Renal transplantation rehabilitates the recipient back to a normal lifestyle situation and post-transplant pregnancy is an ideal example for this statement. Chronic kidney disease is associated with irregular menstrual cycles, anovulatory cycles and decreased libido; a successful transplantation normalizes these abnormalities. Pregnancy is definitely advised for a renal transplant recipient with careful monitoring during pregnancy.

Timing of Pregnancy :

Renal transplant recipients are advised to avoid pregnancy for the first year after transplantation, even if the kidney functions are normal. (1) Normal ovulation starts within months after transplantation and these women should be advised regarding contraception before transplant itself. There is an increased risk of rejection, graft failure and premature births in the first-year post transplantation.

The woman should have a stable kidney function (creatinine less than 1.4 mg%), proteinuria less than 500 mg/day and blood pressure should be well under control with anti-hypertensive medications. There should be no recent episodes of acute rejection.

Detailed counseling regarding these issues during pregnancy should be discussed.

Renal Physiology and Pregnancy:

Normal pregnancy is a state of renal hyperfiltration and the GFR increases by 50%. This is due to the increase in total body water. The threshold for thirst and anti-diuretic hormone secretion is depressed and it leads to increased water consumption and retention of water. This is seen in post-transplant pregnancy also. The transplant kidney withstands this hyperfiltration, that normalizes post-partum.

The blood pressure drops due to angiotensin resistance and due to vasodilatory state of pregnancy. This drop in blood pressure stimulates RAAS and ultimately the increase in aldosterone causes excess sodium retention. (2) Pregnancy is also a state of immune tolerance and this decreases the chances of rejection during pregnancy.

Careful Watch on Medications Prior to Pregnancy:

This is an important aspect which has to be considered before allowing pregnancy in a renal transplant patient. Calcineurin inhibitors (Cyclosporin and Tacrolimus), Azathioprine and steroids are safe during pregnancy; (3) Mycophenolate and Sirolimus should be stopped at least 6 to 8 weeks before pregnancy. The use of Everolimus is not clear and there are reports of successful pregnancies with Everolimus.

Among anti-hypertensive medications, ACE inhibitors and ARBs are contra-indicated during pregnancy, especially after the first trimester.

Problems to Watch for During Pregnancy

1. Blood Pressure: It is estimated that about 50 % of the patients have hypertension post transplantation. This increases the risk of pre-eclampsia and eclampsia to above 30% during pregnancy and this is 4 to 5 times higher compared to normal population (4).
2. Infections: Bacterial UTI is common during pregnancy. The dilatation of pelvicalyceal system increases the chances of infection. Asymptomatic bacteriuria should be treated for 2 weeks. CMV infection in the mother increases the risk of congenital CMV infection in the child.
3. Allograft Functions: Pregnancy is a state of immune tolerance, so that the chances of allograft rejection during pregnancy is less. But the risk increases postpartum. If the pre-pregnancy renal functions are normal, then the risk of graft dysfunction is comparable to normal woman. The hyperfiltration during pregnancy could increase the chances of proteinuria from allograft.
4. Post-transplant diabetes is a common phenomenon and it is due to the steroids and calcineurin inhibitor immune suppression intake, increased appetite, etc. There is also an increased risk of gestational diabetes in post-transplant pregnancy, estimated to be around 8 to 10%. The risk of congenital anomalies, macrosomia and increased fetal deaths are noted. Good glycemic control during gestation is important, (4).

Fetal Complications:

There is an increased chance of low birth weight, pre-term delivery, small for gestational age infants and increased Caesarean sections in post-transplant pregnancies. (5) Pre-pregnancy poor kidney function, higher proteinuria (> 500 mg) and uncontrolled blood pressure increase these risks.

Breast feeding is NOT contraindicated and it is estimated that the exposure of the immunosuppressive medications through breast milk are significantly lesser compared to the exposure through placenta.

Conclusions:

Pregnancy is a normal event in a renal transplant recipient. It is safer to plan for pregnancy after the first year of transplant in a person with normal graft function, with well-controlled blood pressure and with less than 500 mg proteinuria. Pre-pregnancy counseling and modifications of medications are important. Monitoring should be done with regards to blood pressure, diabetes, infections and proteinuria. There is increased chance of pre-eclampsia, low birth weight babies and pre-term deliveries in post-transplant pregnancy.

1. Silvi Shah et al. Pregnancy outcomes in women with kidney transplant: Meta analysis and systematic review. BMC Nephrology volume 20, Article number: 24 (2019)

2.  Neha A Deshpande, BA et al. Pregnancy After Solid Organ Transplantation: A Guide for Obstetric Management. Rev Obstet Gynecol. 2013; 6(3-4): 116–125

3.  Deshpande NA, James NT, Kucirka LM, Boyarsky BJ, Garonzik-Wang JM, Montgomery RA, Segev DL. Pregnancy outcomes in kidney transplant recipients: a systematic review and meta-analysis. Am J Transplant. 2011 Nov; 11(11):2388-404.

4.  Silvi Shah and Prasoon Verma. Overview of Pregnancy in Renal Transplant Patients. International Journal of Nephrology. Volume 2016 |Article ID 4539342

Dr. R. Balasubramaniyam
Consultant Chief Nephrologist
Kauvery Hospital