Performance of the Cockcroft-Gault, MDRD, and New CKD-

EPI Formulas in Relation to GFR, Age, and Body Size

Wieneke Marleen Michels,*† Diana Carina Grootendorst,† Marion Verduijn,†
Elise Grace Elliott,† Friedo Wilhelm Dekker,† and Raymond Theodorus Krediet*
*Division of Nephrology, Department of Medicine, Academic Medical Center, University of Amsterdam, Amsterdam,
The Netherlands; and †Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands

Background and objectives: We compared the estimations of Cockcroft-Gault, Modification of Diet in Renal Disease
(MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations to a gold standard GFR measure-
ment using 125I-iothalamate, within strata of GFR, gender, age, body weight, and body mass index (BMI).
Design, setting, participants, & measurements: For people who previously underwent a GFR measurement, bias, precision,
and accuracies between measured and estimated kidney functions were calculated within strata of the variables. The relation
between the absolute bias and the variables was tested with linear regression analysis.
Results: Overall (n ⴝ 271, 44% male, mean measured GFR 72.6 ml/min per 1.73 m2 [SD 30.4 ml/min per 1.73 m2]), mean bias
was smallest for MDRD (P < 0.01). CKD-EPI had highest accuracy (P < 0.01 compared with Cockcroft-Gault), which did not
differ from MDRD (P ⴝ 0.14). The absolute bias of all formulas was related to age. For MDRD and CKD-EPI, absolute bias
was also related to the GFR; for Cockcroft-Gault, it was related to body weight and BMI as well. In all extreme subgroups,
MDRD and CKD-EPI provided highest accuracies.
Conclusions: The absolute bias of all formulas is influenced by age; CKD-EPI and MDRD are also influenced by GFR.
Cockcroft-Gault is additionally influenced by body weight and BMI. In general, CKD-EPI gives the best estimation of GFR,
although its accuracy is close to that of the MDRD.
Clin J Am Soc Nephrol 5: 1003–1009, 2010. doi: 10.2215/CJN.06870909

W
ith the increasing incidence of kidney dysfunction,
the use of formulas to estimate kidney function is
implemented more frequently in clinical practice
(1). The most frequently used formulas are the Cockcroft-Gault
and (abbreviated) Modification of Diet in Renal Disease
(MDRD) equations (2). The Cockcroft-Gault equation estimates
clearance of creatinine (3), whereas the MDRD estimates GFR
(2). At present, for subgroups of people who are old, under-
weight, or overweight, no clear-cut advice exists regarding
which formula is best used for optimal estimation of kidney
function. Both Cockcroft-Gault and abbreviated MDRD have
been compared in the same population against a gold standard
method for estimating GFR (4 – 8). These studies show conflict-
ing results because of different study populations, different
gold standard GFR measurements, and differences in creatinine
assay calibration (9). Furthermore, the recently developed
Chronic Kidney Disease Epidemiology Collaboration (CKD-
EPI) formula has not been validated yet, outside pf the original
publication (10); therefore, a pragmatic study to evaluate the
most often used formulas, in a study population in which a
GFR measurement is requested, is needed. Furthermore, these
Received September 28, 2009. Accepted February 15, 2010.
Published online ahead of print. Publication date available at www.cjasn.org.
Correspondence: Dr. Wieneke Marleen Michels, Academic Medical Center, Di-
vision of Nephrology, P.O. Box 22660, 1100 DD Amsterdam, Netherlands. Phone:
⫹31-20-566-6139; Fax: ⫹31-20-566-9588; E-mail: w.m.michels@amc.uva.nl
formulas need to be compared with an excellent gold standard
GFR measurement.
In our center, GFR is measured by a method that can be
considered the gold standard in the absence of bladder cathe-
terization, for clinical reasons with a continuous infusion of
125
I-iothalamate (11–13). 131I-hippuran is added to correct for
inaccurate urine collections without using a bladder catheter to
optimize GFR measurement further (13). The aim of this study
was to assess the agreement between kidney function as esti-
mated by the Cockcroft-Gault, MDRD, and CKD-EPI equations
and the GFR as measured by a gold standard method using
125
I-iothalamate. To examine whether the agreement is influ-
enced by the level of GFR, gender, age, body weight, and body
mass index (BMI), we also analyzed the agreement within
clinically relevant strata of these variables.
Materials and Methods
In this cross-sectional study, we used data from potential kidney
donors and adult patients who underwent a GFR measurement with
125
I-iothalamate for clinical reasons between January 1, 2003, and Jan-
uary 1, 2007, at the Academic Medical Center in Amsterdam. To be
included, the measured GFR had to be at least 15 ml/min, and body
weight, height, and plasma creatinine level had to be available from the
patients’ record within 3 months of the GFR measurement. For patients
with multiple GFR measurements, the last available measurement was
used. The data collection was approved by the committee of medical
ethics of the Academic Medical Center.

