renal transplanation in pregnancy

1. Professor Salwa Ibrahim
Cairo university

2.  28 year old transplant recipient came to the clinic asking
about her chances of getting pregnant
 She had renal TX since 4 years and her serum creatinine has
been stable 0.9 mg/dl for the last 12 months
 She is hypertensive on CCB

3.  Fertility after renal transplantation
 Maternal risks
 Fetal risks and outcomes
 Immunosuppressant drugs
 Management
 Pregnancy in kidney donors

4.  Female patients with ESRD commonly have infertility as a result of endocrine
dysfunction, prescribed medications and psychological factors
 Female infertility is caused by increased FSH , LH and prolactin levels
 Endocrine functions improves within months following kidney transplantation
with resumption of ovulatory cycles and fertility.

5.  The first successful pregnancy occurred in a kidney transplant recipient from an
identical twin sister performed in 1958
 Later, The twin had successful full term pregnancies

6. Pregnancy Outcomes

7.  The outcomes of pregnancy depends on pre-pregnancy renal function
 If a woman has a pre-pregnancy serum creatinine level of less than 1.4 mg/dl, the
chances of having a successful pregnancy are 96%
 If pre-pregnancy serum creatinine is more than 1.4 mg/dl, the chances of
successful pregnancy drops to 70-75%

8. Maternal Risks

9.  In the majority of recipients, pregnancy does not appear to cause irreversible
problems with graft function if the function of the organ is stable prior to pregnancy
 In a recent UK renal transplant registry, the 2-year post pregnancy graft survival
was 94%

12.  Preexisting kidney disease is an independent risk factor for pre-eclampsia
 Serum creatinine less than 1.3 mg/dl does not seem to risk worsening kidney
function
 Serum creatinine 1.3 to 1.9 mg/dl or more often experience decline in graft
function
 Proteinuria more than 500 m/day significantly increase risk of irreversible graft loss

13. DD of worsening graft function

14.  Pre-eclampsia
 Acute or chronic rejection
 Recurrent kidney disease
 Dehydration
 Obstruction of the ureter by gravid uterus
 UTI
 Medication toxicity

15.  Rejection is a significant risk during pregnancy as a result of changes in blood
volume
 Immunosuppressive medications dosing can be difficult and needs frequent
monitoring of CNI levels because of increased volume of distribution in adipose
tissues and red cells
 Pregnancy induces hyperfiltration and detection of rejection can be difficult
 Diagnosed by US guided renal biopsy
 Treated with corticosteroids
 Few data on ATG or OKT3

16.  Preexisting chronic hypertension or gestational
hypertension
 During normal pregnancy, BP is lowest during
first trimester and returns to prepregnancy levels
near term
 Those changes occurred in transplant patients
but may be blunted by medications
 Achieve normotensive state is advised

17.  a-Methyldopa
 Beta blocker: atenolol and metoprolol are safe but may be linked to IUGR when stated early,
non selective beta blockers should not be used because of the risk of uterine contractions
 Hydralazine
 Calcium channel blockers
 Labetolol
 ACEI/ARBS are contraindicated
 Thiazide diuretics can be used for chronic hypertension but are contraindicated in
preeclampsia because of associated volume contraction and poor placental perfusion


18.  Renal transplant with hypertension are at increased risk of Preeclampsia
 Diagnosis is difficult as renal transplant patients commonly have hypertension,
proteinuria, hyperuricemia

19.  Aspirin 75mg daily from the end of first trimester until delivery
 Keep BP < 140/90 mmHg
 Those with nephrotic proteinuria should receive LMWH daily

20.  UTIs are the most common bacterial infections in pregnant transplant recipients
 The women should have monthly screening urine cultures
 Asymptomatic bacturia should be treated for 2 weeks and may be treated with
suppressive doses of antibiotics for the rest of pregnancy

21. Fetal risks and outcomes

22.  A recent published meta-analysis of 4706 pregnancies in kidney transplant
recipients:
1. Live birth rates 73.5%
2. Miscarriage rate 14.0%
3. Preeclampsia 27%
4. Gestational diabetes 8%
5. Cesarean section 56.9%
6. Preterm delivery 45.6%
 Lower maternal age, normotension, normal renal function and longer interval
between transplantation and pregnancy was associated with better outcomes

