Original Paper
Nephron Clin Pract 2007;105:c43–c53
DOI: 10.1159/000097597
A New Equation for Estimating Renal
Function Using Age, Body Weight and
Serum Creatinine
Giovambattista Virga a Flavio Gaspari c Karl Thomaseth d Marilena Cara a
Stefania Mastrosimone a Vittorio Rossi b
a
Nephrology and Dialysis Unit and b Laboratory of Provincial Hospital, Camposampiero/Padova, c Mario Negri
Institute for Pharmacological Research, Bergamo, and d Institute of Biomedical Engineering, ISIB-CNR, Padova, Italy
Key Words
Cockcroft-Gault formula
Creatinine clearance

Glomerular filtration rate
Iohexol plasma clearance

MDRD equation
Serum creatinine
Abstract
Background: Many formulas have been developed to esti-
mate glomerular filtration rate (GFR). The aim of our study
was to propose a new, more reliable equation. Methods: The
study considered 530 subjects (training sample) with M/F
280/250, age 57.1 8 17.4, creatinine clearance (CrCl) 55.2 8
38.2 (range 2.1–144.0) for the development the new equa-
tion. A linear model was used to describe Cr production us-
ing serum Cr (sCr), age, and body weight (BW) as variables:
(CrCl + b4)
sCr = b1 – (b2
age) + (b3
BW) subsequently es-
timating parameter values by linear least squares, with CrCl
as the dependent variable, and 1/sCr, age/sCr, BW/sCr as in-
dependent variables. CrCl = {[69.4 – (0.59
age) + (0.79

BW)]/sCr} – 3.0 (males) and {[57.3 – (0.37
age) + (0.51
BW)]/
sCr} – 2.9 (females). A 229-patient renal failure validation
sample with M/F 166/63, age 53.0 8 14.8, GFR 32.0 8 14.3
(range 4.3–69.8), assessed using iohexol Cl, was considered
to compare the Cockcroft-Gault (C-G) and MDRD formulas
with the new equation for estimating GFR. Results: The
mean % error in GFR estimated by the new equation (+2.3 8
28.3%) was better than with the C-G and MDRD formulas
(+5.2 8 30.1% and –11.4 8 25.9%, respectively, p ! 0.0005
© 2007 S. Karger AG, Basel
1660–2110/07/1052–0043$23.50/0
Fax +41 61 306 12 34
E-Mail karger@karger.ch Accessible online at:
www.karger.com www.karger.com/nec
Received: December 21, 2005
Accepted: August 14, 2006
Published online: November 29, 2006
and p ! 0.0001), and so was the mean absolute % error, bor-
dering on statistical significance (19.8 8 20.3 vs. 21.1 8 22.0
and 22.4 8 17.3, p = 0.08 and p ! 0.005). The precision was
also better (RMSE = 7.89 vs. 8.02 and 9.13). The Bland-Altman
test showed no GFR over or underestimation trend (mea-
sured 8 predicted GFR/2 vs. % error, R2 = 0.001). Conclu-
sions: The new equation appears to be at least as accurate
as the C-G and MDRD formulas for estimating GFR.
Copyright © 2007 S. Karger AG, Basel
Introduction
Human renal function is generally assessed on the ba-
sis of the glomerular filtration rate (GFR), which is usu-
ally estimated in clinical practice by calculating the cre-
atinine (Cr) clearance (Cl). Physiologically, Cr crosses the
glomerular capillary wall freely and, when renal func-
tion is normal, it is secreted by tubules in negligible
amounts. When the GFR falls below normal values, tu-
bular Cr secretion increases and the calculated CrCl is
known to overestimate the GFR [1]. This error does not
affect the basic clinical utility of CrCl and endogenous Cr
continues to be the substance most widely used to esti-
mate renal function because, although GFR can be mea-
sured more precisely using filtration markers such as in-
ulin, iothalamate and iohexol, the method is costly and
cumbersome, so it is not used in clinical practice.
Giovambattista Virga
Via Torino 4/A
IT–35142 Padova (Italy)
Tel. +39 049 932 4727, Fax +39 049 632 608
E-Mail virgolino14@libero.it
 Calculating CrCl calls for a 24-hour urine collection
and one blood sample. An accurate 24-hour urine collec-
tion is crucial to the correct assessment of renal function,
but it is more troublesome to obtain than it seems. More-
over, for patients with bladder incontinence or psychiatric
disorders, urine collection is almost always unreliable, and
for patients with a ureterosigmoidostomy it is impossible.
Given the importance of renal function assessments in
clinical decisions (e.g. living kidney donors, diagnosing
initial kidney failure, pharmacological treatment dosage,
and prescription of dialysis) and in evaluating the effec-
tiveness of treatment, its accurate evaluation is crucial to
nephrologists. That is why a reliable formula for estimat-
ing renal function can be very useful.
In the last 25 years, the most widely used equation for
estimating CrCl by age, body weight (BW) and serum Cr
(sCr) has been the one published by Cockcroft and Gault
(C-G) [2]. More recently, the modification of diet in renal
disease (MDRD) formula for estimating GFR [3], using
125I-iothalamate renal Cl-based GFR measurements, was
developed in a training sample of 1,070 nephropathic pa-
tients and validated in a 558-subject sample with renal
failure; this formula was subsequently simplified [4].
GFR estimation from sCr measurements is now rec-
ommended by the National Kidney Foundation as a
method for assessing kidney function and the C-G and
MDRD formulas have been suggested for this purpose in
the K/DOQI guidelines [5].
The relationship between GFR (or CrCl) and BW in
the two formulas and the use of a fixed correction factor
for females are probably the most debatable issues. The
C-G formula [2],
CrCl (males) = [(140 – age)
BW]/(sCr
72)
indirectly estimated Cr excretion = GFR
sCr as being
exactly proportionally to BW, which leads to an expected
GFR overestimation in overweight subjects [6, 7].
In the MDRD equation,
GFR (males) = {[186
(sCr(–1.154))
(age (–0.203))]/1.73 m2}

