Nephrol Dial Transplant (2007) 22: 1236–1240
doi:10.1093/ndt/gfl794
Advance Access publication 20 January 2007
Case Report
Three successive pregnancies in a patient with chronic renal disease
progressing from chronic renal dysfunction through to institution
of dialysis during pregnancy and then on to maintenance dialysis
Francesco Giofrè, Camillo Pugliese, Giovanni Alati, Antonella Messina and Domenico Tramontana
Nephrology and Dialysis Unit, Hospital of Tropea, ASL 8 Vibo Valentia, Calabria, Italy
Keywords: chronic renal failure; haemodialysis;
IgA nephropathy; three successful pregnancies
Introduction
Frequency of conception is lower in women with
chronic renal insufficiency (CRI), and even lower in
those undergoing dialysis [1]. Repeated pregnancies in
women on dialysis appear to be exceptional. In the
literature, there are only two reports of cases of three
successive pregnancies in two different patients on
haemodialysis [2,3]. In both these cases, however, only
the first pregnancy was successful.
Here we present a case of a woman with IgA
nephropathy who had three consecutive, successful
pregnancies, the first during the pre-dialysis phase, and
the other two during chronic maintenance
haemodialysis.
Case report
First pregnancy
Chronic kidney disease due to IgA nephropathy was
first detected at the age of 18 years. The nephropathy
was not very severe—proteinuria <2 g/day, no hypertension—and did not present a rapid progression into
end-stage renal disease (ESRD). The patient first
became pregnant at the age of 25—serum creatinine
2.2 mg/dl, proteinuria 1 g/day and normal arterial
pressure. She followed a low protein diet 0.6–0.8 g/kg
body weight/day, a high calorie intake 35 kcal/kg body
weight/day, and took 100 mg/day aspirin. During this
pregnancy, proteinuria did not increase considerably,
blood pressure (BP) remained normal (Figure 1) but
serum creatinine rose to 5 mg/dl (Figure 2).
Correspondence and offprint requests to: Francesco Giofrè,
U.O. Nefrologia E Dialisi Ospedale G-Jazzolino, Asl 8 89900
vibo Valentia, Italy. Email: [email protected]
Haemoglobin (Hb) ranged between 9.0 g/dl and 10 g/dl
with
oral
iron
and
vitamin
supplements.
Total maternal weight gain was 13 kg. All parameters
of fetal growth were normal—37 week biparietal
diameter (BPD) 97 mm, head circumference (HC)
333 mm, femur length (FL) 71 mm, abdominal circumference (AC) 333 mm, humerus length (HL) 62 mm.
Two weeks before delivery, intracervical dinoprostone
gel was applied in four 0.5 mg successive doses.
The gestation ended in the 38th week with spontaneous
vaginal delivery and the live-born male baby weighed
3150 g—Apgar score 8 and 9 (Table 2). He was
admitted to neonatal intensive care, and was discharged after 20 days, thriving and on a normal diet.
Second pregnancy
In August 1998, at the age of 30 years, with serum
creatinine 8 mg/dl, the second conception occurred,
and at the end of the first trimester with glomerular
filtration rate (GFR) 5 ml/min haemodialysis (HD)
was started. A dialysis machine was used which
prepared ultra-pure dialysate (40085 Fresenius
Medical Care AG, Bad Homberg, Germany). We
also used a biocompatible low-flux polysulfone steamsterilized membrane—1.3 m2 urea clearance 243 ml/
min with Qb 300 ml/min, (F6HPS, Fresenius Medical
Care AG, Bad Homberg, Germany)–[4] standard
bicarbonate with sodium 143 mEq/l, potassium
3 mEq/l, calcium 3.5 mEq/l, glucose 1g/l dialysate
with constant values. Ultrafiltration (UF) <575 ml/h
was maintained constant and blood flow rate was
progressively increased from 180 ml/min to 300 ml/min
during the first 30 min [5]. Low molecular weight
heparin (LMWH) was used—60 IU/kg body weight—
before each session. Time of dialysis of 12 h/week was
maintained throughout the second trimester and
progressively increased to 24 h/week during the third
(Table 1). To monitor the maternal haemodynamic
condition during HD session, transthoracic electrical
bioimpedance with a CDM BOMED 3000 device [6]
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Institution of dialysis during pregnancy
1237
Fig. 1. Average monthly systolic and diastolic blood pressure during the three pregnancies. The upper part of the graph shows the mean
monthly systolic arterial pressure (Syst BP) during each pregnancy (P). In the lower part, the diastolic pressure (Diast BP).
