A Comparison of Podocyturia, Albuminuria and

Nephrinuria in Predicting the Development of

Preeclampsia: A Prospective Study
Belinda Jim1*, Swati Mehta2, Andi Qipo1, Kwanghee Kim3, Hillel W. Cohen4, Robert M. Moore5,
John C. He2,6, Shuchita Sharma6
1 Jacobi Medical Center, Albert Einstein College of Medicine, Department of Nephrology/Medicine, Bronx, New York, United States of America, 2 James J. Peters VA
Medical Center, Department of Nephrology/Medicine, Bronx, New York, United States of America, 3 Providence Alaska Medical Center, Anchorage, Alaska, United States of
America, 4 Albert Einstein College of Medicine, Department of Epidemiology and Population Health, Bronx, New York, United States of America, 5 Jacobi Medical Center,
Albert Einstein College of Medicine, Department of Obstetrics and Gynecology, Bronx, New York, United States of America, 6 Mount Sinai School of Medicine, Department
of Nephrology/Medicine, New York, New York, United States of America

Abstract
Preeclampsia, a hypertensive multisystem disease that complicates 58% of all pregnancy, is a major cause for maternal and
fetal mortality and morbidity. The disease is associated with increased spontaneous and evoked preterm birth and remote
cardio-renal disorders in the mother and offspring. Thus the ability to predict the disease should lead to earlier care and
decreased morbidity. This has led to fervent attempts to identify early predictive biomarkers and research endeavors that
have expanded as we learn more regarding possible causes of the disease. As preeclampsia is associated with specific renal
pathology including podocyte injury, early urinary podocyte (podocyturia), or the podocyte specific proteinuria nephrin in
the urine (nephrinuria), as well as the more easily measured urinary albumin (albuminuria), have all been suggested as
predictive markers. We performed a prospective study recruiting 91 pregnant women (78 of whom were high risk) and
studied the predictive ability of these three urinary biomarkers. The subjects were recruited between 1538 weeks of
gestation. Fourteen patients, all in the high-risk obstetric group, developed preeclampsia. The levels of podocyturia,
nephrinuria, and albuminuria were variably higher in the high-risk pregnant patients who developed preeclampsia. The
sensitivities and specificities for podocyturia were 70% and 43%, for albuminuria were 36% and 96%, and for nephrinuria
were 57% and 58%, respectively. Also, abnormal nephrinuria (69%) and podocyturia (38%) were detected in low risk women
who had uncomplicated gestations; none of these women exhibited albuminuria. In our study, none of the three urinary
markers achieved the minimum predictive values required for clinical testing. The lack of excessive albuminuria, however,
may indicate a preeclampsia-free gestation. Given a discrepant literature, further studies with larger sample size should be
considered.
Citation: Jim B, Mehta S, Qipo A, Kim K, Cohen HW, et al. (2014) A Comparison of Podocyturia, Albuminuria and Nephrinuria in Predicting the Development of
Preeclampsia: A Prospective Study. PLoS ONE 9(7): e101445. doi:10.1371/journal.pone.0101445
Editor: Michael Bader, Max-Delbruck Center for Molecular Medicine (MDC), Germany
Received March 12, 2014; Accepted June 5, 2014; Published July 10, 2014
Copyright: 2014 Jim et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: The authors confirm that all data underlying the findings are fully available without restriction. All data is in manuscript.
Funding: This publication was supported in part by the CTSA Grant 1 UL1 TR001073-01, 1 TL1 TR001072-01, 1 KL2 TR001071-01 from the National Center for
Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
* Email: [email protected]

tyrosine kinase-1 (sFlt-1), and soluble endoglin (sEng) have been

shown to occur prior to the onset of PE and cause phenotypic signs
(e.g., hypertension proteinuria, glomerular endotheliosis) in animal
models [27]. These angiogenic factors also appear to be specific
for PE and help differentiate it from other hypertensive conditions
such as acute and chronic glomerulonephritis [8,9] and other
hypertensive disorders [10]. However, the value of these angiogenic factors in predicting the development of PE in larger
population is still questionable as their test characteristics are wideranging and not consistent [11].
Interest in using podocytes as a predictive and diagnostic
marker for PE stems from the observations that podocyte-specific
protein expression is reduced in renal biopsies of patients with PE
[12]. The same group detected increased urinary podocyte