(BW0.425
height0.725
0.007184),
although BW does not appear as an independent variable
[4], the GFR still correlates with BW due to the normal-
ization for body surface area (which is calculated from
BW and height [8]) – but this correlation is probably too
weak, leading to a predictable underestimation of GFR
for higher body weights [7, 9].
Finally, both formulas use a simple correction factor
for females (
0.85 and
0.742 respectively) which lacks a
clear physiological justification.
c44 Nephron Clin Pract 2007;105:c43–c53
Given the known problems encountered when the
MDRD and C-G formulas are used for certain patient
groups, such as the overweight (MDRD underestimates
[7, 9] and C-G overestimates the GFR [6, 7]) and females
(here again, MDRD underestimates [7, 10] and C-G over-
estimates the GFR [7]), the aim of our study was to de-
velop and validate a new equation based on the same sim-
ple variables (sCr, age, BW), but using a different math-
ematical model and calculating a dedicated formula for
females, with a view to improving the reliability of GFR
estimation.
Material and Methods
Subjects, Laboratory and Calculations for the Training
Sample
For the training sample, the study considered 530 Caucasian
subjects (280 males and 250 females, aged from 20 to 90 years)
evaluated by our Nephrology and Dialysis Unit at Camposam-
piero Hospital (Padova).
For Cr assay, all subjects collected urine for 24 h and under-
went blood sampling. One CrCl calculation per subject was con-
sidered for the study. Cr levels (mg/dl) were determined in all
serum and urine samples (uCr) according to the rate-blanked and
compensated modified Jaffé kinetic method always using the
same analyzer (Hitachi Modular) at our laboratory.
Between 1996 and 2004, the accuracy of rate-blanked com-
pensated Cr measurements at the Camposampiero hospital labo-
ratory was monitored by daily quality control using solutions of
known Cr concentration, e.g. Precinorm
U (for low Cr values)
with a range of 1.08–1.21 mg/dl, and Precipath
U (for high Cr
values) with a range of 4.16–4.21 mg/dl (Roche), revealing a con-
stant error !1 SD (0.06 and 0.25 mg/dl, respectively).
The instructions for 24-hour urine collection were to discard
the first morning urine voiding, then collect all urine up to and
including the next first morning voiding; it was recommended
that the time of the two ‘first voidings’ be the same (e.g. 7 or 8
o’clock).
Patients with acute renal failure, cirrhosis, trauma or burns,
pregnant or postpartum women were not included in the sample,
nor were patients with unstable kidney function, on dialysis, with
transplanted kidneys, arteriovenous fistulas or peritoneal cathe-
ters (even if they were not yet on dialysis). Proteinuric (11 g/24 h)
and diabetic patients with a normal renal function were also ex-
cluded from the study.
All levels of renal function are represented in the study popu-
lation: CrCl 190 ml/min = 63 males and 62 females, 60–89 ml/
min = 59 and 50, 30–59 ml/min = 50 and 59, 15–29 ml/min = 49
and 29, !15 ml/min = 59 and 50 respectively.
For patients admitted to our Unit, multiple CrCl measurements
were taken, starting from the day of their arrival. If two samples
were available, the second was considered for the study because it
was judged to be more reliable, because the first urine collection
during any hospital stay usually begins later than 8 o’clock (carry-
ing a risk of undercollection). If three or more CrCl measurements
were available, the median value was used in the study.
Virga /Gaspari /Thomaseth /Cara /
Mastrosimone /Rossi
 In an attempt to reduce the percentage of urine under- and
overcollections, only samples with 24-hour urine volumes be-
tween 500 and 4,000 ml were considered for the study. All subjects
were weighed and their date of birth, date of urine collection and
gender were recorded. CrCl was calculated as follows: CrCl (ml/
min) = uCr (mg/day)/[sCr (mg/ml)
1,440], where uCr is the total
Cr recovered in the urine.
A linear model was used to describe Cr production using sCr,
age, and BW as variables: (CrCl + b4)
sCr = b1 – (b2
age) +
(b3
BW), thus estimating parameter values by linear least squares,
with CrCl as a dependent variable, and 1/sCr, age/sCr and BW/sCr
as independent variables, using different parameters for males
and females. The selected independent variables (sCr, age, BW)
were chosen because they are the most important variables ca-
pable of influencing the GFR estimate [2, 3, 11].
The values of four parameters (b1, b2, b3, b4) of the new predic-
tion formula including age, BW and sCr were estimated:
CrCl = {[b1 + (b2
age) + (b3
BW)]/sCr} + b4
Renal function was also estimated by means of the most wide-
ly-used formulas:
(1) C-G [2]: CrCl (ml/min) = [(140-age)
BW]/(72
sCr) (
0.85
for females),
(2) abbreviated MDRD [4]: GFR (ml/min/1.73 m2) = 186