23. Immunosuppressive medications

24.  Most of drugs cross the placental barrier and undergo extensive first pass
metabolism in fetal liver
 The incidence of birth defects in the live born was found to be similar to the general
population, except for pregnancies with mycophenolic acid exposure that had a
23% incidence of birth defects.
 Mycophenolate mofetil and sirolimus, are not recommended based on current
information available

25.  FDA category B : No evidence of risks in
humans
 It does not have teratogenic activity in
therapeutic doses
 Higher doses > 40mg/dl increased rates of
abortion, IUFD, IUGR and gestational
hypertension and DM
B

26.  FDA category C : Risks can not ruled out
 Cyclosporine treatment is associated with
increased rates of abortion, IUGR, B cell
depletion
 Does not affect neonatal renal function
 Tacrolimus is associated with preterm birth,
transient hyperkalemia, transient renal
impairment and gestational DM
C

27.  FDA category D : Positive evidence of risk
 Abortion, IUGR, IUFD
 Transient leucopenia, thrombocytopenia
 Usually resolve at 1 YEAR
D

28.  FDA category D : Positive evidence of
risk
 Contraindicated in pregnancy
 Associated with structural abnormalities
like cleft palate hypoplastic nails
D

29.  FDA category C: risks can not ruled out
 Contraindicated in pregnancy
 No data available on safety as both
suppressed VEGF C

30. Management

31.  All renal transplant patients at childbearing age should be encouraged to use
contraception as early as possible because ovulatory cycles may begin within 1-2
months
 The peri-transplantion period is not the optimal time for pregnancy because this is
the time of highest use of potentially teratogenic drugs
 Low dose oral contraception (estrogen-progesterone) and barrier methods of
contraception are advised
 Intrauterine devices should be avoided because of risk of infections

32. The American society of transplantation

33.  Patients may be pregnant at any time as long as graft function is optimal and
immunosuppressive dosing is stable at maintenance levels (i.e. after 12
months of transplantation)
 Serum creatinine < 1.5 mg/dl.
 Urinary protein excretion less than 500 mg/day
 No recent episodes of active rejection, No concurrent infections
 BP <140/90 mmHg on medications
 Normal allograft ultrasound
 MMF and rapamycin should be stopped for 6 weeks before pregnancy

34.  Vaginal delivery is recommended, CS should be performed for standard obstetric
reasons
 Proper wound care and prophylactic antibiotics
 In the perinatal period, steroid dose should be augmented to cover the stress of
labour and prevent postpartum rejection
 Hydrocortisone 100 mg every 6 hours should be given during delivery


35. Steroid and azathioprine transfer in breast milk
is very low.

38. Exposure to tacrolimus and cyclosporine appears not to be a risk for breast-fed
infants, and breast-feeding should not be discouraged in mothers receiving
tacrolimus /CsA therapy.

39. Pregnancy in kidney Donors

41.  Increased Risk of gestational Hypertension or Preeclampsia for Pregnant
Women who Donated Kidney
 Gestational hypertension or preeclampsia occurred in 15 of 131 pregnancies (11%)
among living kidney donors vs. 38 in 788 pregnancies (5%) among nondonors in
new research presented at ASN Kidney Week 2014.
 The findings were published in the New England Journal of Medicine November
2014.

43.  There were no significant differences between donors and
nondonors with respect to rates of preterm birth (8% vs. 7%) or low
birth weight (6% vs. 4%).
 There were no reports of maternal death, stillbirth, or neonatal death
among the donors.
 Most women had uncomplicated pregnancies after donation.

44.  Kidney transplant undergoes major physiological changes in pregnancy
 Contraception and preconception counseling are essential
 Patients should be managed jointly with an obstetrician and should be made ware
of possible maternal complications
 Fetal outcomes are generally good in those with good graft function
 In those with good graft function, pregnancy does not affect long term graft function
