CKD-EPI vs MDRD: eGFR equations compared
MDRD, CKD-EPI 2009 and CKD-EPI 2021 all estimate glomerular filtration rate (GFR) from serum creatinine, age and sex. They give different numbers for the same blood test, most of all at near-normal kidney function. Here are the three formulas, why CKD-EPI replaced MDRD, what removing race changed, and one patient run through all three.
The three equations at a glance
The MDRD, CKD-EPI 2009 and CKD-EPI 2021 equations each turn a standardized serum creatinine into an estimated GFR in mL/min per 1.73 m², but they were fitted to different people and handle creatinine differently. The 4-variable MDRD Study equation, re-expressed for standardized creatinine assays in 2006, uses a single slope for creatinine and adds terms for female sex and Black race. The CKD-EPI 2009 equation, from Levey and colleagues, splits creatinine into two slopes with a knot at 0.7 mg/dL in women and 0.9 mg/dL in men, so it behaves differently at low and high creatinine; it also kept a race coefficient. The CKD-EPI 2021 equation, from Inker and colleagues, keeps the two-slope shape but was refitted without race, using age and sex only. All three need a creatinine assay traceable to isotope-dilution mass spectrometry (IDMS), the standard most laboratories now use.
MDRD (4-variable, IDMS) = 175 × Scr−1.154 × age−0.203 × 0.742 (if female) × 1.212 (if Black)
CKD-EPI 2009 = 141 × min(Scr/κ, 1)α × max(Scr/κ, 1)−1.209 × 0.993age × 1.018 (if female) × 1.159 (if Black); κ = 0.7 (women), 0.9 (men); α = −0.329 (women), −0.411 (men)
CKD-EPI 2021 = 142 × min(Scr/κ, 1)α × max(Scr/κ, 1)−1.200 × 0.9938age × 1.012 (if female); κ = 0.7 (women), 0.9 (men); α = −0.241 (women), −0.302 (men). Scr = serum creatinine in mg/dL (µmol/L ÷ 88.4).
Where the MDRD equation came from
The MDRD equation came from the Modification of Diet in Renal Disease Study, a trial of people who already had chronic kidney disease. Levey and colleagues published it in the Annals of Internal Medicine in 1999 from 1,628 trial participants, whose GFR was measured by urinary clearance of iothalamate. The first version used six variables, including serum urea nitrogen and albumin; the shorter 4-variable form, with creatinine, age, sex and race only, became the one laboratories reported. In 2006 Levey's group re-expressed it for IDMS-calibrated creatinine, changing the constant to 175, and found 90% of estimates within 30% of measured GFR in the MDRD cohort, whose mean measured GFR was 39.8. The same paper noted the weakness that later drove its replacement: differences between measured and estimated GFR were larger for every equation when estimated GFR was 60 or above, and the study had few patients with a GFR over 90.
Why CKD-EPI 2009 replaced MDRD
CKD-EPI 2009 replaced MDRD because it was more accurate across the whole range, especially at higher GFR, where MDRD systematically underestimates. Levey and colleagues developed it from 8,254 people in 10 studies, including people without kidney disease, and validated it in 3,896 people from 16 other studies. Compared with MDRD, the CKD-EPI equation had less bias (a median difference from measured GFR of 2.5 against 5.5 mL/min/1.73 m²), better precision and greater accuracy, with 84.1% of estimates within 30% of measured GFR against 80.6%. Applied to the US NHANES population, it raised the median eGFR from 85.0 to 94.5 and lowered the estimated prevalence of chronic kidney disease from 13.1% to 11.5%, because fewer healthy people were wrongly placed below 60. The authors concluded it could replace MDRD for routine use, and the KDIGO 2012 chronic kidney disease guideline recommended it for adults.
CKD-EPI 2021 vs 2009: removing race
CKD-EPI 2021 differs from CKD-EPI 2009 mainly by dropping the race coefficient, which had raised eGFR by 15.9% for people identified as Black. Inker and colleagues argued that race is a social, not a biologic, construct and refitted the equation on the same 10 development studies (31.5% Black participants), then tested it in 4,050 people from 12 other studies. In that validation set, the 2009 equation overestimated measured GFR in Black participants by a median of 3.7 mL/min/1.73 m², and simply deleting its race term underestimated it by 7.1. The new creatinine equation without race underestimated GFR in Black participants by 3.6 and overestimated it in non-Black participants by 3.9, with 85% or more of estimates within 30% of measured GFR in both groups. The NKF-ASN task force recommended the 2021 equation for US adults, and the version that adds cystatin C was the most accurate of all.
