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A More Accurate Method To Estimate Glomerular Filtration Rate from Serum Creatinine: A New Prediction Equation

Andrew S. Levey, MD; Juan P. Bosch, MD; Julia Breyer Lewis, MD; Tom Greene, PhD; Nancy Rogers, MS; David Roth, MD, for the Modification of Diet in Renal Disease Study Group*
Ann Intern Med. 1999;130(6):461-470. doi:10.7326/0003-4819-130-6-199903160-00002
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Background: Serum creatinine concentration is widely used as an index of renal function, but this concentration is affected by factors other than glomerular filtration rate (GFR).

Objective: To develop an equation to predict GFR from serum creatinine concentration and other factors.

Design: Cross-sectional study of GFR, creatinine clearance, serum creatinine concentration, and demographic and clinical characteristics in patients with chronic renal disease.

Patients: 1628 patients enrolled in the baseline period of the Modification of Diet in Renal Disease (MDRD) Study, of whom 1070 were randomly selected as the training sample; the remaining 558 patients constituted the validation sample.

Methods: The prediction equation was developed by stepwise regression applied to the training sample. The equation was then tested and compared with other prediction equations in the validation sample.

Results: To simplify prediction of GFR, the equation included only demographic and serum variables. Independent factors associated with a lower GFR included a higher serum creatinine concentration, older age, female sex, nonblack ethnicity, higher serum urea nitrogen levels, and lower serum albumin levels (P < 0.001 for all factors). The multiple regression model explained 90.3% of the variance in the logarithm of GFR in the validation sample. Measured creatinine clearance overestimated GFR by 19%, and creatinine clearance predicted by the Cockcroft-Gault formula overestimated GFR by 16%. After adjustment for this overestimation, the percentage of variance of the logarithm of GFR predicted by measured creatinine clearance or the Cockcroft-Gault formula was 86.6% and 84.2%, respectively.

Conclusion: The equation developed from the MDRD Study provided a more accurate estimate of GFR in our study group than measured creatinine clearance or other commonly used equations.

*For members of the Modification of Diet in Renal Disease Study Group, see N Engl J Med. 1994; 330:877-84.

Figures

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Figure 1.
Relation of serum creatinine concentration to measured glomerular filtration rate (GFR).125crnndashed lines and dotssolid lines and circlescrnnPnnP2−2−2

Each point represents the baseline measurement for one patient during the MDRD Study. Glomerular filtration rate was measured as the renal clearance of I-iothalamate. Serum creatinine concentration (P ) was measured by using a kinetic alkaline picrate assay. Values are shown separately for men ( = 915) and women ( = 586) by ethnicity (white persons [ ] and black persons [ ]). Regression lines were computed from the relation 1/P compared with GFR. Black men ( = 113) have higher serum creatinine values than white men ( = 802) ( < 0.001); black women ( = 84) have higher serum creatinine values than white women ( = 502) ( < 0.001). To convert mL/min per 1.73 m to mL • s • m , multiply by 0.00963. To convert mg/dL to µmol/L, multiply by 88.4.

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Figure 2.
Relation of measured creatinine and urea clearances and transformations of serum creatinine concentration (Pcr) to measured glomerular filtration rate (GFR).n125A.B.C.D.E.crcrcrcrcrcr22−2−2

Each point represents the baseline measurement during the Modification of Diet in Renal Disease Study ( = 1628). Correlations are shown for GFR, measured as the renal clearance of I-iothalamate. Solid lines are lines of identity. Creatinine clearance. Urea clearance. The mean of creatinine and urea clearances. Reciprocal of serum creatinine, ×100. Creatinine clearance estimated by the Cockcroft-Gault formula: C = [(140 − age) × weight]/(P × 72) for men or C = [(140 − age) − weight]/(P × 85) for women, where C is creatinine clearance and is given in mL/min, P is serum creatinine concentration and is given in mg/dL, age is given in years, and weight is given in kg. Estimated creatinine clearance was then adjusted for body surface area and expressed per 1.73 m . To convert mL/min to mL/s, multiply by 0.01667; to convert mL/min per 1.73 m to mL • s • m , multiply by 0.00963; to convert mg/dL to µmol/L, multiply by 88.4.

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Figure 3.
Relation of predicted glomerular filtration rate (GFR) to measured GFR.nTop.Bottom.2−2−2

Each point represents the baseline measurement during the Modification of Diet in Renal Disease (MDRD) Study ( = 1628). Glomerular filtration rate predicted by using MDRD Study equation 6. Glomerular filtration rate predicted by using MDRD Study equation 7. Solid lines are lines of identity. To convert mL/min per 1.73 m to mL • s • m , multiply by 0.00963.

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Figure 4.
Comparison of equations to predict glomerular filtration rate (GFR).R 2 nnR 2 crureacr

The values of indicate the percentage of variance of log GFR accounted for in the validation sample ( = 558) by equations derived from the training sample ( = 1070). The values of 1 − indicate the percentage of variance in log GFR that is unexplained by each equation. C = creatinine clearance; C = urea clearance; P = serum creatinine concentration.

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Comments

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Does eGFR reporting perpetuate racism?
Posted on March 1, 2012
Arkady, Synhavsky, MD
Kidney Specialists of Minnesota, Saint Paul, Minnesota
Conflict of Interest: None Declared

To The Editor: I should not have to know the color of my patient's skin in order to provide good medical care. Statisticians created this rift 13 years ago when attempting to provide "A More Accurate Method To Estimate Glomerular Filtration Rate" (eGFR)1. Now most laboratories report "eGFR African American" and a separate "eGFR non African American".

I believe the eGFR is a useful tool to help explain partial kidney function as a percentage of normal. But "estimated" means just that - it's an estimate. If the serum creatinine goes up, the eGFR goes down, regardless of ethnic background.

I ask all clinicians to stand up against using statistics to perpetuate racial differences. We humans have more in common than uncommon.

Arkady Synhavsky MD Kidney Specialists of Minnesota Saint Paul, MN, USA

References:

1. Andrew S. Levey, Juan P. Bosch, Julia Breyer Lewis, Tom Greene, Nancy Rogers, David Roth, and for the Modification of Diet in Renal Disease Study Group. A More Accurate Method To Estimate Glomerular Filtration Rate from Serum Creatinine: A New Prediction Equation. Ann Intern Med March 16, 1999 130:461-470.

Conflict of Interest:

None declared

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