Calcium and Phosphate Excretion in Preeclampsia

Turk J Med Sci
30 (2000) 39–42
© TÜBİTAK
Pervin VURAL1
Calcium and Phosphate Excretion in Preeclampsia
Cemil AKGUL2
Mukaddes CANBAZ1
Received: March 19.1999
Abstract: In preeclampsia, alterations in
0.01) and NTP (p< 0.001) levels. The
renal function, electrolyte and water
glomerular filtration rate measured by
metabolism are common findings. Recent
creatinine clearance was lower in
studies have suggested that preeclampsia is
preeclamptic women than in normotensive
associated with hypocalciuria. A total of 59
pregnant women (p< 0.01). Patients with
women were included in the present study,
preeclampsia had significantly lower (p<
15 of whom were nonpregnant (NP) healthy
0.001) excretion of calcium than the NP and
women, 20 normotensive pregnant women
NTP groups (p< 0.001). Likewise, the
(NTP), and 24 pregnant women with severe
phosphate levels were lower in women with
preeclampsia (PEP). We compared the three
preeclampsia than in the NP and NTP groups
groups in terms of calcium and phosphate
(p< 0.01). There was no correlation between
excretion, and some parameters of renal
parameters of renal function and calcium or
function such as serum urea, creatinine and
phosphate excretion.
creatinine clearance. Urinary calcium and
Hypocalciuria and hypophosphateuria were
phosphate levels in the PEP group were
significantly lower than in the NP group (p<
found to be important features of severe
0.001 and p< 0.01, respectively) and NTP
preeclampsia and probably indirectly are
group (p< 0.001 and p< 0.01, respectively).
related to the altered renal function seen in
The serum urea levels were higher in the PEP
toxemia of pregnancy.
group than in the NP and NTP (p< 0.001)
1
groups. The same pattern of increase in the
Departments of Biochemistry and Clinical
Key Words: Preeclampsia; calcium excretion;
PEP group was valid for serum creatinine
Biochemistry, 2Obstetric and Gynecology,
phosphate excretion; renal function
concentrations as compared with the NP (p<
İstanbul-Turkey
Introduction
It is unclear whether the decrease of calcium is due to
Preeclampsia is a pregnancy-specific disease
disordered renal function or is a compensatory
manifested by hypertension, coagulopathy, and impaired
mechanism in the pathogenesis of preeclampsia. The
tissue perfusion. Its etiology remains unclear, and it is
purpose of this study was to determine whether the
possible that the rise in blood pressure is a manifestation
calcium and phosphate excretion is lower in patients with
of more than one pathophysiological condition (1-4). One
preeclampsia, and what relation there is, if any, between
of these conditions is related to abnormal renal function
calcium/phosphate excretion and the changed renal
(5-8) and probably decreased urinary calcium excretion
function seen in toxemia of pregnancy.
(9-12).
Calcium and phosphate metabolism during normal
Material and Methods
pregnancy is characterized by minor changes in the serum
The cases were divided into three groups: 15
levels of calcium and phosphate; however, urinary calcium
nonpregnant (NP) healthy women (Control I), 20
and phosphate excretion increases (8,13). While urinary
normotensive pregnant (NTP) women with no disease
calcium values in nonpregnant women are about 100 -
(Control II), and 24 pregnant women with severe
250 mg/day, in pregnant women they range between
preeclampsia (PEP) (Study). Severe preeclampsia was
350 - 620 mg/day (8,14). Alongside the many studies
defined as a blood pressure of ≥160/110 mmHg after 30
reporting hypocalciuria in preeclampsia, there are others
minutes of rest on two separate readings at least 6 hours
that have found no such correlation (15).
apart with proteinuria (more than 300mg/day), and
39