Copyright © 2010 by the American Society of Nephrology ISSN: 1555-9041/506 –1003

1004 Clinical Journal of the American Society of Nephrology
Measurements
GFR was measured with 125I-iothalamate in patients in steady state,
whereas the effective renal plasma flow was measured with 131I-hippuran
simultaneously to correct for inaccurate urine collections. This procedure
was described previously as the standard method by Donker et al. (12) and
our group (13). The measurements started in the morning. After the
patients were seated, a blood sample was drawn. Then they received a
loading dose of 125I-iothalamate and 131I-hippuran, followed by a contin-
uous infusion of both tracers. The first 2 hours were used as an equilibra-
tion period; two clearance periods of 2 hours each followed. Patients drank
at least 200 ml/h water during the measurements to maintain sufficient
urine flow. At 2, 4, and 6 hours after the start of the infusion, urine samples
were collected by spontaneous voiding and plasma samples were drawn.
Plasma creatinine was determined with an isotope dilution mass spec-
trometry-validated enzymatic assay on an automated analyzer (Hitachi
H911; Boehringer Mannheim, Mannheim, Germany).
For comparison with renal estimates of the formulas, the measured
GFR was normalized to 1.73 m2 of the body surface area (BSA) by
multiplying the measured GFR by 1.73/BSA. The BSA was calculated
according to Du Bois and Du Bois (14): BSA ⫽ (body weight0.425 [in kg]
⫻ height0.725 [in cm]) ⫻ 0.007184.
Prediction Formulas
The prediction of creatinine clearance (in ml/min) by the Cockcroft-
Gault formula (3) was calculated as (140 ⫺ age) ⫻ body weight/plasma
creatinine ⫻ 72 (⫻ 0.85 if female). For comparison with the prediction
of other formulas, the predicted creatinine clearance by Cockcroft-
Gault was normalized per 1.73 m2 of BSA using the formula of Du Bois
and Du Bois (14) identical to the normalization of the GFR measure-
ment.
The abbreviated MDRD estimate (2) of kidney function was calcu-
lated as 175 ⫻ plasma creatinine⫺1.154 ⫻ age⫺0.203 (⫻ 0.742 if female; ⫻
1.21 if black). The CKD-EPI estimate (10) of renal function was calcu-
lated as recommended: For women with a plasma creatinine ⱕ0.7,
(plasma creatinine/0.7)⫺0.329 ⫻ (0.993)age (⫻ 166 if black; ⫻ 144 if white
or other); for women with a plasma creatinine ⬎0.7, (plasma creati-
nine/0.7)⫺1.209 ⫻ (0.993)age (⫻ 166 if black; ⫻ 144 if white or other); for
men with a plasma creatinine ⱕ0.9; (plasma creatinine/0.9)⫺0.411 ⫻
(0.993)age (⫻ 163 if black; ⫻ 141 if white or other); for men with a
plasma creatinine ⬎0.9, (plasma creatinine/0.9)⫺1.209 ⫻ (0.993)age (⫻
166 if black; ⫻ 144 if white or other).
The estimated renal functions using the (abbreviated) MDRD and the
CKD-EPI equations are expressed as GFR in ml/min per 1.73 m2. Age
was expressed in years, body weight in kg, and plasma creatinine in
mg/dl.
Statistical Analysis
Numbers are presented as means and SD. Relations between various
parameters were tested using linear regression. Differences between
genders were tested with the t test. All statistical analyses were per-
formed in SPSS 16.0 for Windows (SPSS, Chicago, IL).
To compare the performance of the formulas, we calculated bias,
precision, and accuracy as recommended (15). Bias was defined as the
mean difference between estimated and measured kidney function,
whereas precision was expressed as the SD of this difference. To define
the best formula, we used the accuracy, because it is a combination of
bias and precision. Accuracy was calculated as the percentage of pa-
tients who had an estimated kidney function within 30% limits of the
measured GFR. Differences in bias and accuracy between the formulas
were tested with a paired t test or McNemar test, respectively.
Bias, precision, and accuracies were also calculated within strata of
Clin J Am Soc Nephrol 5: 1003–1009, 2010
measured GFR, gender, age, body weight, and BMI because these
variables might influence the performance of the equations. Stratifica-
tion of measured GFR was based on the stages of chronic kidney
disease (CKD) (15). Clinical cutoffs were used for age (18 to 39, 40 to 59,
and ⱖ60 years) and body weight (ⱕ59, 60 to 79, 80 to 99, and ⱖ100 kg).
BMI was calculated as body weight divided by the square of height,
with body weight expressed in kg and height in meters. Stratification
for BMI was performed according to World Health Organization guide-
lines (16,17): ⱕ18.5, 18.5 to 24.9, 25.0 to 29.9, or ⱖ30.0 kg/m2.
Furthermore, we studied the relation between the GFR and measure-
ment error by applying the method as proposed by Bland and Altman
(18). We assessed the bias as well as the limits of agreement, which
were calculated as the bias plus or minus two times the precision.
Because our GFR measurements are far more likely to be closer to the
real GFR than the predicted estimates by the formulas, we used the
measured GFR on the x axes instead of the mean of both methods.
We tested the influence of the previously mentioned variables on the
bias of the formulas by analyzing the relation between the variables and
the magnitude of the absolute bias with univariate linear regression
models. We used the absolute bias instead of the crude bias for this
analysis because the crude bias can have positive and negative values,
which complicates the interpretation of a linear regression on the crude
bias.
Finally, patients were classified into stages of CKD according to level of
measured GFR, as well as on the basis of the estimates of the Cockcroft-
Gault, MDRD, and CKD-EPI formulas. Agreement between the measured
GFR and the estimates of the formulas in their classification of patients into
CKD stages was assessed by calculating Cohen’s ␬.
Results
In total, 685 GFR measurements were performed. After ex-
clusion of measurements in children (n ⫽ 32); those without an
available plasma creatinine level (n ⫽ 38), valid GFR (n ⫽ 2),
body weight (n ⫽ 1), or height (n ⫽ 178); those with a GFR ⬍15
ml/min (n ⫽ 4); and duplicate cases (n ⫽ 159), 271 patients
remained eligible for inclusion. Patient characteristics are pre-
sented in Table 1.
The overall mean bias was smallest for MDRD (P ⬍ 0.01;
Figure 1). CKD-EPI had the highest accuracy (P ⬍ 0.01 com-
Table 1. Characteristics of study population
Value
Characteristic
(N ⫽ 271)
Male gender (n 关%兴) 118 (44)
Age (years; mean ⫾ SD) 44.3 ⫾ 14.5
Body weight (kg; mean ⫾ SD) 75.8 ⫾ 17.3
Height (cm; mean ⫾ SD) 171.3 ⫾ 9.4
BMI (kg/m2; mean ⫾ SD) 25.8 ⫾ 5.5
BSA (m2; mean ⫾ SD) 1.9 ⫾ 0.2
Black race (n 关%兴) 28 (12)
Plasma creatinine (mg/dl; mean 1.2 ⫾ 0.6
⫾ SD)
Measured GFR (ml/min; mean ⫾ 78.2 ⫾ 33.4
SD)
Measured GFR corrected for BSA 72.6 ⫾ 30.4
(ml/min per 1.73 m2; mean ⫾
SD)
Clin J Am Soc Nephrol 5: 1003–1009, 2010 Performance of Formulas to Estimate Kidney Function 1005

Figure 1. Bland-Altman figures of the estimated and measured kidney function. Bland-Altman plots—the difference between the
estimated and measured renal function—is plotted against the measured GFR; therefore, a positive difference suggests an
overestimation by the formula, whereas a negative difference suggests an underestimation. The dashed lines represent the mean
difference between estimated and measured GFR; the solid lines represent the lines of agreement, calculated as mean difference
plus or minus two times the SD of this difference.