Introduction
Preeclampsia (PE) is a hypertensive complication of pregnancy
and a major cause of maternal and fetal morbidity and mortality
worldwide. The disease involves many organs and its lifethreatening events include cerebral hemorrhage, hepatic failure,
pulmonary edema, disseminated intravascular coagulation accounting to 1015 percent of maternal deaths worldwide [1].
Given the ominous outcomes associated with PE, a reliable
diagnostic and predictive tool could lead to early interventions and
substantially decrease poor outcomes. In this respect, a variety of
biomarkers have recently been identified concurrent with progress
made regarding our understanding of the pathogenesis of the
disease. For example, changes in circulating levels of angiogenic
factors, such as placental growth factor (PlGF), soluble fms-like
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Urinary Biomarkers in the Prediction of Preeclampsia

in blood pressure (BP) from baseline (30 mmHg systolic blood

pressure or 15 mmHg diastolic BP) or if there was a 23 fold
increase in proteinuria. This study was approved by the Internal
Review Board of Albert Einstein College of Medicine.

excretion in 15 women with PE, and when stained for podocin, a

podocyte-specific protein, reported 100% sensitivity and specificity
for diagnosing the disease [13]. We evaluated podocyturia as a
marker for diagnosing PE in a high risk obstetric population noting
the test to be neither sensitive nor specific [14]. Podocyturia has
also been evaluated for its predictive accuracy by Craici et al. who
showed the presence of podocyturia at the end of 2nd trimester to
be 100% sensitive and specific in distinguishing subsequent
development of PE from normotensive pregnancies, gestational
hypertension, or from both groups combined [15]. Whether this
finding is reproducible, especially in other high-risk pregnancies
states such as diabetes and other renal disorders, is unclear. Thus
we performed a prediction study comparing the levels of three
different biomarkers, podocyturia, albuminuria, and nephrinuria
in the second and third trimester of pregnancy, assessing the ability
of each test to predict the development of PE in amongst women
who are low risk and high risk for developing PE.

Urinary protein quantification

A single voided urine specimen (20 mL) was obtained immediately following recruitment. Its concentrations of albumin-tocreatinine ratio (alb/Cr) were measured by clinical laboratories at
Jacobi Medical Center, Bronx, NY, USA. And elevated level of
alb/Cr was defined as $30 mg/g. An aliquot of the urine was
frozen at 280uC for urine nephrin measurement. Urinary nephrin
was determined by a competitive enzyme-linked immunosorbent
assay using polyclonal antibodies against the extracellular domain
(amino acids 23322) of human nephrin (Exocell Inc., Philadelphia, PA, USA). The assay was performed by Exocell Inc.
according to manufacturers instructions. Briefly, urine samples
were diluted in the range of 1:10 to 1:500 (depending on degree of
proteinuria in the sample). A 50-ml diluted sample was added to
each well already coated with rat nephrin followed by the addition
of a 50-ml rabbit anti-nephrin antibody for an incubation of
60 minutes at room temperature. Plates were washed followed by
the incubation with 100-ml of anti-rabbit HRP conjugate to each
well for 60 minutes. After plates were washed and color
developed, absorbance was read at 450 nm. An elevated level of
urinary nephrin (nephrinuria) was defined as urine nephrin-tocreatinine ratio (nephrin/Cr) (mg/g) $0.1 mg/g. This value was
based on 10 healthy controls who consistently exhibited nephrin/
Cr ,0.1 mg/g.

Materials and Methods

We recruited both women with apparently uncomplicated
gestation (low risk) and others at risk for pregnancy complications (high-risk group as described below) from the obstetric
outpatient service at Jacobi Medical Center, Bronx, NY, USA.
Random urine samples were obtained from the subjects in the
second (weeks 15 to 26) or third trimesters (weeks 27 to 38) of
gestation. Inclusion criteria for high-risk group were PE in a
previous pregnancy, chronic hypertension (HTN), Type I and
Type II diabetes mellitus (DM), gestational DM, chronic kidney
disease (CKD), obesity (BMI.30), and systemic lupus erythematosis (SLE), all 18 years or older. Chronic HTN was defined as
preexisting HTN or blood pressure of 140/90 mmHg before 20
weeks of gestation. Gestational DM was defined as any degree of
glucose intolerance with onset of first recognition during
pregnancy. All patients were managed until delivery and studied
for the development of PE. Diagnosis of PE fulfilled the criteria of
new onset of HTN with blood pressure of 140/90 mmHg after 20
weeks of gestation and proteinuria of .300 mg of protein in a 24hour urine specimen or 1+ protein on a urinalysis sample without
evidence of another cause. For superimposed PE in patients with
chronic HTN or CKD, the diagnosis was made if there was a rise

