine measurement
procedures to be traceable to IDMS. Because creatinine results that are calibrated to IDMS may
differ by 5 to 30% compared to uncalibrated results,1 use of a non-IDMS traceable equation with
IDMS calibrated results will yield an inaccurate eGFR. Therefore, all laboratories should use an
IDMS traceable equation when estimating and reporting GFR.
Read more about creatinine standardization.

Selecting an Equation
The Modification of Diet in Renal Disease (MDRD) Study equation and the Chronic Kidney
Disease Epidemiology Collaboration (CKD-EPI) equation are the most widely used IDMS
traceable equations for estimating GFR in patients age 18 and over. For estimating GFR from
serum creatinine in patients under age 18 (including infants, toddlers, children, and teens), the
Bedside Schwartz equation should be used.

Both the MDRD Study and CKD-EPI equations include variables for age, gender, and race,
which may allow providers to observe that CKD is present despite a serum creatinine
concentration that appears to fall within or just above the normal reference interval. Direct
comparison of the MDRD and CKD-EPI equations to other equations such as Cockcroft-Gault2,3
and to creatinine clearance measured from 24-hour urine collections has demonstrated this
superiority.4
Note that creatinine clearance should be considered for assessing kidney function when the
patient's basal creatinine production is very abnormal. This may be the case with patients of
extreme body size or muscle mass (e.g., obese, severely malnourished, amputees, paraplegics, or
other muscle-wasting diseases), or with unusual dietary intake (e.g., vegetarian, creatine
supplements).

The MDRD Equation

The following is the IDMS-traceable MDRD Study equation (for creatinine methods calibrated
to an IDMS reference method)
GFR (mL/min/1.73 m2) = 175 (Scr)-1.154 (Age)-0.203 (0.742 if female) (1.212 if African
American)
The equation does not require weight or height variables because the results are reported
normalized to 1.73 m2 body surface area, which is an accepted average adult surface area.
The equation has been validated extensively in Caucasian and African American populations
between the ages of 18 and 70* with impaired kidney function (eGFR < 60 mL/min/1.73 m2) and
has shown good performance for patients with all common causes of kidney disease.2
*The equation has not been validated in patients older than 70, but an MDRD-derived eGFR may
still be a useful tool for providers caring for patients older than 70.

The CKD-EPI Equation

The CKD-EPI equation uses a 2-slope "spline" to model the relationship between GFR and
serum creatinine, age, sex, and race. The equation is given in the following table for creatinine in
mg/dL (see Appendix for creatinine in mol/L). The equation can be expressed in a single
equation (see table legend) or as a series of equations for different race, sex, and creatinine
conditions (see table rows).
Table 1: CKD EPI Equation for Estimating GFR Expressed for Specified Race, Sex and Serum
Creatinine in mg/dL (From Ann Intern Med 2009;150:604-612, used with permission)

Race
Black

Sex
Female

Serum Creatinine,
Scr (mg/dL)
0.7

Equation (age in years for 18)

GFR = 166 (Scr/0.7)-0.329 (0.993)Age

Black

Female

> 0.7
GFR = 166 (Scr/0.7)-1.209 (0.993)Age

Black

Male

0.9
GFR = 163 (Scr/0.9)-0.411 (0.993)Age

Black

Male

> 0.9
GFR = 163 (Scr/0.9)-1.209 (0.993)Age

White or other

Female

0.7
GFR = 144 (Scr/0.7)-0.329 (0.993)Age

White or other

Female

> 0.7
GFR = 144 (Scr/0.7)-1.209 (0.993)Age

White or other

Male

0.9
GFR = 141 (Scr/0.9)-0.411 (0.993)Age

White or other

Male

> 0.9
GFR = 141 (Scr/0.9)-1.209 (0.993)Age

CKD-EPI equation expressed as a single equation:

