renal transplantation and pregnancy
TRANSCRIPT
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Professor Salwa Ibrahim
Cairo university
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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
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Fertility after renal transplantation
Maternal risks
Fetal risks and outcomes
Immunosuppressant drugs
Management
Pregnancy in kidney donors
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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.
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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
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Pregnancy Outcomes
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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%
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Maternal Risks
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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%
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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
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DD of worsening graft function
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Pre-eclampsia
Acute or chronic rejection
Recurrent kidney disease
Dehydration
Obstruction of the ureter by gravid uterus
UTI
Medication toxicity
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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
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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
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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
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Renal transplant with hypertension are at increased risk of Preeclampsia
Diagnosis is difficult as renal transplant patients commonly have hypertension,
proteinuria, hyperuricemia
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Aspirin 75mg daily from the end of first trimester until delivery
Keep BP < 140/90 mmHg
Those with nephrotic proteinuria should receive LMWH daily
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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
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Fetal risks and outcomes
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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
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Immunosuppressive medications
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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
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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
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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
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FDA category D : Positive evidence of risk
Abortion, IUGR, IUFD
Transient leucopenia, thrombocytopenia
Usually resolve at 1 YEARD
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FDA category D : Positive evidence of
risk
Contraindicated in pregnancy
Associated with structural abnormalities
like cleft palate hypoplastic nails D
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FDA category C: risks can not ruled out
Contraindicated in pregnancy
No data available on safety as both
suppressed VEGF C
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Management
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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
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The American society of transplantation
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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
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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
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Steroid and azathioprine transfer in breast milk
is very low.
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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.
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Pregnancy in kidney Donors
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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.
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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.
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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
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