pared with Cockcroft-Gault), although it was not statistically Influence of Gender

significantly different from MDRD (P ⫽ 0.14; Table 2).
Classification of patients according to measured and esti-
mated kidney function for stages of CKD is presented in Table
3. Using Cockcroft-Gault, 63% of the patients were classified
correctly. In 29%, Cockcroft-Gault underestimated kidney func-
tion, and in 8% it overestimated (Cohen’s ␬ ⫽ 0.47). The MDRD
equation classified 65% of the patients correctly, in 15% of the
patients the GFR was underestimated, and in 20% it was over-
estimated (Cohen’s ␬ ⫽ 0.51). CKD-EPI classified most patients
correctly (69%). It underestimated GFR in 23% and overesti-
mated GFR in 8% of the patients (Cohen’s ␬ ⫽ 0.56).
Influence of GFR
Patients with a higher GFR were younger and had a lower
body weight and a lower BMI. Each 1-ml/min per 1.73 m2
higher GFR corresponded to a younger age of ⫺0.20 years (95%
confidence interval [CI] ⫺0.25 to ⫺0.15 years), to a lower body
weight of ⫺0.07 kg (95% CI ⫺0.14 to ⫺0.01 kg), and to a lower
BMI of ⫺0.03 kg/m2 (95% CI ⫺0.05 to ⫺0.01 kg/m2).
The absolute bias of MDRD and CKD-EPI was larger in
patients with a higher GFR (Table 4). Mean bias and precision
of the formulas in subgroups of GFR are presented in Figure 2.
The CKD-EPI provided the highest accuracy in patients with a
GFR in stage 1 CKD (92.7%); however, it did not differ statis-
tically from the accuracy of Cockcroft-Gault (87.8%; P ⫽ 0.29) or
MDRD (89.0%; P ⫽ 0.51). In the group with the lowest GFR,
MDRD had the highest accuracy, although it was close to the
accuracy of CKD-EPI (P ⫽ 0.63, compared with Cockcroft-Gault
P ⫽ 0.04).
Compared with men, women had a lower body weight; men
83 kg (SD 14 kg), women 71 kg (SD 18 kg; P ⬍ 0.01). The
absolute bias of MDRD was larger in woman than in men
(Table 4). For both genders, mean bias and precision are pre-
sented in Figure 2. In men, the highest accuracy was reached by
MDRD (86.4%), whereas in women, CKD-EPI had the highest
accuracy (84.3%). These accuracies were higher than those of
Cockcroft-Gault (men 76.3%, women 72.5%; P ⱕ 0.01), but
MDRD and CKD-EPI did not differ from each other (CKD-EPI
in men 84.7% [P ⫽ 0.69]; MDRD in women 77.1% [P ⫽ 0.31]).
Influence of Age
Elderly patients had a lower GFR, a higher body weight, and
a higher BMI. Each additional year of age corresponded to a
lower GFR of ⫺0.87 ml/min per 1.73 m2 (95% CI ⫺1.10 to ⫺0.64
ml/min per 1.73 m2), a higher body weight of 0.18 kg (0.04 to
0.32 kg), and a higher BMI of 0.08 kg/m2 (0.03 to 0.12 kg/m2).
All formulas had a smaller absolute bias in patients with a
higher age (Table 4). Figure 2 presents mean bias and precision
for subgroups of age. The accuracies of the MDRD and the
CKD-EPI equations were similar in youngest and oldest sub-
groups (82.6% for the youngest and 81.8% for the oldest group).
Both differed from the Cockcroft-Gault formula (69.7%; P ⱕ
0.01) in the youngest group but not in the oldest group (75.0%;
P ⫽ 0.45).
Influence of Body Weight and BMI
Furthermore, patients with a higher body weight had a lower
GFR, were older, and had a higher BMI. Each 1-kg higher body

Table 2. Comparison of the estimation of the formulas to the gold standard GFR
Mean Overall Mean Absolute Accuracy
Parameter Overall Bias Precision Absolute Bias Precision within 30% (%)