Fig. 2. Renal decline and proteinuria, time of pregnancies, start dialysis and transplantation. The figure shows the initial period of
renal dysfunction, the progression during the years of renal decline, together with the proteinuria values, the start dialysis and the date
of transplantation (downward arrow). At the top of the figure, the patient’s age and the timing of each pregnancy (upward arrow)
are indicated.
was utilized and, in general, normal vasoactivity,
normal blood volume, hyperinotropism and reduced
peripheral resistance were detected, as was normal
maternal AP, rhythmic fetal heart beat (FHB) with no
intra-dialysis variation rate. Normal placental insertion and fetal maternal fluxometry profiles, detected by
the Doppler velocimetry at the 13th, 18th, 24th and
30th weeks, were found to be in the normal range.
The amniotic fluid volume was normal until 28 weeks,
when it gradually increased into polyhydramnios.
The weight gain during this pregnancy was 19.3 kg.
Fetal growth was evaluated via the usual biometric
parameters—32 week BPD mm 82, HC mm 286,
FL mm 59, AC mm 293, HL mm 54. We encouraged
a high protein caloric diet—1.8/2 g/kg/day of protein
and 35 kcal/kg/day. At the end of the first trimester,
Hb decreased to 7.1 g/dl and anaemia was corrected
with Epo 175 IU/kg/week. The patient took 2 g/day of
calcium carbonate orally as a phosphorus chelating
agent and 0.25 mcg of vitamin D3; the calcium and
phosphorus values were checked weekly and remained
within the normal range; the intact PTH, which was
measured each trimester, was around 80 pg/dl. At the
beginning of the 29th week contractions began and
1238
F. Giofrè et al.
Table 1. Comparison of the main maternal parameters during the three trimesters of each pregnancy
Total weight gain (kg)
Protein intake (range in g/kg/day)
S Albumin (range g/dl)
S Transferrin (N 230–430 mg/dl)
nPCR(g/kg/day)
Hb (g/dl)
Hct
rHuEpo (IU/kg/week)
Dialysis time (h/week)
BUN(mg/dl) average
Kt/V urea (% d.p.) average
St bicarbonate mEq/l average
1st Trim
2nd Trim
3rd Trim
1st Trim
2nd Trim
3rd Trim
1st Trim
2nd Trim
3rd Trim
1st Trim
2nd Trim
3rd Trim
1st Trim
2nd Trim
3rd Trim
1st Trim
2nd Trim
3rd Trim
1st Trim
2nd Trim
3rd Trim
1st Trim
2nd Trim
3rd Trim
1st Trim
2nd Trim
3rd Trim
First pregnancy
Second pregnancy
Third pregnancy
13,100
0.6–0.8
3.4–3.8
255
246
288
19,300
1.8
3–3.6
275
278
298
13
1.8–2
3–4
169
292
291
1 02
1.15
0.77
10.1
10.3
10.3
30
31
31
30
130
135
13
15
17
68.8a
67.2a
48.9a
1.47
1.51
1.26
20.3a–26.3b
15.9a–22.6b
19.7a–23.0b
9.5
9.8
9.2
31
31
30
0.95
0.96
7.1
11.1
11.8
21
33
34
70
175
130
52.1
54
60.2
12
21
67.2
58.1a
45.2a
22.5
23.2
24.0
1.36
1.48
20.02
19.5a–23.9b
20.7a–24.2b
In the first column we have represented the class of tests relating, in order; to total weight gain and nutritional state, anaemia, dialysis
adequacy and the acid/base balance. The second, third and the fourth columns set out the average and range values registered during each
pregnancy.
