Pregnancy and Successful Full‐Term Delivery in a Patient on Peritoneal Dialysis: One Center's Experience and Review of the Literature

Pregnancy in patients on chronic peritoneal dialysis has been reported before,1–4 but because of its infrequency, we believe that the nephrology community can learn from each new case report. In this article we share our experience and the lessons learned with our first patient on CAPD who became pregnant and carried it through successfully while she remained on CAPD. A 32-year-old woman was suffering from chronic tubulointerstitial nephritis secondary to vesicoureteral reflux. She had had a ureteral re-implantation at age 11. In October 2004 she was started on CAPD of 4 exchanges of 1.5 L a day, mainly because of her small size and weight (height: 146 cm, weight: 32 kg, BMI: 14). She had never been pregnant before, and her menstruation was continuing regularly. She did not follow any regular contraceptive measures. Her dialysis went on uneventfully until April 2005, when she complained of lower abdominal pain at her regular clinic. An ultrasound of her lower pelvis showed that she was 10 weeks' pregnant. Both she and her partner strongly desired to have a child, and they asked to continue with the pregnancy. The risks of such a decision were discussed with them, and both agreed that the pregnancy would continue with the patient on CAPD for as long as possible under close supervision and agreed to change to hemodialysis (HD) if the need arose. It was reassuring that the patient already had a functioning AV fistula, which was created before she was started on CAPD. Initially the patient was seen monthly, then twice a month during the second trimester, and weekly during the 3rd trimester. Her clinical status, laboratory values, adequacy of dialysis, and residual renal function were assessed at each visit. Initially, fetal heart sounds and ultrasonographic monitoring of fetal growth were performed monthly, then weekly beginning in the 28th week, and daily in the last 2 weeks. In the 18th week of her pregnancy, she underwent amniocentesis after the peritoneal cavity had been drained, and examination of the fluid did not show any genetic disorder. CAPD was reinstituted after amniocentesis without any side effects. She was hospitalized in the nephrology ward from the 28th week to the end of her pregnancy. Dialysate exchange volume was adjusted to the patient's comfort and distention, and at her request, the volume was gradually decreased from the initial 1,500 mL/exchange to 600 mL/exchange at the end (Figure 1). Patient's change in fill volume from the initiation of PD. The patient's urine volume, which had decreased to 800 mL/day before pregnancy, started increasing, and by the end of her pregnancy, it had reached 1,500 mL/day. This was accompanied by an increase in creatinine and urea clearance, which allowed the patient to have an adequate total Kt/V and weekly creatinine clearance throughout her pregnancy despite the decreased volume of the exchanges (Figures 2 and 3). Changes in fluid volumes. Changes in Kt/V. Figure 4 shows changes in the patient's weight. She gained a total of 11.7 kg, and following delivery her weight dropped from 43.7 to 37 kg. Changes in patient's body weight. As the pregnancy progressed, her erythropoietin requirements continued to increase in order to maintain her hemoglobin at 100 g/L, reaching about a 4-fold increase by the 29th week. Her serum ferritin was maintained between 338 and 124 ng/mL, with oral supplements of ferrous hydroxide (200 mg/day). From the 32nd week, 1400 mg of calcium carbonate 3 times a day, 2 tablets of ketosteril (keto-/amino acid) 3 times a day, and 1 g of magnesium citrate a day were added to her treatment. Because of an increase in her PTH level (from 25.7 to 63.3 pmol/L), 0.25 µg of calcitriol on alternate days was added for 1 month. In the 32nd week, she received 1 intramuscular injection of 7 mg of betamethasone (Diprophos; Schering-Plough, Kenliworth, NJ) for fetal lung maturation. Because fetal development stopped, her pregnancy was terminated in her 35th week through an elective cesarean section. Peritoneal dialysis (PD) was stopped on the morning of delivery, the catheter was capped but not removed, and a healthy boy (Apgar scores: 7/8, weight: 1,100 g) was delivered. Analysis of the amniotic fluid showed a creatinine level of 358µM/L (baby/s serum creatinine: 222 µM/L). Because her biochemical status was stable, she did not need any HD. From the second post-operative day we performed daily peritoneal