Cockcroft-Gault 9.9 19.2 15.3 15.2 74.2

MDRD 0.8a 24.7 14.6 19.9 81.2
CKD-EPI 4.5 16.7 12.3a 12.1 84.5b
See the Materials and Methods section for definitions of (absolute) bias, precision, and accuracy.
a
P ⱕ 0.01 versus both other formulas.
b
P ⬍ 0.01 versus Cockcroft-Gault, P ⫽ 0.14 versus MDRD.
1006 Clinical Journal of the American Society of Nephrology Clin J Am Soc Nephrol 5: 1003–1009, 2010

Table 3. Cohen’s ␬ table, comparison of classification of patients in stages of CKD according to measured and
estimated GFR by the formulas
Measured GFR (ml/min per 1.73 m2)
Estimated GFR
ⱖ90 60 to 89 30 to 59 15 to 29 Total

Cockcroft-Gault (ml/min per 1.73 m2; Cohen’s

␬ ⫽ 0.47)
ⱖ90 70 33 6 0 109
60 to 89 12 50 24 0 86
30 to 59 0 10 39 16 65
15 to 29 0 0 0 11 11
MDRD (ml/min per 1.73 m2; Cohen’s ␬ ⫽ 0.51)
ⱖ90 53 13 7 0 73
60 to 89 28 59 12 0 99
30 to 59 1 21 47 10 79
15 to 29 0 0 3 17 20
CKD-EPI (ml/min per 1.73 m2; Cohen’s ␬ ⫽ 0.56)
ⱖ90 73 30 6 0 109
60 to 89 9 50 17 0 76
30 to 59 0 13 45 9 67
15 to 29 0 0 1 18 19
Total 82 93 69 27 271
The bold numbers indicate the number of patients classified to the same CKD stage according to both compared methods.

Table 4. Influence of GFR, age, body weight, BMI, and gender on the absolute bias
Parameter Cockcroft-Gault MDRD CKD-EPI

GFR (ml/min per 1.73 m2) 0.030 (⫺0.030 to 0.090) 0.150 (0.070 to 0.220) 0.050 (0.004 to 0.100)
Age (years) ⫺0.26 (⫺0.38 to ⫺0.14) ⫺0.27 (⫺0.43 to ⫺0.11) ⫺0.17 (⫺0.27 to ⫺0.07)
Body weight (kg) 0.140 (0.040 to 0.25) ⫺0.130 (⫺0.270 to 0.004) ⫺0.090 (⫺0.170 to 0.003)
BMI (kg/m2) 0.55 (0.23 to 0.88) ⫺0.14 (⫺0.57 to 0.29) ⫺0.21 (⫺0.47 to 0.05)
Female gender 3.57 (⫺0.09 to 7.23) 7.77 (3.06 to 12.47) 2.19 (⫺0.72 to 5.10)
The numbers represent the change of the absolute bias in ml/min per 1.73 m2 for an increase per unit of the given variables
(␤ values) and their accompanying 95% CIs. One unit of GFR represents 1 ml/min per 1.73 m2; for age, one unit represents 1
year; for body weight, one unit represents 1 kg; for BMI, one unit represents 1 kg/m2; and for gender one unit represents
being a woman compared with being a man.