Podocyturia measurement
Pellets containing cellular material were retrieved from an
aliquot of the patients urine that had been centrifuged at 700 g for
5 min. These pellets were carefully recovered by aspirating the
supernatant, washed twice with PBS and resuspended in 1 mL of
PBS. Aliquots of 100 ml of the resuspended sediment were
centrifuged onto slides using the Shandon Cytospin 4 Cytocentrifuge (Thermo Electron Corporation, Asheville, NC, USA), airdried and fixed with 1:1 acetone/methanol for 10 minutes. The
slides were immersed with PBS/1% H202 for 15 minutes and

Table 1. Patient Characteristics According to Preeclampsia Outcome.

Patient Characteristic

High Risk Patients with

Preeclampsia

High Risk Patient without

Preeclampsia

n = 14

n = 64

P value

Maternal Age

31.0 (27.036.0)

31.5 (26.336.8)

p = 0.98

Gestational Age at Recruitment

24.5 (18.832.5)

27.5 (21.833.00)

p = 0.29

Gestational age at delivery

36.0 (31.837.2)

38.4 (37.339.1)

p,0.0001

SBP at time of recruitment

129.0 (121.8146.0)

119.0 (111.0127.8)

p = 0.0002

DBP at time of recruitment

70.5 (64.878.3)

67.0 (60.071.0)

p = 0.11

151.0 (143.8164.8)

126.0 (116.0138.0)

p,0.0001

86.0 (81.5101.5)

75.0 (65.084.0)

p = 0.0002

7.5 (6.0010.5)

8.0 (6.5010.00)

p = 0.84

Serum creatinine (mg/dl)

0.5 (0.400.62)

0.5 (0.500.70)

p = 0.59

SBP at time of delivery

DBP at time of delivery
BUN (mg/dl)

Data median (interquartile range) or (#/%).

1
SBP: systolic blood pressure.
2
DBP: diastolic blood pressure.
3
BUN: blood urea nitrogen.
doi:10.1371/journal.pone.0101445.t001

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Urinary Biomarkers in the Prediction of Preeclampsia

Figure 1. Images of Urinary Podocytes. A) Representative immunofluorescent images of urinary podocytes in high risk patients with PE stained
with podocin (pod), synaptopodin (syn) and colocalized (merged). B) Representative immunofluorescent images of urinary podocytes in high risk
patients without PE stained with podocin (pod), synaptopodin (syn) and colocalized (merged). C): Representative immunofluorescent images of
urinary podocytes in healthy pregnant control patients stained with podocin (pod), synaptopodin (syn) and colocalized (merged). D): Negative
control in absence of primary antibody E) Positive control of podocin (pod) and synaptodin (syn) on normal kidney tissue.
doi:10.1371/journal.pone.0101445.g001

washed with deionized water and blocked with 10% donkey serum
in PBS and 2% BSA for 30 minutes. Slides were incubated
overnight with monoclonal mouse anti-human synaptopodin
antibody at 1:1 dilution and rabbit polyclonal podocin antibody
at 1:500 dilution (both gifts from Dr. Peter Mundel, Massachusetts
General Hospital, Boston, MA, USA). This was followed by

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incubation with FITC-conjugated anti-rabbit and TRITC-conjugated anti-mouse secondary antibodies at 1:500 dilution (Life
Technologies, Grand Island, NY, USA) for 30 minutes. The
nuclei were counterstained with DAPI (1:10,000 dilution). Slides
were then washed and mounted with Vectashield mounting
medium (Vector Laboratories, Burlingame, CA, USA). Normal

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Urinary Biomarkers in the Prediction of Preeclampsia

Figure 2. Dot plots of urine podocyte-to-creatinine ratios. A) Urine podocyte-to-creatinine ratio measurements in 2nd and 3rd trimester
recruited patients who developed PE vs. patients who did not develop PE B) Urine podocyte-to-creatinine ratio measurements in 2rd trimester
recruited patients who developed PE vs. patients who did not develop PE C) Urine podocyte-to-creatinine ratio measurements in 3rd trimester
recruited patients who developed PE vs. patients who did not develop PE.
doi:10.1371/journal.pone.0101445.g002

continues variables. Data were expressed as median (interquartile

range) or % as appropriate. A two-tailed P value of ,0.05 was
considered to be statistically significant.

kidney tissue biopsy specimen was stained in a similar manner to

obtain positive control, while negative controls were carried out by
incubation in the absence of the primary antibody. Staining was
evaluated by using immunofluorescent microscopy (Zeiss Axioplane2 IE microscope) and the images were obtained using the
Zeiss AxioCAm MRm camera (200X magnification). Images were
analyzed by two investigators and podocytes were identified by colocalization of podocin and synaptopodin; these counts were
expressed as number of podocytes per mg of creatinine (#pod/
mg) (pod/Cr).