GFR = 141 min (Scr /, 1) max(Scr /, 1)-1.209 0.993Age 1.018 [if female] 1.159 [if
black]
where:
Scr is serum creatinine in mg/dL,
is 0.7 for females and 0.9 for males,
is -0.329 for females and -0.411 for males,
min indicates the minimum of Scr / or 1, and
max indicates the maximum of Scr / or 1.
A laboratory that reports eGFR numeric values > 60 mL/min/1.73 m2 should use the CKD-EPI
equation, because the CKD-EPI equation is more accurate for values > 60 mL/min/1.73 m2 than
is the MDRD Study equation. However, the influence of imprecision of creatinine assays on the
uncertainty of an eGFR value is greater at higher eGFR values and should be considered when
determining the highest eGFR value to report.

MDRD and CKD-EPI Equation Performance

As shown in the figure below, the CKD-EPI equation and the MDRD Study equation were
equally accurate in a subgroup with estimated GFR (eGFR) less than 60 mL/min/1.73 m2.
However, the CKD-EPI equation was more accurate in a subgroup with eGFR between 60 and
120 mL/min/1.73 m2. The receiver operator curves (ROC) for detecting GFR categories less than
90, 75, 60, 45, 30 and 15 mL/min per 1.73 m2 did not differ between the CKD-EPI and MDRD
Study equations1, 2.

Figure 1. Accuracy of the CKD-EPI and MDRD equations to estimate GFR for the validation
data set (N=3896). Both panels show the difference between measured and estimated (y-axis) vs.
estimated GFR (x-axis). A smoothed regression line is shown with the 95% CI for the
distribution of results, using quantile regression, excluding the lowest and highest 2.5% of
estimated GFR. From Ann Intern Med 2009;150:604-612, used with permission.

Reduce Rounding Errors

NKDEP recommends using serum creatinine values in mg/dL to two decimal places (e.g., 0.95
mg/dL) OR values in mol/L to the nearest whole number (e.g., 84 mol/L) when calculating
eGFR using the MDRD Study or CKD-EPI equation. This practice will reduce rounding errors
that may contribute to imprecision in the eGFR value.

When Not to Use Creatinine-based Estimating Equations

Creatinine-based estimating equations may not be suitable for all populations. Creatinine-based
estimates of kidney function are only useful when renal function is stable; serum creatinine
values obtained while kidney function is changing will not provide accurate estimates of kidney
function.
Creatinine-based estimating equations are not recommended for use with:

Individuals with unstable creatinine concentrations. This includes pregnant women;

patients with serious co-morbid conditions; and hospitalized patients, particularly those
with acute renal failure. Creatinine-based estimating equations should be used only for
patients with stable creatinine concentrations.

Persons with extremes in muscle mass and diet. This includes, but is not limited to,
individuals who are amputees, paraplegics, bodybuilders, or obese; patients who have a

muscle-wasting disease or a neuromuscular disorder; and those suffering from

malnutrition, eating a vegetarian or low-meat diet, or taking creatine dietary supplements.
Application of the equation to these patient groups may lead to errors in GFR estimation8. GFR
estimating equations have poorer agreement with measured GFR for ill hospitalized
patients9 than for community-dwelling patients.
As noted above, providers should exercise judgment regarding clinical status when presented
with an MDRD Study- or CKD-EPI-derived eGFR for a patient with an unstable creatinine level
or other condition for which the equation is not suitable. Providers may not understand that
estimating equations like the MDRD and CKD-EPI are derived from large populations of
patients and provide the best estimate of mean GFR for a group of people of a certain age, race,
gender, and serum creatinine value. Thus, the reported eGFR is the best estimate of a patient's
GFR; it is not the patient's actual GFR.