weight corresponded to a ⫺0.23-ml/min per 1.73 m2 (95% CI
⫺0.44 to ⫺0.02 ml/min per 1.73 m2) lower GFR, a 0.13-year
(0.03 to 0.23 year) older age, and a 0.28-kg/m2 (0.26 to 0.30
kg/m2) higher BMI.
Patients with a higher BMI were older and had a higher body
weight and a lower GFR. Each 1-kg/m2 higher BMI corresponded
to a 0.53-year (95% CI 0.23 to 0.84 year) older age, 2.71-kg (2.53 to
2.90 kg) higher body weight, and a ⫺0.81-ml/min per 1.73 m2
(⫺1.46 to ⫺0.161 ml/min per 1.73 m2) lower GFR.
The absolute bias of Cockcroft-Gault was greater in patients
with a higher body weight or BMI (Table 4). In the subgroup
with lowest body weight, Cockcroft-Gault and CKD-EPI had a
similar accuracy (71.4%), almost the same as that of MDRD
(69.0%; P ⫽ 1.00). MDRD provided greatest accuracy (97.0%) in
those with the highest body weight. This was different from the
Cockcroft-Gault (57.1%; P ⫽ 0.02) but not from CKD-EPI
(87.0%; P ⫽ 1.00).
The mean bias and precisions of the formulas per subgroup of
BMI are presented in Figure 2. For patients who were under-
weight, Cockcroft-Gault had the greatest accuracy (80.0%). This
was not statistically different from the accuracy of MDRD or
CKD-EPI (66.7 and 60.0%, respectively; P ⱖ 0.25). In the most
overweight patients, accuracy was highest using CKD-EPI
(85.7%), which differed from the accuracy of Cockcroft-Gault
(57.1%; P ⬍ 0.01) but was close to that of MDRD (77.6%; P ⫽
0.29).
Discussion
This pragmatic study comparing the Cockcroft-Gault,
MDRD, and CKD-EPI formulas in a clinical setting showed that
overall mean bias was smallest for MDRD. The highest accu-
racy, however, was reached with CKD-EPI and MDRD. As
expected, CKD-EPI estimated GFR closest to the directly mea-
sured GFR in patients with a GFR of ⱖ90 ml/min per 1.73 m2,
Clin J Am Soc Nephrol 5: 1003–1009, 2010
Figure 2. Comparison of the bias and precisions over subgroups. Mean bias and precision between estimated and measured GFR
for to various strata of GFR, gender, age, and BMI. The mean bias was calculated as the mean of the differences between the
estimated and measured GFR per subgroup, whereas the precision was the SD of this difference.
whereas MDRD remained best when GFR ranged from 15 to 29
ml/min per 1.73 m2. Differences in accuracy between MDRD
and CKD-EPI, however, were small and not statistically signif-
icant. Our finding that the CKD-EPI formula gave the best
overall accuracy and agreement after classification in sub-
groups of GFR is in line with the original publication on this
formula (10). The present data add that the performance of the
CKD-EPI formula is dependent on age and GFR.
The graphs show that the relation between mean biases of the
formulas over subgroups of GFR was not linear. Mean bias was
largest in those with a GFR in stage 3 CKD. Most studies
showed a larger bias in stage 2 than in stage 3 CKD for Cock-
croft-Gault or MDRD (6,7,19,20), which is in contrast to our
findings. The relatively small number of patients in the sub-
groups in our study as well as in some of the aforementioned
studies (7,19) could be an explanation for this difference; how-
ever, studying the accuracies over the subgroups, all formulas
showed a pattern in which the accuracies became smaller per
GFR subgroup, which is in line with others (6,20). Furthermore,
the regression analysis that was based on the absolute bias per
patient did show a linear relation between the GFR and the
absolute bias.
In this study, we found no significant differences in accura-
cies between MDRD and CKD-EPI formulas within subgroups.
It could be that the number of patients within subgroups was
too small to detect these differences; however, most subgroups
were large enough to measure a difference of the MDRD and
CKD-EPI formulas to Cockcroft-Gault. This makes it more
likely that the accuracy of MDRD and CKD-EPI are indeed
highly in line with each other; however, in the elderly and in
Performance of Formulas to Estimate Kidney Function 1007
