NDT Advance Access originally published online on January 20, 2007
Nephrology Dialysis Transplantation 2007 22(4):1236-1240; doi:10.1093/ndt/gfl794
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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
Nephrology and Dialysis Unit, Hospital of Tropea, ASL 8 Vibo Valentia, Calabria, Italy
Correspondence and offprint requests to: Francesco Giofrè, U.O. Nefrologia E Dialisi Ospedale G-Jazzolino, Asl 8 89900 vibo Valentia, Italy. Email: dialtrop{at}tiscali.it
Keywords: chronic renal failure; haemodialysis; IgA nephropathy; three successful pregnancies
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Introduction |
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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.
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Case report |
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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). 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.
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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 steam-sterilized 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] 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 therapy with ritodrin 15 mg/day was administered. Following the failure of tocolysis at the 33rd week, delivery by Caesarean section was performed. The live-born 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.
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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, 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.
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Discussion |
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TopIntroductionCase reportDiscussionAcknowledgementsReferences |
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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.
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Acknowledgements |
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We thank Dr F. Pantano for his obstetric assistance and our dialysis nursing team for their humane and professional contribution.
Conflict of interest statement. None declared.
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References |
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- Hou S. (1999) Pregnancy in chronic renal insufficiency and end-stage renal disease. Am J Kidney Dis 2:235–252.
- Malik GA, Al-Wakeel JS, Shaik JF, et al. (1997) Three successive pregnancies in a patient on haemodialysis. Nephrol Dial Transplant 12:1991–1993.
[Abstract/Free Full Text] - Gnanasekaran J and Barula U. (2003) Hemodialysis patient having three successive pregnancies. Dial Transplant 12:768–771.
- Parker TF III, Wingard RL, Husni L, et al. (1996) Effect of the membrane biocompatibility on nutritional parameters in chronic hemodialysis patients. Kidney Int 49:551–556.[Web of Science][Medline]
- Giatras I, Delphine P, Levy P, et al. (1998) Pregnancy during dialysis: case report and management guidelines. Nephrol Dial Transplant 13:3266–3272.
[Abstract/Free Full Text] - Masaki D, Greenspoon J, Ouzunion J. (1989) Mesurement of cardiac output in pregnancy by thoracic electrical bioimpedence and thermodiluition. Am J Obstetrics Ginecology 161:1101–1105.
- Hou SH. (2002) Modifications of dialysis regimens for pregnancy. Int J Artif Organs 25:823–826.[Web of Science][Medline]
- Brost BC, Newman RB, Fries M, Calhoun BC. (1996) The effects of hemodialysis on total intrauterine volume. Ultrasound Obstetrics Ginecology 8:34–36.
- Horighuchi H, Oguma E, Kayama F. (2005) The effects of iron deficiency on estradiol-induced suppression of erythropoietin induction in rats: implications of pregnancy-related anemia. Blood 106:67–74.
[Abstract/Free Full Text]
Accepted in revised form: 6.12.06
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