(sCr(–1.154))
(age (–0.203)) (
0.742 for females,
1.212 for African-
American).
In all formulas, sCr is expressed in mg/dl, BW in kg and age
in years. Before drawing comparisons, both the new equation and
the C-G formula were normalized for 1.73 m2 of body surface area
(BSA) using the Du Bois formula [8]:
BSA = BW (kg) 0.425
height (m) 0.725
0.007184.
Subjects, Laboratory and Calculations for the Validation
Sample
A group of 229 patients belonging to the REIN-2 trial [12] was
used as a validation sample. They were non-diabetic patients with
renal failure (CrCl !70 ml/min/1.73 m2) treated with ramipril to
prevent the progression of their renal disease.
Blood samples were collected to measure Cr concentration on
the morning of the GFR measurement based on iohexol plasma
Cl. Blood samples were analyzed for Cr using the modified ki-
netic rate Jaffé method (coefficient of variation 3.70%) with an
automatic device (Beckman Synchron CX5, Beckman Coulter
SpA, Cassina De’ Pecchi, Italy).
Details on how the iohexol plasma concentration was deter-
mined and iohexol Cl was estimated (at the ‘Aldo e Cele Daccò’
Clinical Research Center for Rare Diseases of the Mario Negri
Institute for Pharmacological Research) are available elsewhere
[13].
The demographic and anthropometric data needed to esti-
mate renal function using prediction equations were recorded by
each center taking part in the trial on the day when iohexol plas-
ma Cl was determined, and were obtained from the electronic
database managed at the Clinical Research Center for Rare Dis-
eases, responsible for coordinating the study. The purpose of the
study was explained in detail to all patients before admission and
their informed consent was obtained in each instance.
A New Equation for Estimating Renal
Function
Statistics
Continuous variables were expressed as means 8 SD or me-
dians.
Bias, a measure of systematic error, was defined by the mean
prediction error =
(predicted – measured GFR)/n, where n is the
number of GFR studies performed.
Scatter was calculated for each equation as the median abso-
lute difference (
measured – predicted GFR
) and the predictive
power of each formula was assessed by Pearson’s linear correla-
tion coefficient (r) (GFR estimates vs. iohexol plasma Cl).
Precision was assessed by calculating the root mean square er-
ror (RMSE) for each equation. The RMSE represents the SD of the
prediction error (1 SD of bias) calculated as the square root of the
mean square of the response variable minus the fitted value: the
smaller the RMSE, the greater the precision of the formula.
Accuracy was considered as the mean absolute percentage er-
ror (MAPE), as a percentage of GFR (%) = (
measured – predicted
GFR
! 100/measured GFR)/n.
The mean percentage error (MPE) was also calculated.
The relative accuracy, defined as the percentage of patients
whose estimates came within 15, 30 and 50% above and below the
measured GFR, was calculated for all three equations, as recom-
mended [5].
A modified Bland-Altman test [14] was used to represent the
trend of the errors, plotting the percentage error versus the mean
of the measured plus the estimated GFR.
All statistical evaluations were also performed separately for
males and females.
The t test for paired data was used to compare the results of
the new equation versus the C-G formula (p1) and the MDRD
equation (p2), and of the C-G versus the MDRD formula (p3).
All statistical calculations involving the validation sample
were done at the Mario Negri Institute for Pharmacological Re-
search, Bergamo, Italy.
A normal probability test was used to compare the coefficients
for age and BW between males and females in the new equa-
tions.
The null hypothesis was rejected for all tests with two-tailed
 values ! 0.05.
The statistical analysis was performed using JMP 4.0.0 statisti-
cal software (SAS Institute Inc., Cary, N.C., USA), Instat 3.05 sta-
tistical software (GraphPad Software Inc., San Diego, Calif., USA)
and Excel 2000 (Microsoft Inc., Richmond, Va., USA).
Results
New Equation
The characteristics of the training sample are summa-
rized in table 1. The new equation for predicting GFR,
developed using linear least squares analysis, was:
CrCl = {[69.4 – 0.59
age + 0.79
BW]}/sCr – 3.0 for males
and
CrCl = {[57.3 – 0.37
age + 0.51
BW]}/sCr – 2.9 for females.
Nephron Clin Pract 2007;105:c43–c53 c45
 Table 1. Characteristics of training population: mean values 8 SD (range)