those with a low body weight or BMI, Cockcroft-Gault remains
a good alternative. Our finding that the MDRD or the CKD-EPI
formula seems to be the best option for young patients is in
agreement with the results of Donadio et al. (5). Using these
formulas in the elderly is also supported by others (8,21),
although not by all (5,22). This difference might be caused by
small differences in bias and precision between the formulas in
the elderly, because all formulas had smaller absolute biases in
these subjects. For Cockcroft-Gault, a relation between its bias
and age has been shown before (5,8,22).
The influence of body composition on the performance of the
formulas can be assessed by studying the influence of body
mass or BMI. Our results showed that the absolute bias of
Cockcroft-Gault was dependent on both of these parameters.
For the CKD-EPI and MDRD formulas, this relation was not
statistically significant; however, the regression analysis did
show point estimates suggesting a smaller absolute bias in
patients with a higher body weight or BMI. The relation of the
absolute bias with body weight and BMI is surprising given
their normalization for BSA. In line with our results, others also
found the estimation of Cockcroft-Gault to be more dependent
on body weight or BMI than MDRD (8,19,20). The influence of
BMI on the bias of Cockcroft-Gault has been described before
(5,23), although not all studies found this relationship (6,21).
This study has its limitations. Ideally, we would have mea-
sured the plasma creatinine on the same day the GFR measure-
ment was performed in all patients. A plasma creatinine mea-
surement on the same day as the GFR measurement was
available for 48 (18%) patients, because of the retrospective data
collection; however, a sensitivity analysis of patients with an
1008 Clinical Journal of the American Society of Nephrology
available plasma creatinine value within 14 days of the GFR
measurement (n ⫽ 204 [75%]) did not change our conclusions
(data not shown). Furthermore, the stable state of the patients
was judged by the clinician who requested the GFR measure-
ment. For 144 (53%) subjects, a previous plasma creatinine
value was available within 3 months of the GFR measurement
(mean 1.24 mg/dl; SD 0.65 mg/dl). The difference between this
plasma creatinine and the one used in our study was 0.002
mg/dl (SD 0.18 mg/dl). Given the small differences between
the previous plasma creatinine and the used one, we conclude
that indeed only stable patients were selected. Another limita-
tion of this study is the relatively limited numbers of patients in
the subgroups. This was mainly due to the absence of data on
height. We needed this parameter for the normalization of
Cockcroft-Gault and measured GFR for BSA to make a valid
comparison, because MDRD and CKD-EPI are expressed that
way; however, we were able to include a relevant number of
patients, sufficient to allow stratification. Some of the studied
parameters were correlated, such as age and GFR. We chose not
to correct our findings for these influences because this de-
scribes clinical practice in which age and GFR are also corre-
lated.
A strong feature of this study is that we were able to compare
both the two most frequently used and the newest equations to
estimate kidney function in one heterogeneous cohort against
an excellent gold standard method to measure GFR (13). We
were able to study the influence of measured GFR, gender, age,
body weight, and BMI on the performance of the formulas by
stratification on these parameters.
In conclusion, the absolute bias of all formulas is influenced
by age. The CKD-EPI and MDRD formulas are also influenced
by GFR, and the Cockcroft-Gault equation is additionally in-
fluenced by body weight and BMI. In general, CKD-EPI gives
the best estimation of GFR, although the performance is close to
that of MDRD.
Acknowledgments
M. Langedijk, N. Glas, N. Scheper, and S. Duis are acknowledged for
the performance of the GFR determinations. Dr. J. Korevaar and Dr.