Limitations of the CKD-EPI and MDRD Equations

Limitations using creatinine as a filtration marker: both the MDRD study and CKD-EPI
equations are based on serum creatinine. Despite modest reduction in bias with the CKDEPI equation, estimates remain imprecise, with some people showing large differences
between the measured and estimated GFR. Like all other creatinine-based estimation
equations, they suffer from physiologic limitations of creatinine as a filtration marker4, 10.
The terms for age, sex, and race in both equations only capture some of the non-GFR
determinants of creatinine concentration in blood plasma, and the coefficients represent
average effects observed in the population used to develop the equations.
All estimates of GFR based on serum creatinine will be less accurate for patients at the
extremes of muscle mass (including frail elderly, critically ill, or cancer patients), those
with unusual diets, and those with conditions associated with reduced secretion or extrarenal elimination of creatinine. Confirmatory tests with exogenous measured GFR or
measured creatinine clearance should be performed for people in whom estimates based
on serum/plasma/blood creatinine alone may be inaccurate.

Populations not well represented in the development or validation cohorts: Elderly people
and blacks with higher levels of GFR, racial and ethnic minorities other than blacks.

The influence of creatinine measurement imprecision at low creatinine concentrations

(high eGFR) has not been carefully studied but has likely contributed to the variability at
higher eGFR values.

Appendix
Table 2: CKD EPI Equation for Estimating GFR Expressed for Specified Race, Sex and Serum
Creatinine in mol/L(Adapted from Ann Intern Med 2009;150:604-612, used with permission)
Race

Sex

Serum
Creatinine,
Scr mol/L

Equation (age in years for 18)

Black

Female

61.9

GFR = 166 (Scr/61.9)-0.329 (0.993)Age

Black

Female

> 61.9

GFR = 166 (Scr/61.9)-1.209 (0.993)Age

Black

Male

79.6

GFR = 163 (Scr/79.6)-0.411 (0.993)Age

Black

Male

> 79.6

GFR = 163 (Scr/79.6)-1.209 (0.993)Age

White or other

Female

61.9

GFR = 144 (Scr/61.9)-0.329 (0.993)Age

White or other

Female

> 61.9

GFR = 144 (Scr/61.9)-1.209 (0.993)Age

White or other

Male

79.6

GFR = 141 (Scr/79.6)-0.411 (0.993)Age

White or other

Male

> 79.6

GFR = 141 (Scr/79.6)-1.209 (0.993)Age

GFR = 141 min (Scr /, 1) max(Scr /, 1)-1.209 0.993Age 1.018 [if female] 1.159 [if
black]
where:
Scr is serum creatinine in mol/L,
is 61.9 for females and 79.6 for males,

 is -0.329 for females and -0.411 for males,

min indicates the minimum of Scr / or 1,
and max indicates the maximum of Scr / or 1.

References
1

Miller WG, Myers GL, Ashwood ER, et al. Creatinine measurement: state of the art in accuracy
and interlaboratory harmonization. Arch Pathol Lab Med. 2005;129:297-304.
2

Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, 3rd, Feldman HI, et al. A new
equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604-12.
3

Stevens LA, Schmid CH, Zhang YL, Coresh J, Manzi J, Landis R, et al. Development and
validation of GFR-estimating equations using diabetes, transplant and weight. Nephrol Dial
Transplant. 2010;25:449-57.
4

Shemesh O, Golbetz H, Kriss JP, Myers BD. Limitations of creatinine as a filtration marker in
glomerulopathic patients. Kidney Int. 1985;28(5):830-8.
8

Perrone RD, Madias NE, Levey AS. Serum creatinine as an index of renal function: new
insights into old concepts. Clin Chem. 1992;38(10):1933-53.
9

Rule AD, Teo BW. GFR estimation in Japan and China: what accounts for the difference? Am J
Kidney Dis. 2009;53(6):932-5.
10

Rule AD, Bailey KR, Schwartz GL, Khosla S, Lieske JC, Melton LJ, 3rd. For estimating
creatinine clearance measuring muscle mass gives better results than those based on
demographics. Kidney Int. 2009;75(10):1071-8.