Number 530
Male/female 280/250
Age, years 57.1817.4 (20.2–90.7)
Body weight, kg 72.0814.7 (40.3–136.0)
sCr, mg/dl 2.6682.61 (0.50–15.4)
CrCl, ml/min 55.2838.2 (2.1–144.0)

Males Females

Number 280 250

Age, years 57.9816.4 (20.2–88.7) 56.2818.5 (20.4–90.7)
Body weight, kg 78.3813.2 (50.0–136.0) 64.9813.1 (40.3–114.0)
sCr, mg/dl 3.182.8 (0.72–14.2) 2.282.3 (0.50–15.4)
CrCl, ml/min 54.7839.6 (4.0–144.0) 55.7836.7 (2.1–124.8)

Males Females
uCr, mg/kg/day age n uCr, mg/kg/day age n

CrCl, ml/min
>90 20.483.3 46.2814.7 63 18.082.9 45.0814.7 62
60–89 17.083.4 57.0813.6 59 15.983.1 48.6816.9 50
30–59 16.084.1 60.8816.3 50 13.683.2 60.9817.2 59
15–29 14.183.3 65.2815.6 49 12.383.1 65.4816.4 29
<15 12.783.4 62.8815.0 59 10.183.4 66.8816.6 50

Table 2. Features of validation population: mean values 8 SD A normal probability test demonstrated a statistically
(range) significant difference between males and females in the
coefficients for age (–0.59 vs. –0.37) and BW (+0.79 vs.
Number 229 +0.51) in the new equations, with a z value of 2.73 (p =
Male/female 166/63
Age, years 53.0814.8 (17.7–87.1) 0.006) and 2.29 (p = 0.022), respectively.
Body weight, kg 73.9814.2 (46.0–130.0)
sCr, mg/dl 3.0081.40 (0.97–9.70) Validation Test
GFR, ml/min/1.73 m2 32.0814.3 (4.3–69.8) Table 2 shows the features of the 229-patient valida-
tion sample. The results (MPE and MAPE) of the com-
parison in the validation group between the new equa-
tion and the C-G and MDRD formulas, using the GFR
For males (8SE): measured by iohexol plasma Cl as a gold standard, are
b1 = +69.4 8 9.12; b2 = –0.59 8 0.07; b3 = +0.79 8 0.10; b4 = summarized in table 3. The bias was –0.3 8 8.1 vs. +0.2
–3.0 8 1.58, p ! 0.0001 in each case, except for b4 (p = 0.06) 8 8.0 and –4.4 8 8.0 (p1 ! 0.05, p2 ! 0.0001, p3 ! 0.0001),
while the scatter was 4.48 vs. 4.22 and 5.45 (p1 = 0.99,
and for females (8SE): p2 ! 0.001, p3 = 0.001). The relative accuracy was 52.0–
b1 = +57.3 8 4.39; b2 = –0.37 8 0.04; b3 = +0.51 8 0.07; b4 = 80.3–93.4% vs. 51.1–79.0–90.8% vs. 38.4–74.2–94.8% for
–2.9 8 1.50, p ! 0.0001 in each case, except for b4 (p = 0.05). the three equations within 15, 30 and 50% of subjects re-
spectively.
These results demonstrate a significant influence of We considered accuracy (MAPE), precision (RMSE)
age and BW on GFR estimates, which is more important and relative accuracy as the most important parameters
in males, while the negative b4 value is consistent with an for evaluating the reliability of a predictive model.
extrarenal CrCl. The new equations and the C-G formula both slightly
overestimated the GFR (mean MPE = +2.3% and +5.2%),

c46 Nephron Clin Pract 2007;105:c43–c53 Virga /Gaspari /Thomaseth /Cara /

Mastrosimone /Rossi
 Table 3. Comparison of results about MPE (mean % error), accuracy (MAPE, mean absolute % error) and pre-
cision (RMSE, root mean square error) in validation sample between new vs. C-G and MDRD equations