M.M. Zweers commented on a previous version of the manuscript.
Disclosures
None.
References
1. Fawaz A, Badr KF: Measuring filtration function in clinical
practice. Curr Opin Nephrol Hypertens 15: 643– 647, 2006
2. Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL,
Hendriksen S, Kusek JW, Van Lente F: Using standardized
serum creatinine values in the Modification of Diet in
Renal Disease study equation for estimating glomerular
filtration rate. Ann Intern Med 145: 247–254, 2006
3. Cockcroft DW, Gault MH: Prediction of creatinine clear-
ance from serum creatinine. Nephron 16: 31– 41, 1976
4. Boudville N, Salama M, Jeffrey GP, Ferrari P: The inaccu-
racy of cystatin C and creatinine-based equations in pre-
Clin J Am Soc Nephrol 5: 1003–1009, 2010
dicting GFR in orthotopic liver transplant recipients. Neph-
rol Dial Transplant 24: 2926 –2930, 2009
5. Donadio C, Consani C, Ardini M, Caprio F, Grassi G,
Lucchesi A: Prediction of glomerular filtration rate from
body cell mass and plasma creatinine. Curr Drug Discov
Technol 1: 221–228, 2004
6. Froissart M, Rossert J, Jacquot C, Paillard M, Houillier P:
Predictive performance of the Modification of Diet in Renal
Disease and Cockcroft-Gault equations for estimating renal
function. J Am Soc Nephrol 16: 763–773, 2005
7. Rigalleau V, Lasseur C, Perlemoine C, Barthe N, Raffaitin
C, Chauveau P, Combe C, Gin H: Cockcroft-Gault formula
is biased by body weight in diabetic patients with renal
impairment. Metabolism 55: 108 –112, 2006
8. Verhave JC, Fesler P, Ribstein J, du Cailar G, Mimran A:
Estimation of renal function in subjects with normal serum
creatinine levels: Influence of age and body mass index.
Am J Kidney Dis 46: 233–241, 2005
9. White CA, Huang D, Akbari A, Garland J, Knoll GA:
Performance of creatinine-based estimates of GFR in kid-
ney transplant recipients: A systematic review. Am J Kidney
Dis 51: 1005–1015, 2008
10. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF
3rd, Feldman HI, Kusek JW, Eggers P, Van LF, Greene T,
Coresh J: A new equation to estimate glomerular filtration
rate. Ann Intern Med 150: 604 – 612, 2009
11. Apperloo AJ, de Zeeuw D, Donker AJ, de Jong PE: Preci-
sion of glomerular filtration rate determinations for long-
term slope calculations is improved by simultaneous infu-
sion of 125I-iothalamate and 131I-hippuran. J Am Soc
Nephrol 7: 567–572, 1996
12. Donker AJ, van der Hem GK, Sluiter WJ, Beekhuis H: A
radioisotope method for simultaneous determination of
the glomerular filtration rate and the effective renal plasma
flow. Neth J Med 20: 97–103, 1977
13. Michels WM, Grootendorst DC, Rozemeijer K, Dekker FW,
Krediet RT: Glomerular filtration rate measurements by
(125)I-iothalamate should be corrected for inaccurate urine
collections with (131)I-hippuran. Clin Nephrol 72: 337–343,
2009
14. Du Bois D, Du Bois EF: A formula to estimate the approx-
imate surface area if height and weight are known. Arch
Intern Med 17: 863– 871, 1917
15. National Kidney Foundation: K/DOQI clinical practice
guidelines for chronic kidney disease: Evaluation, classifi-
cation, and stratification: Am J Kidney Dis 39[Suppl 1]:
S1–S266, 2002
16. Clinical guidelines on the identification, evaluation, and
treatment of overweight and obesity in adults: The evi-
dence report. National Institutes of Health [published er-
ratum appears in Obes Res 6: 464, 1998]. Obes Res 6[Suppl
2]: 51S–209S, 1998
17. Obesity: Preventing and managing the global epidemic.
Report of a WHO consultation: World Health Organ Tech
Rep Ser 894: i–xii, 1–253, 2000
18. Bland JM, Altman DG: Statistical methods for assessing
agreement between two methods of clinical measurement.
Lancet 1: 307–310, 1986
19. Poggio ED, Wang X, Weinstein DM, Issa N, Dennis VW,
Braun WE, Hall PM: Assessing glomerular filtration rate
by estimation equations in kidney transplant recipients.
Am J Transplant 6: 100 –108, 2006
Clin J Am Soc Nephrol 5: 1003–1009, 2010 Performance of Formulas to Estimate Kidney Function 1009

