Open Journal of Obstetrics and Gynecology, 2011, 1, 13-16
doi:10.4236/ojog.2011.12003 Published Online June 2011 (
Published Online June 2011 in SciRes.
Isolated proteinuria as an initial sign of severe preeclampsia
Takahir o Ya mada, Takashi Ya mada, Mamoru Morikawa, Masamitsu Takeda, Ryutaro Nishida,
Rina Akaishi, Hisanori Minakami
Department of Obstetrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Received 21 April 2011; revised 20 May 2011; accepted 27 May 2011.
Two pregnant women who initially developed pro-
teinuria alone followed by serious preeclampsia are
presented to emphasize that there is no adequate
technical term to express the period of proteinuria
alone based on the current criteria of pregnancy-
induced hypertension. Case 1 exhibited a urinary
protein concentration of 46 mg/dL in the absence of
hypertension, and abdominal pain due to placental
abruption with hypertension at gestational week
(GW) 29–3/7 and 29–4/7, respectively. Case 2 exhibited a
urinary protein/creatinine ratio of 2.67, developed
hypertension, required cesarean section, and devel-
oped posterior reversible encephalopathy syndrome
at GW 28–1/7, 29–6/7, and 32–0/7, and on postpartum
day 2, respectively. As women with proteinuria alone
are not diagnosed as having preeclampsia and as a
diagnosis of gestational proteinuria can be made only
at 12 weeks postpartum, a prospective technical term
applicable to the condition of proteinuria alone is
needed to increase physicians’ attention to this co ndi-
Keywords: Posterior Reversible Encephalopathy
Syndrome; Proteinuria; Placental Abruption;
Pregnancy-Induced Hypertension
Based on the current criteria adopted in many countries,
women with proteinuria alone are not diagnosed as hav-
ing preeclampsia until they also exhibit hypertension [1];
in Japan, those who do not develop hypertension are
diagnosed as having had gestational proteinuria. Thus,
gestational proteinuria is a retrospective diagnosis. These
criteria may have been based on the belief that clinical
presentation of preeclampsia involves initial hyperten-
sion and subsequent proteinuria. However, whether
some pregnant women who initially exhibit proteinuria
subsequently develop hypertension had not been exten-
sively studied. The clinical outcomes of such women
with gestational proteinuria, defined as those exhibiting
transient proteinuria of 0.3 g/day appearing at or after
20 weeks of gestation and disappearing by 12 weeks
postpartum, had been believed to be favorable, and pro-
teinuria had been thought not to be an independent pre-
dictor of an adverse outcome [2].
However, a recent report indicated that approximately
50% of women who develop proteinuria 0.3 g/day at
and after 20 weeks of gestation in the absence of hyper-
tension progress to preeclampsia [3]. If this is the case, it
is misleading to suggest that the outcome of pregnancy
in patients with isolated proteinuria is favorable.
Here, we present two patients who showed proteinuria
initially and subsequently developed hypertension, and
finally experienced severe clinical conditions. We em-
phasize that physicians have no adequate technical term
to express the period of proteinuria alone in such pa-
tients according to the current criteria of pregnancy-in-
duced hypertension.
This study was approved by the institutional review
board of the Hokkaido University Hospital.
Case 1: A 43-year-old nulliparous woman showed
blood pressure (BP) of 124/75 mmHg and proteinuria (1
+ on dipstick) at a regular antenatal visit at gestational
week (GW) 28–3/7 in July 2008. She exhibited BP of
119/78 mmHg, urinary protein concentration of 46
mg/dL (Ta bl e 1 ), and weight gain of 1.7 kg in 1 week,
and was diagnosed as having fetal growth restriction
(FGR, estimated fetal body weight of 1082 g) the fol-
lowing week (GW 29–3/7). Blood chemistry revealed
anemia only. The patient requested treatment on an out-
patient basis despite our recommendation of hospitaliza-
tion. Thirty-four hours later, the patient presented with
abdominal pain, hypertension (BP of 176/98 mmHg),
and urinary protein concentration of 120 mg/dL. Placen-
tal abruption was suspected based on ultrasonography
findings and was confirmed by uneventful emergency
cesarean section. A female infant with Apgar scores of 3
T. Yamada et al. / Open Journal of Obstetrics and Gynecology 1 (2011) 13-16
and 7 at 1 and 5 min, respectively, weighing 1086 g was
born. Postpartum course was uneventful in both the mother
and neonate. The BP normalized to 121/69 mmHg and
urinary protein concentration decreased to <10 mg/dL on
postpartum days 3 and 6, respectively. Blood tests to
screen for anti-phospholipid antibody syndrome were
not performed.