All (n = 229) New C-G MDRD p1 p2 p3

Mean % error +2.3828.3 +5.2830.1 –11.4825.9 <0.0005 <0.0001 <0.0001

Mean absolute % error 19.8820.3 21.1822.0 22.4817.3 0.08 <0.005 0.32
RMSE (precision) 7.89 8.02 9.13 0.54 <0.0005 <0.01
Males (n = 166)
Mean % error +0.5827.5 +2.0827.5 –11.5825.7 <0.05 <0.0001 <0.0001
Mean absolute % error 19.1819.7 19.6819.4 21.9817.6 0.51 <0.005 0.05
RMSE 8.05 8.15 8.85 0.70 <0.05 0.13
Females (n = 63)
Mean % error +7.1830.1 +13.5834.9 –11.1826.7 <0.005 <0.0001 <0.0001
Mean absolute % error 21.6821.9 25.2827.5 23.7816.4 0.09 0.32 0.64
RMSE 7.44 7.68 9.84 0.58 <0.005 <0.05

with the new equations performing a little better, while

the MDRD confirmed its known tendency to underesti-
mate the GFR (MPE = –11.4%). The new equations were 100 New
as precise as the C-G formula, with an improvement in
accuracy that bordered on statistical significance (p = 80
0.08) and a tendency to overestimate GFR much less in
females (MPE = +7.1 vs. +13.5%). The new equation is
60
therefore not significantly more precise than the C-G
equation, but its accuracy tends to be better. The new
equations were also both more accurate and more precise 40
than the MDRD formula.
Figure 1 shows the linear correlation for the predicted 20
and measured GFR using the new equation in the valida- r = 0.856
tion sample. All the equations displayed a highly signifi-
0
cant correlation (p ! 0.01), but the new equation had a 0 20 40 60 80 100
slightly better correlation coefficient (r): 0.856 vs. 0.849
vs. 0.838.
The modified Bland-Altman test revealed no tendency
for the % error to increase or decrease with rising GFR Fig. 1. Linear correlation analysis between measured (x) versus
values when the new equations were used (fig. 2), and lin- predicted (y) GFR (ml/min/1.73 m2) using the new equation. The
ear regression analysis for % errors showed y = –0.05 + identity line is dashed.
3.94 for new equations, y = –0.24 + 12.80 for C-G, and
y = +0.06–13.21 for MDRD. The 95% limits of agreement
for the mean % error (mean 81.96 SD) were +57.7/–53.2%
vs. +64.1/–53.7% vs. +39.3/–62.2% for the three equa- due to the small size of the sample (table 3). The bias was
tions. The Bland-Altman test demonstrated no increas- –0.5 8 7.5 vs. +0.5 8 7.7 and –5.4 8 8.3 (p1 ! 0.05, p2 !
ing errors for the new equation in renal failure, therefore 0.0001, p3 ! 0.0001), while the scatter was 3.81 vs. 3.51 and
a lack of progressive GFR overestimation because of Cr 4.46 (p1 = 0.79, p2 ! 0.01, p3 = 0.06). Pearson r coefficient
tubular secretion. was 0.895 vs. 0.888 vs. 0.883 and the relative accuracy was
In the group of 63 females, the difference in accuracy 49.2–73.0–92.1% vs. 52.4–73.0–84.1% vs. 39.7–71.4–93.7%
between the new equations and the C-G falls just short of for the three equations within 15, 30 and 50% of subjects
the mark for statistical significance (p = 0.09), probably respectively.

A New Equation for Estimating Renal Nephron Clin Pract 2007;105:c43–c53 c47
Function
 180
New
120

60

-60

–120
Fig. 2. Modified Bland-Altman test with R2 = 0.0007
y = % error with mean (dashed lines)
–180
81.96 SD (dotted lines) and x = (measured
0 20 40 60 80 100
+ predicted GFR)/2 using the new equa-
tion.

150 150

140 140
GFR (ml/min/1.73 m2)
GFR (ml/min/1.73 m2)

130 130

120 120

110 110

100 100

90 90

80 80

50 60 70 80 90 100 110 120 130 50 60 70 80 90 100 110 120 130

a BW (kg) b BW (kg)

Fig. 3. Young males (175 cm, 25 years old, sCr 1.10 mg/dl) (a) and young females (165 cm, 25 years old, sCr
0.85 mg/dl) (b) with normal renal function and BW from 60 to 120 kg. The C-G formula estimates a higher
GFR as BW (kg) increases, and more so among females. The MDRD formula estimates a lower GFR: the cal-
culated GFR is below normal (90 ml/min/1.73 m2) for all BW in both populations (mild renal failure). x = GFR
estimated by C-G; _ = MDRD; X = new equation.