20. Poggio ED, Wang X, Greene T, Van LF, Hall PM: Perfor-
mance of the Modification of Diet in Renal Disease and
Cockcroft-Gault equations in the estimation of GFR in
health and in chronic kidney disease. J Am Soc Nephrol 16:
459 – 466, 2005
21. Cirillo M, Anastasio P, De Santo NG: Relationship of gen-
der, age, and body mass index to errors in predicted kid-
ney function. Nephrol Dial Transplant 20: 1791–1798, 2005
22. Fontsere N, Bonal J, Navarro M, Riba J, Fraile M, Torres
F, Romero R: A comparison of prediction equations for
estimating glomerular filtration rate in adult patients
with chronic kidney disease stages 4 –5: Effect of nutri-
tional status and age. Nephron Clin Pract 104: c160 – c168,
2006
23. Rigalleau V, Lasseur C, Raffaitin C, Perlemoine C, Barthe
N, Chauveau P, Combe C, Gin H: Nutritional status
partly explains the overestimation of GFR by the Cock-
croft and Gault formula in diabetic subjects with severe
chronic renal failure. Nephrol Dial Transplant 21: 822– 823,
2006

See related editorial, “The CKD-EPI Equation for Estimating GFR from Serum Creatinine: Renal Improvement or More
of the Same?” on pages 951–953.