Case 2: A 38-year-old woman with a history of two
uneventful vaginal deliveries was admitted to hospital
due to urinary protein/creatinine ratio (u-PCR) of 2.67
and FGR (estimated fetal body weight, 830 g) with BP
of 130/81 mmHg at GW 28–1/7 in January 2011. She did
not have proteinuria before GW 27. BP remained normal
until GW 29–6/7, at which time the patient was diagnosed
as having preeclampsia because hypertension (158/90
mmHg) appeared (Table 1). Although thrombocytopenia
of 117 × 109/L was seen, her first-trimester platelet count
was also relatively low (161 × 109/L). As u-PCR in-
creased over the gestational period—3.28 at GW 29–3/7
(Table 1), 6.81 at GW 30–6/7, and 10.78 at GW 31–6/7
with relatively stable BP, ranging from 120/70 mmHg to
165/90 mmHg—an uneventful cesarean section was
performed at GW 32–0/7. A female infant with Apgar
scores of 4 and 9 at 1 and 5 min, respectively, weighing
1234 g was born. The patient complained of contracted
visual field on postpartum day 2. Magnetic resonance
imaging (MRI) of the brain performed on postpartum
days 2 and 9 revealed the presence and disappearance of
posterior reversible encephalopathy syndrome, respec-
tively (Figure 1). The visual field was normalized by
postpartum day 6. The patient had u-PCR of 6.25 and
normal BP (129/81 mmHg) on postpartum day 9, and
was discharged from hospital on postpartum day 10. The
u-PCR decreased to 1.03 on postpartum day 31. The
patient was negative for anti-nuclear antibody, anti-car-
diolipin antibody, anti-2GPI antibody, and lupus antico-
As shown in Table 1, there were no marked differ-
ences in any blood test variables between before and
after the diagnosis of preeclampsia. Uric acid level was
somewhat high in both cases.
Significant proteinuria (0.3 g/day) preceded the onset
of hypertension in the two patients in this study. In addi-
tion, these two patients developed serious clinical condi-
tions, i.e., placental abruption and posterior reversible
encephalopathy syndrome. Posterior reversible encepha-
lopathy syndrome is a characteristic finding frequently
seen in patients with eclampsia [4] and/or visual distur-
bance irrespective of the presence or absence of preg-
nancy [5] and represents subcortical edema without in-
farction [6].
Table 1. Blood pressure, proteinuria, and blood chemistry before and after the diagnosis of preeclampsia.
Case 1 Case 2
Before After* Before After*
(29 - 3/7 GW) (29 - 4/7 GW) (29 - 3/7 GW) (29 - 6/7 GW)
Blood pressure (mmHg) 119/78 176/98 125/79 158/90
Protein in the urine (mg/dL) 46 120 200 223
Creatinine in the urine (mg/dL) nd nd 61 56
Hemoglobin (g/dL) 7.8 8.2 11.9 11.9
Platelet (× 109/L) 336 283 125 117
Total protein (g/dL) 5.9 5.8 4.9 4.8
AST (U/L) 10 12 24 25
LDH (U/L) 225 270 223 227
Uric acid (mg/dL) 6.2 6.8 5.1 5.6
Creatinine (mg/dL) 0.7 0.7 0.56 0.54
Fibrinogen (mg/dL) 388 337 330 345
D-dimer (μg/mL) 0.8 26.7 1.6 1.5
Antithrombin activity (%) 92 84 79 76
*Just before the performance of cesarean section. nd, not determined; AST, aspartate aminotransferase; LDH, lactate dehydrogenase
opyright © 2011 SciRes. OJOG
T. Yamada et al. / Open Journal of Obstetrics and Gynecology 1 (2011) 13-16 15
Figure 1. Findings of brain magnetic resonance imaging performed on postpartum days 2 (A) and 9 (B) in Case
2. The arrow indicates a small lesion of posterior reversible encephalopathy syndrome, which disappeared on
postpartum day 9.
