Preconception switch from mycophenolate to azathioprine

Transplantmedium

A 32-year-old woman presents for preconception counseling. She has ESRD due to immunoglobulin A (IgA) nephropathy. She received a kidney transplant from her husband 3 years ago. She had an episode of acute rejection 18 months ago that was successfully treated with glucocorticoids, and kidney function has subsequently been stable. Her current immunosuppressive medications are mycophenolate, tacrolimus, and prednisone. She feels well and reports no symptoms. Vital signs include a BP of 114/68 mm Hg and pulse 76/min. Physical examination is normal. Laboratory data are significant for a creatinine of 1.2 mg/dL (reference range, 0.5‒1.1). Which one of the following is the MOST APPROPRIATE recommendation regarding pregnancy planning?

  1. A.Pregnancy is contraindicated
  2. B.Change tacrolimus to cyclosporine
  3. C.Change mycophenolate to azathioprineCorrect
  4. D.Delay pregnancy for one year

Explanation

The most appropriate recommendation for this patient with ESRD status post kidney transplantation with good kidney function is to change mycophenolate to azathioprine before proceeding with pregnancy. Managing immunosuppression in kidney transplant recipients is important because of concerns about teratogenic risk. Mycophenolate mofetil is a category D drug for pregnancy and has been associated with fetal limb and facial congenital anomalies, including microtia, hypoplastic nails, shortened fifth finger, and cleft lip and palate; congenital diaphragmatic hernia; congenital heart defects; and increased risk of spontaneous abortion. Azathioprine, low-dose corticosteroids (prednisone <20 mg/day or equivalent), and calcineurin inhibitors (CNIs) are considered relatively safe during pregnancy. Medications that are teratogenic should be changed or stopped in kidney transplant recipients at least 6 weeks before conception. Typically, mycophenolate is changed to azathioprine, and sirolimus is changed to a CNI. Counseling about childbearing and risk of teratogenicity with immunosuppression should start at the pre-transplant evaluation and should be continued during post-transplant visits. Women of childbearing potential should follow a risk evaluation and mitigation strategy (REMS) and should be advised to use contraception while taking mycophenolate. Changing tacrolimus to cyclosporine would be unnecessary because both are CNIs and would not be expected to alter pregnancy outcomes. Conversely, changing mycophenolate to sirolimus would substitute one teratogenic medication for another. Pregnancy is not absolutely contraindicated, but maternal and fetal complications occur with greater frequency in transplant recipients, and careful counseling and close management are required. Most transplant programs ask patients to delay pregnancy for at least one year after surgery. A 2019 meta-analysis found that complications were fewer in the cohort who became pregnant 3 years or longer after surgery, but there did not appear to be an advantage to a longer delay.

Why each option

A.
Pregnancy is not contraindicated with stable graft function 3 years after transplant, though it needs careful counseling and high-risk obstetric care.
B.
Tacrolimus and cyclosporine are both calcineurin inhibitors considered relatively safe in pregnancy, so switching between them would not alter outcomes.
C.
Correct. Mycophenolate causes embryopathy and miscarriage, so it should be replaced with azathioprine at least 6 weeks before conception.
D.
Further delay is unnecessary because she is already 3 years post-transplant with stable function, beyond the usual one-year waiting period.

Reference: KDIGO 2009 Clinical Practice Guideline for the Care of Kidney Transplant Recipients; Shah S, Venkatesan RL, Gupta A, et al, BMC Nephrol 2019 (Pregnancy outcomes in women with kidney transplant: systematic review and meta-analysis)

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