Journal of Perinatology (2008) 28, 461467

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ORIGINAL ARTICLE

Urinalysis vs urine proteincreatinine ratio to predict significant

proteinuria in pregnancy
BK Dwyer1, M Gorman2, IR Carroll3 and M Druzin1
1

Division of Maternal Fetal Medicine, Department of Gynecology and Obstetrics, Stanford University, Stanford, CA, USA;
Department of Family and Community Medicine, University of California, Davis, CA, USA and 3Division of Pain Medicine,
Department of Anesthesiology, Stanford University, Stanford, CA, USA

Objective: To compare the urine proteincreatinine ratio with urinalysis

to predict significant proteinuria (X300 mg per day).

Study Design: A total of 116 paired spot urine samples and 24-h urine
collections were obtained prospectively from women at risk for
preeclampsia. Urine proteincreatinine ratio and urinalysis were
compared to the 24-h urine collection.
Result: The urine proteincreatinine ratio had better discriminatory
power than urinalysis: the receiver operating characteristic curve had a
greater area under the curve, 0.89 (95% confidence interval (CI) 0.83 to
0.95) vs 0.71 (95% CI 0.64 to 0.77, P<0.001). When matched for
clinically relevant specificity, urine proteincreatinine ratio (cutoff
X0.28) is more sensitive than urinalysis (cutoff X1 ): 66 vs 41%,
P 0.001 (with 95 and 100% specificity, respectively). Furthermore, the
urine proteincreatinine ratio predicted the absence or presence of
proteinuria in 64% of patients; urinalysis predicted this in only 19%.
Conclusion: The urine proteincreatinine ratio is a better screening
test. It provides early information for more patients.
Journal of Perinatology (2008) 28, 461467; doi:10.1038/jp.2008.4;
published online 21 February 2008
Keywords: pregnancy; urinalysis; urine proteincreatinine ratio;
proteinuria; preeclampsia; sensitivity and specificity

Introduction
The diagnosis of preeclampsia is determined by the presence of
elevated blood pressure and significant proteinuria (X300 mg per
24 h) after the 20th week of gestation.1 The gold standard for
measuring proteinuria is the 24-h urine collection. Unfortunately,
the 24-h urine collection takes an entire day to collect and is,
therefore, not available to guide clinical decisions upon first
Correspondence: Dr BK Dwyer, Division of Maternal Fetal Medicine, Department of
Gynecology and Obstetrics, Stanford University, 300 Pasteur Drive, Stanford, CA 94305-5317,
USA.
E-mail: dwyerb@stanford.edu
Received 4 June 2007; revised 19 December 2007; accepted 4 January 2008; published online
21 February 2008

evaluation. A rapid screening test to predict 24-h proteinuria, in

combination with other presenting signs and symptoms, can help a
clinician determine the appropriate amount of surveillance and
guide care during the initial 24-h period. Traditionally, the dipstick
urinalysis has been used as this screening test.2
The dipstick urinalysis measures the concentration of protein in
the urine and is susceptible to fluctuations in the water content of
the urine. Dilute urine may underestimate the amount of protein
that would be collected in a 24-h urine collection, whereas
concentrated urine may overestimate it. Prior studies have reported
that dipstick urinalysis has varying degrees of accuracy, with
sensitivities ranging from 22 to 82%. Specificities also vary
widely.25 Differences in methodology contribute to this large
discrepancy. For example, automated dipstick urinalysis is more
specific for predicting 24-h proteinuria than is ward dipstick
urinalysis.6 Furthermore, discrepancies in the reported sensitivity
and specificity of the dipstick urinalysis may be due to differences
in the spectrum of illness in the populations studied or the time of
day that the spot urine was collected.
Recently, the urine proteincreatinine ratio has been
considered important for predicting proteinuria. It compares the
spot urine protein excretion to the spot urine creatinine excretion,
thereby normalizing protein excretion to the glomerular filtration
rate. Thus, the urine proteincreatinine ratio is not subject to
variation due to hydration status. In pregnant women, the urine
proteincreatinine ratio and the 24-h urine are highly
correlated.613 Many studies have evaluated the urine protein
creatinine ratio but, they differ in their recommended cutoffs and
differ in their assessment of the tests utility.69,12,13 Different
methodologies, such as the spectrum of illness in the population
studied, retrospective study design,9 exclusion of patients with
comorbid illness,9,13 and nonexclusion of incomplete or infected
samples613 probably account for these discrepancies.
No study has directly compared the diagnostic ability of the
automated dipstick urinalysis to that of the urine protein
creatinine ratio using the same group of subjects, which would
allow appropriate statistical comparisons. In this study, we directly
compared the two tests in a prospective fashion on a group of