lavage with 500 mL of Dianeal for 2 weeks without any leakage through the incision. The initially bloody effluent cleared on the third day. Two weeks after the C-section, we restarted PD with a lower fill volume (600 mL 4 times a day) and discharged her home. We decided to dialyze her with small volumes partly because of the short period after the operation and partly because of her abdominal distention. In the 3rd month after delivery, we increased the exchange volume to 1,500 mL 4 times a day, which she tolerated well. The newborn was placed in the perinatal intensive care unit. Two hours after birth, he required continuous positive airway pressure because of a drop in oxygen saturation; otherwise, all parameters were normal. On the third day the mother's lactation commenced, and the baby was breastfed. The baby's post-delivery serum creatinine (222 µM/L) dropped to 77 µM/L 3 days later. Hemoglobin was normal all along. The baby was discharged home after 6 weeks with a weight of 2000 g. Because of decrease in lactation flow, the baby was fed with formula milk after the end of the sixth week. Lactation stopped completely at the eighth week. The possibility of pregnancy in the early stage of chronic kidney disease is much reduced mainly because of amenorrhea, anovulation secondary to hormonal abnormalities, the uremic milieu, anemia, reduced libido, a low concentration of vitamins and trace elements, and side effects of the medications used.5-9 In patients with stage 5 chronic kidney disease, the incidence of pregnancy is even lower, with the probability of conception 0.75%–7.0%.1, 10, 11 The European Dialysis and Transplant Association Registry reported an incidence of 0.5%.12 However this incidence is misleading because registries do not show the proportion of fertile women, their sexual activity, their use of contraceptives, their previous pregnancies, and the treatments they are receiving. Also the number of early spontaneous abortions is not known. In the 35 years since Confortini et al.13 first reported a successful pregnancy in a hemodialysis patient, an increasing number of pregnancies have been reported in both HD and PD patients, probably because of the increased use of and improvement in dialysis techniques. Despite increased experience and improvement in dialysis techniques, the risks of pregnancy for mother and fetus are invariably higher for women on dialysis than for healthy women.3 Surveys of medical centers before 1990 reported a rate of successful pregnancy ranging between 21% and 52%,2, 11, 14, 23 but in the second half of the 1990s, this rate increased to more than 50%. Romao et al.23 and Giatras et al.4 described infant survival of 70.6% and 64.5%, respectively, and in a study of pregnancy in chronic hemodialyzed women by Nakabayashi et al.,28 73.3% of the pregnancies ended in live births. According to Okundaye et al., pregnancy is more common in women on HD than in those on PD (2.4% versus 1.1%), whereas the probability of a successful pregnancy is higher on PD.2 Hou et al.27 summarized the experience of women on PD with pregnancy. At the same time, it seems that having higher residual renal function (RRF) increases the probability of a successful pregnancy.9, 11, 15, 23 In this respect, PD may have an advantage over HD because it tends to maintain RRF for longer periods. Furthermore, the continuous and gentle removal of waste and the steady blood levels help to maintain a stable intrauterine metabolic milieu, and therefore the risk of developing polyhydramnion is lower. Although the pathophysiology of polyhydramnion in pregnant HD patients is unknown, it seems that having a higher urea level before an HD session may induce solute diuresis by normal fetal kidneys, thus increasing amniotic fluid production. An alternative or additional explanation may be that frequent and relatively rapid removal of solutes during hemodialysis in patients with decreased oncotic pressure may shift free water into the amniotic cavity.19 The probability that pregnant women on peritoneal dialysis will develop polyhydramnion is lower because of constant lower urea levels.20 At the same time, the stable volume balance (without intrauterine and systemic hypotensive episodes because of continous and consistent volume removal) may help to prevent fetal distress.16-18 Polyhydramnion increases the risk of premature labor.24 Hypotensive episodes during hemodialysis increase the risk of retardation of fetal growth in addition to increasing the risk of premature birth and fetal death.21, 22 In women on PD