Vol.3, No.1, 32-36 (2011) Health
Copyright © 2011 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
Clinical use of estimating glomerular filtration rate equ-
ations during pregnancy
Luiz Paulo José Marques1*, Regina Rocco2, Maria Helena Victor1,
Benedita Calheiros de Novaes2, Ana Luiza Batista de Carvalho1, Omar da Rosa Santos1
1Renal Unit of Gaffrèe and Guinle University Hospital-Department of Medicine, Federal University of Rio de Janeiro State, Rio de
Janeiro, Brazil; marqueslpj@iG.com.br
2Obstetric Unit of Gaffrèe and Guinle University Hospital-Department of Medicine, Federal University of Rio de Janeiro State, Rio
de Janeiro, Brazil
Received3 November 2010; revised 5 November 2010; accepted 8 November 2010.
Background: Kidney disease, even when mild,
was once considered so major an impediment
to successful pregnancy and so dangerous to
the mother’s wellbeing. High-risk pregnancy
mainly associated to renal impairment may oc-
cur in 10-20% of gestations and it is very im-
portant that renal function is closely monitored
to prevent or minimize maternal and fetal com-
plications. This study was designed to investi-
gate the performance of Cockcroft-Gault CGeq
and the simplified MDRDeq equations in healthy
pregnant women to assess renal function. Me-
thods: We studied 167 normal ambulatory
pregnant women and kidney function was con-
temporaneously estimated through the CGeq
and the simplified MDRDeq and calculated
through the creatinine clearance (Ccr). Serum
and urinary creatinine were assa yed using Jaffé
reaction method in the same AutoAnalyser.
Results: When we compared calculated and es-
timated clearences for measurement of kidney
function we observed that CGeq overestimated
renal function (CGeq = 168.41 ± 38.80 ml/
min/1.73 m2, Ccr = 146.27 ± 30.49 ml/min / 1.73 m2,
p < 0.001), MDRDeq underestimated renal func-
tion (Ccr = 146.27 ± 30.49 ml/min / 1.73 m2,
MDRDeq = 129.15 ± 29.28 ml/min / 1.73m2, p <
0.001). Conclusions: Our results demonstrated
that CGeq overestimated, MDRDeq underesti-
mated significantly kidney function during ges-
tation in healthy women and cannot be recom-
mended to assess renal function in obstetric
practice. Ccr remains a useful clinical tool in
pregnant women until the development of a
specific equation that considers the several
important maternal renal physiological altera-
tions and provides the measure of GFR the
most unbiased and precise as possible.
Keywords: Pregnancy, Kidney function,
Glomerular Fi l tration Rate, MDRD equation,
Cockcroft-Gault equation.
The pregnancy promotes several important changes in
renal hemodynamics. There are increases in cardiac
output and plasma volume that appear to parallel those
of Glomerular filtration rate (GFR) and Renal Plasma
Flow (RPF), but vascular resistance and blood pressure
fall at the same time [1]. Maternal renal adaptation is
characterized markedly increase in GFR, approximately
50% greater than pre-pregnant value [2]. High-risk
pregnancies, mainly associated to renal impairment, may
occur in 10-20% of pregnant women and increase ma-
ternal and fetal morbidity and mortality [3]. Furthermore,
in the last years, the number of gestations in kidney dis-
eases patients increased markedly. So, it is very impor-
tant that renal function is closely monitored during
pregnancy to prevent or minimize maternal and fetal
Glomerular filtration rate (GFR) is considered to be
the key marker of kidney function, critical for detection,
evaluation and management of renal impairment [4].
However, the precise measurement of GFR is invasive,
time consuming, expensive and technically difficult.
More recently, calculation of estimated GFR (eGFR)
using an empirical mathematical prediction formula
based on single point endogenous serum markers have
been encouraged as a simple, rapid and reliable means o f
assessing kidney function with varying degrees of suc-
cess. These methods are generally accepted as a better
L. P. J. Marques et al. / Health 3 (2011) 32-36
Copyright © 2011 SciRes. Openly accessible at http://www.scirp. or g/journal/ HE ALTH/
tool for estimating renal function than serum creatinine
alone. National and international organizations recom-
mend that clinical labor atories report est imated GFR and
that clinicians use estimated GFR to evaluate kidney
function for all patients. [5] However, the guidelines
specifically exclude interpretation in pregnant women in
the absence of validation.