S, serum; N, normal; trim, trimester; nPCR, protein catabolic rate normalized to body weight; Hb, haemoglobin; Hct, haematocrite; rHuEpo,
recombinant human Erythropoietin; BUN, blood urea nitrogen; d.p., double pool St, standard.
a
pre-dialysis.
b
post-dialysis.
therapy with ritodrin 15 mg/day was administered.
Following the failure of tocolysis at the 33rd week,
delivery by Caesarean section was performed. The liveborn male infant weighed 2190 g with Apgar score 7
and 8 (Table 2). The infant was immediately admitted
to the neonatal intensive care unit with respiratory
distress requiring assisted ventilation for 6 h; he was
subsequently discharged, in good health, after 20 days.
Third pregnancy
At the age of 32 years, 2 years after entering dialysis,
the patient conceived for the third time. This pregnancy was diagnosed by means of human corionic
gonadotropin dosage, following a delay in her menstrual cycle. Dialysis was performed with ultra-pure
dialysate and a biocompatible low-flux polysulfone
steam-sterilized membrane—1.60 m2 urea clearance
247 ml/min with Qb 300 ml//min, (F7HPS, Fresenius
Medical Care AG, Bad Homberg, Germany). Sodium
profiles were applied between 146 mEq/l at the beginning, and 140 mEq/l at the end of each session,
and in the 3rd trimester the bicarbonate buffer was
reduced to 27 mEq/l. Decreasing UF was set so that
70–75% of the retained fluid was removed during
the first 2 h of dialysis. LMWH was administered for
anti-coagulation in the usual i.v. dose. The weekly time
of dialysis was increased gradually from 12 h in the first
8 weeks to 18 h during the last week—average 15 h
40 min [7]. The results of Kt/V, protein catabolic rate
normalized to body weight (nPCR), start dialysis BUN
and bicarbonate is reported in Table 1. At the 9th
week, due to Hb decreasing to 8.9 g/dl, we introduced
rHuEpo 35 IU/kg, with subsequent increased dosage
130 IU/kg, to maintain Hb target 11g/dl. The patient
took calcium carbonate 3-4 g/day with vitamin D3
0.25 mcg, and was put on a high protein and caloric
diet, as for the previous pregnancy. Surfactant by
infusion was also administered, in order to prevent or
to reduce respiratory distress syndrome. Every 2 weeks
the amniotic fluid volume was evaluated by pre- and
post-dialysis ultrasound, which proved useful to
modulate the dry weight [8]. Obstetric surveillance
and fetal growth evaluation were carried out as for the
previous pregnancy with normal results—32 week
BPD mm 85, HC mm 292, FL mm 61, AC mm 295,
Institution of dialysis during pregnancy
1239
Table 2. Biometric and neonatal parameters. Complications at birth and growth data of the children
FHB
AFV
Gestational age at birth (weeks)
Birth weight (g)
Apgar score
Fetal crnplications
Outcome (Age–Height–weighta)
1st pregnancy
2nd pregnancy
3rd pregnancy
rhythmic
normal
38
3150
8 and 9
rhythmic
normal/polyhydraminos
33
2190
7 and 8
PJM-RD
6–110–20
rhythmic
normal/polyhydraminos
33
2500
5 and 8
RD-RCVL
4–110–14
11–140–35
The table compares the data taken into consideration during the three pregnancies.
FHB, fetal heart beat, AFV, amniotic fluid volume; g, grams; PMJ, pulmonary jaline membranes; RD, respiratory distress; RCLV, reduced
contractility left ventricular;
a
years–cm–kg, normal in percentiles.
