U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
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 the Modification of Diet in Renal Disease (MDRD) Study 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. Providers also may use eGFR to monitor patients already diagnosed with CKD.
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.
Laboratories should program their information systems to use the MDRD Study equation to automatically estimate and report GFR for patients ages 18 and older, when appropriate and feasible.
There are several reasons for using the MDRD Study equation to estimate GFR, including:
The MDRD Study equation is not for all patients. Although an excellent tool for assessing kidney function, eGFR derived from the MDRD Study equation may not be suitable for all populations. MDRD-based estimates of GFR, like all creatinine-based estimates of kidney function (e.g., Cockcroft-Gault, reciprocal of serum creatinine), 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.
Additionally, the equation is not recommended for use with:
Application of the equation to these patient groups may lead to errors in GFR estimation4. GFR estimating equations have poorer agreement with measured GFR for ill hospitalized patients5 and for people with near normal kidney function1 than for the patients in the MDRD Study.
*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.
As noted above, providers should exercise judgment regarding clinical status when presented with an MDRD Study-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 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.
NKDEP recommends using serum creatinine values in mg/dL to two decimal places (e.g., 0.95 mg/dL) OR values in µmol/L to the nearest whole number (e.g., 84 µmol/L) when calculating eGFR using the MDRD Study equation. This practice will reduce rounding errors that may contribute to imprecision in the eGFR value.
The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is a new equation, published in 2009, to estimate glomerular filtration rate (GFR) from serum creatinine, age, sex, and race for adults age ≥ 18 years 1. The National Kidney Disease Education Program has not made a recommendation on general implementation of this equation. The equation is still being validated and, while offering some improvement for eGFR between 60 and 120 mL/min/1.73 m2, it is not clear that implementing CKD-EPI in place of the Modification of Diet in Renal Disease (MDRD) equation would alter clinical detection or management of patients with CKD. However, a laboratory that reports eGFR numeric values > 60 mL/min/1.73 m2 should consider using the CKD-EPI equation. Although the CKD-EPI equation is, on average, more accurate for values > 60 mL/min/1.73 m2 than is the MDRD Study equation, 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.
The equation is based on the same four variables as the MDRD Study equation but 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 µmol/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 | Sex | Serum Creatinine, Scr (mg/dL) |
Equation (age in years for ≥ 18) |
---|---|---|---|
Black | Female | ≤ 0.7 | 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 /κ, 1)α × max(Scr /κ, 1)-1.209 × 0.993Age × 1.018 [if female] × 1.159 [if black] where Scr is serum creatinine in mg/dL, κ is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr /κ or 1, and max indicates the maximum of
Scr /κ or 1.
As shown in the figure below, the CKD-EPI equation was as accurate as the MDRD Study equation in a subgroup with estimated GFR (eGFR) less than 60 mL/min/1.73 m2 and more accurate in a subgroup with eGFR between 60 and 120 mL/min/1.73 m2. However, 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.
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 CKD-EPI 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 marker3, 6. 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 extra-renal 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.
1. 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.
2. 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.
3. 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.
4. 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.
5. Rule AD, Teo BW. GFR estimation in Japan and China: what accounts for the difference? Am J Kidney Dis. 2009;53(6):932-5.
6. 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.
Table 2: CKD EPI Equation for Estimating GFR Expressed for Specified Race, Sex and Serum Creatinine in µmol/L(Adapted from Ann Intern Med 2009;150:604-612, used with permission)
Race | Sex | Serum Creatinine, Scr µmol/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 /κ, 1)κ × max (Scr /κ, 1)-1.209 × 0.993Age × 1.018 [if female] × 1.159 [if black] where Scr is serum creatinine in µmol/L, κ is 61.9 for females and 79.6 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr /κ or 1, and max indicates the maximum of Scr /κ or 1.
Page last updated: February 6, 2013