Serum creatinine has been pivotal for renal function
evaluation because it is an inexpensive, common test in
clinical practice. The factors associated with creatinine
measure are well understood: Creatinine is derived from
the metabolism of creatine in skeletal muscle and from
dietary protein intake; it is released into the circulation at
a relative ly constant rate and has a stable plasma concen-
tration. Creatinine is freely filtered across the glomerulus
and is neither reabsorbed nor metabolized by the kidney.
However, approximately 10 to 40 percent of urinary crea-
tinine is derived from tubular secretion by the organic
cation sec retory pat hways in the proxi m al tubule [6].
There are no fewer than 47 predictions equations cur-
rently available that use creatinine as endogenous mark-
er of renal function, although the most common equa-
tions used to estimate renal function in adults are the
Cockcroft-Gault (CG eq) and the simplified equation from
the Modification of Diet in Renal Disease Study
(MDRDeq) [7]. These two equations differ in many as-
pects, including the predicted index (creatinine clearance
for CGeq and GFR for MDRDeq), units of predictions
(ml/mim for CGeq and ml/mim/1,73 m2 for MDRDeq)
and variables used for the prediction (serum creatinine,
gender, age and body weight for CGeq and serum creati-
nine , gender, age, and race for MDRDeq) [8,9].
Recently, other endogenous proteins easily measured
in clinical laboratories have been suggested as better
markers of GFR. Cystatin C, considered superior to
creatinine in non pregnant women, has been recom-
mended as an alternative and possibly superior marker in
pregnancy. However, others factors such as diabetes, fat
mass and inflammation may alter serum Cystatin C level
and some reports have shown substantial variability in
the relationship between GFR and Cystatin C among
different populations [10], and more r ecent data serious-
ly question its use in pregnant populations [11].
Inulin clearance may be considered the gold standard
method to measure GFR in pregnancy, but it is costly,
cumbersome and not practical outside a clinical research
setting. The endogenous creatinine clearance (Ccr), the
primary tool to assess kidney function in non pregnant
subjects, is equally useful in clinical practice for eva-
luating renal function during the gestational period. Cli-
nicians caring for obstetrics patients are still waiting data
if GFR estimating equations are accurate in pregnancy to
use in clinical practice.
In the present study, we investigated the performance
of CGeq and MDRDeq equations while using ClCr as the
best approximation for GFR in healthy pregnant women.
We aimed to analyse the performance of these estimating
equations to predict renal function in pre gnancy.
One hundred sixty seven normal ambulatory pregnant
women accepted to participate in the study that was
conducted from January to December 2008 and renal
function was contemporaneously estimated and calcu-
lated. All subjects were normoten sive with no history of
renal, cardiac, diabetic or vascular disease, and individu-
als having treatment with drugs affecting creatinine se-
cretion were excluded. The normal pregnant women
selected were between 20th and 30th weeks of gestation.
All subjects gave written informed co nsent for creatin ine
clearance studies and the clinical research was approved
by the local Human Research Ethics Committee.
Each pregnant woman on whom the study was carried
out on an outpatient basis was carefully instru cted in the
collection of a 24 hour urine specimen. Blood samples
were drawn at the morning before their usual morning
meal when weight and height were obtained. They
stayed on a free diet and on their normal physical activi-
ty. Creatinine was measured using a kinetic colourime-
tric assay (Jaffé method) on the same Roche Hitachi 917
equipment (Roche Diagnostic GmbH, Mannheim, Ger-
many) and the assay was calibrated with an IDMS ref-
erence laboratory. Two samples were collected with in-
terval of one week and the mean of the results was used
to calculate renal function by creatinine clearance (Ccr),
Cockcroft-Gault eq uation (CGeq) and the simplified equ-
ation from the Modification of Diet in Renal Disease
Study (MDRDeq).
Ccr was calculated (ml/min):
Ccr = urinary creatinine mg/dl X 24 hour urinary vo lume
ml/min / serum creatinine mg/dl
The prediction equations were calculated:
CGeq (ml/min) = 140 age years X weightkg/72 X se-
rum creatinine mg/dl with use of the 0,850 multiplier for
female gender.
Simplified MDRDeq (ml/min/1.73 m2) = 175 [serum
creatinine mg/dl X 0.011312]-1.154 X Ageyears-0.205 X
To make allowance for comparison with Ccr, MDRDeq
and CGeq results were adjusted for 1.73 m2 of body sur-
face area (BSA) according to the formula:
BSA (m2) = 0.007184 X height cm0.725 X weight kg0.425.