fetal growth requires a decrease in inflow volumes, leading to a decrease in dialysis efficiency; this may increase the incidence of fetal retardation and premature birth and of the development of polyhydramnion. To avoid these complications, the dialysis dose has to be increased to provide optimal dialysis. To increase the efficiency of peritoneal dialysis under these circumstances, it is necessary either to increase the frequency of exchanges or to increase the daily dialysate volume by changing from CAPD to CCPD with a cycler.3 Okunday et al.2 suggested a goal of 2.2–2.4 for Kt/V in pregnant women on dialysis, whereas William et al.3 recommended a weekly Kt/V of at least 2.5–2.6 Kt/V. Chang et al.25 proposed an even higher Kt/V value of 3.7 in patients treated with cycler by increasing the total daily volume to 19.5 L, but others have suggested that a Kt/V of 2.2–2.4 with a daily exchange volume of up to 20 L is adequate.3, 26 However, most investigators emphasize concentrating on a patient's condition and adjusting the dialysis dose accordingly rather than following the Kt/V number. Furthermore, residual kidney function plays an important role in the success of PD in pregnant women.9, 11, 15, 23 In our patient, we observed distinct improvement in her residual kidney function during pregnancy. Others have described alterations of renal hemodynamics and glomerular filtration in pregnant women.29-36, 40 Pregnant renal allograft recipients and those with single kidneys have an increase in GFR similar to that in a normal pregnancy, despite the denervation of transplanted kidney and the compensatory anatomical and functional hypertrophy of a single kidney.37, 38 We have no data on the pathogenesis of alterations in renal hemodynamics in patients with advanced renal failure who are pregnant. Normally, during the first trimester of pregnancy, women have an increased glomerular filtration rate (40%–65%) and increased effective renal plasma flow (50%–85%).30-35 Many hormonal alterations, especially a change in the production of relaxin, may decrease vascular resistance.40 This increased relaxin level in the first trimester is followed by increases of up to 45% in GFR and ERPF levels.41, 42 Administration of relaxin improves creatinine clearance, increases residual diuresis, and decreases deposition of glomerular and interstitial collagen IV, thus diminishing the severity of the glomerular lesion.43 In addition to the increase in relaxin, the level of nitric oxide increases, leading to renal vasodilatation and hyperfiltration.44, 45 Higher RRF increases the probability of a successful pregnancy. PD may have an advantage here, because it tends to maintain RRF for longer periods. Pregnant women treated with peritoneal dialysis are more likely to need a C-section than those treated with HD.23 In an effort to continue PD, performing an extraperitoneal C-section to maintain the integrity of peritoneum may be considered.23 However after a transperitoneal Csection (if there are no complications), the peritoneum that is not sutured (usually because it adheres to the abdominal wall) heals spontaneously, and the wound heals without any complications. Because of the small stature of our patient, we planned her C-section in advance and performed it through a transperitoneal route. After removing the living fetus, the surgeon looked for the dislocated Tenckhoff catheter, and after suturing the uterus, he replaced it in the pelvis. Contrary to the standard practice, the peritoneum was sutured before closing of the abdomen wall. On the second day after her operation, she was transferred to the care of the nephrology department. We have reported a successful pregnancy of a patient on CAPD. The maintenance and gradual increase in her residual function contributed to her optimal dialysis. We emphasize that although the pregnancy of a dialysis patient requires the cooperation of several specialists, coordination of the patient's treatment should remain in the hands of the nephrology team. This article was not written to encourage patients with end-stage renal disease to become pregnant, pregnant, which is still a risky undertaking; rather, the intent was to emphasize that if the parents very strongly desire a child or if the pregnancy is accidental but the patient wants to continue to term, a pregnancy can be managed effectively. We thank Professor Dimitrios Oreopoulos (Toronto, Western Hospital, Canada) for his very kind assistance in the preparation of this manuscript.

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