Pregnancy after kidney transplantation can be successful but carries increased risks for both mother and baby. Close monitoring by a multidisciplinary team is important. It is generally recommended to wait at least one year after transplantation for stable graft function before attempting pregnancy. Medications like mycophenolate and mTOR inhibitors should be discontinued or switched prior to conception due to teratogenic risks. Counseling discusses the impact of pregnancy on the allograft and risks of maternal complications like preeclampsia and fetal issues such as prematurity. Careful management of immunosuppression levels, blood pressure, and infections can help support a healthy pregnancy outcome.

1. Pregnancy and renal transplantation
MOHAMED ABDELMONEM MD (CAIRO),FRCP (LONDON)
SENIOR SPECIALIST-TRANSPLANT NEPHROLOGY
ORGAN TRANSPLANT CENTER -KUWAIT
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2. Is pregnancy safe after kidney transplant
 What is the ideal time to become pregnant after kidney transplant
 What increases the risk of poor pregnancy after renal transplant
 What are the possible maternal complications
 What are the possible fetal complications
 Does pregnancy increase the risk of graft failure
 What changes to immune suppression are required before and during
pregnancy
 Does pregnancy increase the risk of infection
 Is breast-feeding safe in renal transplant recipients
2

3. Fertility
In CKD and ESRD:
- Delayed onset of puberty
-Elevated LH levels with decease pulsatile secretion
,absent midcycle LH surge, increase LH/FSH
ratio, increase prolactin.
-Anouulation due to HPO- axis dysfunction.
-Decreased libido
Following a kidney transplant :
-Most resume menstrual cycles within one year
-average time 5 months
-Luteal phase defects are more common
- Premature ovarian failure is 4-20%
-contraceptive counseling at every visit more than 50% of
pregnancies are unplanned
Duglas , NC 2007
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4. Successful pregnancies after human renal transplantation
Murray JE,1963
4

5. Physiology of pregnancy
24 hours creatinine cl earance at 10 weeks
124 + 15.9 in healthy women (38% increase )
125+ 28.1 in transplant recipients (34% increase )
In late pregnancy
Cr Cl decreased by 19% in healthy and 34% in transplant recipients Davison
JM,1985
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6. Physiology
:Proteinuria
Proteinuria increased
through out pregnancy
-More than 500 mgs in the
3rd trimester in transplant
recipient
-Returned to pre pregnancy
by b 8-12 weeks post
partum
Davison JM,1985 6

7. Introductions
 Epidemiology
 Complications
 Criteria for considering pregnancy
 Antenatal management
 Labor management
 Breast feeding
 Contraception
 Pregnancy counselling
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8. Epidemiology
 Pregnancy is estimated to occur in 12% of transplanted women of
childbearing age .
 The number of kidney transplant recipients who conceive seems to be
increasing
 The incidence of preterm delivery premature rupture of membranes and
fetal growth retardation is as high as 60 %
 Acute rejection in pregnancy occurs in ˜ 4-9 %
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9. Epidemiology
 Most women treated with azathioprine and prednisolone
 The ectopic pregnancy rate is higher and this is related to adhesions from
previous surgery and peritoneal dialysis
 If pregnancy continued beyond 1St trimester ,90% has successful outcome
 Superimposed pre-eclampsia and urinary tract infection occur in up to
40%
9

10. complications
Fetal complications
Maternal complications
1.Miscarriage
2.Ectopic pregnancy
3.Preterm delivery
4.IUGR
1.Hypertension
2.Preeclampsia
3.Allograft rejection
4.Infections
5.Diabetes
10

