Klinisch II - P28 - Pregnancy in patients with a renal transplant: role of immune­suppressive drugs in pregnancy outcome

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D. Feyaerts, O.W.H. van der Heijden, H. Zweers, B. van Cranenbroek, I. Joosten, H.W. van Hamersvelt, R.G. van der Molen

Chair(s): dr. Arjan van Zuilen, UMCU

Thursday 10 march 2016

13:30 - 14:00h at Foyer

Categories: Postersessie

Parallel session: Postersessies XI - Opgesplitst in 3 tijdblokken en 3 categoriëen (klinisch, basaal, donatie)

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Pregnancy in women with a renal transplant (RTX) is associated with an increased risk of maternal and fetal complications, such as preeclampsia (PE) and preterm birth (PTB). In these patients, azathioprine (AZA) and calcineurin inhibitors (CNI) are the preferred immunosuppressive drugs (ISD) during pregnancy. Previous research has shown that ISD influence the composition and function of peripheral immune cells. Since uterine immune cells play an essential role in embryonic implantation, placentation and fetal tolerance, we hypothesize that the use of ISD in RTX patients influences the pathogenesis of pregnancy related complications.

We performed a retrospective study between 1997 and 2013 of 26 RTX patients (mean age 31 ± 4 years) who carried a total of 40 pregnancies. We investigated the maternal and fetal outcomes according to ISD use. Furthermore, we initiated a prospective study to characterize lymphocytes isolated from peripheral blood (PBMC) and placental tissue by flowcytometry, obtained at the time of delivery from RTX patients compared to healthy pregnant controls.

Results of the retrospective study showed that 40% of pregnancies were complicated by PE , 47% by PTB and 43% by low birth weight. Patients using CNI developed PE earlier as compared to patients using AZA (gestational age at onset respectively 32 wks and 37 wks, p=0.009). Mean protein levels rose during pregnancy for our total study population (AZA 0.50 g/L, p=0.008; CNI 0.84 g/L, p=0.002). No statistical differences were found in the course of renal function with respect to immunosuppressive regimens. Patients using CNI showed a higher diastolic blood pressure within 6 months post-delivery (p=0.005). Fetal outcomes were similar, although newborns of patients using CNI tended to have a lower birth weight. 

Preliminary results from the immunological study of 5 RTX pregnant patients showed an increased percentage of CD4⁺FoxP3⁺CD25^high  regulatory  T cells (Treg) in placental derived lymphocytes from RTX patients compared to controls (n=9), while the percentage of Treg in PBMC was significantly lower in RTX patients as compared to controls.

Our data pertaining to maternal and fetal outcome to pregnancy favors the use of AZA above CNI as a preferred immunosuppressive choice for pregnant RTX patients. Our preliminary data from immunological assays showed an altered lymphocyte phenotype and suggests a role for Treg in the pathogenesis of pregnancy related complications in pregnant RTX recipients.