Among the males, the bias was +0.3 8 8.1 vs. +0.1 8
8.2 and –4.1 8 7.9 (p1 = 0.16, p2 ! 0.0001, p3 ! 0.0001),
while the scatter was 4.76 vs. 4.40 and 5.66 (p1 = 0.85,
p2 ! 0.005, p3 = 0.008). Pearson r coefficient was 0.844 vs.
0.840 vs. 0.833 and the relative accuracy 53.0–83.1–94.0%
vs. 50.6–81.3–93.4% vs. 38.0–75.3–95.2% for the three
equations within 15, 30 and 50% of subjects respec-
tively.
Comparative Check on the Three Equations
In figure 3, the renal function of young subjects (25-
year-olds) with low levels of sCr (1.10 and 0.85 mg/dl for

c48 Nephron Clin Pract 2007;105:c43–c53 Virga /Gaspari /Thomaseth /Cara /

Mastrosimone /Rossi
 40 40

35 35

30 30

GFR (ml/min/1.73 m2)

GFR (ml/min/1.73 m2)

25 25

20 20

15 15

10 10

5 5

0 0

2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
a sCr (mg/dl) b sCr (mg/dl)

Fig. 4. Young normal-weight males (175 cm, 70 kg, 25 years old) (a) and young normal-weight females (165 cm,
60 kg, 25 years old) (b). GFR is estimated using the C-G formula and the MDRD equation in renal failure. x =
GFR estimate by C-G; _ = MDRD; X = new equation.

males and females, respectively) was calculated using the
three equations. At all levels of BW (kg), from normal to
overweight, the GFR estimated by the MDRD equation
was below the normal range (90 ml/min/1.73 m2), which
is consistent with a diagnosis of mild renal failure and a
plausible GFR underestimation [6, 7, 10, 15, 16], particu-
larly among females [7, 10]. Conversely, the GFR overes-
timation using the C-G formula in normal renal function
is clearly represented as BW (kg) increases [7] and seems
more evident among females [7].
Figure 4 shows GFR estimates of young normal-weight
males and females with renal failure. In renal failure,
GFR overestimation by the C-G formula [6, 7, 17] and
underestimation by the MDRD equation [10, 17] have al-
ready been reported. The new equation produces an esti-
mate that comes in between the two, proving capable of
partially correcting the two opposite biases. At very low
GFR values (GFR = 5 ml/min/1.73 m2), an initial slight
GFR overestimation by the MDRD equation has been
demonstrated [9, 17] while the new equation’s estimate
begins to show a somewhat lower value.
Figure 5 shows the GFR estimates for elderly nor-
mal-weight males and females with renal failure for the
three equations. In severe renal failure (GFR !30 ml/
min/1.73 m2), there are no differences of clinical inter-
est in the GFR estimates obtained by the three equa-
tions.
Summarizing, the errors of the two most widely-used
formulas seem to occur in the same subpopulations: the
C-G’s formula overestimates GFR mainly in the young
[7], females [7] and overweight [6, 7], while the MDRD
underestimates GFR mainly in the young [7], females [7,
10] and overweight [7].
Discussion
In 1976, Cockcroft and Gault [2] published their study
on a sample of 249 males aged 18–92 with measured CrCl
ranging from as low as 11 ml/min to normal values. The
mean 24-hour uCr/kg was plotted for each age group
against the mean age in each decade and the resulting
regression line was:
24-hour uCr/kg (mg/kg) = 28 – (0.2
age in years).
So, after simple mathematical conversions, they were
able to obtain a formula for males. A female population
was not studied and the authors simply suggested using
the formula for males with a correction factor of 0.85,
which was defined as ‘appropriate’ [2].

A New Equation for Estimating Renal Nephron Clin Pract 2007;105:c43–c53 c49
Function
 80 80

70 70

60 60

GFR (ml/min/1.73 m2)

GFR (ml/min/1.73 m2)

50 50

40 40

30 30

20 20

10 10

0 0

0 1 2 3 4 5 6 7 8 9 10 11 12 13 0 1 2 3 4 5 6 7 8 9 10 11 12 13
a sCr (mg/dl) b sCr (mg/dl)

Fig. 5. Elderly normal-weight males (175 cm, 70 kg, 75 years old) (a) and females (165 cm, 60 kg, 80 years old)
(b) with sCr from 1.0 to 12.0 mg/dl. In severe renal failure (GFR !30 ml/min/1.73 m2) there are no differences
of clinical interest in the GFR estimated by the three equations. x = GFR estimate by C-G; _ = MDRD;
X = new equation.