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462

women being evaluated for preeclampsia, including those with

comorbid illness to determine which was more predictive of 24-h
proteinuria.
Methods
This prospective study was performed on the Labor and Delivery
unit at Stanford University Hospital from September 2002 to March
2004 after approval by the Institutional Review Board, Medical
Human Subjects Panel. Written informed consent was obtained
from all participating patients. To mimic the experience of treating
physicians we included all women being evaluated for
preeclampsia, regardless of the alerting sign or symptom, suspected
severity or comorbid conditions. Study patients underwent initial
triage on the Labor and Delivery unit. Most women completed the
24-h urine collection as outpatients, but some remained in the unit
as clinically indicated. The study design allowed for patients to be
enrolled when they presented to Labor and Delivery for an
independent evaluation of preeclampsia. Therefore, women could
be enrolled more than once. There were 155 enrollments. Of these,
19 were excluded because the 24-h urine was not done, 4 because
the urinalysis was not done and 6 because the urine protein
creatinine ratio was not done. Six were excluded because the 24-h
urine was not complete or the collection was improper by the
criteria below. Four were excluded because the urinalysis had>10
white blood cells (WBCs) per high-power field (h.p.f.) on
microscopy, concerning for contamination. A total of 116
enrollments from 95 women were ultimately included in the study.
Thus, 21 of the 116 samples were from women who were enrolled
in the study more than once.
The main measures were the urinary protein concentration
by automated dipstick urinalysis, the urinary protein to urinary
creatinine ratio by random (spot) direct measurement and the
24-h urinary protein excretion by a 24-h urine collection. The
urinalysis and the urine proteincreatinine ratio were usually
obtained immediately before the 24-h urine collection was begun.
If that sample was not available at the time of enrollment, a
sample was obtained immediately after the 24-h collection. All
samples were collected via clean catch unless the membranes had
been ruptured, in which case specimens were obtained by catheter.
Given that outpatient and inpatient urine collections may have
been collected with different degrees of completeness and/or
contamination, subjects were excluded if the urinalysis contained
>10 WBCs per h.p.f., if a catheter was not used after membrane
rupture or if an outpatient 24-h urine collection was incomplete.
A complete collection was defined as having a total creatinine
of >1000 mg (850 mg for obese women) or a total creatinine
of 13 mg per kg body weight.14
The urinary protein and creatinine were measured using
Synchron LX Systems (Beckman Coulter Inc., Fullerton, CA, USA),
which uses the pyrogallol red/molybdate and Jaffe rate methods,
Journal of Perinatology