Results
Clinical variables
A total of 78 high risk obstetric patients as well as 13 women
with low risk gestations were recruited. Clinical characteristics of
patients presented according to the outcome of PE are seen in
Table 1. Of the 78 high risk patients, 38 were recruited during the
2nd trimester, and 40 during the 3rd trimester, the distribution
among women with low risk pregnancies were 7 recruited during
the second and 6 in the third trimester respectively; each
pregnancy was evaluated until delivery. The high risk women
consisted of 15 women considered to be obese, 12 with Type I or
II DM, 24 with gestational DM, 26 chronic hypertensives, 2 with
SLE, and 1 patient with CKD. Urine alb/Cr and nephrin/Cr
were measured in all volunteers, while only 72 of the 78 high risk
patients had a urine pod/Cr determination. Fourteen high-risk
women developed PE, while none of the low risk patients did.
Among those who later had PE, the urine samples were collected
an average of 13.8 weeks before onset of PE in the 2nd trimester,

Ethics
The protocol titled Serum and Urine Biomarkers for
Preeclampsia which was approved by the Institutional Review
Board of the Albert Einstein College of Medicine of Yeshiva
University. This included a consent form signed by each volunteer.

Statistical methods
GraphPad Prism version 5.02 (GraphPad Software, Inc. La
Jolla, CA) and SPSS (version 20) were used for statistical analysis
and for the graphs. Mann-Whitney non-parametric tests were
performed to assess the differences between two given groups.
Spearman correlations were calculated to assess trends for

Figure 3. Dot plots of albumin-to-creatinine ratios. A) Urine albumin-to-creatinine ratio measurements in 2nd and 3rd trimester recruited
patients who developed PE vs. patients who did not develop PE B) Urine albumin-to-creatinine ratio measurements in 2rd trimester recruited patients
who developed PE vs. patients who did not develop PE C) Urine albumin-to-creatinine ratio measurements in 3rd trimester recruited patients who
developed PE vs. patients who did not develop PE.
doi:10.1371/journal.pone.0101445.g003

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Urinary Biomarkers in the Prediction of Preeclampsia

Figure 4. Dot plots of urine nephrin-to-creatinine ratios. A) Urine nephrin-to-creatinine ratio measurements in 2nd and 3rd trimester recruited
patients who developed PE vs. patients who did not develop PE B) Urine nephrin-to-creatinine ratio measurements in 2rd trimester recruited patients
who developed PE vs. patients who did not develop PE C) Urine nephrin-to-creatinine ratio measurements in 3rd trimester recruited patients who
developed PE vs. patients who did not develop PE.
doi:10.1371/journal.pone.0101445.g004

and 6.8 weeks before onset of PE in the 3rd trimester, with an

average of 10.0 weeks of both trimesters combined.

Urinary nephrin-to-creatinine ratio

Measurements of the nephrin/Cr ratio revealed significant
differences when the women who developed PE were compared to
those who did not (p = 0.04) (Figure 4A). Subgroup analysis
revealed that neither the 2nd nor the 3rd trimester recruited
patients showed significant differences between any of the groups
(p = 0.15 and p = 0.14 respectively) (Figure 4BC).

Urinary podocyte-to-creatinine ratio

Images of podocyturia are shown in Figures 1A1C, where
Figure 1D demonstrates the negative control and Figure 1E
represents the positive control. Measured pod/Cr is shown in
Figures 2AC. We did not observe significant differences in pod/
Cr in patients who developed PE vs. those who did not (p = 0.41)
(Figure 2A). When divided amongst trimesters, the differences
remained statistically non-significant (p = 0.43 for 2nd trimester
and p = 0.71 for 3rd trimester) (Figure 2BC).

