Estimation of Renal Function in Subjects With Normal Serum
Creatinine Levels: Influence of Age and Body Mass Index
Jacobien C. Verhave, MD, Pierre Fesler, MD, Jean Ribstein, MD, Guilhem du Cailar, MD,
and Albert Mimran, MD
● Background: The Cockcroft-Gault (CG) and simplified Modification of Diet in Renal Disease (MDRD) formulas are
the most widely used estimates of renal function. The influence of age and body mass index (BMI) on the
performance of these equations was analyzed in 850 subjects with serum creatinine levels less than 1.5 mg/dL
(<133 mol/L). Methods: Glomerular filtration rate (GFR) was measured as urinary clearance of continuously
infused technetium Tc 99m–labeled diethylene triaminopentaacetic acid. Performance was assessed as bias,
precision, and accuracy. Results: In the total population, the CG and MDRD calculations based on enzymatic
measurement of serum creatinine (which is constantly less than that obtained by using the alkaline picrate [Jaffé]
method) significantly underestimated GFR by 4.9 and 12.4 mL/min/1.73 m
2
(0.08 and 0.21 mL/s/1.73 m
2
), respec-
tively. In patients 65 years and older, underestimation by means of the CG formula was enhanced, whereas that by
means of the MDRD formula was blunted, compared with the group younger than 65 years (11.3 versus 3.7
mL/min/1.73 m
2
[0.19 versus 0.06 mL/s/1.73 m
2
] for CG and 3.7 versus 14.0 mL/min/1.73 m
2
[0.06 versus
0.23 mL/s/1.73 m
2
] for MDRD). GFR was underestimated to a large extent by means of the MDRD equation
irrespective of BMI. Conversely, the underestimation by means of the CG formula found in lean people (13.0
mL/min/1.73 m
2
[0.22 mL/s/1.73 m
2
]) was blunted in overweight people (BMI, 25 to 30 kg/m
2
) and reversed to
overestimation (10.1 mL/min/1.73 m
2
[0.17 mL/s/1.73 m
2
]) in obese subjects (BMI > 30 kg/m
2
). Conclusion: As
suggested by estimations obtained using enzymatic serum creatinine measurement, the MDRD equation may be
the estimation of choice in elderly patients, whereas the CG estimate is preferable in subjects younger than 65
years. Nevertheless, when obesity is present, no reliable estimation can be obtained by using the CG or MDRD
formula. Am J Kidney Dis 46:233-241.
© 2005 by the National Kidney Foundation, Inc.
INDEX WORDS: Glomerular filtration rate (GFR); renal function estimates; Cockcroft-Gault; Modification of Diet in
Renal Disease; aging; obesity.
T
HE NUMBER OF patients with end-stage
renal disease is increasing worldwide.
1,2
Defined by using the sex-specific 95th percen-
tiles of serum creatinine of a reference popula-
tion (cutoff values, 1.4 mg/dL [124 mol/L] in
women, 1.5 mg/dL [133 mol/L] in men), the
prevalence of impaired renal function was 8% to
9% in the Framingham Heart Study.
3
In the Third
National Health and Nutrition Examination Sur-
vey cohort, a prevalence of impaired renal func-
tion of 11% to 13% (defined as a glomerular
filtration rate [GFR] estimate 60 mL/min/1.73
m
2
[1.00 mL/s/1.73 m
2
] by means of the Modi-
fication of Diet in Renal Disease [MDRD] for-
mula) was observed.
4,5
Of note, recent studies
have shown that even modest impairment in
renal function may be an independent predictor
of cardiovascular morbidity and mortality.
6-8
Urinary clearance of intravenously infused
inulin or labeled tracers with timed urine collec-
tions is considered the gold standard for determi-
nation of GFR. When rapid assessment of renal
function is required (ie, for dosing of drugs with
renal excretion in elderly patients) and in large
clinical trials, several estimates of renal function
using formulas based on serum creatinine level
were proposed, including the Cockcroft-Gault
(CG) and MDRD equations. The CG formula
was designed in 1976 as an estimate of creatinine
clearance calculated from 24-hour urine collec-
tion and within a range of 11 to 186 mL/min
(0.18 to 3.10 mL/s) in 236 hospitalized male
patients aged 18 to 92 years.
9
The MDRD equa-
tion was developed in 1,628 patients with chronic
kidney disease with reference to GFR (renal
clearance of subcutaneously-injected iodine 125–
iothalamate) and within a range of 10 to 130
mL/min/1.73 m
2
(0.17 to 2.17 mL/s/1.73 m
2
).
10
From the Department of Internal Medicine, CHU Montpel-
lier, France.
Received January 3, 2005; accepted in revised form May
2, 2005.
Originally published online as doi:10.1053/j.ajkd.2005.05.011
on June 24, 2005.
Address reprint requests to Albert Mimran, MD, Depart-
ment of Internal Medicine, Hôpital Lapeyronie, 34295 Mont-
pellier Cedex 5, France. E-mail: amimran@wanadoo.fr
© 2005 by the National Kidney Foundation, Inc.
0272-6386/05/4602-0006$30.00/0
doi:10.1053/j.ajkd.2005.05.011
American Journal of Kidney Diseases, Vol 46, No 2 (August), 2005: pp 233-241 233