respectively. The automated dipstick urinalysis was performed with

Iris test strips and either the IRIS 500 (IRIS Inc., Chatsworth, CA,
USA) or Autionmax (Arcray Inc., Kyoto, Japan), autoanalyzers
using 30 300 50 500 -tetrachlorophenol-3,4,5,6-tetrabromosulfopthalein,
a protein error of pH indicator. These machines were calibrated
such that 1 protein 30 mg per 100 ml, 2 protein 100 mg
per 100 ml, 3 protein 300 mg per 100 ml and
4 protein 1000 mg per 100 ml. Trace protein was not reported
by these machines. All measurements were performed by laboratory
technicians blinded to the clinical status of the study patients.
Statistical analysis
The strengths of the correlation between the automated dipstick
urinalysis and 24-h proteinuria and the urine proteincreatinine
ratio and 24-h proteinuria were determined by Spearmans correlation
coefficients with corresponding 95% confidence intervals (CI).
Significant proteinuria was defined as X300 mg of protein in
the 24-h urine collection, as recommended by the International
Society for the Study of Hypertension in Pregnancy and the
American College of Obstetrics and Gynecology.1,15 The sensitivity
and specificity16 as well as the positive and negative predictive
values17 were calculated using each observed level of the urinalysis
and the urine proteincreatinine ratio as the threshold for a
positive test with the 24-h collection as the reference standard.
Differences in selected sensitivities and specificities were examined
using the McNemars test. The likelihood ratios (LRs) for ranges of
the urine proteincreatinine ratio and urinalysis were calculated.18
Additionally, we examined the test characteristics for predicting a
severe level of proteinuria of 5000 mg or greater.
The relationship between sensitivity and the false-positive rate
(1specificity) for both the urinalysis and the urine protein
creatinine ratio was evaluated by constructing receiver operating
characteristic (ROC) curves for both measures. As a summary of
the diagnostic utility of the urinalysis and the urine protein
creatinine ratio, the areas under the ROC curves were calculated
and directly compared using the method described by Delong
et al.19 Data analysis was performed using STATA statistical
software (Release 8; Stata Corp., College Station, TX, USA).
To examine whether a lack of independence due to some
subjects contributing more than one set of paired spot urine and
24-h urine samples led to inaccurate estimates in our analysis,
a sensitivity analysis was performed comparing the statistical
outcome of the data from the initial 116 samples to that of 95
samples (using only first samples if there had been additional
enrollments).

Results
Population studied
A total of 116 paired samples were evaluated. Of those 48% had
significant proteinuria. Forty-one percent were from primigravidas.

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463

In total, 41% of the samples were from Caucasian women, 31%

from Hispanic women, 16% from Asian women and 12% from
African-American women. Many subjects had medical conditions
that predisposed them to preeclampsia (Table 1).
Correlation of the urine proteincreatinine ratio vs the
urinalysis to 24-h proteinuria
Both the urine proteincreatinine ratio and the urinalysis were
correlated to the gold standard, 24-h proteinuria. The correlation
coefficient for the urine proteincreatinine ratio was 0.83 (95% CI
0.76 to 0.88). For the urinalysis, it was 0.64 (95% CI 0.52 to 0.74).
Receiver operating characteristic curves
The ROC curves for both the urine proteincreatinine ratio and
the urinalysis are presented in Figure 1. A diagnostic test with an
area under the ROC curve closest to 1.0 has the best discriminatory
power. The area under the ROC curve for the urine protein
creatinine ratio was 0.89 (95% CI 0.83 to 0.95), and the area under
the ROC curve for the urinalysis was 0.71 (95% CI 0.64 to 0.77).
The areas under these curves were significantly different
(P<0.001).

sensitivity to maximum specificity. Note that trace proteinuria is

not reported by automated dipstick machines.
The sensitivity for the urine proteincreatinine ratio varied
depending on the cutoff used. We highlight two clinically useful
cutoffs derived from the ROC curve, one that maximizes sensitivity
and the other that maximizes specificity. A cutoff of X0.15 had a
sensitivity of 96% (95% CI 87 to 99%) and a specificity of 53% (95%
CI 40 to 66%). A cutoff of X0.28 had a sensitivity of 66% (95% CI
52 to 78%) and a specificity of 95% (95% CI 86 to 99%). Note that
a cutoff of X0.19 maximizes both sensitivity (89, 95% CI 78 to
96%) and specificity (70, 95% CI 59 to 83%), but significantly
compromises both measures.
The sensitivity for the urinalysis ranged from 11 to 41%
depending on the cutoff used (Table 2). Greater than or equal to

Sensitivity and specificity of the urine proteincreatinine ratio

and the urinalysis for predicting significant proteinuria
(X300 mg proteinuria per 24-h period)
The urine proteincreatinine ratio is the more sensitive test for
predicting 24-h proteinuria compared to the urinalysis, even when
matched for specificity. Table 2 demonstrates the sensitivity and
specificity for both tests at selected cutoffs. These points were
selected because they demonstrate the range from maximum

Table 1 Demographic and clinical characteristics of study participants by

presence or absence of significant proteinuria in a 24-h urine collection
(n 116)
Characteristic

Age, mean (s.d.)