11. Criteria for renal transplant recipients contemplating
pregnancy:(David et.al 2015)
 At least 6 months after transplantation
 Stable allograft function and creatinine < 1.4 mg/dL
 No recent episodes of acute rejection
 Blood pressure ≤ 140/90 mmHg or minimal antihypertensive medication
 No or minimal proteinuria ≤ 500 mg/24 hours
 Prednisone ≤ 15 mg/day
 Azathioprine ≤ 2 mg/kg/day
 Stopping mycophenolate mofetil and sirolimus 6
weeks prior to conception
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12. Antenatal management
 All pregnant renal transplant recipients should have access to high level
multidisciplinary prenatal care (maternal fetal medicine specialist,
obstetricians, renal physicians and renal transplant surgeons)
 Close observation
 Treatment of bacteriuria
 Follow up of immunosuppressive medications
 Monitoring renal function and blood pressure
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13. Antenatal management
 Women should tested for CMV,HIV,HSV,HBV and HCV
 Those found to have CMV negative should have their titers rechecked in
each trimester
 Oral glucose tolerance tests should be arranged to diagnose gestational
diabetes
13

14. Transplant physician monitoring scheme. Josephson MA etal.,
2007
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15. Proposed frequency of controls during pregnancy in women with a
kidney transplantation
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16. Labor management
 Delivery is timed for 38-40 weeks of gestation in absence of any obstetric
complications
 Vaginal birth is the preferred route
- Prostaglandins and syntocinon both safe to use for
cervical ripening or induction
-The allograft located in the false pelvis ,does not
obstruct delivery of the fetus
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17. Labor management
Cesarean section may be necessary for obstetric indications or if there are
concerns related to severe pelvic osteodystrophy
Multiple studies have demonstrated higher cesarean section rates in
transplant recipients when compared to the general obstetric population due
to higher risk of severe early onset pre eclampsia and fetal growth restriction
necessitating early delivery prior to 34 weeks
Available help from the urology surgical team or renal transplant surgeons
when elective section is planned
Stress dosage of steroids should be administered
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18. Breast feeding
 Transplant recipient taking prednisolone, azathioprine, cyclosporine and
tacrolimus should not be discouraged from breast feeding
 Clinical information on breast feeding is inadequate for mycophenolate
,sirolimus and everolimus ,breast feeding should be avoided
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19. Contraception
 Low dose of estrogen/progesterone or progestin only oral contraceptive in
renal transplant recipients if hypertension is well controlled
 IUD may may increase the chance of infection and in addition lead to
contraceptive failure due to reduced anti-inflammatory properties
 Barrier method is safe but not an optimal from contraception due to
potential for contraception failure
 Tubal ligation should be advised in women who have completed their
families
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20. Contraceptive Methods
20

21. PREGNANCY COUNSELING
 This must include a discussion on the impact of pregnancy on acute rejection
and graft loss
 The risk of acute rejection correlates with pre-pregnancy serum creatinine levels
as well as the interval between transplant and pregnancy
21

22. Immunosuppressive and other drug regimens
during pregnancy
22

23. Immunosuppressive regimens during pregnancy
23

24. Medication in women in relation to conception, pregnancy and
lactation.( Adapted from Wiles et al.)
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25. Medication in women in relation to conception, pregnancy and
lactation. (Adapted from Wiles et al.)
25

26. Medication in women in relation to conception, pregnancy and
lactation. (Adapted from Wiles et al.)
26

27. Medication in women in relation to conception, pregnancy and
lactation. (Adapted from Wiles et al.)
27

28. Medication in women in relation to conception, pregnancy and
lactation. (Adapted from Wiles et al.)
28

29. Medication in women in relation to conception, pregnancy and
lactation.
29

30. Management of hypertension
 Alpha methyldopa : Safe
 Beta blokes (atenolol and metoprolol): Safe especially in late pregnancy
 Hydralazine: Safe
 Calcium channel blockers(Nifedipine, nicardipine and verapamil ) can be
used safely in first trimester (avoid use with magnesium ---- can potentiate
hypotension especially in pre eclampsia
 Labetalol: Safe
 ACEi :contraindicated
 Diuretics: contraindicated
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31. Management of infection
 Bacterial:
UTI ------- The most common 40%
Asymptomatic bacteriuria: should be treated for 2 week
The selection of antibiotics should consider potential fetal
toxicity
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32. Management of infection
Viral:
CMV : The most common viral infection post transplant
HSV: Infection before 20 weeks of gestation is associated with an increased
risk of abortion
-Positive HSV cervical culture at term is indication for CS to minimize the
risk of neonatal herpes
-Acyclovir can be used safely in pregnancy
HBV: An infant of HBsAg Positive mother Hepatitis B immunoglobulin within 12
hours of birth
HBV vaccine within 48 hours then booster injection at 1 and 6 months
HCV: Vertical transmission is low ( less than 7%) unless the patient is also
infected with HIV
32