HL mm 57. The total weight gain was 13 kg. At the
30th week polyhydramnios and contractions occurred,
and increased doses of ritodrin 10/20/30/mg/day only
managed to postpone the onset of early labour by
3 weeks. At the 33rd week, the patient underwent
a Caesarean section. The live-born male child, weighing 2500 g—Apgar score 5 and 8—was admitted to the
neonatal intensive care unit with respiratory distress
requiring oxygen therapy for 2 days.
After 30 days the infant was discharged home,
healthy and on a normal diet. One year later the
mother received a cadaver kidney transplant, which to
date is perfectly functional.
Discussion
Pregnant women with serum creatinine levels of
1.4 mg/dl, are at risk of accelerated loss of renal
function [1]. In this case, the first pregnancy occurred
about 8 years after the onset of renal dysfunction with
serum creatinine 2.2 mg/dl. During this pregnancy,
we registered a greater increase in serum creatinine to
5.0 mg/dl, but only a slight increase in proteinuria
(Figure 2), with no changes in diet, BP and
diuresis. We observed no other reasons for progressive
renal insufficiency, so we assume that it was the
pregnancy itself which hastened renal deterioration.
Nevertheless, if in this current case we observe all
three pregnancies against a background of a IgA
nephropathy, which slowly progresses to severe dysfunction into dialysis, it needs to be pointed out
that these pregnancies not only span the long period
of renal decline (Figure 2), but go beyond it,
apparently not significantly influencing the course of
renal disease.
We adopted biocompatible steam-sterilized membrane, preferring a medium-sized surface rather than a
small one, so as to increase small and medium
molecular clearance and to set the necessary ultrafiltration rate more easily.
We gradually increased the time and the number of
the weekly dialysis sessions. The current case suggests
that the weekly time of dialysis should not be
considered an absolute, but should provide the patient
with an adequate HD and the achievement of dry
weight. The constant evaluation of dry weight allowed
us to prevent both dehydratation and hyperhydratation, the first causing oligohydramnios and intrautrine
growth retardation, the second polyhydramnios and
premature delivery.
In order to reach the objectives commonly indicated
in the treatment of anaemia in these particular
circumstances, a relatively low dosage of rHuEpo
was necessary in our patient (Table 1). Moreover
differing dosages were necessary for the same patient
during the three pregnancies and during the various
trimesters. Substantial differences in the maximum
dose of Epo have also been reported in the various
series of reports, and anyway there is a general
consensus that it is necessary to increase the dosage
in women in dialysis who then become pregnant. New
implications regarding the link between anaemia and
pregnancy come from studies in rats, which suggest a
possible suppressive effect of endogenous estradiol on
erythropoietin induction through iron restoration [9].
We dedicated constant attention to nutrition and we
provided a protein-rich diet with 1.8-2 g/kg/day.
Since our patient lives in a geographical context
where the so-called Mediterranean diet is widespread,
she merely followed a diet rich in white meat, fish, olive
oil for dressing, fruit and vegetables. Furthermore,
we advised moderate physical activity, and a serene
acceptance of the patient’s own condition.
In conclusion, we believe that this multifactorial
approach was relevant to the favourable outcome of
the case presented, even though this cannot be
established only on the basis of our data. Even if the
number of pregnancies is still relatively limited and the
success of the current case very unusual, we feel that
this reflects a better outcome in general of the report
series over the last 15 years. This is probably due to
the improved quality of materials and dialysis techniques, new drugs—such as rHuEpo,—more attention to
nutritional needs and consequently to a better quality
of life for these patients.
Acknowledgements. We thank Dr F. Pantano for his obstetric
assistance and our dialysis nursing team for their humane and
professional contribution.
1240
Conflict of interest statement. None declared.
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Received for publication: 19.5.06
Accepted in revised form: 6.12.06