Caucasian, no. (%)
Primigravida, no. (%)
Weight lbs, mean (s.d.)
High systolic blood pressure,
mean (s.d.)
High diastolic blood pressure,
mean (s.d.)
Chronic hypertension, no.
(%)
Diabetes mellitusa, no. (%)
Total 24-h protein, median
(IQR) mg

<300 mg protein per

24 h (n 60)
30.8
25
19
189.5
141.4

(6.2)
(41.7)
(32.7)
(37.1)
(13.1)

X300 mg protein per

24 h (n 56)
30.8
22
22
193.9
143.4

(6.5)
(39.3)
(39.3)
(41.5)
(16.3)

89.3 (11.3)

91.5 (12.8)

10 (16.7)

16 (28.6)

7 (11.7)
210 (165242)

Abbreviations: IQR, interquartile range; lbs, pounds.

a
Includes pregestational and gestational diabetes.

1 (1.8)
580 (3901246)

Figure 1 Receiver operating characteristic curves (ROCs) for the urine protein
creatinine ratio (a) and for the urinalysis (b). The area under the ROC curve for
the urine proteincreatinine ratio is 0.89 (95% CI 0.83 to 0.95) and the area
under the ROC curve for the urinalysis is 0.71 (95% CI 0.64 to 0.77). The areas
under these curves are significantly different (P<0.001). Selected values for each
measure, along with the sensitivity or specificity, are highlighted.
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464
Table 2 Sensitivity, specificity, positive predictive value and negative predictive
value for selected cutoffs for the urine proteincreatinine ratio and the urinalysis
for predicting X300 mg protein per 24 h urine
Test result

Sensitivity (%)

UPCR
X0.15a
X0.17
X0.19
X0.24
X0.28
X0.39

96
91
89
73
66
55

Specificity (%)

53
58
70
87
95
100

PPV (%)

100
41
23
11

0
100
100
100

66
67
74
84
93
100

94
88
88
78
75
71

48
100
100
100

65
58
55

Abbreviations: UA, urinalysis; UPCR, urine proteincreatinine ratio.

a
Using a cutoff of X0.15, two subjects with significant 24-h proteinuria (304 and
336 mg) were missed.
b
This number could not be calculated due to 0 in the denominator.

1 proteinuria on the dipstick had a sensitivity of 41% (95% CI

28 to 55%) and a specificity of 100% (95% CI 93 to 100%).
These data demonstrate that when using a cutoff of X0.15, the
urine proteincreatinine ratio is significantly more sensitive than
the urinalysis (96 vs 41%, P<0.001). Even when matching the two
tests for clinically relevant specificity with a urine protein
creatinine ratio cutoff of X0.28 and a urinalysis cutoff of X1
(specificity is 95 and 100%, respectively), the sensitivity of the urine
proteincreatinine ratio is better than that of the urinalysis (66 vs
41%, P 0.001).
Likelihood ratios for the urine proteincreatinine ratio and the
urinalysis
Unlike predictive values, LRs are less subject to variation in the
prevalence of disease in a given population.17 We list the LRs for
ranges of each test (Table 3). In general, a diagnostic test with an
LR of>10 or <0.10 changes pretest probability dramatically and is
considered a strong diagnostic test.20
Likelihood ratios calculated for values of the urine protein
creatinine ratio <0.15 and X0.28 have a large effect on pretest
probability. For example, with a urine proteincreatinine ratio of
<0.15 (LR 0.07, 95% CI 0.02 to 0.27), pretest probabilities of 40,
50 and 60% transform to posttest probabilities of 4, 6 and 9%,
respectively. Similarly, with values X0.28 (LR 13.2, 95% CI 4.3
to 40.1), pretest probabilities of 40, 50 and 60% transform to
posttest probabilities of 90, 93 and 95%, respectively. A urinalysis of
X1 (LR 49.7, 95% CI 3.1 to 792.3) also has an LR that is
strongly diagnostic.
Journal of Perinatology

Test result

Likelihood ratioa (95% CI)

Interpretation

0.07 (0.020.27)
0.73 (0.441.2)
13.21 (4.340.5)

Negative
Indeterminate
Positive

0.59 (0.470.73)
49.29 (3.1792.8)

Indeterminate
Positive

NPV (%)

UA
XNegative
X1+
X2+
X3+

Table 3 Likelihood ratios for the urine proteincreatinine ratio and the
urinalysis for different ranges of test results

UPCR
<0.15
0.150.27
X0.28
UA
Negative
X1+

Abbreviations: UA, urinalysis; UPCR, urine proteincreatinine ratio.

a
0.05 was added to empty cells to allow for the calculation of the likelihood ratios.