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Calcium and phosphate excretion in preechampsia
edema. Liver enzyme levels of preeclamptic pregnant
(0.71 ± 0.18 mg/dl) (p< 0.01) and NTP group (0.69 ±
women were found to be in normal ranges. Preeclamptic
0.06 mg/dl) (p< 0.001). No significant difference was
and normotensive pregnant women were nullipara, and
found between the urea and creatinine values of NTP
the gestational age was 33.25 ± 4.20 and 31.90 ± 5.89
women and those of NP ones. The creatinine clearance of
weeks, respectively (Table1). Nonpregnant healthy
PEP women (104.38 ± 29.63 ml/min) was lower than
women were 25-32 years of age. All women (Control I,
that of NTP women (126.20 ± 15.14 ml/min) (p< 0.01).
II and Study groups) did not take any medication for at
However, there was no difference in comparison between
least 10 days prior the sample collection. Nonpregnant
the PEP and NP (113.04 ± 14.98 ml/min) groups. The
women were not on oral contraceptives and were in the
creatinine clearance of normotensive pregnant women
follicular phase of the menstrual cycle at the time of
was higher than that of nonpregnant ones (p< 0.05).
sampling. Patients who had a history of hypertension
before the 20th week of pregnancy, diabetes mellitus, or
Table 2.
Renal function values in nonpregnant healthy (NP) women,
any renal disease were excluded from the study. All
normotensive pregnant women (NTP) and preeclamptic
participants were on a free range diet. Twenty-four urine
pregnant women (PEP)
collections were taken from Control I, Control II and
Serum Urea
Serum Creatinine
Creatinine
Study groups. Venous blood was obtained after overnight
(mg/dl)
(mg/dl)
(mg/dl)
Clearance (ml/min)
fasting at 1000 hours with each 24-hour urine collection,
and centrifuged at 2000 g to remove the serum. Serum
NP (n = 15)
19.33±1.44
0.71±0.18
113.04±14.98
and urinary creatinine and urea levels were determined by
NTP(n = 20)
19.10±1.51
0.69±0.06
126.20±15.14
the Jaffe and Kowarski methods, respectively. Creatinine
+
+
+
NS
NS
p<0.05
clearance was then calculated. Urinary calcium and
PEP(n = 24)
23.08±3.11
0.88±0.17
104.38±29.63
phosphate were determined by the Kramer-Tisdall and
*
*
a
p<0.001
p<0.01
p<0.01
phosphomolibdic acid methods, respectively. Data are
a
a
p<0.001
p<0.001
given as mean ± standard deviation. Student’s t test and
simple correlation analysis were used as statistical
* Between PEP and NP
methods to test the results.
a Between PEP and NTP
+ Between NTP and NP
Results
Patients with preeclampsia had significantly lower
excretion of calcium (92.14 ± 40.87 mg/l) than the NP
Table 1 presents the gestational age and systolic and
(152.53 ± 25.60 mg/l) and NTP (171.80 ± 60.01 mg/l)
diastolic blood pressure values of normotensive and
groups (p< 0.001). Likewise, the phosphate levels (0.43
preeclamptic pregnant women.
± 0.38 g/l) were lower in women with preeclampsia than
Table 1.
Clinical findings of normotensive pregnants (NTP) and
in the NP (0.80 ± 0.40 g/l) and NTP (0.76 ± 0.34 g/l)
preeclamptic pregnants (PEP)
groups (p< 0.01).
There was no correlation between urinary calcium,
Gestationa
Systolic Blood
Diastolic Blood
phosphate and parameters of renal function.
Age(week)
Pressure(mmHg)
Pressure(mmHg)
Table 3.
Urinary calcium and phosphate in nonpregnant healthy
(NP), normotensive pregnant women (NTP) and
NTP(n = 20)
31.9 ± 5.89
115 ± 10.51
74 ± 6.8
preeclamptic pregnant women (PEP)
PEP(n = 24)
33.25 ± 4.20
164.58 ± 20.79
104.79 ± 12.63
Urine Ca (mg/l)
Urine P (g/l)
P
NS
p < 0.001
p < 0.001
NP (n = 15)
152.53 ± 25.60
0.80 ± 0.40
Table 2 lists the renal function values in NP healthy,
NTP(n = 20)
178.8 ± 60.01
0.76± 0.34
NTP and PEP women. Serum urea concentrations of the
+NS
+NS
PEP group (23.08 ± 3.11 mg/dl) were significantly
PEP(n = 24)
92.14± 40.87
0.43± 0.38
higher than those of the NP women (19.33 ± 1.44
*p<0.001
*p<0.01
mg/dl) and NTP ones (19.10 ± 1.51 mg/dl) (p< 0.001).
ap<0.001
ap<0.01
The same pattern was seen in serum creatinine
* Between PEP and NP
concentrations, which were significantly higher in the
a Between PEP and NTP
Study group (0.88 ± 0.17 mg/dl) than in the NP group
+ Between NTP and NP
40

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P. VURAL, C. AKGUL, M. CANBAZ
Discussion
excretion of calcium in preeclamptic pregnant women was
Preeclampsia can cause changes in virtually all organ
lower in the third trimester than it was in normotensive
systems, especially the cardiovascular, renal,
pregnant women (21). Because parathyroid hormone and
hematological and immunological systems. The reason for
calcitonin levels were not altered in the patients with
these changes is unknown, but it is believed that they may
preeclampsia, it was concluded that the differences in
be associated with an inadequate vasoactive prostaglandin
calcium metabolism were not related to alterations in the
synthesis (16-18), which can cause disorders of
secretion of these hormones. Decreased renal filtration
uteroplacental circulation (19), and renal tissue (5) and
rate and increased tubular reabsorption of calcium and
renal perfusion deffects (20). In association with these
phosphate may result in hypocalciuria, and
alterations renal blood flow and glomerular filtration
hypophosphateuria in toxemia. This may be a
rates decrease with the development of toxemia (20),
compensatory mechanism. Decreased calcium excretion
which results in the decrease of urea and creatinine
may result in a slight but significant increase in serum
excretion (7). Similar to the reports of many
levels, so that phospholipase A is activated to stimulate
2
investigators, in our study we also found serum urea and
impaired prostaglandin synthesis. It is reported that
creatinine levels to be higher in preeclamptic pregnant
adaily supplement of 2000 mg calcium had significant
women than in nonpregnant healthy women and
results in lowering the incidence of toxemia (22). In
normotensive pregnant women, while creatinine
addition, nonpregnant women with a calcium intake of at
clearance values in preeclampsia were lower than in
least 1000mg/day had a 20% lower risk of hypertension
normotensive pregnant women.
than women with an intake of less than 400 mg/day
during four years of follow-up (23). These facts support
Renal excretion of calcium and phosphate increases
our hypothesis.
during pregnancy (8). Excretion usually increases during
each trimester, with maximum levels reached during the
Lower calcium excretion may result from dietary
third trimester. Proteinuria and alterations of phosphate
variation. All participants in our study were on a free
and most notably calcium excretion are common findings
range diet. Because we did not advise any of our patient
of hypertension and some renal disorders in general.
to alter their diets, however, we believe it is unlikely that
There is a decrease in urinary calcium levels in
dietary calcium intake played an important role in our
preeclampsia (9-12). Our findings in preeclampsia
findings.
confirm the results of Sanchez-Ramos, Yoshida and
As a conclusion, hypocalciuria and hypophosphateuria
Taufield (9-11). The reason for hypercalciuria in
are important features of severe preeclampsia and
pregnancy is probably the increased glomerular filtration
probably are indirectly related to the altered renal
rate (11). Pedersen et al. reported that the fractional
function seen in toxemia of pregnancy.
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