Although these two women had a period of patho-
logical proteinuria alone (34 hours in Case 1 and 12 days
in Case 2), there is no adequate technical term to express
the period of proteinuria alone in these patients accord-
ing to the current criteria [1]. So-called “gestational pro-
teinuria” is applicable only to women who show tran-
sient proteinuria (0.3 g/day) alone between 20 weeks of
gestation and 12 weeks postpartum. Thus, the definite
diagnosis of gestational proteinuria must wait until 12
weeks postpartum. From the prospective viewpoint,
physicians are unable to determine which women with
isolated proteinuria (new-onset proteinuria 0.3 g/day in
the absence of hypertension) will develop hypertension.
If pregnancy outcomes of such women with initial pro-
teinuria and subsequent hypertension (which we tenta-
tively call proteinuria-preceding preeclampsia) were
similar to those of women with gestational proteinuria,
no problems would emerge during or after counseling
for women with isolated proteinuria. However, preg-
nancy outcomes differ markedly between women with
gestational proteinuria and proteinuria-preceding pree-
clampsia [3]. In addition, proteinuria-preceding pree-
clampsia is relatively common among women with iso-
lated proteinuria [3]. Morikawa et al. reported that 19
(51%) of 37 women with isolated proteinuria exhibited
additional hypertension and progressed to proteinuria-
preceding preeclampsia [3]. These 19 women with pro-
teinuria-preceding preeclampsia gave birth at <37 weeks
of gestation (57.9% vs. 11.1%) and gave birth to FGR
infants (36.8% vs. 5.6%) at a significantly higher rate
than the remaining 18 who remained normotensive and
were diagnosed as having gestational proteinuria [3].
Meanwhile, the outcomes of women with gestational
proteinuria do not differ largely from those of healthy
control subjects [3,7]. Thus, a significant number of
women with isolated proteinuria progress to preeclamp-
sia, and the outcomes of these women are not optimistic,
as also suggested in the present study. Therefore, it is
misleading to suggest that proteinuria is not independ-
ently predictive of adverse outcome [2].
In the UK, 32 (10%) of 325 women with eclampsia in
1992 and 16 (7.5%) of 214 women with eclampsia be-
tween February 2005 and February 2006 exhibited pro-
teinuria alone at the time of their last antenatal visit
within one week of their first convulsion [8,9]. In a study
performed in Japan in 2004, pregnancy-induced hyper-
tension was not diagnosed before the eclamptic fit in 30
of 54 (56%) women with eclampsia [10]. In Sweden,
during the period from 1991 to 1992, the incidence rate
of eclampsia (3.3/10,000 pregnancies) increased signifi-
cantly compared with the incidence (1.5/10,000 preg-
nancies) in 1976 to 1980 [11], raising the question of
whether the incidence of eclampsia can be reduced by
the earlier diagnosis and treatment of hypertension.
These reports suggest the need for greater attention in
women with proteinuria alone to predict the develop-
ment of eclampsia and thereby prevent its occurrence.
In conclusion, some women with preeclampsia ini-
tially exhibit proteinuria followed by subsequent devel-
opment of hypertension. Although the outcomes of such
women with proteinuria alone are not optimistic, there is
no adequate technical term to express the period of pro-
opyright © 2011 SciRes. OJOG
T. Yamada et al. / Open Journal of Obstetrics and Gynecology 1 (2011) 13-16
teinuria alone according to the current criteria of preg-
nancy-induced hypertension. The occurrence of women
who develop eclampsia in the presence of proteinuria
alone [8,9], in addition to the two women discussed in
this report, indicates the need for a prospective technical
term that is applicable to the clinical condition of pro-
teinuria alone to increase physicians’ attention to preg-
nant women with newly developed proteinuria in the
absence of hypertension.
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