Worked example: one creatinine, three answers
The three equations disagree most when creatinine is near normal and converge as kidney function falls. Take a 60-year-old woman, not identified as Black, with a creatinine of 0.9 mg/dL (80 µmol/L). MDRD gives about 64 mL/min/1.73 m², CKD-EPI 2009 about 70 and CKD-EPI 2021 about 73: all category G2, but MDRD sits close to the CKD threshold of 60. For a 40-year-old man with a creatinine of 1.0 mg/dL, MDRD gives about 83 (G2) while CKD-EPI 2009 and 2021 give about 94 and 98 (G1), so the category changes with the equation. For a 70-year-old man with a creatinine of 2.0 mg/dL, the three give about 33, 33 and 35, all G3b. This pattern matches the 2009 validation: MDRD underestimates most at higher GFR, so switching equations reclassifies many people near 60 and above, and very few with advanced disease.
| Patient | MDRD | CKD-EPI 2009 | CKD-EPI 2021 |
|---|---|---|---|
| Woman, 60, Scr 0.9 mg/dL | 64 (G2) | 70 (G2) | 73 (G2) |
| Man, 40, Scr 1.0 mg/dL | 83 (G2) | 94 (G1) | 98 (G1) |
| Man, 70, Scr 2.0 mg/dL | 33 (G3b) | 33 (G3b) | 35 (G3b) |
Values are in mL/min/1.73 m², rounded, for people not identified as Black. Check any of them in the CKD-EPI 2021 eGFR calculator.
Questions
Which eGFR equation should I use now?
In the United States, the NKF-ASN task force recommends CKD-EPI 2021 for adults, and KDIGO 2024 recommends a validated creatinine equation, adding cystatin C when a more accurate estimate is needed. MDRD is no longer the equation either recommends.
Why does MDRD give a lower eGFR than CKD-EPI?
MDRD was fitted only to people with chronic kidney disease, with a mean measured GFR near 40, and uses one creatinine slope. In people with near-normal function it underestimates GFR, which is the bias CKD-EPI 2009 reduced from a median of 5.5 to 2.5 mL/min/1.73 m².
Is Cockcroft-Gault the same kind of equation?
No. Cockcroft-Gault estimates creatinine clearance in mL/min from creatinine, age, weight and sex, and it is not indexed to body surface area. In the 1999 MDRD analysis, predicted creatinine clearance by Cockcroft-Gault overestimated measured GFR by 16%.
Do these equations work in acute kidney injury?
No. All three assume creatinine is stable. While creatinine is rising or falling, none of them reflects the true GFR. Creatinine also feeds other scores, such as the MELD score in liver disease.
Can AskMed explain an eGFR result with sources?
Yes. AskMed answers with a citation after every claim, from journals and guidelines such as KDIGO, so you can check what a guideline says about each stage. It is on the App Store and Google Play, or use it on the web. Low albumin in kidney disease also affects calcium, covered by the corrected calcium calculator.
Sources
- Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med. 1999;130(6):461–470. doi:10.7326/0003-4819-130-6-199903160-00002
- Levey AS, Coresh J, Greene T, et al. Using standardized serum creatinine values in the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate. Ann Intern Med. 2006;145(4):247–254. doi:10.7326/0003-4819-145-4-200608150-00004
- Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604–612. doi:10.7326/0003-4819-150-9-200905050-00006
- Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Chapter 1: Definition and classification of CKD. Kidney Int Suppl. 2013;3(1):19–62. doi:10.1038/kisup.2012.64
- Inker LA, Eneanya ND, Coresh J, et al. New creatinine- and cystatin C–based equations to estimate GFR without race. N Engl J Med. 2021;385(19):1737–1749. doi:10.1056/NEJMoa2102953
- Delgado C, Baweja M, Crews DC, et al. A unifying approach for GFR estimation: recommendations of the NKF-ASN Task Force on reassessing the inclusion of race in diagnosing kidney disease. Am J Kidney Dis. 2022;79(2):268–288. doi:10.1053/j.ajkd.2021.08.003
- Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 2024;105(4S):S117–S314. doi:10.1016/j.kint.2023.10.018
