Pregnancy In Kidney Transplant Flashcards
Introduction
A 32-year-old female with a past medical history of end-stage kidney disease
(ESKD) secondary to IgA nephropathy who underwent a deceased donor kidney
transplantation 4years ago is seen in the transplant clinic for follow-up.
Her immunosuppression regimen consists of tacrolimus 4 mg twice a day, mycophenolate mofetil (MMF) 500 mg BID, and prednisone 5 mg.
She has evidence of stable allograft function with a serum creatinine of 1.2mg/dL with no microscopic hematuria or proteinuria on urinalysis.
She wants to discuss aspects relating to pregnancy.
Criteria for Safe Pregnancy in Kidney Transplant Recipient
- Avoidance of pregnancy in first 1-2 years post-transplant
- No rejection within past year
- Stable maintenance immunosuppression
- No recent acute infections impeding fetal growth
- Serum creatinine < 132 umol/L (<1.5 mg/dL)
- Minimal or no proteinuria
- Notmal allograft ultrasound
- Good hypertension control
- Transition to pregnancy-safe drug
Estimated 3% of women of childbearing age conceive after transplantation
Incidence of spontaneous abortion 15%
About 1/3 patients may seek therapeutic abortion
If able continue beyond first trimester, >90% will be successful
Complications In Pregnancy with Kidney Transplant - Maternal and Fetal
Maternal complications
1. Hypertension
2. Pre-eclampsia (up to 31% cases)
3. GDM
4. Miscarriage
5. Allograft rejection
6. UTI
Fetal complications
1. Low birth weight/growth restriction (52%)
2. Stillbirths
3. Pre-term delivery (60%)
4. Neonatal death
5. Birth defects
6. Fetal distress
7. Premature rupture of membrane
8. NICU admission (35%)
Preparation and Monitoring of Pregnancy in Transplant Recipient
- Screen timing, fitness, Cr, urine PCR
- Adequate pre-pregnancy counseling
- Transition from MMF to azathioprine, mTOR to CNI
- Good control of hypertension
- Frequent monitoring of Cr, U PCR
- Start low dose aspirin between 12-18 weeks of pregnancy
- Withdrawal of ACEi/ARBs - neonatal nephropathy/renal agenesis
HPA axis restored by 6 months post-transplantation
- Improved fertility and sexual function
Safety Categories of immunosuppressants
Class C (animal studies, no well controlled studies in humans)
- CNI: tacrolimus, cyclosporin
- Corticosteroids
Class D (evidence of human fetal risk)
- MMF
- Azathioprine (but can be used in pregnancy)
- mTOR - everolimus, sirolimus
How to distinguish Pre-eclampsia from allograft rejection?
- Pre-pregnancy risks
- high baseline serum creatinine
- rejection before pregnancy
- suboptimal immunosuppressants - Specific telltale investigations
(Pre-eclampsia and allograft rejection signs and symptoms are quite similar)
Pre-eclampsia - Increased proteinuria
Allograft rejection - Raised creatinine - Definitive investigations
IR guided allograft biopsy
Treatment for Allograft Rejection in Pregnancy
- High dose Corticosteroids - safe
- KIV thymoglobulin, rituximab - sparse data
MMF is contraindicated in pregnancy.
What are the complications of MMF on fetus?
- Congenital malformations - ear malformation, face
- Spontaneous abortions
Always switch MMF to azathioprine before pregnancy
Prednisolone in pregnancy
Class C - potential harm in animal studies
Congenital malformations in animals
- Cleft lip and palate in large doses
Thought to be safe - alleged does not suppress fetal corticotropin
–> However there are still reports of neonatal adrenal insufficiency
Overall: low dose prednisolone is considered safe for use in pregnancy
Azathioprine in pregnancy
Class D - evidence of human fetal risk
Theoretical risk: transient gaps or breaks in lymphocytes chromosomes, potentially developing malignancy
–> No such malignancies are observed yet after several decades of use
Dose: 2mg/kg or lesser
No anomalies attributable so far
CNI in pregnancy
Class C - potential harms
Cyclosporin - chronic vasoconstriction
- Causes intrauterine growth restriction
Increased volume of distribution - cyclosporin distributed into fetal circulation
–> Dose adjustment and increment required
Not recommended for breastfeeding, CNI enters breast milk
Management of Antepartum to Postpartum
- Management of hypertension
- Suggest: nifedipine, labetalol, hydralazine, methyldopa
- Avoid: ACEi, ARB - Augmentation of steroids
- IV hydrocortisone 100mg Q6-12H during labor and delivery
- Prevents postpartum rejection - Vaginal delivery preferred
- Transplanted kidney in false pelvis, thus very little risk for obstruction of birth canal or mechanical injury to allograft - LSCS only if indicated
- Great care to identify and protect transplanted ureter, avoid accidental injury to transplanted kidney - Continued monitoring first 3 months post-partum
- Graft function
- Immunosuppressive regimen
- Watch for haemolytic uraemic syndrome