33. Pre existing disease in RTR pregnant
Thrombotic microangiopathies
 ESRD due to TTP/HUS-risk of recurrence during pregnancy in RTR.
Management similar to patients without renal transplant.
SLE
 Pregnancy and renal outcomes in RTR women caused by lupus nephritis are
comparable with outcome in RTR with other cases of ESRD
Reflux nephropathy
 Common in women of childbearing age
 Antenatal and post natal surveillance for presence of hereditary disease in
offspring is recommended
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34. Pregnancy outcomes
34

35. Pregnancy outcomes reported by major registries:
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36. Maternal outcomes
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37. Fetal outcome
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38. Preterm delivery and low birth weight
Increased risk of preterm- 45% (13% general population).
Low birthweight infants are common- RTR 2420 gms compared to 3298 gms in general population.
Predictors are:
Pre pregnancy graft function
Proteinuria
Conception on MMF
Pre existing hypertension
Diabetes, and
Black ethnicity
Few studies show two or more transplants and acute graft rejection episode are also
Risk predictors.
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39. 39

40. Pre eclampsia and renal
transplantation
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41. Pre eclampsia and renal transplantation
 Rate of recovery decreases the more severe the stage of AKI
 Risk of preeclampsia in subsequent pregnancies increases 4 fold, despite
complete resolution
 Therefore flag these patients for high risk obstetric care in future
pregnancies.
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42. Maternal organ dysfunction on pre-eclampsia :
 New proteinuria(u PCR >30 mg/mmol or ACR >8 mg/mmol)
 AKI (S. creatinine ≥ 90 µmol/l in a woman with previously normal
creatinine concentrations)
 Liver involvement(ALT or AST > 40 IU/L) with or without right upper
quadrant or epigastric pain.
 Neurological complications(eclampsia, altered mental status, blindness,
stroke, clonus, severe headache, persistent visual scotomata)
 Hematological complications(platelet count < 150,000/ µL, disseminated
intravascular coagulation, hemolysis)
 Uteroplacental dysfunction(fetal growth restriction, abnormal umbilical
artery Doppler wave form analysis, still birth.
42

43. Pre eclampsia and renal transplantation
 Is a major cause of renal dysfunction in pregnancy
 Results in glomerular endotheliosis
 They usually have a mild reduction in GFR but
 When complicated by HELLP syndrome ,may progress to AKI and cortical
necrosis
 They require meticulous fluid management to avoid pulmonary oedema
 Ultimate treatment to prevent further deterioration is delivery
43

44. Differential diagnosis for pregnancy-related AKI in kidney transplant
recipients based on pregnancy trimester
44

45. Pregnancy-related acute kidney injury classified by prerenal, renal,
and postrenal etiologies in the kidney transplant population
45

46. Does twin or triple pregnancy occurs
in renal transplant recipient
46

47. Description of studies reporting the number of pregnancies, number
of twin pregnancies, and
complications in twin pregnancy after kidney transplantation
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48. Rejection episodes in renal transplant
recipients
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49. Causes of elevated creatinine in pregnant kidney transplant
recipients
Cause Clinical features
Pre renal /Renal
Normal physiologic return to pre pregnancy levels
in 3rd trimester
No concerning features identified
Hypoperfusion Hyperemesis, antepartum hge, sepsis, excessive
antihypertensive medications
Pre eclampsia Worsening or new onset HTN, worsening or new
onset proteinuria, abnormal LFTs, low platelets,
fetal restriction
CNI toxicity High trough drug levels
UTI Positive midstream urine
Viral infection Polyoma virus (decoy cells in urine), CMV PCR
Acute rejection Diagnosis confirmed by kidney biopsy
Post renal(obstruction) Hydronephrosis on U/S with no other cause
identified ; exclude urinary retention
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50. Renal graft biopsy in renal transplant pregnant
 Data for native kidneys
 Can be done safely in women with well-controlled blood pressure
 Biopsy after 32 weeks is not recommended (if applies to transplant
patients )
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51. Allograft rejection during pregnancy and postpartum
 Uncommon .metanalysis (102/2412) incidence is 4.2%.
 Timing and nature of rejection is not known due to small and limited
studies.
 Renal allograft biopsy at early gestation is necessary for management
 Acute rejection optimal management –unknown.
 High dose corticosteroid treatment is safe
 Baziliximab, aletuzumab and ATG –not recommended in pregnancy
51