However, values of the urine proteincreatinine ratio from 0.15

to 0.27 (LR 0.73, 95% CI 0.44 to 1.20) and a negative urinalysis
(LR 0.59, 95% CI 0.47 to 0.73) do not significantly affect pretest
probability. Therefore, urine samples with these results are
indeterminate.
Thus, the urine proteincreatinine ratio is useful diagnostically
when the value is <0.15 or X0.28, but is indeterminate in the
middle range. Similarly, the urinalysis is useful when the value is
X1 protein, but is indeterminate when it is negative for protein.
In our study the urine proteincreatinine ratio was diagnostic in
64% our samples, whereas, the urinalysis was diagnostic in only
19% of our samples (P<0.001).
Sensitivity and specificity of the urine proteincreatinine ratio
and the urinalysis for predicting severe proteinuria
(X5000 mg proteinuria per 24-h period)
Sensitivities, specificities and positive and negative predictive values
were calculated for many cutoffs of the urine proteincreatinine
ratio and each cutoff of the urinalysis to demonstrate the accuracy
of each test for predicting X5000 mg proteinuria per 24-h period
(Table 4 ). Only three patients in our study had proteinuria
X5000 mg of protein. As a screening test for identifying patients
who may have severe proteinuria, the urine proteincreatinine
ratio and the urinalysis are very good. They also both have good
specificity, in particular the urine proteincreatinine ratio X5.0
and the urinalysis X3 . In fact, to predict severe proteinuria it
appears that the urine proteincreatinine ratio is unlikely to add
utility to the urinalysis alone. Caution should be used in using spot
urine studies rather than 24-h urine collections to make a
diagnosis of severe proteinuria because this analysis is limited by
the relatively few number of patients with severe proteinuria in this
study and, therefore, the inability to accurately describe a range.
Sensitivity analysis
Given concern that 21 paired samples from our cohort were from
patients who previously contributed samples, we conducted a

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465

sensitivity analysis comparing the results of our initial cohort to the

cohort minus these 21 samples. Each statistic reported above was
calculated for each group, including Spearmans correlation
Table 4 Sensitivity, specificity, positive predictive value and negative predictive
value for selected cutoffs for the urine proteincreatinine ratio and the urinalysis
for predicting X5000 mg protein per 24 h urine
Test result

Sensitivity (%)

Specificity (%)

PPV (%)

NPV (%)

UPCR
X2
X3
X4
X5
X13.53

100
100
100
100
67

96
97
98
100
100

38
50
60
100
100

100
100
100
100
99

100
100
100
100

0
83
92
98

3
14
25
60

a
100
100
100

UA
XNegative
X1+
X2+
X3+

Abbreviations: UA, urinalysis; UPCR, urine proteincreatinine ratio.

a
This number could not be calculated due to 0 in the denominator.

coefficients, the area under the ROC curves, sensitivity and

specificity for chosen cutoffs, and LRs for chosen ranges. All of
these test results were identical or nearly identical to the values
calculated for the entire study group. As expected, the CIs around
sensitivity, specificity and LRs were slightly wider for the group with
fewer samples.

Discussion
Our study demonstrated that the urine proteincreatinine ratio
can be more sensitive than the automated dipstick urinalysis, and
therefore, is the better screening test (96 vs 41%, P<0.001). The
urinalysis is very specific, but at its most sensitive diagnostic level
(1 ) will miss more than half (59%) of patients at risk for
preeclampsia. The urine proteincreatinine ratio also allows for
early diagnosis in more patients (64 vs 19%, P<0.001).
Other studies have previously evaluated the urine protein
creatinine ratio in pregnancy for its ability to predict 24-h
proteinuria at different cutoffs.69,12,13 Our data are nearly
identical to studies that evaluated a similar patient population, and
therefore, should be applicable to institutions screening individuals
who are clinically suspicious for preeclampsia.79,13 Despite the