No formula is more widely used to predict GFR than
the one proposed by C-G. The original aim of the C-G
formula was to predict CrCl, but its power to predict GFR
is quite satisfactory. The C-G equation was judged the
most accurate among several formulas for estimating
CrCl in comparative studies using inulin [18] and iohex-
ol [19] GFR measurements.
It has been demonstrated that the C-G formula can
overestimate GFR at low renal function levels [6, 7, 17]
and underestimate high GFR values [15]. Other GFR
overestimation biases were demonstrated for overweight
patients [6, 7], young [7] and females [7] subjects.
The MDRD formula emerged from the MDRD study,
which measured patients’ GFR from renal 125I-iothal-
amate Cl using a training sample of 1,070 cases and a
validation sample of 558 [3]. Several equations were de-
veloped from data on the training sample, but the abbre-
viated, four-variable MDRD equation (considering age,
sCr, gender and race) [4] is the most widely used.
The MDRD equation clearly underestimates GFR in
subjects with high renal function levels [6, 7, 10, 15, 16]
and Levey et al. [3] emphasized the need for caution in
applying the MDRD formula to individuals with a sCr
within the ‘normal’ range because it has not been vali-
dated in people without renal disease. That the MDRD
underestimates GFR was also recently demonstrated in
renal failure [10, 17], in females [7, 10], and in overweight
patients [7, 9], while the opposite is true of lean subjects
[9]. In uremia, compared to inulin Cl, the GFR predicted
by the MDRD equation underestimates GFR up to a val-
ue 18 ml/min/1.73 m2 but it overestimates GFR when it
drops to !8 ml/min/1.73 m2 [9].
The only two studies comparing the MDRD and C-G
equations using GFR measured by reference to iohexol
plasma Cl confirmed these findings: C-G was relatively
more accurate in subjects with little or no renal insuffi-
ciency [19], while the MDRD performed better in kidney-
transplanted patients with renal failure [8].
The validation test using the GFR measured using io-
hexol plasma Cl as a gold standard demonstrated that the
new equation is certainly not less accurate and precise
than the two most widely-used formulas. Moreover, it ap-
pears to correct some known biases (table 3), such as GFR
overestimation by the C-G in renal failure, and underes-
timation by the MDRD in cases of renal failure. More-
over, the absence of a rising percentage error with a de-
clining GFR (fig. 2, Bland-Altman test) confirms that the
new equation does not progressively overestimate GFR in