Test characteristics of all biomarkers

The test characteristics for all three biomarkers are listed in
Table 2. The sensitivities proved to be the highest for pod/Cr at
70%, as compared with lower values for alb/Cr and nephrin/Cr
(36% and 57% respectively). Only the alb/Cr ratio had a high
specificity (96%). All three biomarkers exhibited poor positive
predictive values (1462%) but acceptable negative predictive
values (8991%). When analyzed amongst only the high risk
individuals, the sensitivities of nephrin/Cr and pod/Cr improve to
86% and 79% respectively, while alb/Cr did not change. The
positive and negative predictive values, however, do not change to
any significant degree when examined only in high risk patients

Urinary albumin-to-creatinine ratio

There was a significant difference on the alb/Cr between
patients who developed PE from those who did not (p = 0.006)
(Figure 3A). When divided amongst trimesters, the significance
remained in the 3rd but not 2nd trimester (p = 0.04 vs. p = 0.07
respectively) (Figures 3BC).

Table 2. Predictive characteristics of Markers Patients.

A: Predictive Characteristics of Markers in All Patients

Biomarker

Sensitivity

Specificity

Positive Predictive Value

Negative Predictive Value

Urine albumin-to-creatinine
ratio (mg/g)

36%

96%

63%

89%

Urine nephrin-to-creatinine
ratio (mg/g)

57%

58%

19%

89%

Urine Podocyte-to-creatinine
ratio (#/mg)

70%

43%

14%

91%

B: Predictive Characteristics of Markers in High Risk Patients

Biomarker

Sensitivity

Specificity

Positive Predictive Value

Negative Predictive Value

Urine albumin-to-creatinine
ratio (mg/g)

36%

94%

56%

87%

Urine nephrin-to-creatinine
ratio (mg/g)

86%

36%

23%

92%

Urine Podocyte-to-creatinine
ratio (#/mg)

79%

41%

22%

90%

doi:10.1371/journal.pone.0101445.t002

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Urinary Biomarkers in the Prediction of Preeclampsia

Table 3. Correlation of Biomarkers with Clinical Parameters.

1

Urine Alb/Cr (mg/g)

Urine Neph/Cr (mg/g)

Urine Pod/Cr (#/g)

P value

P value

P value

Urine Protein-to-creatinine (g/g)

0.96

,0.0001

0.52

,0.0001

0.07

0.47

Delivery 5SBP

0.36

0.0005

0.16

0.12

0.25

0.021

Delivery 6DBP

0.26

0.012

0.15

0.14

0.17

0.10

Urine Alb/Cr: Urine albumin to creatinine ratio.

Urine Neph/Cr: Urine nephrin to creatinine ratio.
Urine Pod/Cr: Urine podocyte to creatinine ratio.
4
R: Spearman rho correlation.
5
SBP: systolic blood pressure.
6
DBP: diastolic blood pressure.
doi:10.1371/journal.pone.0101445.t003
2
3

(Table 2B). Strong correlations were noted between alb/Cr and

nephrin/Cr with urine protein-to-creatinine ratio (p,0.0001)
(Table 3). Other significant correlations include alb/Cr and
systolic BP (p = 0.0005), alb/Cr and diastolic BP (p = 0.01) as well
as pod/Cr with systolic BP at delivery (p = 0.02). Interestingly,
there was no significant correlation between pod/Cr with urine
protein-creatinine ratio.