Statistical procedures included analysis of mean and
SD for categorical and numerical data, analysis of 95%
confidence intervals (95%CIs) and analysis of variance
(ANOVA) associated with Bonferroni multiple compar-
isons test.
L. P. J. Marques et al. / Health 3 (2011) 32-36
Copyright © 2011 SciRes. Openly accessible at http://www.scirp.or g/journal/H E A LTH/
A total of 167 normal ambulatory pregnant women;
mean age 32.06 ± 5.04 years were included in this study.
Calculated creatinine clearance, CGeq and MDRDeq
Tabl e 1 . Clinical and laboratorial data at the time of creatinine
Number of Pregnant women 167
Age (year) 32.06 ± 5.04
Time of Pregnancy (week) 25.08 ± 3.03
Weight gain (Kg) 12.04 ± 3.11
Serun creatinine (mg%) 0.59 ± 0.12
Creatinine Clearance (ml/min/1.73 m2) 146.27 ± 30.49
Cockcroft-Gaulteq (ml/ mi n/1.73 m2) 168.41 ± 38.80
MDRDeq ( ml /min/1.73 m2) 129.15 ± 29.28
Tabl e 2. Renal function (ml/min/1.73 m2) measured by creati-
nine clearance (Ccr), Cockcroft-Gault (CGeq) and MDRDeq and
comparison among the measurements.
Ccr CGeq MDRDeq Bias 95% con-
CGeq x
Ccr 146.27
± 30.49 168.41
± 38.80 - 22.13 16.69 To
Ccr x
MDRDeq 146.27
± 30.49 - 129.15 ±
29.28 17.12
11.68 To
CGeq x
MDRDeq - 168.41
± 38.80 129.15 ±
29.28 39.26
33.82 To
equations were performed from 20 to 29 weeks of preg-
nancy (25.80 ± 3.03 weeks) and the weight gain during
gestation until laboratory tests was 12.04 ± 3.11 kg. ( Ta-
ble 1).
The main analyses for indices of kidney function were
with data normalized per 1.73 m2 and the results ob-
served were Ccr = 146.27 ± 30.49 ml/min / 1.73 m2, CGeq
= 168.41 ± 38.80 ml/min/1.73 m2, MDRDeq = 129.15 ±
29.28 ml/min/1.73 m2. (Figure 1).
When we compared calculated and estimated clear-
ances for measurement of kidney function during preg-
nancy we observed that CGeq overestimated renal func-
tion (168.41 ± 38. 80 ml/min/1.73 m2 and 146.27 ± 30.49
ml/min/1.73 m2, CGeq versus Ccr respectively, p < 0.001
and the bias 22.13 ml/min) and MDRDeq underestimated
renal function (129.15 ± 29.28 ml/min/1.73 m2 and
146.27 ± 30.49 ml/min/1.73 m2, MDRDeq versus Ccr
respectively, p < 0.001 and the bias 17,12 ml/min). (Ta-
ble 2, Figure 2 and Figure 3).
Effective renal plasma flow increase and Glomerular
filtration rate change in pregnancy. GFR increase mar-
kedly during gestation, approximately 50% greater than
non pregnant values during the second trimester, these
high levels are maintained through gestational period
until the 36th week, after which a decrease of 15% to
20% may occur (2). We studied kidney function of 167
normal ambulatory pregnant women from 20 to 29
Figure 1. Renal function measured by creatinine clearance (a),
Cockcroft-Gaulteq (b) and MDRDeq (c) during pregnancy.
Figure 2. Poor correlation between renal function measured by
Creatinine Clearance (ClCr) and Cockcroft-Gaulteq (CG) in
normal pregnancy.
Figure 3. Poor correlation between renal function measur e d by
Creatinine Clearance (ClCr) X MDRDeq in normal pregnancy.
weeks of pregnancy (25.80 ± 3.03 weeks), in the period
L. P. J. Marques et al. / Health 3 (2011) 32-36
Copyright © 2011 SciRes. Openly accessible at http://www.scirp. or g/journal/ HE ALTH/
of pregnancy where the renal function is more stable.
