Professor Salwa Ibrahim

Cairo university

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

Fertility after renal transplantation

Maternal risks

Fetal risks and outcomes

Immunosuppressant drugs

Management

Pregnancy in kidney donors

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.

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

Pregnancy Outcomes

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%

Maternal Risks

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%

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

DD of worsening graft function

Pre-eclampsia

Acute or chronic rejection

Recurrent kidney disease

Dehydration

Obstruction of the ureter by gravid uterus

UTI

Medication toxicity

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

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

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

Renal transplant with hypertension are at increased risk of Preeclampsia

Diagnosis is difficult as renal transplant patients commonly have hypertension,

proteinuria, hyperuricemia

Aspirin 75mg daily from the end of first trimester until delivery

Keep BP < 140/90 mmHg

Those with nephrotic proteinuria should receive LMWH daily

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

Fetal risks and outcomes

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

Immunosuppressive medications

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

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

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

FDA category D : Positive evidence of risk

Abortion, IUGR, IUFD

Transient leucopenia, thrombocytopenia

Usually resolve at 1 YEARD

FDA category D : Positive evidence of

risk

Contraindicated in pregnancy

Associated with structural abnormalities

like cleft palate hypoplastic nails D

FDA category C: risks can not ruled out

Contraindicated in pregnancy

No data available on safety as both

suppressed VEGF C

Management

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

The American society of transplantation

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

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

Steroid and azathioprine transfer in breast milk

is very low.

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.

Pregnancy in kidney Donors

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.

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.

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