c50 Nephron Clin Pract 2007;105:c43–c53 Virga /Gaspari /Thomaseth /Cara /

Mastrosimone /Rossi
spite of the possible influence of Cr tubular secretion on
GFR estimation by CrCl.
As in other studies [6, 7, 9, 10, 15, 16], our computer
checks show that the two most important biases of the C-
G and MDRD formulas go in the opposite direction, i.e.
they respectively overestimate and underestimate the
GFR in healthy and overweight subjects, particularly
among females (fig. 3). A certainly normal sCr (0.85 mg/
dl) gives rise to a GFR estimation of 87 ml/min/1.73 m2
by the MDRD formula (which is likely to prompt an er-
roneous diagnosis of ‘mild renal failure’), while the C-G’s
formula would suggest ‘hyperfiltration’ (fig. 3). The new
equation seems able to reduce these errors.
Computer simulations demonstrate the new equa-
tion’s power to partially correct another clinically impor-
tant bias when the C-G and MDRD formulas are used for
estimating GFR in renal failure among young subjects:
up to end-stage renal disease, they respectively overesti-
mate and underestimate GFR [6, 7, 17] (fig. 4), while the
results obtained by the new equation invariably come in
between the two up to a GFR = 5 ml/min/1.73 m2 when
(maybe for good reason [17]) the new equation estimates
a slightly lower GFR than the MDRD (fig. 4).
In severe renal failure (GFR 5–30 ml/min/1.73 m2),
however, the GFR estimated by the MDRD and the new
equation are very similar in normal-weight young people
(fig. 4) and almost identical in normal-weight elderly pa-
tients (fig. 5).
Computer analysis is very useful for ascertaining
whether the biases described in published equations are
credible, and whether a new equation is more or less able
to correct them, overcoming problems related to different
sCr assay methods or the lack of specific study subpopu-
lations (e.g. obese, very elderly, severely uremic). Com-
puter simulations can also be verified by any researcher
or reviewer.
Although it makes sense to assume that the best GFR
estimate would result from a formula obtained using a
subject sample with real GFR measurements, we chose to
develop a new equation from a training sample with CrCl.
The results of the validation test and our computer simu-
lations are encouraging (table 3, fig. 4). While the overes-
timation of GFR based on CrCl in renal failure report-
edly varies from 17 to 32% (27% with a GFR of 25 ml/
min/1.73 m2) [20], the mean % error of our new equation
was +2.3% (mean GFR overestimation), low enough to be
clinically negligible.
There are many differences between the C-G and
MDRD formulas and ours, the first of which concerns the
role of BW (kg), which is fundamental in the C-G, absent
A New Equation for Estimating Renal
Function
in the MDRD, and limited in ours. The main difference,
however, lies in that a separate equation was developed
for females instead of simply assuming their GFR as a
proportional fraction of a man’s of the same age, BW and
sCr (C-G = 0.85, MDRD = 0.742).
The decision to develop two distinct equations for
males and females stemmed from important gender-re-
lated physiological differences in the relationships be-
tween lean body mass (LBM) and age, and between LBM
and BW. The amount of uCr excreted (which equates to
Cr production in a steady state) is related directly to LBM.
With aging, the loss of total LBM is greater in men than
in women, both in absolute terms and relative to BW [21].
As for BW, the relative LBM differs between males and
females at all ages and increases in different proportions
for BW gains in males and females, rising less in males
[21]. In our new equations, the different coefficients for
males and females are related to age and BW and reflect
these physiological gender discrepancies. To be more spe-
cific, if the ratio of the proportion of LBM between the
two genders (female LBM%/male LBM%) is considered as
a possible correction factor, this value is not constant at
all ages, it increases from 0.783 in 30- to 40-year-olds to
0.839 in people 170 years of age [21]. It is worth noting
that said interval includes neither the 0.742 of the MDRD,
nor the 0.85 of the C-G. The statistically significant dif-
ferences between males and females in the coefficients for
age and BW in our new equations are consistent with
these findings.
Some biases in GFR estimation using the C-G and
MDRD are of particular clinical relevance, especially in
dealing with females. Using the C-G formula may delay
the diagnosis of renal failure in young overweight females
(i.e., 25 years old, cm 165, kg 95, sCr 1.2 mg/dl, GFR =
92.2 ml/min/1.73 m2) or the initiation of dialysis (sCr
11.0 mg/dl, GFR = 10.1 ml/min/1.73 m2). Using the
MDRD formula can lead to an erroneous diagnosis of
early renal failure in young females (i.e., 25 years old,
165 cm, 60 kg, sCr 0.85, GFR = 86.6 ml/min/1.73 m2)
(fig. 3).
Clinical practitioners – and not only the nephrolo-
gist – need an equation for estimating GFR that is appli-
cable to all patient subpopulations, young and old, lean
and obese, with normal or compromised renal function.
An equation can only be defined as ‘reliable’ (or ‘more
reliable’ than another) on the strength of several com-
parisons with GFR measurements obtained by different
tracers and their subsequent global evaluation.
Inulin renal Cl is considered the gold standard for GFR
measurement [22]. The analysis of prediction equations
Nephron Clin Pract 2007;105:c43–c53 c51
should consequently take the type of GFR measurement
into account, and caution is needed in comparing the re-
sults of such investigations if different GFR measurement
methods have been used. The suitability of a new equa-
tion for estimating GFR could be tested using more than
one tracer, one of which should preferably always be inu-
lin.
Recent studies have emphasized the importance of
carefully calibrating sCr measurements to estimate GFR
reliably from Cr-based equations particularly at low lev-
els of sCr [20]. We, like others [10, 17], were unfortunate-
ly unable to recalibrate our sCr measurements, but in our
validation sample the sCr was measured using a Beck-
man analyzer and patients all suffered from renal insuf-
ficiency (GFR !70 ml/min/1.73 m2), which reduces the
importance of our inaccuracy.
In conclusion, the new equation seems able to estimate
subnormal value of GFR with an accuracy that is certain-
ly no lower than the C-G and MDRD formulas, particu-
larly in the case of females, who appear to be at greatest
risk of GFR estimation errors using the two most widely
used formulas. The advantage of our formula in this
population is probably due to our equation being female-
dedicated, instead of simply using a mathematical factor
to correct the formula for males when it is applied to
females.
The new equation seems to partially correct some
clinically important biases of the other two formulas that
can potentially lead to an erroneous diagnosis of renal
failure, or its late detection, and a delay in starting dialy-
sis therapy. Although our formula was developed using
CrCl to estimate GFR, it does not have the drawback of
overestimating GFR in a clinical significant way.
Given the influence of dietary habits and differences
in body composition for non-Caucasian populations, the
accuracy and precision of this new equation cannot be
guaranteed if it is applied to other populations, e.g. Black
and Americans, though the physiologically-based para-
digm of fitting a linear model to Cr excretion, with age
and BW as covariates, could be readily applied to other
groups of subjects.
Our equations are not suitable to cirrhotic patients,
paraplegic or pregnant subjects, people !18 years of age,
non-Caucasians, diabetics or, more generally, subjects in
an unsteady state. Caution is needed in applying the new
equation to subjects with a normal renal function be-
cause it has not yet been validated appropriately for this
range of GFR values. This new equation probably de-
serves further comparative validations using different
tracers.
Acknowledgement
Very special thanks go to nurse Rina Peron, without her in-
valuable help this work would never have been completed.

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