The Clearance of endogenous creatinine (Ccr) was the
best approximation of GFR in pregnancy to assess renal
function in clinical practice. Because there is, at most, a
small increase in the production and excretion of creati-
nine during normal gestation, the large increments
in Ccr lead to reduction in its plasma level. Lower seru m
creatinine levels observed in pregnancy are a reflection
of haemodilution due to the increase of plasma volume
as well as hyperfiltration. Thus, values considered nor-
mal in nonpregnant women may reflect abnormal renal
function in preg nancy [12].
Accurate GFR measurements using inulin infusion are
impractical for large-scale application in pregnant popu-
lation, while Ccr is made complex by the need of obtain-
ing accurate 24 hour urine collection. To minimize this
last limitation we instructed women to take note of the
start and end time of urine collection to allow for com-
putation of the length of collection, and used the mean of
two creatinine samples collected with interval of one
week to calculate renal function. All the creatinine as-
says were performed in the same Technican AutoAna-
lyser to prevent the high inter-laboratory variations of
creatinine [13] and the kidney function was contempo-
raneously estimated and calculated.
When we compared the results of estimating renal
function using CGeq and MDRD eq equations with Ccr, we
observed that CGeq overestimated (168.41 ± 38.80
ml/min/1.73 m2 and 146.27 ± 30.49 ml/min/1.73 m2, p <
0.001 ) and MDRDeq underestimated renal function
(129.15 ± 29.28 ml/min/1.73 m2 and 146.27 ± 30.49
ml/min/1.73 m2, p < 0.001), which demonstrated that
CGeq and simplified MDRDeq equations are not useful
measure of GFR in normal pregnancy to estimate renal
function. Some studies have also demonstrated in normal,
hypertensive and preeclamptic pregnancy, that both the
CGeq and MDRDeq were also inaccurate in predicting
kidney function when compared with Ccr [14-16].
Bias (difference between measured (Ccr) and esti-
mated (CGeq and MDRDeq) kidney function) was used as
a measure of performance. Bias of CGeq prediction in
pregnant women (22.13 from 16.69 to 27.57 ml/min)
may be explained by the rule that weight coefficients of
the CGeq do not differentiate between muscular mass
(relevant to creatinine generation) and non-muscular
mass (not relevant to creatinine generation). Thus, the
CGeq during gestation transforms any weight gain dif-
ference into a difference in predicted kidney function
that tends to be overestimated in overweight. Generally
in obstetric population, healthy women gain approx-
imately 12.5 kg in the first pregnancy and 1 kg less in
subsequent gestation and increase the body surface area.
In our pregnant women group weight gain was 12.04 ±
3.11 kg during gestation until laboratory tests to assess
renal function and may have contributed to overesti-
mated renal function by CGeq. However, the correction
of clearance results to 1.73 m2 of body surface area was
not capable to correct th is overesti mated resu lt [17].
In normal gestation, our results demonstrated that
MDRDeq underestimated renal function (Bias of 17.12
from 11.68 to 22.56 ml/min) and is not us eful measur e in
pregnant women on whom GFR increases markedly.
Some large studies have recently concluded that using
the MDRDeq in healthy subjects is problematic. MDRD eq
was derived from an adult population with chronic kid-
ney disease most of whom had a GFR less than 60
ml/min/1.73 m2. Perhaps more important, GFR was sys-
tematically underestimated by MDRDeq when GFR rises
above 60 ml/ min/1.73 m2 in healthy subjects and clini-
cal laboratory that estimate GFR by MDRDeq usually
report the result as GFR > 60 ml/min/1.73 m2 [18,19 ].
Similarly in pregnancy, recent studies comparing
MDRDeq with inulin clearance in a small sample of
healthy pregnant women have also demonstrated that
MDRDeq underestimated GFR during gestation [20,21].
In conclusion: CGeq overestimated and MDRDeq un-
derestimated significantly kidney function during gesta-
tion in healthy women and are not accurate enough to be
used as screening tests to assess renal function in obste-
tric population. At present, 24-h urine collection for en-
dogenous Ccr, and that may also be used for proteinuria
measurement, remains as the best method to measure
renal function during pregnancy in clinical practice, and
there is no estimating equation that provides accurate
eGFR during pregnancy. So, it is necessary to develop
an accurate equation to pregnant women that considers
the several important changes in maternal renal hemo-
dynamics and provides an eGFR the most unbiased and
precise as possible. Our results clearly demonstrated that
CGeq and MDRDeq cannot be recommended as a useful
clinical tool in obstetric pra ctice and c linicians caring for
obstetric patients may soon see eGFR routinely reported
alongside the traditional biochemistry.
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