52. Conclusions
A successful outcome of pregnancy was shown with
close monitoring and daily dialysis in a kidney
transplant patient with thymoglobulin-resistant
T-cell-mediated rejection. The risks and uncertainties
of treating rejection episodes should always be
discussed with and understood by the patient before
an informed decision is made
52

53. Long term graft survival outcomes
 According to US National transplant Pregnancy Registry (NTPR)
-Lower pre pregnancy graft function (pre pregnancy creatinine
>105 mg/dl
-Rising creatinine during pregnancy
-Black women (13 %) within 2 years post pregnancy
Are predictive of graft loss post partum, independent of hypertension
,preeclampsia ,and immunosuppression
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54. Long term graft survival outcomes
 Post partum –there is restoration of immunity and reactivation of T –cell
mediated activity and hypothetic increase in risk of allograft rejection
 Studies comparing RTR with pregnancy /without pregnancy – No
difference in graft outcomes (1/2/5 years -5.8%/8.1%/6.9% respectively)
 Hence, due to absence of evidence –postpartum empirical increase in
immunosuppression is not recommended
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55. KDIGO guidelines :
 We suggest waiting for at least 1 year after transplantation before
becoming pregnant, and only attempting pregnancy when kidney
function is stable with <1 g/day proteinuria. (2C)
 We recommend that MMF and MPS be discontinued or replaced with
azathioprine before pregnancy is attempted. (1A)
 We suggest that mTORi be discontinued or replaced before pregnancy
is attempted. (2D)
55

56. KDIGO guidelines :
-Counsel female KTRs with child-bearing potential and their partners about
fertility and pregnancy as soon as possible after transplantation. (Not Graded)
-Counsel pregnant KTRs and their partners about the risks and benefits of
breastfeeding. (Not Graded)
-Refer pregnant patients to an obstetrician with expertise in managing high-risk
pregnancies. (Not Graded)
56

57. Summary of Obstetric Management for Pregnancy After
Transplantation
 After Transplantation
 1.Delay conception for at least 1 year with adequate contraception
 2.Assess and monitor graft function
 3.Maintain immunosuppressive regimen
 4.Manage comorbid conditions
 Preconception counseling
 1.Discuss the effect of pregnancy on transplant function
 2.Discuss the risks of maternal complications: hypertension, pre eclampsia ,diabetes,
rejection and graft loss
 3.Obtain good control of hypertension and diabetes
 4.Discuss risks of neonatal complications prematurity and low birth weights
 5.Modification of immunosuppressive regimen if necessary
 6.Test for CMV and other potential infections 57

58. Summary of Obstetric Management for Pregnancy After
Transplantation
 Early pregnancy
 1.Accurate and early diagnosis and dating of pregnancy
 2.Close monitoring of graft function and immunosuppressive drug levels
 3.Surveillance for bacterial infection urine (C/S )and viral infection (CMV
and HSV)
 4.Fetal surveillance for malformations, fetal growth, and well being
 5.Maternal surveillance for hypertension, gestational diabetes, and pre
eclampsia
58

59. Summary of Obstetric Management for Pregnancy After
Transplantation
Labor and delivery
 1.Aim to delivery at term
 2.Perform cesarian delivery for appropriate obstetric reasons
Postpartum
 1.Monitor immunosuppressive drug levels and alter doses and
regimen as necessary
 2.Begin contraception when appropriate
 3.The documented benefits of breastfeeding may outweigh the
potential risks of infant immunosuppressive exposure
 4.Mental health counselling if needed for postpartum depression
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