decrease the specificity of podocyturia as they are known to be

present in non-pregnant individuals; the study by Craici et al, in
contrast, examined podocyturia only in previously healthy women
or those with gestational HTN.
As enticing as it may be to pursue a novel method to predict PE,
the methodologic limitations of isolating podocytes in the urine
persist. As mentioned above, there are practical concerns
associated with isolating and identifying podocytes [17]. In
addition, podocyte counting must be performed by an experienced
cytopathologist, obviously impractical for a clinical test. Thus
investigators have sought to avoid this highly technical procedure
by measuring their urinary mRNA levels. Kelder and colleagues
demonstrated that urinary mRNA levels were elevated in terms of
nephrin, podocin in PE patients as compared with healthy
pregnant women, the significance, interestingly, was lost amongst
podocin mRNA levels between PE and gestational HTN [18].
This method is worth exploring as it has higher reproducibility,
though it is also challenged by the inherent instability of RNA and
the larger urine volume required for adequate RNA retrieval.
Importantly, there also appears to be normal shedding of
podocytes during pregnancy, as demonstrated by increased levels
of intact podocytes [19] and urinary mRNA of podocin and
nephrin in pregnant control patients as compared with nonpregnant controls [18]. This fact was re-iterated when human
urinary podocytes were isolated in healthy patients [20]. We also
detected podocyturia in healthy cohort. Hence, it appears that
physiologic shedding of podocyte occurs both in the pregnant and
non-pregnant population, and that this threshold must be
quantified before we can use podocyturia to predict PE.
The strengths of this study are that it is prospective and includes
a high risk patient population which may also present with
podocyturia, such as DM and SLE [21,22]. In order for a
predictive marker to be validated, it needs to be studied in a
confounding population. We also investigated alb/Cr and
nephrin/Cr as comparison markers. The major limitation of this
study is the sample size of the patients. However, our sample size is
comparable to all other podocyturia studies we could locate to
date. In fact, we have analyzed more samples for podocyturia in
total (72 high risk and 13 low risk pregnant patients) when
compared to other studies [13,15,19]. The non-significance of
podocyturia patients who developed PE vs. those who did not may
reflect insufficient statistical power. Nonetheless, the association of
podocyturia with PE is not as strong as that for alb/Cr and
nephrin/Cr. Thus, it appears unlikely that podocyturia would add
additional information to existing clinical estimates of risk, and
even more so if alb/Cr and nephrin/Cr were used.

Discussion
There has been substantial progress in research that focuses on
the cause of PE (once dubbed the disease of theories). Though
the exact causes have yet to be determined, identification of many
possibly involved molecules has increased studies focusing both on
prediction and verification of diagnosis [11]. For example, the
circulating levels of pro- and anti-angiogenic proteins (e.g., sFlt-1,
sEng, PlGF) have been linked to PEs manifestations, including
hypertension, proteinuria, and glomerular endotheliosis [16].
There are also data suggesting that podocyte associated protein
expression is reduced, specifically synaptopodin and nephrin,
while podocin expression remained unchanged [12]. This was
accompanied by studies showing increases in the excretion of
podocytes (podocyturia) using podocin as the marker which had a
100% sensitivity and specificity for the diagnosis of PE. We, on the
other hand, were not able to reproduce these results using
synaptopodin as our podocyte marker. In fact, in a study focusing
on high risk patients, we observed a sensitivity and specificity of
podocyturia to diagnose PE to be but 38% and 70% respectively
[14]. More recently, Craici studying women during at the end of
their second trimester described a 100% sensitivity using a podocin
as a marker of podocyturia to predict PE [15]. Our results do not
support such optimism as our sensitivities for all three markers do
not appear to be high enough for clinical use.
The contrasting results between our findings and those reported
by Craici et al might relate to methodologies and patient
populations. We utilized the cytospin technique in which the
urine samples are fixed immediately to avoid the errors that occur
with cultivation of urinary cells. Growing urinary podocytes in cell
culture is frequently limited by bacterial or fungal contamination.
Furthermore, cells may proliferate, undergo apoptosis, or not
attach to the culture dish, thereby falsely representing the true
podocyte count [17]. Also, we identified podocytes by positive colocalization of podocin and synaptopodin to avoid false positive
staining that may occur with the polyclonal antibody used to
detect podocin. Craici et al reported using only the podocin
antibody for staining. Furthermore, we included other high risk
pregnant patients including DM, SLE, and CKD which may
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Urinary Biomarkers in the Prediction of Preeclampsia

prevails, a panel of biomarkers reflective of this complexity may be

ideal for diagnosis.

Conclusions
Podocyturia, nephrinuria, or albuminuria does not appear to be
reliable markers to predict PE, though a normal alb/Cr may be
useful to help rule out disease. We realize our notation of a
relatively low sensitivity and specificity is not conclusive, but given
the discrepancy of these observations to studies published prior to
them, we suggest further studies are warranted. Currently, some
underscore complex pathophysiology of the disease, suggesting
different pathomechanisms especially between early and late PE,
and suggest it is unlikely that any single test or cell type will be able
to predict PE, while others disagree [23]. If the former view

Acknowledgments
We thank Dr. Mimi Kim for her statistical support and Dr. Elizabeth
Phipps for her contribution in staining for podocytes.

Author Contributions
Conceived and designed the experiments: BJ JCH SS. Performed the
experiments: BJ SM SS. Analyzed the data: BJ AQ KK JCH SS HWC.
Contributed reagents/materials/analysis tools: SM RMM KK SS. Wrote
the paper: BJ SM AQ JCH SS.

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July 2014 | Volume 9 | Issue 7 | e101445