Figure 2 Flow diagram of the two-step triage strategy. At triage, an automated dipstick urinalysis should be performed. If it is positive, a patient can be assumed to have
significant proteinuria. If it is negative, the test is indeterminate and a urine proteincreatinine ratio should be performed to further define risk. In parentheses are the
number of samples in the current study that fell into each category. UPCR, urine proteincreatinine ratio.
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similarity in data, conclusions regarding the optimal cutoff and

the whether the urine proteincreatinine ratio is useful have
varied. This is because an optimal cutoff that simultaneously
maximizes sensitivity and specificity (0.19 in our case)
significantly compromises each measure. We recommend using
two cutoffs. A cutoff of X0.15 will increase sensitivity to well above
90%, and a cutoff of X0.28 will maximize specificity. The urine
proteincreatinine ratio cutoff is thus dictated by the
physicians needs.
Our study has limitations. A small number of our spot samples
were collected immediately after the 24-h urine specimen rather
than before. We do not think that this alters our ability to compare
the two tests given that the paired urinalysis and urine protein
creatinine ratios were collected at the same time in relation to the
24-h urine collection. Therefore, the direct comparison between the
two tests was achieved because the timing of the sample collection
was consistent within subjects. It is also important to emphasize
that these results demonstrate that the urine proteincreatinine
ratio can detect significant 24-h proteinuria (X300 mg per 24 h)
better than the urinalysis, but this study does not address whether
the urine proteincreatinine ratio can distinguish between mild
and severe preeclampsia by predicting the extent of proteinuria. A
24-h urine may still be needed in settings where the diagnosis of
preeclampsia or severe preeclampsia by proteinuria would imply a
preterm delivery.
Concern has been raised that the urine proteincreatinine ratio
may be effected by body type or by race, as people with higher
muscle mass have more total urinary creatinine excretion and
nonpregnant African Americans may have a higher concentration of
urine creatinine. It is unclear how these differences effect the validity
of the urine proteincreatinine ratio in different subpopulations.21
Unfortunately, our study was underpowered to conduct appropriate
stratified analyses by race/ethnicity to address these issues. Future
studies should be done to address these variations.
On the basis of our study results, we recommend a two-step
triage algorithm to identify patients with preeclampsia (Figure 2).
On initial screen, an automated dipstick urinalysis should be
performed. If the urinalysis has 1 protein or greater, the patient
most likely has significant proteinuria. If the urinalysis is negative
for protein (an indeterminate result), a urine proteincreatinine
ratio should be ordered to further define risk. If the urine protein
creatinine ratio is <0.15, the patient most likely does not have
significant proteinuria. In this setting, whether the 24-h urine
collection is still an appropriate test is debatable and may not be
cost effective. If the urine proteincreatinine ratio is X0.28, the
patient most likely has significant proteinuria. If the urine
proteincreatinine ratio is between 0.15 and 0.27, this is an
indeterminate result and further evaluation with a 24-h urine
collection is warranted.
This diagnostic algorithm is better at providing more accurate
and earlier diagnostic information than the traditional automated
Journal of Perinatology

dipstick urinalysis alone. With the traditional urinalysis, using

X1 as a cutoff, the presence of significant proteinuria was
predicted in only 19% of our subjects prior to 24-h urine collection.
A negative urinalysis cannot predict the absence of significant
proteinuria (LR 0.59, 95% CI 0.47 to 0.73). Using the urinalysis
combined with the urine proteincreatinine ratio, the absence or
presence of significant proteinuria was predicted in 66% of patients.
In summary, the urine proteincreatinine ratio may be a
useful adjunct test for diagnosis and triage of a patient being
evaluated for preeclampsia. Its use as an initial screen in
combination with the urinalysis will prevent underdiagnosis of
preeclampsia and provide an accurate diagnosis 66% of the time
before a 24-h collection is completed. Earlier distinction between
preeclampsia and other forms of hypertension in triage may allow
for earlier diagnosis and treatment of preeclampsia with a
subsequent decrease in morbidity and a decrease in resource
utilization.

Acknowledgments
This study was financially supported by the Department of Gynecology and
Obstetrics, Stanford University.

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